Comparing the Evolution of Risk Culture in Radiation Oncology, Aviation, and Nuclear Power.

OBJECTIVES: All organizations seek to minimize the risks that their operations pose to public safety. This task is especially significant if they deal with complex or hazardous technologies. Five decades of research in quantitative risk analysis have generated a set of risk management frameworks and practices that extend across a range of such domains. Here, we investigate the risk culture in three commercial enterprises that require exceedingly high standards of execution: radiation oncology, aviation, and nuclear power. METHODS: One of the characteristics of high reliability organizations is their willingness to learn from other such organizations. We investigate the extent to which this is true by compiling a database of the major publications on risk within each of the three fields. We conduct a bibliographic coupling analysis on the combined database to identify connections among publications. This analysis reveals the strength of engagement across disciplinary boundaries and the extent of cross-adoption of best practices. RESULTS: Our results show that radiation oncology is more insulated than the other two fields in its adoption and propagation of state-of-the-art risk management tools and frameworks that have transformed aviation and nuclear power into high reliability enterprises with actuarially low risk. CONCLUSIONS: Aviation and nuclear power have established risk cultures that cross-pollinate. In both nature and extent, we found a distinct difference in radiation oncology's engagement with the risk community, and it lags behind the other two fields in implementing best practices that might mitigate or eliminate risks to patient safety.

NRG Oncology/RTOG 0438: A Phase 1 Trial of Highly Conformal Radiation Therapy for Liver Metastases.

PURPOSE: This study aimed to determine the feasibility and maximally tolerated dose of hypofractionated, conformal radiation therapy (RT) in patients with liver metastases. METHODS AND MATERIALS: Nonsurgical patients with ≤5 liver metastases (sum of maximal diameter of all lesions ≤8 cm) were included in the study. There were 4 dose levels: 35 Gy, 40 Gy (starting level), 45 Gy, and 50 Gy, in 10 fractions. The clinical target volume included metastases identified on contrast computed tomography or magnetic resonance imaging with a 5-mm margin within the liver. The planning target volume margin ranged from 4 to 30 mm, depending on breathing motion. Dose-limiting toxicities were defined as RT-related grade ≥4 hepatic or gastrointestinal toxicities or thrombocytopenia occurring within 90 days of the start of RT. RESULTS: A total of 26 patients with metastases from colorectal (8 patients), breast (7 patients) and other malignancies (11 patients) were enrolled between November 2005 and December 2010. Twenty-three patients were evaluable (8, 7, and 8 on the 40, 45, and 50 Gy dose levels, respectively). Two patients assigned to 50 Gy received 35 Gy owing to normal tissue limits, so 2 additional patients were treated to 50 Gy. There were no dose-limiting toxicities on any of the dose levels. On the 45 Gy dose level, 1 patient developed reversible grade 3 enteritis (37 days from RT start) and diarrhea (22 days); another patient developed grade 3 lymphopenia (23 days). At the 50 Gy dose level, 1 patient had grade 3 hyperglycemia (74 days), and another patient developed grade 3 lymphopenia (13 days), colonic hemorrhage (325 days), and colonic gastrointestinal obstruction (325 days). With a potential median follow-up of 66.1 months (range, 34.6-89.0 months), no other late toxicities were observed. CONCLUSIONS: Treatment of liver metastases with 50 Gy in 10 fractions was feasible and safe in a multi-institutional setting.

AAPM medical physics practice guideline 10.a.: Scope of practice for clinical medical physics.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline (MPPG) represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiation requires specific training, skills, and techniques as described in each document. As the review of the previous version of AAPM Professional Policy (PP)-17 (Scope of Practice) progressed, the writing group focused on one of the main goals: to have this document accepted by regulatory and accrediting bodies. After much discussion, it was decided that this goal would be better served through a MPPG. To further advance this goal, the text was updated to reflect the rationale and processes by which the activities in the scope of practice were identified and categorized. Lastly, the AAPM Professional Council believes that this document has benefitted from public comment which is part of the MPPG process but not the AAPM Professional Policy approval process. The following terms are used in the AAPM's MPPGs: Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances.

Anatomical Study of Percutaneous Trigeminal Compressive Balloon Positioning on Merged 3-D Rotational X-Ray and Preprocedural Magnetic Resonance Imaging.

