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Purpose: Flattening-filter-free (FFF) linac-based SRS is a new technology that allows SRS doses to be delivered using volumetric modulated arc therapy (RapidArc). The purpose of this study was to compare the treatment times and normal brain tissue doses for multiple metastases planned using TrueBeam FFF, Leksell Gamma Knife Perfexion (PFX), CyberKnife, and Novalis SRS platforms. Methods: A single patient with 12 brain metastases (volume 0.06-0.1 mL) treated with the PFX was selected, and all lesions and organs-at-risk were contoured by a single radiation oncologist. SRS plans for 3, 6, 9 and12 targets were performed at different institutions with expertise in each platform to minimize bias (2 independent institutions created FFF-based RapidArc plans). Identical dose-volume constraints were applied. Each target had to be covered by at least 99% of the 20 Gy prescription dose. Dose-volume histogram data were centrally reviewed and analyzed. Results: All target and organ-at-risk dose-volume constraints were satisfied by each platform. The beam-on times were shortest with TrueBeam FFF (6, 9, 9,10 min at 1200 MU/min) but longest with PFX (27, 54, 72, 108 min at 3 Gy/min) for 3, 6, 9,12 metastases respectively. However, normal brain tissue doses were greatest by TrueBeam FFF but lowest by PFX. When grouping the four treatment plans together for 3 targets (1.8 mL), 6 targets (3.2 mL), 9 targets (4.2 mL) and 12 targets (5.7 mL), the mean normal brain volumes averaged over these treatment plans for the two modalities (TrueBeam FFF vs. PFX) were: (16.3 mLvs. 8.7 mL) at 12 Gy, (52.9 mL vs, 20.6 mL) at 8 Gy and (277.6 mL vs. 96.7 mL) at 4 Gy. Thus, the mean FFF normal brain volumes were greater by 81.5% (range: 57.3% to 105.5%) at 12 Gy, 126.4% (range: 70.4% to 196.4%) at 8 Gy and 217.3% (range: 140.3% to 310.9%) at 4 Gy, when referenced to the PFX. Conclusions: Radiosurgery beam-on times were shortest with the FFF but longest with the PFX. However, the normal brain tissue doses were highest with the FFF but lowest with the PFX at 4 to 12 Gydose levels. As this was a treatment planning study, the clinical consequences of these normal brain tissue doses are unknown. Disclosure: No significant relationships. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the influence of stereotactic radiosurgery on the risk of hemorrhage from brain metastases form malignant melanoma. Methods: A cohort of 110 patients treated with stereotactic radiosurgery (SRS) for 358 melanoma brain metastases was identified. The incidence of hemorrhage before and after SRS was determined by review of serial MRI scans. Statistical analysis was performed to determine the influence of SRS on rate of hemorrhage. Overall survival and local control were assessed and prognostic factors, including hemorrhage pre- or post-SRS were analyzed. Results: At presentation 83 of 358 (23.2%) melanoma metastases had hemorrhaged. Following SRS 73 hemorrhages occurred in 358 treated tumors (20.4%). These rates were not significantly different; p=0.362, HR=0.846 (95% CI 0.591-1.211.) The risk of post-SRS hemorrhage in patients was statistically significantly linked to previous hemorrhage. Fourteen of 65 patients (21.5%) who presented without hemorrhage prior to SRS subsequently demonstrated hemorrhage. Twenty-four of 45 patients (53.3%) who presented with hemorrhage went on to demonstrate further hemorrhage following SRS; p=0.005, HR=2.47 (95% CI 1.24-11.3). Overall survival (OS) at 1 year was 30% and was not influenced by hemorrhage either pre- or post -SRS. OS at 1 year was better for patients presenting with a single metastasis (41.2%) compared to multiple metastases (20.3%, p=0.009.) Overall local control (LC) was 60.4% at 1 year following SRS. LC was significantly lower for metastases demonstrating hemorrhage either pre-SRS (51.7 vs 64.9%. p=0.03) or post-SRS 32.7 vs. 67.8%, p<0.001.) Conlcusion: Hemorrhage of brain metastases from melanoma is more frequent than for non-melanoma primaries. The current data show that stereotactic radiosurgery does not alter the risk of subsequent hemorrhage of treated metastases. However, hemorrhage may complicate follow-up assessment of response and local control following SRS. Careful assessment of imaging following SRS should include awareness that hemorrhage may mimic treatment failure in these patients. Disclosure: No significant relationships. [ABSTRACT FROM AUTHOR]

