Increased cochlear radiation dose predicts delayed hearing loss following both stereotactic radiosurgery and fractionated stereotactic radiotherapy for vestibular schwannoma.

PURPOSE: Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) are noninvasive therapies for vestibular schwannomas providing excellent tumor control. However, delayed hearing loss after radiation therapy remains an issue. One potential target to for improving hearing rates is limiting radiation exposure to the cochlea. METHODS: We retrospectively reviewed 100 patients undergoing either SRS with 12 Gy (n = 43) or fSRT with 50 Gy over 28 fractions (n = 57) for vestibular schwannoma. Univariate and multivariate analysis were carried out to identify predictors of hearing loss as measured by the Gardner Robertson scale after radiation therapy. RESULTS: Deterioration of hearing occurred in 30% of patients with SRS and 26% with fSRT. The overall long term (> 2 year) progression rates were 20% for SRS and 16% for fSRT. Patients with a decrease in their Gardner Robertson hearing score and those that loss serviceable hearing had significantly higher average minimal doses to the cochlea in both SRS and fSRT cohorts. ROC analysis showed that a cut off of 5 Gy and 35 Gy, for SRS and fSRT respectively, predicted hearing loss with high sensitivity/specificity. CONCLUSION: Our data suggests the minimal dose of radiation that the cochlear volume is exposed to is a predictor of delayed hearing loss after either SRS or fSRT. A threshold of 5 Gy/35 Gy may lead to improved hearing preservation after radiotherapy. Further prospective multi center studies can further elucidate this mechanism.

A child with gemcitabine-induced severe radiation recall myositis resulting in a compartment syndrome.

Chemotherapeutic induction of radiation recall (RR) is a rare event in which a chemotherapeutic agent given days to years after radiation therapy causes an inflammation reaction of the tissues within the irradiated area-"recalling" increased radiation effects to that area. In this unique case, a 14-year-old girl with a synovial sarcoma of the forearm was treated with neoadjuvant chemotherapy and radiation therapy. Gemcitabine was administered in an adjuvant setting inducing a RR reaction. The severity of the inflammation resulted in a forearm myositis secondarily causing a compartment syndrome that was treated with several prolonged courses of corticosteroids. The symptoms of RR and compartment syndrome have resolved 1 year postonset, although magnetic resonance imaging continues to show myositis and soft-tissue edema. This case highlights the need to maintain a heightened awareness to recognizing the signs and symptoms of RR and the potential severity of RR in pediatric cancer patients in conjunction with chemotherapeutic agents used more frequently in adults.

Stereotactic radiation therapy for progressive residual pilocytic astrocytomas.

This report shows the results of stereotactic radiation therapy for progressive residual pilocytic astrocytomas. Medical records of patients who had undergone stereotactic radiation therapy for a progressive residual pilocytic astrocytoma were reviewed. Between 1995 and 2010, 12 patients with progression of a residual pilocytic astrocytoma underwent stereotactic radiation therapy at UCLA. Presentation was headache (4), visual defects (3), hormonal disturbances (2), gelastic seizures (2) and ataxia (1). MRI showed a cystic (9), mixed solid/cystic (2) or solid tumor (1); located in the hypothalamus (5), midbrain (3), thalamus (2), optic chiasm (1) or deep cerebellum (1). Median age was 21 years (range 5-41). Nine tumors received stereotactic radiotherapy (SRT). Three tumors received stereotactic radiosurgery (SRS), two of them to their choline positive regions. SRT median total dose was 50.4 Gy (40-50.4 Gy) in a median of 28 fractions (20-28), using a median fraction dose of 1.8 Gy (1.8-2 Gy) to a median target volume of 6.5 cm(3). (2.4-33.57 cm(3)) SRS median dose was 18.75 Gy (16.66-20 Gy) to a median target volume of 1.69 cm(3) (0.74-2.22 cm(3)). Median follow-up time was 37.5 months. Actuarial long-term progression-free and disease-specific survival probabilities were 73.3 and 91.7 %, respectively. No radiation-induced complications were observed. Stereotactic radiation therapy is a safe and effective modality to control progressive residual pilocytic astrocytomas. Better outcomes are obtained with SRT to entire tumor volumes than with SRS targeting choline positive tumor regions.