BACKGROUND: Percutaneous trigeminal rhizotomy or balloon compression for trigeminal neuralgia carries a potential risk for the brainstem, the carotid artery, and the basilar artery. OBJECTIVE: To detail the relation of critical neural and vascular structures to expanded balloons used for percutaneous compression of the trigeminal ganglion. METHOD: A retrospective analysis of preprocedural magnetic resonance imaging (MRI) and procedural X-ray-based imaging for 9 patients detailed balloon proximity to the brainstem, carotid artery, and basilar artery. RESULTS: Balloons extended 10.96 ± 5.54 mm (mean ± SD) posterior to the clival line. The average distance from the balloon to the brainstem was 6.89 mm, and that to the basilar artery was 12.12 mm (range: 0-18.2). The medial edge of the balloon was an average distance of 1.39 mm from the baseline position of the carotid lumen. CONCLUSION: Preprocedural MRI, merged with 3-D rotational angiography suite imaging, detailed the proximity of the balloon to critical neural and vascular structures. Our study found that the standard technique for percutaneous trigeminal compression, with balloon placement at an average depth of 10.96 mm posterior to the clival line, on average, provided an additional 6.89 mm of space before the brainstem would have been encountered, demonstrating safe positioning.

Single-Fraction Radiosurgery Using Conservative Doses for Brain Metastases: Durable Responses in Select Primaries With Limited Toxicity.

BACKGROUND: Optimal doses for single-fraction stereotactic radiosurgery (SRS) in the treatment of brain metastases are not well established. Our institution utilized conservative dosing compared to maximum-tolerated doses from the Radiation Therapy Oncology Group 90-05 Phase I study. OBJECTIVE: To report individual lesion control (LC) from conservative single-fraction doses and determine factors affecting LC. METHODS: From 2003 to 2015, patients who underwent linear accelerator-based single-fraction SRS for cerebral/cerebellar metastases and receiving at least 1 follow-up magnetic resonance imaging (MRI) were identified. Lesion response was assessed by a size-based rating system and modified "Response Assessment in Neuro-Oncology Brain Metastases" (RANO-BM) criteria. RESULTS: Among 188 patients with 519 lesions, median survival was 13.1 mo; median follow-up time with MRI was 9.6 mo per course. Median tumor-periphery dose was 15 Gy (range: 7.5-20.7). Median lesion volume was 0.5 cc and diameter was 9 mm (range: 2-45). Concordance between RANO-BM and size-based system was 93%. Crude 1-yr LC was 80%, 73%, 56%, and 38% for lesions 1 to 10, 11 to 20, 21 to 30, >31 mm, respectively. On multivariate analysis, increased size, melanoma and colorectal histology, and progression after whole brain radiation therapy predicted worse LC. When excluding lesions treated as a boost, dose was a significant predictor of LC in multivariate models (hazard ratio 0.89, P = .01). Symptomatic radiation necrosis occurred in 10 lesions in 10 patients. CONCLUSION: Histology predicts LC after conservative SRS doses with evidence of a dose-response relationship. Conservative single-fraction SRS doses confer minimal toxicity and acceptable control in certain subgroups (breast cancer, <5 mm), with suboptimal control in larger lesions and in combination with whole brain radiation therapy.

Local control rates with five-fraction stereotactic body radiotherapy for oligometastatic cancer to the lung.

