Stabilization of disease progression by hydroxyurea in patients with recurrent or unresectable meningiomas

2002 ◽  
Vol 97 (2) ◽  
pp. 341-346 ◽  
Author(s):  
Warren P. Mason ◽  
Fred Gentili ◽  
David R. Macdonald ◽  
Subramanian Hariharan ◽  
Charlene R. Cruz ◽  
...  

Object. The management of certain meningiomas of the skull base and those involving the dural venous sinuses remains a challenge. In recent reports it has been suggested that hydroxyurea chemotherapy can cause regression of unresectable and recurrent meningiomas. The authors report their experience in using hydroxyurea for the treatment of patients with recurrent or unresectable meningiomas. Methods. Hydroxyurea was administered at a dosage of approximately 20 mg/kg/day to 11 women and nine men (median age 59 years, range 31–75 years) with recurrent or unresectable intracranial meningiomas (12 basal, two parasagittal, and six multiple). In 16 patients the meningiomas were benign, in three they had atypical features, and in one the meningioma was malignant. All patients had measurable residual disease. Four patients with benign meningiomas had previously received radiotherapy (two were treated with conventional fractionated radiotherapy and two with stereotactic radiosurgery), three with atypical meningiomas received conventional fractionated radiotherapy, and the one with a malignant meningioma received conventional radiotherapy with additional stereotactic radiosurgery. Tumor enlargement was documented in all patients on neuroimages obtained before initiation of hydroxyurea therapy. All patients were evaluable for response to therapy. In 12 patients with benign meningiomas, the disease had stabilized on neuroimages obtained posttreatment (median duration of treatment 122 weeks, range 8–151 weeks), and two of these showed clinical improvement. One patient with a benign meningioma experienced a minor partial response that was noted after 39 weeks of treatment and was confirmed on neuroimaging and clinical evaluations. In three others with benign meningiomas, progression was confirmed on neuroimages obtained after 41, 55, and 66 weeks, respectively; the 1-year freedom from progression rate was 0.93 (standard error 0.07) in patients with benign meningiomas. In three patients with atypical meningiomas, the tumors had progressed on neuroimages obtained after 12, 19, and 45 weeks, respectively. In the patient with a malignant meningioma, progression was confirmed on neuroimages obtained at 24 weeks. Hydroxyurea has been reasonably well tolerated, although one patient discontinued therapy because of moderate myelosuppression. Conclusions. Although tumor regression appears uncommon, these results indicate that hydroxyurea may arrest progression of unresectable or recurrent benign meningiomas.

1998 ◽  
Vol 88 (6) ◽  
pp. 1002-1008 ◽  
Author(s):  
Alex M. Landolt ◽  
Dieter Haller ◽  
Nicoletta Lomax ◽  
Stefan Scheib ◽  
Othmar Schubiger ◽  
...  

Object. The authors tested the assumption that gamma knife radiosurgery is more effective than fractionated radiotherapy for the treatment of patients with acromegaly who have undergone unsuccessful resective surgery. Untreated and uncured acromegaly causes illness and death. Acromegalic patients in whom growth hormone and, particularly, insulin-like growth factor I are not normalized must undergo further treatment. Methods. After unsuccessful operations, 16 patients suffering from recurrent and uncured acromegaly underwent stereotactic radiosurgery (25 Gy to the tumor margin, 50 Gy maximum), the outcome of which was compared with the result obtained in 50 patients who received fractionated radiotherapy (40 Gy). The cumulative distribution functions of the two groups (Kaplan—Meier estimate) differed significantly (p < 0.0001 in the log-rank test of Mantel). The mean time to simultaneous normalization of both parameters was 1.4 years in the group treated with the gamma knife and 7.1 years in the group treated with fractionated radiotherapy. Conclusions. The authors suggest the use of stereotactic radiosurgery as the preferred treatment for recurrent acromegaly resulting from unsuccessfully resected tumors.


1977 ◽  
Vol 47 (3) ◽  
pp. 329-335 ◽  
Author(s):  
Victor A. Levin ◽  
David C. Crafts ◽  
David M. Norman ◽  
Paul B. Hoffer ◽  
Jean-Paul Spire ◽  
...  