Phase II study of pre-irradiation chemotherapy for childhood intracranial ependymoma. Children's Cancer Group protocol 9942: a report from the Children's Oncology Group.

PURPOSE: Standard therapy for childhood intracranial ependymoma is maximal tumor resection followed by involved-field irradiation. Although not used routinely, chemotherapy has produced objective responses in ependymoma, both at recurrence and in infants. Because the presence of residual tumor following surgery is consistently associated with inferior outcome, the potential impact of pre-irradiation chemotherapy was investigated. METHODS: Between 1995 and 1999, the Children's Cancer Group undertook a Phase II trial of pre-irradiation chemotherapy in children 3-21 years of age with intracranial ependymoma and radiological evidence of post-operative residual tumor. RESULTS: Of 84 patients, 41 had residual tumor, and were given four cycles of cisplatin-based chemotherapy prior to irradiation. Of 35 patients fully evaluable for response to chemotherapy, 14 (40%) demonstrated complete response, 6 (17%) partial response, 10 (29%) minor response or stable disease, and 5 (14%) demonstrated progressive tumor growth. For the entire group, 5-year overall survival (OS) and event-free survival (EFS) was 71 ± 6%, and 57 ± 6%, respectively. The pre-irradiation chemotherapy group demonstrated EFS comparable to that of patients with no residual tumor who received irradiation alone (55 ± 8% vs. 58 ± 9%, P = 0.45). Any benefit of chemotherapy was restricted to patients with greater than 90% tumor resection. CONCLUSIONS: Children with near total resection of ependymoma may benefit from pre-irradiation chemotherapy. Patients with subtotal resection have inferior outcome despite responses to chemotherapy, and should be considered for second-look surgery prior to irradiation. Pediatr Blood Cancer 2012; 59: 1183-1189. © 2012 Wiley Periodicals, Inc.

Image-guided radiosurgery for spinal tumors: methods, accuracy and patient intrafraction motion.

Image-guided frameless extracranial radiosurgery has become an established treatment option; however, without a frame to restrict patient movements, intrafraction field mispositioning becomes more probable. The primary aim of this study is to determine the intrafraction motion of spinal radiosurgery patients. This aim was approached in two steps. First, a phantom study demonstrated that the system can detect movements accurately within 0.1 mm and rotational changes within 0.2 degrees. Second, patient positioning and monitoring were carried out for a group of 15 patients with 20 treatment sites. For the patient pool in the study, vertebral anatomy movement was observed to vary as much as 3 mm between sequential measurements and could occur in as little as 5 min. These results suggest a need for intrafraction patient monitoring and correctional shifts, even for patients whose overall treatment times are expected to be relatively short. Small relative rotations with standard deviations of less than 1.5 degrees were observed. The small relative rotational movements observed do not, alone, justify patient monitoring using the image-guidance system during the treatments of generally small radiosurgical targets.

Long-term Outcomes With Ifosfamide-based Hypofractionated Preoperative Chemoradiotherapy for Extremity Soft Tissue Sarcomas.