Objectives: To determine the ability of a second course of stereotacctic radiosurgery (SRS) to control brain metastases as well as to document the incdience of radiation necrosis (RN) after SRS reirradiation. Methods: All patients with brain metastases treated with two or more courses of single fraction, linear accelerator based SRS to the same lesion were identified. Patients were excluded if they did not have follow-up imaging after the second course of SRS. Patient characteristics and radiotherapy and surgery data were collected. MRI scans were evaluated for tumor response, and axial dimensions were documented. Lesions were categorized as complete response, partial response (<20% increase in size), or progressive disease (>20% increase in size). Development of RN as confirmed by pathology or spectroscopy/imaging, was recorded. Results: A total of 43 lesions in 38 patients were evaluable. The most common histology was melanoma (20/38, 53%) followed by lung and breast. RN was identified in 7/43 (16%) lesions. Three cases were confirmed by pathologic evaluation, and 4 cases were identified by imaging. Of lesions without RN, 17 (47%) were stable, 7 (19%) had a partial response, 1(3%) had a complete response, and 11 (31%) had progressive disease after the second course of SRS. In patients without RN, the median SRS dose for both courses was 20 Gy. For patients with RN, the median dose was 18 Gy for both courses. The mean maximum tumor dimension at the time of the 2nd course of SRS was 14.7 mm and 19.3 mm for patients without and with RN, respectively. The mean number of days between courses of SRS was 326 for patients without RN and 255 for patients with RN. Of lesions with RN, 3/7 (43%) were resected prior to the first course of SRS. In lesions without RN, 10/36 (28%) were resected (6 prior to the first course of SRS and 4 between courses of SRS). Whole brain radiotherapy was delivered in 18 (50%) without RN and in 3 (43%) with RN. Conclusion: Reirradiation with SRS can lead to tumor response in the majority of patients with a low incidence of RN. RN did not appearto be associated with SRS dose or use of whole brain radiotherapy but may be associated with the time interval between courses of SRS, size of the treated lesion, and use of surgery. Disclosure: No significant relationships. [ABSTRACT FROM AUTHOR]

Background: Local excision (LE) has been used in an attempt to preserve anal function in T1-2 rectal carcinoma. The current study compares LE to radical resection (RR), each with or without radiation therapy (RT)., Methods: Patients reported to the SEER registry of the National Cancer Institute from 1988 to 2003 who had T1-2N0M0 rectal carcinoma were identified. A retrospective analysis of survival was performed using the Kaplan-Meier method. Comparative risks of mortality were evaluated using multivariate adjusted Cox regression models., Results: Of 4,320 patients, 13% underwent LE alone, 7% underwent LE plus RT, 70% underwent RR alone, and 10% underwent RR plus RT. On multivariate analysis, patients who underwent LE without RT had inferior overall survival compared to patients who underwent RR (P < .05). Patients who underwent LE with or without RT had inferior cause-specific survival compared to patients who underwent RR (P < .05)., Conclusions: RR without RT was associated with superior overall survival compared to LE without RT, and RR without RT was associated with superior cause-specific survival compared to LE with or without RT. Randomized trials are necessary to determine if LE with or without RT can offer equivalent survival compared to RR in early stage rectal carcinoma.