✓ The authors describe their criteria for evaluating brain-tumor patients, and present a numerical rating scale devised to designate response to testing. They discuss the reliability of test combinations that permit accurate prediction of response or deterioration during therapy in their experience with 100 patients treated on the Chemotherapy Service at the Brain Tumor Research Center, University of California, San Francisco School of Medicine. Specifically, the paper summarizes the predictive value of the neurological examination, radionuclide scintiscan, computerized tomographic brain scan (CT scan), and electroencephalogram (EEG), in the determination of response (tumor regression) or deterioration (tumor growth) during brain-tumor chemotherapy and chemotherapy-radiotherapy. By retrospective analysis, the neurological examination, radionuclide scintiscan, and CT scan were of equal value individually as tests to predict response to therapy. However, the prognostic values of the neurological examination or the radionuclide scintiscan proved moderately superior to the CT scan in predicting deterioration during therapy. Under circumstances whereby a neurological examination, radionuclide scintiscan, and CT scan were all performed during the same testing session, and steroid dosage was carefully monitored, two of the three tests accurately predicted deterioration in 65% of patients, and response to therapy in 82% of patients. Two of the three tests correctly established deterioration in the remaining 35% of patients, and response in the remaining 18% of patients, when the two positively correlated tests had occurred within a mean period of 7 weeks.


2005 ◽  
Vol 102 (4) ◽  
pp. 678-691 ◽  
Author(s):  
Jason P. Sheehan ◽  
Ajay Niranjan ◽  
Jonas M. Sheehan ◽  
John A. Jane ◽  
Edward R. Laws ◽  
...  

Object. Pituitary adenomas are very common neoplasms, constituting between 10 and 20% of all primary brain tumors. Historically, the treatment armamentarium for pituitary adenomas has included medical management, microsurgery, and fractionated radiotherapy. More recently, radiosurgery has emerged as a viable treatment option. The goal of this research was to define more fully the efficacy, safety, and role of radiosurgery in the treatment of pituitary adenomas. Methods. Medical literature databases were searched for articles pertaining to pituitary adenomas and stereotactic radiosurgery. Each study was examined to determine the number of patients, radiosurgical parameters (for example, maximal dose and tumor margin dose), duration of follow-up review, tumor growth control rate, complications, and rate of hormone normalization in the case of functioning adenomas. A total of 35 peer-reviewed studies involving 1621 patients were examined. Radiosurgery resulted in the control of tumor size in approximately 90% of treated patients. The reported rates of hormone normalization for functioning adenomas varied substantially. This was due in part to widespread differences in endocrinological criteria used for the postradiosurgical assessment. The risks of hypopituitarism, radiation-induced neoplasia, and cerebral vasculopathy associated with radiosurgery appeared lower than those for fractionated radiation therapy. Nevertheless, further observation will be required to understand the true probabilities. The incidence of other serious complications following radiosurgery was quite low. Conclusions. Although microsurgery remains the primary treatment modality in most cases, stereotactic radiosurgery offers both safe and effective treatment for recurrent or residual pituitary adenomas. In rare instances, radiosurgery may be the best initial treatment for patients with pituitary adenomas. Further refinements in the radiosurgical technique will likely lead to improved outcomes.


2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 184-188 ◽  
Author(s):  
Gerald Langmann ◽  
Gerhard Pendl ◽  
Georg Papaefthymiou ◽  
Helmuth Guss ◽  

Object. The authors report their experience using gamma knife radiosurgery (GKS) to treat uveal melanomas. Methods. Between 1992 and 1998, 60 patients were treated with GKS at a prescription dose between 45 Gy and 80 Gy. The mean diameter of the tumor base was 12.2 mm (range 3–22 mm). The mean height of the tumor prominence was 6.7 mm (range 3–12 mm). The eye was immobilized. The follow-up period ranged from 16 to 94 months. Tumor regression was achieved in 56 (93%) of 60 patients. There were four recurrences followed by enucleation. The severe side effect of neovascular glaucoma developed in 21 (35%) patients in a high-dose group with larger tumors and in proximity to the ciliary body. A reduction in the prescription dose to 40 Gy or less and excluding treatment to tumors near the ciliary body decreased the rate of glaucoma without affecting the rate of tumor control. Conclusions. Gamma knife radiosurgery at a prescription dose of 45 Gy or more can achieve tumor regression in 85% of the uveal melanomas treated. Neovascular glaucoma can develop in patients when using this dose in tumors near the ciliary body. It is advised that such tumors be avoided and that the prescription dose be reduced to 40 Gy.