OBJECTIVES: The objective of this study was to analyze outcomes for patients with soft tissue sarcoma of the extremities using neoadjuvant ifosfamide-based chemotherapy and hypofractionated reduced dose radiotherapy, followed by limb-sparing surgery. MATERIALS AND METHODS: An Institutional Review Board (IRB)-approved retrospective review of patients treated at a single institution between 1990 and 2013 was performed. In total, 116 patients were identified who received neoadjuvant ifosfamide-based chemotherapy and 28 Gy in 8 fractions of preoperative radiation (equivalent dose in 2 Gray fractions, 31.5 Gy [α/ß 10] 36.4 Gy [α/ß 3]) followed by limb-sparing surgery. Local recurrence (LR), distant failure (DF), and overall survival (OS) were calculated. Univariate and multivariate analysis for LR, DF, and OS were performed using Cox analysis. Statistical significance was set at a P<0.05. RESULTS: Median follow-up was 5.9 years (range, 0.3 to 24 y). Actuarial LR at 3/6 years was 11%/17%, DF at 3/6 years was 25%/35%, and OS at 3/6 years was 82%/67%. On multivariate analysis, only a positive surgical margin was significantly correlated with worse local control (P=0.005; hazard ratio [HR], 18.33; 95% confidence interval (CI), 2.41-139.34). Age over 60 years (P=0.03; HR, 2.34; 95% CI, 1.10-4.98) and tumor size over 10 cm compared with tumor size ≤5 cm (P=0.03; HR, 3.32; 95% CI, 1.15-9.61) were associated with worse OS. CONCLUSIONS: Soft tissue extremity sarcoma patients treated using reduced dose hypofractionated preoperative radiotherapy in combination with ifosfamide-based chemotherapy shows acceptable local control and warrants further investigation.

Stereotactic radiation treatment for recurrent nonbenign meningiomas.

OBJECT: The authors analyzed the results of stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) for the treatment of recurrent meningiomas that were described at initial resection as showing aggressive, atypical, or malignant features (nonbenign). METHODS: Twenty-five patients who underwent SRS and/or SRT for nonbenign meningiomas between December 1992 and August 2004 were included. Thirteen of these patients underwent treatment for multiple primary or recurrent lesions. In all, 52 tumors were treated. All histological sections were reviewed and reclassified according to World Health Organization (WHO) 2000 guidelines as benign (Grade I), atypical (Grade II), or anaplastic (Grade III) meningiomas. The median follow-up period was 42 months. Seventeen (68%) of the cases were reclassified as follows: WHO Grade I (five cases), Grade II (11 cases), and Grade III (one case). Malignant progression occurred in eight cases (32%) during the follow-up period; these cases were considered as a separate group. The 3-year progression-free survival (PFS) rates for the Grades I, II, and III, and malignant progression groups were 100, 83, 0, and 11%, respectively (p < 0.001). In the Grade II group, the 3-year PFS rates for patients treated with SRS and SRT were 100 and 33%, respectively (p = 0.1). After initial treatment, 22 new tumors required treatment using SRS or SRT; 17 (77%) of them occurred inside the original resection cavity. Symptomatic edema developed in one patient (4%). CONCLUSIONS: Stereotactic radiation treatment provided effective local control of "aggressive" Grade I and Grade II meningiomas, whereas Grade III lesions were associated with poor outcome. The outcome of cases in the malignant progression group was intermediate between that of the Grade II and Grade III groups, with the lesions showing a tendency toward malignancy.

Brainstem and trigeminal nerve changes after radiosurgery for trigeminal pain.

PURPOSE: To evaluate the significance of radiological changes on follow-up MRIs after SRS for TN. MATERIALS AND METHODS: Thirty-seven patients with follow-up MRI because of paresthesias, bilateral treatment, or failure were analyzed regarding pain outcome and complications. Mean age was 64.4 years; 14 underwent previous treatment. Twenty-nine had ETN, 5 secondary TN due to tumor or multiple sclerosis, and 3 had atypical TN. Ninety gray was prescribed for 20 patients, 70 Gy for 5, and 80/85 Gy for 2. A 5-mm collimator was used in 32 (88.9%) cases. Mean follow-up was 15 months (range, 4-52 months). RESULTS: Excellent/good pain relief was sustained in 67% of cases at 13 months' follow-up. Enhancement on MRIs was observed in 21 cases (56.75%) with nerve enhancement in 9, pons enhancement in 4, pons-nerve enhancement in 4, and tumor enhancement in 4. Magnetic resonance images were unremarkable in 16 cases. Pain recurred in 4 cases (5.5-10 months). Pons enhancement correlated with pain relief (P = .0087) but not with nerve enhancement (P = .22). Incidence of slight paresthesias was 66.6%. No anesthesia dolorosa or ophthalmologic problems were observed. Paresthesias correlated with enhancement (P = .02), but not with brainstem volume encompassed by the 20%, 30%, and 50% isodoseline (P = .689, .525, .908). Enhancement free probability at 12 months was 48.5% (Kaplan-Meier). CONCLUSIONS: Pons enhancement seems to be prognostic for pain relief without higher incidence of complications. Pons volume irradiated did not predict enhancement occurrence. Radiation delivery to the brainstem-REZ interface seems to improve pain outcome, although more paresthesias should be expected.