Accurate prediction of human tumor response to radiation therapy and concomitant chemoradiation would be an important tool to assist the physician in making recommendations for tumor treatment. Most of the studies that define the molecular markers for prediction of radiation response are based on the observation of gene expression using immunostaining, Northern blot, or Western blot analysis of a single or several genes. The results vary among different studies, and some results are contradictory. However, the studies agree that the change in expression of the tumor-related gene affects the radiation response. In this study, we explored a novel approach to predict the radiation response of human tumor using Atlas human cancer 1.2 cDNA array to analyze the expression profile of 1187 tumor-related genes in radiation-resistant and radiation-sensitive tissues. Sixty tumor-related genes were selected as predictors of radiation response of squamous cell carcinoma of the head and neck. Using the expression intensity of these 60 tumor-related genes, in combination with cluster analysis, we successfully predicted the radiation identity of two tumor samples.

Object: To assess the value of stereotactic radiosurgery (SRS) as adjunct therapy in patients suffering from glioblastoma multiforme (GBM), the authors analyzed their experience with 78 patients., Methods: Between June 1988 and January 1995, 78 patients underwent SRS as part of their initial treatment for GBM. All patients had undergone initial surgery or biopsy confirming the diagnosis of GBM and received conventional external beam radiotherapy. Stereotactic radiosurgery was performed using a dedicated 6-MV stereotactic linear accelerator. Thirteen patients were alive at the time of analysis with a median follow-up period of 40.8 months. The median length of actuarial survival for all patients was 19.9 months. Twelve- and 24-month survival rates were 88.5% and 35.9%, respectively. Patient age and Radiation Therapy Oncology Group (RTOG) class were significant prognostic indicators according to univariate analysis (p < 0.05). Twenty-three patients aged younger than 40 years had a median survival time of 48.6 months compared with 55 older patients who had 18.2 months (p < 0.001). Patients in this series fell into RTOG Classes III (27 patients), IV (29 patients), or V (22 patients). Class III patients had a median survival time of 29.5 months following diagnosis; this was significantly longer than median survival times for Classes IV and V, which were 19.2 and 18.2 months, respectively (p = 0.001). Only patient age (< 40 years) was a significant prognostic factor according to multivariate analysis. Acute complications were unusual and limited to exacerbation of existing symptoms. There were no new neuropathies secondary to SRS. Thirty-nine patients (50%) underwent reoperation for symptomatic necrosis or recurrent tumor. The rate of reoperation at 24 months following SRS was 54.8%., Conclusions: The addition of a radiosurgery boost appears to confer a survival advantage to selected patients.

Object: The study was conducted to determine the association between dual-isotope single-photon emission computerized tomography (SPECT) scanning and histopathological findings of tumor recurrence and survival in patients treated with high-dose radiotherapy for glioblastoma multiforme., Methods: Studies in which SPECT with 201Tl and 99mTc-hexamethypropyleneamine oxime (HMPAO) were used were performed 1 day before reoperation in 47 patients with glioblastoma multiforme who had previously been treated by surgery and high-dose radiotherapy. Maximum uptake of 201Tl in the lesion was expressed as a ratio to that in the contralateral scalp, and uptake of 99mTc-HMPAO was expressed as a ratio to that in the cerebellar cortex. Patients were stratified into groups based on the maximum radioisotope uptake values in their tumor beds. The significance of differences in patient gender, histological characteristics of tissue at reoperation, and SPECT uptake group with respect to 1-year survival was elucidated by using the chi-square statistic. Comparisons of patient ages and time to tumor recurrence as functions of 1-year survival were made using the t-test. Survival data at 1 year were presented according to the Kaplan-Meier method, and the significance of potential differences was evaluated using the log-rank method. The effects of different variables (tumor type, time to recurrence, and SPECT grouping) on long-term survival were evaluated using Cox proportional models that controlled for age and gender. All patients in Group I (201Tl ratio < 2 and 99mTc-HMPAO ratio < 0.5) showed radiation changes in their biopsy specimens: they had an 83.3% 1-year survival rate. Group II patients (201Tl ratio < 2 and 99mTc-HMPAO ratio of > or = 0.5 or 201Tl ratio between 2 and 3.5 regardless of 99mTc-HMPAO ratio) had predominantly infiltrating tumor (66.6%); they had a 29.2% 1-year survival rate. Almost all of the patients in Group III (201Tl ratio > 3.5 and 99mTc-HMPAO ratio > or = 0.5) had solid tumor (88.2%) and they had a 6.7% 1-year survival rate. Histological data were associated with 1-year survival (p < 0.01): however, SPECT grouping was more closely associated with 1-year survival (p < 0.001) and was the only variable significantly associated with long-term survival (p < 0.005)., Conclusions: Dual-isotope SPECT data correlate with histopathological findings made at reoperation and with survival in patients with malignant gliomas after surgical and high-dose radiation therapy.