Author(s):  
Deborah L. Benzil ◽  
Mehran Saboori ◽  
Alon Y. Mogilner ◽  
Ronald Rocchio ◽  
Chitti R. Moorthy

Object. The extension of stereotactic radiosurgery treatment of tumors of the spine has the potential to benefit many patients. As in the early days of cranial stereotactic radiosurgery, however, dose-related efficacy and toxicity are not well understood. The authors report their initial experience with stereotactic radiosurgery of the spine with attention to dose, efficacy, and toxicity. Methods. All patients who underwent stereotactic radiosurgery of the spine were treated using the Novalis unit at Westchester Medical Center between December 2001 and January 2004 are included in a database consisting of demographics on disease, dose, outcome, and complications. A total of 31 patients (12 men, 19 women; mean age 61 years, median age 63 years) received treatment for 35 tumors. Tumor types included 26 metastases (12 lung, nine breast, five other) and nine primary tumors (four intradural, five extradural). Thoracic tumors were most common (17 metastases and four primary) followed by lumbar tumors (four metastases and four primary). Lesions were treated to the 85 to 90% isodose line with spinal cord doses being less than 50%. The dose per fraction and total dose were selected on the basis of previous treatment (particularly radiation exposure), size of lesion, and proximity to critical structures. Conclusions. Rapid and significant pain relief was achieved after stereotactic radiosurgery in 32 of 34 treated tumors. In patients treated for metastases, pain was relieved within 72 hours and remained reduced 3 months later. Pain relief was achieved with a single dose as low as 500 cGy. Spinal cord isodoses were less than 50% in all patients except those with intradural tumors (mean single dose to spinal cord 268 cGy and mean total dose to spinal cord 689 cGy). Two patients experienced transient radiculitis (both with a biological equivalent dose (BED) > 60 Gy). One patient who suffered multiple recurrences of a conus ependymoma had permanent neurological deterioration after initial improvement. Pathological evaluation of this lesion at surgery revealed radiation necrosis with some residual/recurrent tumor. No patient experienced other organ toxicity. Stereotactic radiosurgery of the spine is safe at the doses used and provides effective pain relief. In this study, BEDs greater than 60 Gy were associated with an increased risk of radiculitis.


2004 ◽  
pp. 373-380 ◽  
Author(s):  
Timothy D. Solberg ◽  
Steven J. Goetsch ◽  
Michael T. Selch ◽  
William Melega ◽  
Goran Lacan ◽  
...  

Object. The purpose of this work was to investigate the targeting and dosimetric characteristics of a linear accelerator (LINAC) system dedicated for stereotactic radiosurgery compared with those of a commercial gamma knife (GK) unit. Methods. A phantom was rigidly affixed within a Leksell stereotactic frame and axial computerized tomography scans were obtained using an appropriate stereotactic localization device. Treatment plans were performed, film was inserted into a recessed area, and the phantom was positioned and treated according to each treatment plan. In the case of the LINAC system, four 140° arcs, spanning ± 60° of couch rotation, were used. In the case of the GK unit, all 201 sources were left unplugged. Radiation was delivered using 3- and 8-mm LINAC collimators and 4- and 8-mm collimators of the GK unit. Targeting ability was investigated independently on the dedicated LINAC by using a primate model. Measured 50% spot widths for multisource, single-shot radiation exceeded nominal values in all cases by 38 to 70% for the GK unit and 11 to 33% for the LINAC system. Measured offsets were indicative of submillimeter targeting precision on both devices. In primate studies, the appearance of an magnetic resonance imaging—enhancing lesion coincided with the intended target. Conclusions. Radiosurgery performed using the 3-mm collimator of the dedicated LINAC exhibited characteristics that compared favorably with those of a dedicated GK unit. Overall targeting accuracy in the submillimeter range can be achieved, and dose distributions with sharp falloff can be expected for both devices.