Tomotherapy improves local control and changes failure patterns in locally advanced malignant pleural mesothelioma.

PURPOSE: The purpose of the study was to determine whether intensity modulated radiation therapy delivered via helical tomotherapy improves local control (LC) after pleurectomy/decortication (P/D) for malignant pleural mesothelioma compared with 3-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS: Forty-five consecutive patients were treated with adjuvant radiation to 45 Gy in 1.8 Gy fractions after P/D between 2006 and 2014; 23 received 3D-CRT, and 22 received tomotherapy. Kaplan-Meier analysis was used to calculate overall survival, time to in-field or local failure (LF), and time to out-of-field failure. The Student t test and Fisher exact test were used to detect between-group differences. RESULTS: Median follow-up time was 19.4 months and 12.7 months for the 3D-CRT and tomotherapy groups, respectively. Eighty-two percent of patients had T3/T4 disease, and 64% had positive nodes; 17.4% and 41% of patients in the 3D-CRT and tomotherapy groups had nonepithelioid histology, respectively. Mean planning target volume dose, percentage of planning target volume receiving 100% of the prescription dose, and lung doses were significantly greater with tomotherapy (P < .05), but toxicity rates (including radiation pneumonitis rates) were equivalent. LC was significantly improved with tomotherapy on Kaplan-Meier analysis with outcomes censored at 2 years (P < .05); uncensored, this became a trend (P = .06). Median time to LF was 19 months with tomotherapy and 10.9 months in 3D-CRT (the latter interval being less than the median follow-up in the tomotherapy group). On univariate analysis, treatment modality was the only significant predictor of LC (P < .05). Isolated LF was significantly more frequent with 3D-CRT (P < .05). Conversely, isolated out-of-field failure was significantly more frequent with tomotherapy (P < .05). Overall survival and out-of-field control were not significantly different. CONCLUSION: Tomotherapy after P/D for malignant pleural mesothelioma is associated with improved target coverage that translates into improved LC compared with 3D-CRT. This is related to a change in failure patterns, with isolated LF being more common in the 3D-CRT group and isolated out-of-field failures predominating in the tomotherapy group.

Stereotactic radiotherapy for treatment of cavernous sinus meningiomas.