OBJECTIVE: To report our institutional experience with five fractions of daily 8-12 Gy stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic cancer to the lung. METHODS: Thirty-four consecutive patients with oligometastatic cancers to the lung were treated with image-guided SBRT between 2008 and 2011. Patient age ranged from 38 to 81 years. There were 17 males and 17 females. Lung metastases were from the following primary cancer types: colon cancer (n=13 patients), head and neck cancer (n=6), breast cancer (n=4), melanoma (n=4), sarcoma (n=4) and renal cell carcinoma (n=3). The median prescription dose was 50 Gy in five fractions (range, 40-60 Gy) to the isocenter, with the 80% isodose line encompassing the planning target volume (PTV) [defined as gross tumor volume (GTV) + 7-11 mm volumetric expansion]. The follow-up interval ranged from 2.4-54 months, with a median of 16.7 months. RESULTS: The 1-, 2-, and 3-year patient local control (LC) rates for all patients were 93%, 88%, and 80% respectively. The 1-, 2-, and 3-year overall survival (OS) rates were 62%, 44%, and 23% respectively. The 1- and 2-year patient LC rates were 95% and 88% for tumor size 1-2 cm (n=25), and 86% for tumor size 2-3 cm (n=7). The majority (n=4) of local failures occurred within 12 months. No patient experienced local failure after 12 months except for one patient with colon cancer whose tumors progressed locally at 26 months. All five patients with local recurrences had colorectal cancer. Statistical analyses showed that age, gender, previous chemotherapy, previous surgery or radiation had no significant effect on LC rates. No patient was reported to have any symptomatic pneumonitis at any time point. CONCLUSIONS: SBRT for oligometastatic disease to the lung using 8-12 Gy daily fractions over five treatments resulted in excellent 1- and 2-year LC rates. Most local failures occurred within the first 12 months, with five local failures associated with colorectal cancer. The treatment is safe using this radiation fractionation schedule with no therapy-related pneumonitis.

A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: Radiation Therapy Oncology Group 0320.

BACKGROUND: A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. METHODS AND MATERIALS: NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy × 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m(2)/day × 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m(2)/day × 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS. RESULTS: After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). CONCLUSION: The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms.

Stereotactic body radiation for the spine: a review.

Stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) for spinal metastases are emerging treatment paradigms in the multidisciplinary management of metastases located within or adjacent (paraspinal) to the vertebral bodies/spinal cord. In this review, we provide a brief overview of spine SBRT/SRS indications, technology, planning, and treatment delivery; review the current state of the literature; and discuss the radiobiology, toxicity, and limitations of SBRT/SRS for metastatic disease of the spine.

Stereotactic radiosurgery and hypofractionated stereotactic radiotherapy: normal tissue dose constraints of the central nervous system.

Single-fraction stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (SRT) are radiation planning and delivery techniques used for the treatment of intracranial and spine/spinal cord tumors and targets. For cranial SRS and SRT, critical normal tissues/structures include the brainstem, cranial nerves, cochlea and normal brain parenchyma. For spine SRS/SRT, critical normal tissues/structures include the spinal cord, cauda equina as well as neighboring organs. This paper reviews clinical studies investigating central nervous system dose tolerances after cranial or spinal SRS/SRT. The impact of dose, volume, fractionation, and other relevant clinic-pathologic variables are discussed, as are limitations of the published data.

Stereotactic body radiation therapy: the report of AAPM Task Group 101.

Task Group 101 of the AAPM has prepared this report for medical physicists, clinicians, and therapists in order to outline the best practice guidelines for the external-beam radiation therapy technique referred to as stereotactic body radiation therapy (SBRT). The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality. Information is provided for establishing a SBRT program, including protocols, equipment, resources, and QA procedures. Additionally, suggestions for developing consistent documentation for prescribing, reporting, and recording SBRT treatment delivery is provided.

Stereotactic radiosurgery for glioblastoma: retrospective analysis.

PURPOSE: This retrospective study was done to better understand the conditions for which stereotactic radiosurgery (SRS) for glioblastoma may be efficacious. METHODS: Between 2000 and 2007, 33 patients with a pathological diagnosis of glioblastoma received SRS with the Novalis Shaped Beam Radiosurgery system. Eighteen patients (54%) underwent salvage SRS for recurrence while 15 (45%) patients received upfront SRS following standard fractionated RT for newly diagnosed glioblastoma. RESULTS: There were no RTOG grade >2 acute side effects. The median survival after SRS was 6.7 months (range 1.4 - 74.7). There was no significant difference in overall survival (from the time of initial diagnosis) with respect to the timing of SRS (p = 0.2). There was significantly better progression free survival in patients treated with SRS as consolidation versus at the time of recurrence (p = 0.04). The majority of patients failed within or at the margin of the SRS treatment volume (21/26 evaluable for recurrence). CONCLUSION: SRS is well tolerated in the treatment of glioblastoma. As there was no difference in survival whether SRS is delivered upfront or at recurrence, the treatment for each patient should be individualized. Future studies are needed to identify patients most likely to respond to SRS.

Central thoracic lesions treated with hypofractionated stereotactic body radiotherapy.