2004 ◽  
Vol 101 (Supplement3) ◽  
pp. 351-355 ◽  
Author(s):  
Javad Rahimian ◽  
Joseph C. Chen ◽  
Ajay A. Rao ◽  
Michael R. Girvigian ◽  
Michael J. Miller ◽  
...  

Object. Stringent geometrical accuracy and precision are required in the stereotactic radiosurgical treatment of patients. Accurate targeting is especially important when treating a patient in a single fraction of a very high radiation dose (90 Gy) to a small target such as that used in the treatment of trigeminal neuralgia (3 to 4—mm diameter). The purpose of this study was to determine the inaccuracies in each step of the procedure including imaging, fusion, treatment planning, and finally the treatment. The authors implemented a detailed quality-assurance program. Methods. Overall geometrical accuracy of the Novalis stereotactic system was evaluated using a Radionics Geometric Phantom Chamber. The phantom has several magnetic resonance (MR) and computerized tomography (CT) imaging—friendly objects of various shapes and sizes. Axial 1-mm-thick MR and CT images of the phantom were acquired using a T1-weighted three-dimensional spoiled gradient recalled pulse sequence and the CT scanning protocols used clinically in patients. The absolute errors due to MR image distortion, CT scan resolution, and the image fusion inaccuracies were measured knowing the exact physical dimensions of the objects in the phantom. The isocentric accuracy of the Novalis gantry and the patient support system was measured using the Winston—Lutz test. Because inaccuracies are cumulative, to calculate the system's overall spatial accuracy, the root mean square (RMS) of all the errors was calculated. To validate the accuracy of the technique, a 1.5-mm-diameter spherical marker taped on top of a radiochromic film was fixed parallel to the x–z plane of the stereotactic coordinate system inside the phantom. The marker was defined as a target on the CT images, and seven noncoplanar circular arcs were used to treat the target on the film. The calculated system RMS value was then correlated with the position of the target and the highest density on the radiochromic film. The mean spatial errors due to image fusion and MR imaging were 0.41 ± 0.3 and 0.22 ± 0.1 mm, respectively. Gantry and couch isocentricities were 0.3 ± 0.1 and 0.6 ± 0.15 mm, respectively. The system overall RMS values were 0.9 and 0.6 mm with and without the couch errors included, respectively (isocenter variations due to couch rotation are microadjusted between couch positions). The positional verification of the marker was within 0.7 ± 0.1 mm of the highest optical density on the radiochromic film, correlating well with the system's overall RMS value. The overall mean system deviation was 0.32 ± 0.42 mm. Conclusions. The highest spatial errors were caused by image fusion and gantry rotation. A comprehensive quality-assurance program was developed for the authors' stereotactic radiosurgery program that includes medical imaging, linear accelerator mechanical isocentricity, and treatment delivery. For a successful treatment of trigeminal neuralgia with a 4-mm cone, the overall RMS value of equal to or less than 1 mm must be guaranteed.


1996 ◽  
Vol 85 (6) ◽  
pp. 1013-1019 ◽  
Author(s):  
William M. Mendenhall ◽  
William A. Friedman ◽  
John M. Buatti ◽  
Francis J. Bova

✓ In this paper the authors evaluate the results of linear accelerator (LINAC)—based stereotactic radiosurgery for acoustic schwannomas. Fifty-six patients underwent LINAC-based stereotactic radiosurgery for acoustic schwannomas at the University of Florida between July 1988 and November 1994. Each patient was followed for a minimum of 1 year or until death; no patient was lost to follow up. One or more follow-up magnetic resonance images or computerized tomography scans were obtained in 52 of the 56 patients. Doses ranged between 10 and 22.5 Gy with 69.6% of patients receiving 12.5 to 15 Gy. Thirty-eight patients (68%) were treated with one isocenter and the dose was specified to the 80% isodose line in 71% of patients. Fifty-five patients (98%) achieved local control after treatment. The 5-year actuarial local control rate was 95%. At the time of analysis, 48 patients were alive and free of disease, seven had died of intercurrent disease, and one was alive with disease. Complications developed in 13 patients (23%). The likelihood of complications was related to the dose and treatment volume: 10 to 12.5 Gy to all volumes, three (13%) of 23 patients; 15 to 17.5 Gy to 5.5 cm3 or less, two (9%) of 23 patients; 15 to 17.5 Gy to more than 5.5 cm3, five (71%) of seven patients; and 20 to 22.5 Gy to all volumes, three (100%) of three patients. Linear accelerator—based stereotactic radiosurgery results in a high rate of local control at 5 years. The risk of complications is related to the dose and treatment volume.