Objective: We report the outcomes of patients treated with linear accelerator-based radiosurgery for intracranial meningiomas at our institution., Methods: We reviewed 127 patients with 155 meningiomas treated with stereotactic radiosurgery (SRS) at the study institutions between October 1988 and December 1995., Results: There were 86 female and 41 male patients (median age, 61.5 yr; range, 19.9-87.9 yr). The median follow-up period was 31 months (range, 1.2-79.8 mo). The median tumor volume was 4.1 cc (range, 0.16-51.2 cc), and the median marginal dose was 15 Gy (range, 9-20 Gy). The tumor locations were as follows: convexity, 31 tumors; parasagittal/falcine, 39 tumors; cranial base, 82 tumors; and ventricular/pineal, 3 tumors. There were 106 benign, 26 atypical, and 18 malignant meningiomas and 5 cases of meningiomatosis. SRS was performed on 48 lesions as the initial treatment and on 107 lesions as adjunct therapy. Freedom from progression was observed in 107 patients (84.3%) at a median time of 22.9 months (range, 1.2-79.8 mo). Twenty patients (15.7%) had disease progression (16 marginal [12.6%] and 4 local [3.1%]) at a median time of 19.6 months (range, 4.1-69.3 mo); the median time for freedom from progression for the benign, atypical, and malignant meningiomas was 20.9, 24.4, and 13.9 months, respectively. Actuarial tumor control for the patients with benign meningiomas was 100, 92.9, 89.3, 89.3, and 89.3% at 1, 2, 3, 4, and 5 years, respectively. Six patients (4.7%) had permanent complications attributable to SRS (median time, 10.3 mo; range, 4.3-18.0 mo); 13 patients died as a result of causes related to the meningiomas (median, 17.5 mo; range, 4.3-37.3 mo). The 1-, 2-, 3-, 4-, and 5-year survival probability for the entire group of patients was 90.3, 82.6, 73.6, 70.5, and 68.2%, respectively; for patients with benign meningiomas, excluding death resulting from intercurrent disease, the survival probability was 97.6, 94.8, 91.0, 91.0, and 91.0%, respectively. The 1-, 2-, 3-, and 4-year survival probability for the patients with atypical and malignant meningiomas was 91.7, 83.3, 83.3, and 83.3% and 92.3, 64.6, 43.1, and 21.5%, respectively., Conclusion: Even though complications from SRS are expected more frequently with large tumors near critical structures, SRS is a safe and effective means of treating selected meningiomas.

Stereotactic irradiation is a precise method for the delivery of focused radiation beams to small intracranial targets. Treatment can be administered in single or multiple fractions (radiosurgery or stereotactic radiotherapy, respectively). The technology has evolved rapidly because of advances in both hardware and software design. Clinical indications are unfolding through the prospective trial mechanism.

Beginning in 1987, selected patients with metastatic brain tumors were treated with permanent implants of low-activity radioactive iodine-125(125I) seeds. These patients underwent craniotomy, gross total resection of the metastatic lesion, and placement of the seeds. In general, criteria for treatment included the presence of a recurrent tumor with a volume too large to permit radiosurgery, and a Karnofsky Performance Score of 70 or higher. Thirteen patients underwent 14 implant procedures; all received external whole-brain radiotherapy. Implant dose ranged from 43 Gy to 132 Gy, with a mean of 83 Gy. Survival after implantation ranged from 2 weeks to almost 9 years, with a median of 9 months. Clinical and radiographic local control was obtained in 9 patients. Two patients died of acute, postoperative complications within a month of implantation, so no information regarding tumor control is available for them. Late complications included a bone flap infection in one patient and a CSF leak in another; both were treated without further sequelae. These results demonstrate that permanent 125I implants can results in good survival and quality of life, and occasionally can yield long-term survival. Potentially, it is a cost-effective treatment in that a separate procedure for stereotactic implantation or radiosurgery is not needed, as is the case with the use of temporary high-activity seeds. The permanent implantation itself adds less than 10 minutes to the craniotomy, and the risk of symptomatic radiation necrosis is low. We recommend consideration of this procedure in patients harboring large, recurrent metastatic tumors that require further surgery.