PURPOSE: To investigate the toxicity and outcome after moderately hypofractionated stereotactic body radiotherapy (SBRT) for central thoracic lesions. METHODS: Fifty-three patients undergoing 63 courses of SBRT for central thoracic lesions were retrospectively reviewed. Ninety-eight lesions received 30-63 Gy in 2.5-5.0 Gy fractions using the Novalis ExacTrac patient positioning platform. RESULTS: The 2-year lesion local control was 73%. Larger lesion volume was associated with poorer local control. The 2-year overall survival of patients with Stage I NSCLC, Stages II-III NSCLC and limited metastatic disease was 72%, 12% and 49%, respectively. There were four patient deaths from pulmonary causes, potentially grade 5 toxicities, though three had comorbid pulmonary conditions which may have contributed to the cause of death. One patient died from hemoptysis after undergoing two courses of SBRT to a mediastinal lesion. Most other deaths were attributable to metastatic progression. CONCLUSIONS: Moderately hypofractionated SBRT to central thoracic lesions is effective with respect to local control and toxicity. Further dose escalation can provide an opportunity for better tumor control. Even with less aggressive dose fractionation, pulmonary deaths can occur, though it is difficult to ascertain the extent to which SBRT contributed to the death of patients with comorbid pulmonary conditions.

Descriptive analysis of oligometastatic lesions treated with curative-intent stereotactic body radiotherapy.

PURPOSE: To characterize oligometastases in patients enrolled on two prospective pilot studies, treating oligometastases with hypofractionated stereotactic body radiotherapy and stereotactic radiosurgery to cranial lesions. METHODS AND MATERIALS: We describe the characteristics and local control (LC) of 293 lesions in 121 patients with five or fewer metastases treated with stereotactic body radiation and/or cranial stereotactic radiosurgery. For each lesion, the primary cancer site, tumor histology, site of metastasis, gross tumor volume, and prescribed dose were ascertained. The prescribed dose is expressed by the biologically effective dose in 2-Gy fractions (BED2), calculated using the linear quadratic model, assuming an alpha/beta ratio of 10. RESULTS: Lung lesions were significantly smaller than other lesions in our cohort, whereas liver lesions were significantly larger, possibly reflecting a detection and/or referral bias. The 2-year and 4-year tumor LC rates were 77% and 73% respectively. A larger gross tumor volume was significantly (p < 0.0001) correlated with worse lesion LC. Lesions originating from primary pancreatic, biliary or liver cancer exhibited significantly poorer LC, as did lesions from colorectal cancer. Lesions from breast cancer were better controlled. A higher BED2 did not correlate with improved tumor control. CONCLUSIONS: Stereotactic body radiation to aggressively treat oligometastatic lesions results in good local tumor control. Bulkier lesions are more difficult to control and may benefit from dose escalation.

A prospective pilot study of curative-intent stereotactic body radiation therapy in patients with 5 or fewer oligometastatic lesions.

BACKGROUND: It is hypothesized that oligometastatic disease represents a state of potentially curable, limited metastases. Stereotactic body radiation therapy (SBRT) is an option for patients who are not amenable to or do not want resection. METHODS: From 2001 to 2006, 121 patients with < or =5 detectable metastases were enrolled in 2 prospective studies that used curative-intent SBRT. Most patients were treated with 10 fractions of 5 Gray. Stereotactic radiosurgery was offered to patients with brain metastases. RESULTS: The 2-year overall survival (OS), progression-free survival (PFS), local control (LC), and distant control (DC) rates were 50%, 26%, 67%, and 34%, respectively; and the respective 4-year rates values were 28%, 20%, 60%, and 25%. A greater net tumor volume predicted significantly worse OS, PFS, LC, and DC. Patients with breast cancer fared significantly better with respect to OS, PFS, LC, and DC; and patients with adrenal metastases had significantly worse OS, PFS, and DC despite the small number of such patients enrolled. Neither the number of metastatic lesions nor the number of organs involved was a significant predictor of outcome. Among 45 patients who remained alive at the last follow-up, 29 patients had no evidence of disease, including 23 patients with > or =2 years of follow-up. CONCLUSIONS: Oligometastatic disease is a potentially curable state of distant cancer spread. In this hypothesis-generating analysis, patients with less volume burden of their metastatic disease and those with primary breast cancer fared better. SBRT delivered with curative intent in patients with limited metastases should be investigated further. The Southwest Oncology Group is developing a prospective protocol to treat women who have limited breast cancer metastases with SBRT.