1998 ◽  
Vol 88 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Klaus A. Leber ◽  
Jutta Berglöff ◽  
Gerhard Pendl

As the number of patients treated with stereotactic radiosurgery increases, it becomes particularly important to define with precision adverse effects on distinct structures of the nervous system. Object. This study was designed to assess the dose—response tolerance of the visual pathways and cranial nerves after exposure of the cavernous sinus to radiation. Methods. A total of 66 sites in the visual system and 210 cranial nerves of the middle cranial fossa were investigated in 50 patients who had undergone gamma knife treatment for benign skull base tumors. The mean follow-up period was 40 months (range 24–60 months). Follow-up examinations consisted of neurological, neuroradiological, and neuroophthalmological evaluations. The actuarial incidence of optic neuropathy was zero for patients who received a radiation dose of less than 10 Gy, 26.7% for patients receiving a dose in the range of 10 to less than 15 Gy, and 77.8% for those who received doses of 15 Gy or more (p < 0.0001). Previously impaired vision improved in 25.8% and was unchanged in 51.5% of patients. No sign of neuropathy was seen in patients whose cranial nerves of the cavernous sinus received radiation doses of between 5 and 30 Gy. Because tumor control appeared to have been achieved in 98% of the patients, the deterioration in visual function cannot be attributed to tumor progression. Conclusions. The structures of the visual pathways (the optic nerve, chiasm, and tract) exhibit a much higher sensitivity to single-fraction radiation than other cranial nerves, and their particular dose—response characteristics can be defined. In contrast, the oculomotor and trigeminal nerves have a much higher dose tolerance.


1985 ◽  
Vol 62 (1) ◽  
pp. 18-24 ◽  
Author(s):  
René O. Mirimanoff ◽  
Daniel E. Dosoretz ◽  
Rita M. Linggood ◽  
Robert G. Ojemann ◽  
Robert L. Martuza

✓ The rates of survival, tumor recurrence, and tumor progression were analyzed in 225 patients with meningioma who underwent surgery as the only treatment modality between 1962 and 1980. Patients were considered to have a recurrence if their studies verified a mass effect in spite of a complete surgical removal, whereas they were defined as having progression if, after a subtotal excision, there was clear radiological documentation of an increase in the size of their tumor. There were 168 females and 57 males (a ratio of 2.9:1), with a peak incidence of tumor occurrence in the fifth (23%), sixth (29%), and seventh (23%) decades of life. Anatomical locations were the convexity (21%), parasagittal area (17%), sphenoid ridge (16%), posterior fossa (14%), parasellar region (12%), olfactory groove (10%), spine (8%), and orbit (2%). The absolute 5-, 10-, and 15-year survival rates were 83%, 77%, and 69%, respectively. Following a total resection, the recurrence-free rate at 5, 10, and 15 years was 93%, 80%, and 68%, respectively, at all sites. In contrast, after a subtotal resection, the progression-free rate was only 63%, 45%, and 9% during the same period (p < 0.0001). The probability of having a second operation following a total excision after 5, 10, and 15 years was 6%, 15%, and 20%, whereas after a subtotal excision the probability was 25%, 44%, and 84%, respectively (p < 0.0001). Tumor sites associated with a high percentage of total excisions had a low recurrence/progression rate. For example, 96% of convexity meningiomas were removed in toto, and the recurrence/progression rate at 5 years was only 3%. Parasellar meningiomas, with a 57% total excision rate, had a 5-year probability of recurrence/progression of 19%. Only 28% of sphenoid ridge meningiomas were totally resected, and at 5 years the probability of recurrence/progression was 34%. In patients undergoing a second resection, the probability of a third operation at 5 and 10 years was 42% and 56%, respectively. There was no difference in the recurrence/progression rates according to the patients' age or sex, or the duration of symptoms. Implications for the potential role of adjunctive medical therapy or radiation therapy for meningiomas are discussed.


Sign in / Sign up

Export Citation Format

Share Document