Purpose: Between June 1988 and June 1994. 38 hemangioblastomas were treated with stereotactic radiosurgery (SR) at three SR centers to evaluate the efficacy and potential toxicity of this therapeutic modality as an adjuvant or alternative treatment to surgical resection., Methods and Materials: SR was performed using either a 201-cobalt source unit or a dedicated SR linear accelerator. Of the 18 primary tumors treated, 16 had no prior history of surgical resection and were treated definitively with SR and two primary lesions were subtotally resected and subsequently treated with SR. Twenty lesions were treated with SR after prior surgical failure (17 tumors) or failure after prior surgery and conventional radiotherapy (three tumors). Eight patients were treated with SR for multifocal disease (total, 24 known tumors). SR tumor volumes measured 0.05 to 12 cc (median: 0.97 cc). Minimum tumor doses ranged from 12 to 20 Gy (median: 15.5 Gy)., Results: Median follow-up from the time of SR was 24.5 months (range: 6-77 months). The 2-year actuarial over-all survival was 88 +/- 15% (95% confidence interval). Two-year actuarial freedom from progression was 86 +/- 12% (95% confidence interval). The median tumor volume of the lesions that failed to be controlled by SR was 7.85 cc (range: 3.20-10.53 cc) compared to 0.67 cc (range: 0.05-12 cc) for controlled lesions (p - 0.0023). The lesions that failed to be controlled by SR received a median minimum tumor dose of 14 Gy (range: 13-17 Gy) compared to 16 Gy (range: 12-20 Gy) for controlled lesions (p = 0.0239). Seventy-eight percent of the surviving patients remained neurologically stable or clinically improved. There were no significant permanent complications directly attributable to SR., Conclusions: This report documents the largest experience in the literature of the use of SR in the treatment of hemangioblastoma. We conclude that SR: (a) controls the majority of primary and recurrent hemangioblastomas; (b) offers the ability to treat multiple lesions in a single treatment session, which is particularly important for patients with Von Hippel-Lindau Syndrome; and that (c) better control rates are associated with higher doses and smaller tumor volumes.

Despite important advances in surgery and chemotherapy, much of the recent progress that has been achieved in the treatment of brain tumors has resulted from developments in radiation therapy. This article reviews some of the recent advances in radiotherapeutic strategies being used in the treatment of brain tumors in adults. The overall management of each specific tumor type is discussed.

Despite intense research, progress in the treatment of patients with HGA has remained slow. New therapeutic strategies are emerging, however, based on technologic advances in surgery and radiotherapy, improved understanding of the molecular, cellular, and immunobiology of astrocytomas, and advances in gene therapy, It is likely that these new strategies will result in significant progress in the treatment of HGA in the next decade.