PURPOSE: To assess the safety and efficacy of stereotactic radiotherapy (SRT) using a linear accelerator equipped with a micromultileaf collimator for cavernous sinus meningiomas. METHODS AND MATERIALS: Forty-five patients with benign cavernous sinus meningiomas were treated with SRT between November 1997 and April 2002. Sixteen patients received definitive treatment on the basis of imaging characteristics of the cavernous sinus tumor. Twenty-nine patients received SRT either as immediate adjuvant treatment after incomplete resection or at documented recurrence. Treatment planning in all patients included CT-MRI image fusion and beam shaping using a micromultileaf collimator. The primary tumor volume varied from 1.41 to 65.66 cm(3) (median, 14.5 cm(3)). The tumor diameter varied from 1.4 to 7.4 cm (median, 3.8 cm). Tumor compressed the optic chiasm or optic nerve in 30 patients. All tumors were treated with a single isocenter plus a margin of normal parenchyma varying from 1 to 5 mm (median, 2.5 mm). The prescribed dose varied from 4250 to 5400 cGy (median, 5040 cGy). The prescription isodose varied from 87% to 95% (median, 90%). The maximal tumor dose varied from 5000 to 6000 cGy (median, 5600 cGy). The follow-up varied from 12 to 53 months (median, 36 months). RESULTS: The actuarial 3-year overall and progression-free survival rate was 100% and 97.4%, respectively. One patient (2%) developed local relapsed at 18 months. A partial imaging response occurred in 18% of patients, and the tumor was stable in the remaining 80%. Preexisting neurologic complaints improved in 20% of patients and were stable in the remainder. No patient, tumor, or treatment factors were found to be predictive of imaging or clinical response. Transient acute morbidities included headache responsive to nonnarcotic analgesics in 4 patients, fatigue in 3 patients, and retroorbital pain in 1 patient. No treatment-induced peritumoral edema, cranial neuropathy, endocrine dysfunction, cognitive decline, or second malignancy occurred. One patient had an ipsilateral cerebrovascular accident 6 months after SRT. CONCLUSION: Stereotactic radiotherapy is both safe and effective for patients with cavernous sinus meningiomas. Field shaping using a micromultileaf collimator allows conformal and homogeneous radiation of cavernous sinus meningiomas that may not be amenable to single-fraction stereotactic radiosurgery because of tumor size or location. Additional clinical experience is necessary to determine the position of SRT among the available innovative fractionated RT options for challenging skull base meningiomas.

Investigations of a minimally invasive method for treatment of spinal malignancies with LINAC stereotactic radiation therapy: accuracy and animal studies.

PURPOSE: A new method for stereotactic irradiation of spinal malignancies is presented, with evaluations of the theoretic and practical limitations of localization accuracy and the implementation of the method in swine. MATERIALS AND METHODS: In a percutaneous procedure, a minimum of three small (1.7-mm-diameter) titanium markers are permanently affixed to a vertebra. Markers are localized on biplanar radiographs while isocenter positions are determined on CT. An external fiducial frame defines a three-dimensional coordinate system through the patient. Radiographs coupled with a rigid body rotation algorithm account for daily differences in patient position. Phantom studies were used to verify theoretic uncertainty calculations from a simulation program. A swine model was used to evaluate the difficulty and duration of the implant technique, the suitability of the vertebral process as an implant site, vertebral motion due to normal respiration, and the ability to target one vertebra with markers in an adjacent vertebra. RESULTS: Theoretic accuracy studies confirmed that localization accuracy is a function of marker separation. Phantom studies involving 296 measurements showed that individual implants could be localized within +/-0.25 mm. The largest targeting error observed in 3,600 measurements of 100 implant configurations was 1.17 mm. The implant procedure took 5-10 minutes per site. No significant migration of implants was observed up to 35 days postimplantation, and respiratory motion had no detectable influence on vertebral position. Adjacent vertebrae may be useful for targeting one another with a small sacrifice in localization accuracy. CONCLUSIONS: The use of implanted markers for localization of spinal malignancies has potential for applications in stereotactic radiotherapy. Phantom measurements suggest that localization accuracy similar to intracranial stereotactic radiotherapy techniques is achievable. Swine studies suggest that the implant technique is expedient and feasible for tumor targeting purposes.

Initial clinical results of stereotactic radiotherapy for the treatment of craniopharyngiomas.

The efficacy and toxicity of stereotactic radiotherapy (SRT) for the treatment of craniopharyngioma has been retrospectively evaluated in 16 patients. The median tumor diameter was 2.8 cm (range 1.5-6.1) and the median tumor volume was 7.7 cc (range 0.7-62.8). SRT was delivered to a single isocenter using a dedicated 6 MV linear accelerator to patients immobilized with a relocatable stereotactic head frame. The three-year actuarial overall survival was 93% and the rate of survival free of any imaging evidence of progressive disease was 75%. The three-year actuarial survival rates free of solid tumor growth or cyst enlargement were 94% and 81% respectively. Our results suggest that SRT is a safe and effective treatment approach for patients with craniopharyngioma. Long-term follow-up is required to determine whether the normal tissue-sparing inherent with SRT results in reduction of the neurocognitive effects of conventional radiotherapy for craniopharyngioma. SRT can be delivered to craniopharyngioma that may be difficult to treat with stereotactic radiosurgery due to proximity of the optic chiasm. Further clinical experience is necessary to determine the clinical utility of beam shaping in the setting of SRT.