Hypofractionated stereotactic body radiation therapy (SBRT) for limited hepatic metastases.

PURPOSE: To evaluate the feasibility and efficacy of hypofractionated stereotactic body radiation therapy (SBRT) for the treatment of liver metastases. METHODS AND MATERIALS: The records of 69 patients with 174 metastatic liver lesions treated with SBRT between April 2001 and October 2004 were reviewed. The most common primary tumors were colorectal (n = 20), breast (n = 16), pancreas (n = 9), and lung (n = 5). The mean number of lesions treated per patient was 2.5 (range, 1-6). The longest diameter of the lesions ranged in size from 0.6 to 12.2 cm (median, 2.7 cm). Dose per fraction ranged from 2 Gy to 6 Gy, with a median total dose of 48 Gy (range, 30-55 Gy). Dose was prescribed to the 100% isodose line (IDL), with the 80% IDL covering the gross tumor volume with a minimum margin of 7 mm. RESULTS: The median follow up was 14.5 months. Sixty patients were evaluable for response based on an abdominal computed tomography scan obtained at a minimum of 3 months after completion of SBRT. The actuarial overall infield local control rate of the irradiated lesions was 76% and 57% at 10 and 20 months, respectively. The median overall survival time was 14.5 months. The progression-free survival rate was 46% and 24% at 6 and 12 months, respectively. None of the patients developed Grade 3 or higher toxicity. CONCLUSION: Hypofractionated SBRT provides excellent local control with minimal side effects in selected patients with limited hepatic metastases.

Stereotactic Body Radiation Therapy (SBRT) for lung metastases.

The curative treatment of oligometastases with radiotherapy remains an area of active investigation. We hypothesise that treating oligometastases with SBRT can prolong life and potentially cure patients, while in patients with multiple lung metastases SBRT can improve quality of life. Fifty patients with lung metastases were treated on this study. Individuals with five or fewer total lesions were treated with curative intent. Individuals with > five metastases were treated palliatively. Most patients (62%) received 5 Gy/fraction for a total of 50 Gy. The number of targets treated per patient ranged from one to five (mean 2.6). Tumor sizes ranged from 0.3-7.7 cm in maximal diameter (median 2.1 cm). Mean follow-up was 18.7 months. Local control of treated lesions was obtained in 42 of 49 evaluable patients (83%). Of the 125 total lesions treated, eight progressed after treatment (94% crude local control). The median overall survival time from time of treatment completion of the curatively treated patients was 23.4 months. The progression-free survival of the same group of patients was 25% and 16% at 12 and 24 months, respectively. Grade 1 toxicity occurred in 35% of all the patients, 6.1% had grade 2 toxicity, and 2% had grade 3 toxicity. Excellent local tumor control rates with low toxicity are seen with SBRT. Median survival time and progression-free survival both appear better than that achieved with standard care alone. Long-term progression-free survival can be seen in a subset of patients when all tumors are targeted.

Bouquet brachytherapy: feasibility and optimization of conically spaced implants.

PURPOSE: To examine the dosimetric feasibility of a conical implantation approach to robotic-assisted prostate brachytherapy. METHODS AND MATERIALS: An in-house inverse planning software based on the genetic algorithm (GA) was used to optimize the needle angulations and the seed positions along needles that form one or two bouquets. Volume data from 20 prostate seed implant patients (six 125I and 14 103Pd) previously treated using the conventional rectilinear template approach were used. The dosimetry outcomes of the optimized treatment plan in the conical approach were compared with those from the original treatment plans based on the conventional rectilinear template approach. RESULTS: When seed spacing is restricted to nominal 1 cm center-to-center spacing, dosimetry results in the conical approach suffer from a higher urethra dose and higher dose heterogeneity compared with the original rectilinear template plans. When the seed loading patterns are optimized as part of inverse planning, the resulting dosimetry plans exhibit adequate dose coverage and uniformity through the target volume, as well as satisfactory sparing of the urethra and rectum. CONCLUSIONS: Conically spaced implantation for prostate brachytherapy with 125I and 103Pd seeds is feasible in terms of dosimetry outcomes. Techniques for optimized inverse planning for this approach have been developed.