Stereotactic radiotherapy for the treatment of acoustic neuromas.

OBJECT: The authors sought to assess the safety and efficacy of stereotactic radiotherapy when using a linear accelerator equipped with a micromultileaf collimator for the treatment of patients with acoustic neuromas. METHODS: Fifty patients harboring acoustic neuromas were treated with stereotactic radiotherapy between September 1997 and June 2003. Two patients were lost to follow-up review. Patient age ranged from 20 to 76 years (median 59 years), and none had neurofibromatosis. Forty-two patients had useful hearing prior to stereotactic radiotherapy. The fifth and seventh cranial nerve functions were normal in 44 and 46 patients, respectively. Tumor volume ranged from 0.3 to 19.25 ml (median 2.51 ml). The largest tumor dimension varied from 0.6 to 4 cm (median 2.2 cm). Treatment planning in all patients included computerized tomography and magnetic resonance image fusion and beam shaping by using a micromultileaf collimator. The planning target volume included the contrast-enhancing tumor mass and a margin of normal tissue varying from 1 to 3 mm (median 2 mm). All tumors were treated with 6-MV photons and received 54 Gy prescribed at the 90% isodose line encompassing the planning target volume. A sustained increase greater than 2 mm in any tumor dimension was defined as local relapse. The follow-up duration varied from 6 to 74 months (median 36 months). The local tumor control rate in the 48 patients available for follow up was 100%. Central tumor hypodensity occurred in 32 patients (67%) at a median of 6 months following stereotactic radiotherapy. In 12 patients (25%), tumor size increased 1 to 2 mm at a median of 6 months following stereotactic radiotherapy. Increased tumor size in six of these patients was transient. In 13 patients (27%), tumor size decreased 1 to 14 mm at a median of 6 months after treatment. Useful hearing was preserved in 39 patients (93%). New facial numbness occurred in one patient (2.2%) with normal fifth cranial nerve function prior to stereotactic radiotherapy. New facial palsy occurred in one patient (2.1 %) with normal seventh cranial nerve function prior to treatment. No patient's pretreatment dysfunction of the fifth or seventh cranial nerve worsened after stereotactic radiotherapy. Tinnitus improved in six patients and worsened in two. CONCLUSIONS: Stereotactic radiotherapy using field shaping for the treatment of acoustic neuromas achieves high rates of tumor control and preservation of useful hearing. The technique produces low rates of damage to the fifth and seventh cranial nerves. Long-term follow-up studies are necessary to confirm these findings.

Functional stereotactic radiosurgery involving a dedicated linear accelerator and gamma unit: a comparison study.

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 degrees arcs, spanning +/-60 degrees 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.

Novalis Shaped Beam Radiosurgery of arteriovenous malformations.