Long-term management of patients with multiple brain metastases after shaped beam radiosurgery. Case report and review of the literature.

The role of radiosurgery in the treatment of patients with advanced-stage metastatic disease is currently under debate. Previous randomized studies have not consistently supported the use of radiosurgery to treat patients with numbers of brain metastases. In negative-results studies, however, intracranial tumor control was high but extracranial disease progressed; thus, patient survival was not greatly affected, although neurocognitive function was generally maintained until death. Because the future promises improved systemic (extracranial) therapy, the successful control of brain disease is that much more crucial. Thus, for selected patients with multiple metastases to the brain who remain in good neurological condition, aggressive lesion-targeting radiosurgery should be very useful. Although a major limitation to success of this therapy is the lack of control of extracranial disease in most patients, it is clear that well-designed, aggressive treatment substantially decreases the progression of brain metastases and also improves neurocognitive survival. The authors present the management and a methodology for rational treatment of a patient with breast cancer who has harbored 24 brain metastases during a 3-year period.

Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial.

BACKGROUND: Brain metastases occur in up to 40% of all patients with systemic cancer. We aimed to assess whether stereotactic radiosurgery provided any therapeutic benefit in a randomised multi-institutional trial directed by the Radiation Therapy Oncology Group (RTOG). METHODS: Patients with one to three newly diagnosed brain metastases were randomly allocated either whole brain radiation therapy (WBRT) or WBRT followed by stereotactic radiosurgery boost. Patients were stratified by number of metastases and status of extracranial disease. Primary outcome was survival; secondary outcomes were tumour response and local rates, overall intracranial recurrence rates, cause of death, and performance measurements. FINDINGS: From January, 1996, to June, 2001, we enrolled 333 patients from 55 participating RTOG institutions--167 were assigned WBRT and stereotactic radiosurgery and 164 were allocated WBRT alone. Univariate analysis showed that there was a survival advantage in the WBRT and stereotactic radiosurgery group for patients with a single brain metastasis (median survival time 6.5 vs 4.9 months, p=0.0393). Patients in the stereotactic surgery group were more likely to have a stable or improved Karnofsky Performance Status (KPS) score at 6 months' follow-up than were patients allocated WBRT alone (43% vs 27%, respectively; p=0.03). By multivariate analysis, survival improved in patients with an RPA class 1 (p<0.0001) or a favourable histological status (p=0.0121). INTERPRETATION: WBRT and stereotactic boost treatment improved functional autonomy (KPS) for all patients and survival for patients with a single unresectable brain metastasis. WBRT and stereotactic radiosurgery should, therefore, be standard treatment for patients with a single unresectable brain metastasis and considered for patients with two or three brain metastases.

Low-dose radiosurgery for benign intracranial lesions.

This study assesses the efficacy and neurotoxicity of radiosurgical treatment of benign intracranial tumors using a linear accelerator, with relatively low dose and homogeneous dosimetry. Between June 1998 and July 2000, 27 patients were treated for benign lesions with radiosurgery using a 6-MV linear accelerator-based X-knife system and circular collimators. The lesions included schwannoma, meningioma, papillary cyst adenoma, and hemangioblastoma. Five patients had tissue diagnosis. The mean peripheral dose to the tumor margin was 12.8 Gy. The mean dose to the isocenter was 16.3 Gy. One to five isocenters were used to treat these lesions, with a mean of 10 arcs per isocenter and mean collimator size of 1.25 cm. Follow-up information was available on all patients, with a mean follow-up duration of 33 months. Six patients (22%) had improved symptoms and 21 (78%) had stable symptoms. Eight patients (30%) had regression of tumor and 19 had stable disease (70%). No patient had tumor progression, and Radiation Therapy Oncology Group (RTOG) grade III or IV toxicity did not occur in any patients. In 3 patients (11%), RTOG grade I or grade II neurotoxicity developed. Of these, one patient had worsening of a preexisting VIIth nerve deficit that required temporary oral methylprednisolone, and in two patients a mild trigeminal deficit developed that did not require any medical intervention. Low-dose homogeneous radiosurgery using a linear accelerator is an effective treatment for benign intracranial tumors. If lower, more homogeneous radiation doses produce responses as durable as higher doses, then toxicity might be further reduced.