OBJECT: The authors studied outcomes and complications in patients who harbored arteriovenous malformations (AVMs) and underwent stereotactic radiosurgery involving the Novalis shaped beam unit. METHODS: Between January 1998 and January 2002, 83 patients were treated with radiosurgery at University of California, Los Angeles. The mean patient age was 37.8 years. Forty-four patients completed follow up. There were 24 women. Sixteen patients underwent repeated radiosurgery. Embolization was performed in 13 patients and radiosurgery alone in 31. The mean follow-up period after embolization was 54.4+/-21.9 months and 37.4+/-14.6 months for radiosurgery alone. The mean peripheral dose was 15 Gy (range 12-18 Gy). The mean preradiosurgery lesion volume was 9.7+/-11.9 ml for radiosurgery alone and 16.2+/-11.3 ml for embolization. The AVMs in 13 patients (29.8%) were Spetzler-Martin Grade II, 12 (27.5%) were Grade III, eight (18.2%) Grade IV, and five (11.3%) were Grade V and VI each. Spetzler-Martin grade, volume, and peripheral dose were analyzed in consideration to outcome. A positive trend (p = 0.086) was observed between Spetzler-Martin grade and obliteration rate. Volume per se did not predict obliteration (p = 0.48). A peripheral dose of 18 Gy was shown to be the most important predictor for occlusion (p = 0.007). The overall obliteration rate was 52.5%. A transient complication was noticed in one case (2.3%) and but no permanent deficits due to radiosurgery have been detected so far. Three patients (6.8%) bled after radiosurgery. CONCLUSIONS: The range of the prescribed peripheral dose was narrow. An association between the mean peripheral dose of 15 Gy, high conformality, and homogeneous dose distribution permitted no permanent complications. Volume per se did not correlate with outcome. The next step will be to increase the peripheral dose shaping the beam and to achieve higher obliteration rates without increasing complications.

Spinal lesions treated with Novalis shaped beam intensity-modulated radiosurgery and stereotactic radiotherapy.

OBJECT: Spinal radiosurgery was implemented to improve quality of life (QOL) in patients with malignancies. It may also be applicable to the treatment of benign lesions. METHODS: Between July 2002 and January 2004, 14 patients harboring 22 lesions were treated; 13 received single-dose stereotactic radiosurgery. Six were women. The mean age was 60.2 years (range 48-82 years). There were 11 metastases, two neurofibromas, and one meningioma. Six lesions were cervical, 10 thoracic, and six lumbar. Ten patients suffered pain, three paresthesias, two weakness, and three were asymptomatic. Seven patients underwent spinal surgery, with four receiving instrumentation. Twelve patients underwent conventional irradiation before stereotactic radiosurgery/stereotactic radiotherapy. A mean dose of 12+/-2.7 Gy (range 8-21 Gy) was prescribed to the 91% isodose line (range 85-97%). The mean tumor volume was 25+/-27.1 ml (range 0.75-91.8 ml). Treatment was planned using intensity-modulated radiosurgery (IMRS) fields in 15 cases, dynamic arcs in five, and conformal beams in two. The mean follow-up period was 6.1+/-3.9 months (range 1-16 months). Three patients became pain free and four experienced considerable relief. Weakness improved in the two patients with this preoperative symptom and the asymptomatic patients remained so. Four lesions decreased in size, five remained stable, seven progressed, and six were not followed up (two patients died before follow up). Four patients in all died, three of systemic disease and one of thoracic lesion progression. No complications due to shaped beam and IMRS/intensity-modulated radiotherapy (IMRT) techniques were observed. CONCLUSIONS: Shaped beam and IMRS/IMRT involving the Novalis system may delay neurological deterioration, improving QOL. The lack of complication suggests that higher doses can be delivered to improve the control rate in patients with metastases.

Stereotactic radiotherapy for the treatment of lymphocytic hypophysitis. Report of two cases.

Lymphocytic hypophysitis is a rare inflammatory disorder of the pituitary gland. Standard therapy consists of transsphenoidal resection or oral administration of corticosteroid medications. Two patients with symptomatic lymphocytic hypophysitis, which recurred after standard therapy, were treated with low-dose stereotactic radiotherapy. On imaging studies both lesions demonstrated a response to radiation and each patient experienced relief of symptoms. There has been no adverse sequela of the radiation treatment. The authors conclude that stereotactic radiotherapy represents an effective, noninvasive treatment option for patients with lymphocytic hypophysitis, particularly if the disease is recurrent after surgery or resistant to corticosteroid medications.

Evaluation of high ipsilateral subventricular zone radiation therapy dose in glioblastoma: a pooled analysis.

PURPOSE: Cancer stem cells (CSCs) may play a role in the recurrence of glioblastoma. They are believed to originate from neural stem cells in the subventricular zone (SVZ). Because of their radioresistance, we hypothesized that high doses of radiation (>59.4 Gy) to the SVZ are necessary to control CSCs and improve progression-free survival (PFS) or overall survival (OS) in glioblastoma. METHODS AND MATERIALS: 173 patients with glioblastoma pooled from 2 academic centers were treated with resection followed by chemoradiation therapy. The SVZ was segmented on computed tomography to calculate radiation doses delivered to the presumptive CSC niches. The relationships between high SVZ doses and PFS and OS were examined using Cox proportional hazards models. Five covariates were included to estimate their impact on PFS or OS: ipsilateral and contralateral SVZ doses, clinical target volume dose, age, and extent of resection. RESULTS: Median PFS and OS were 10.4 and 19.6 months for the cohort. The mean ipsilateral SVZ, contralateral SVZ, and clinical target volume doses were 49.2, 35.2, and 60.1 Gy, respectively. Twenty-one patients who received high ipsilateral SVZ dose (>59.4 Gy) had significantly longer median PFS (12.6 vs 9.9 months, P=.042) and longer OS (25.8 vs 19.2 months, P=.173). On multivariate analysis, high radiation therapy doses to ipsilateral SVZ remained a statistically significant independent predictor of improved PFS but not of OS. The extent of surgery affected both PFS and OS on multivariate analysis. CONCLUSION: High radiation therapy doses to ipsilateral CSC niches are associated with improved PFS in glioblastoma.

Radiation options for high-grade gliomas.

Radiotherapy has become a part of the standard treatment of high-grade gliomas. Studies have shown that high-dose radiation results in more effective tumor control but at the cost of radionecrosis and other radiation-related side effects. Despite advancing techniques in stereotaxy and precise radiotherapy delivery techniques, studies published for stereotactic radiosurgical treatment of high-grade gliomas have not been unanimous, with large trials showing no survival benefit compared with conventional conformal radiotherapy. New imaging modalities have been studied with the hope to improve accuracy in the planning of radiosurgical treatments. However, further large scale studies are needed to confirm these results.

Image-guided linear accelerator-based spinal radiosurgery for hemangioblastoma.

PURPOSE: To retrospectively review the efficacy and safety of image-guided linear accelerator-based radiosurgery for spinal hemangioblastomas. METHODS: Between August 2004 and September 2010, nine patients with 20 hemangioblastomas underwent spinal radiosurgery. Five patients had von Hipple-Lindau disease. Four patients had multiple tumors. Ten tumors were located in the thoracic spine, eight in the cervical spine, and two in the lumbar spine. Tumor volume varied from 0.08 to 14.4 cc (median 0.72 cc). Maximum tumor dimension varied from 2.5 to 24 mm (median 10.5 mm). Radiosurgery was performed with a dedicated 6 MV linear accelerator equipped with a micro-multileaf collimator. Median peripheral tumor dose and prescription isodose were 12 Gy and 90%, respectively. Image guidance was performed by optical tracking of infrared reflectors, fusion of oblique radiographs with dynamically reconstructed digital radiographs, and automatic patient positioning. Follow-up varied from 14 to 86 months (median 51 months). RESULTS: Kaplan-Meier estimated 4-year overall and solid tumor local control rates were 90% and 95%, respectively. One tumor progressed 12 months after treatment and a new cyst developed 10 months after treatment in another tumor. There has been no clinical or imaging evidence for spinal cord injury. CONCLUSIONS: Results of this limited experience indicate linear accelerator-based radiosurgery is safe and effective for spinal cord hemangioblastomas. Longer follow-up is necessary to confirm the durability of tumor control, but these initial results imply linear accelerator-based radiosurgery may represent a therapeutic alternative to surgery for selected patients with spinal hemangioblastomas.