The purpose of this study was to compare the efficacy of stereotactic radiosurgery (SRS) and brachytherapy in the treatment of recurrent glioblastoma multiforme (GBM). The patients had either progressive GBM or pathologically proven GBM at recurrence after previous treatment for a lower grade astrocytoma. Thirty-two patients were treated with interstitial brachytherapy, and 86 received treatment with stereotactic radiosurgery (SRS). The patient characteristics were similar in the two groups. Those patients treated with SRS had a median tumor volume of 10.1 cm3 and received a median peripheral tumor dose of 13 Gy. Patients treated with brachytherapy had a median tumor volume of 29 cm3. Median dose to the periphery of the tumor volume was 50 Gy delivered at a median dose rate of 43 cGy/hour. Twenty-one patients (24%) treated with SRS were alive, with a median follow-up of 17.5 months. Median actuarial survival, measured from the time of treatment for recurrence, for all patients treated with SRS was 10.2 months, with survivals of 12 and 24 months being 45 and 19%, respectively. A younger age and a smaller tumor volume were predictive of better outcome. The tumor dose, the interval from initial diagnosis, and the need for reoperation were not predictive of outcome after SRS. Five patients (16%) treated with brachytherapy were alive, with a median follow-up of 43.3 months. The median actuarial survival for all patients treated with brachytherapy was 11.5 months. Survivals of 12 and 24 months were 44 and 17%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Between June 1989 and January 1994, 14 patients with recurrent (n = 11) or posttreatment residual (n = 3) medulloblastoma were enrolled in a program to evaluate the efficacy and toxicity of stereotactic radiosurgery (SR). Initial treatment consisted of subtotal surgical resection in 12 patients and complete surgical resection in 2. Thirteen patients received systemic chemotherapy, and all had craniospinal irradiation prior to SR. SR was used as a technique for boosting sites of posttreatment residual disease in 3 patients (3 tumors) and as salvage therapy in 11 patients (14 tumors) with radiographically well-defined, discrete recurrent tumors. Patients underwent SR 1-97 (median 20) months after completing craniospinal irradiation. The median minimum peripheral tumor dose was 12 Gy. The median tumor volume at the time of SR was 6.9 cm3. With a median follow-up period from diagnosis of 27 (range 8-39) months, all patients treated with SR as a boost to sites of residual disease are alive without evidence of disease. In contrast, 6 of 11 patients who underwent SR for treatment of recurrent disease have died of progressive medulloblastoma. The median survival from the time of SR for patients treated for recurrent disease was 10 (range 5-59+) months. The predominant site of failure after SR was distant within the central nervous system, with 6 patients (43%) failing outside the posterior fossa. No patient failed locally within the radiosurgical target volume. Two patients (14%) developed marginal recurrences.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose: This pilot study was designed to test the tolerance and effectiveness of concurrent continuous infusion cisplatin and radiotherapy in the treatment of unresectable nonsmall cell lung (NSCL) cancer., Methods and Materials: Between July 1989 and July 1991, 92 consecutive patients with either medically or technically inoperable NSCL cancer were treated with thoracic radiotherapy and concomitant chemotherapy. Radiotherapy consisted of a total dose of 70 Gy delivered in 2 Gy daily fractions over 9 weeks with a planned 2-week break after 40 Gy. During the second week of each cycle of radiotherapy, cisplatin was administered, 20 mg/m2/day for 5 days as a continuous infusion. Eighty-five patients were evaluable., Results: Overall response rate was 81.7% (65.9% complete response). Medically operable patients were considered for curative surgical resection following 40 Gy and one cycle of chemotherapy; 11 patients underwent resection with 3/11 having no pathologic evidence of tumor. Median survival for all 85 patients was 11.4 months with a median follow-up of 27 months. Overall survival was 48.2%, 27.5%, and 25% at 12, 24, and 36 months, respectively. Survival was independent of tumor stage, histology and grade, and patient age and gender. Patients having a complete response (n = 54) had a 2-year survival of 42.1% compared to 3.2% for partial-responders and nonresponders (n = 31; p < 0.0001). Patients undergoing surgical resection (n = 11) had a 2-year survival of 75.8% compared to 20.6% for those treated with chemoradiotherapy alone (n = 74). Forty-eight patients have died of their disease. There were two treatment-related deaths, seven deaths of intercurrent disease and three of unknown causes. Eighteen of 25 patients alive at the time of analysis were without evidence of disease. Actuarial local control was 50.6% at 1 year, and 33.3% at 2 years. The distant failure rate was 47.8% at 2 years. Major acute toxicities, mainly hematologic or gastrointestinal, occurred in less than 10% of patients. Esophagitis was mild and infrequent (8.4%). Severe late pulmonary fibrosis occurred in 5.2% of patients and resulted in two treatment-related deaths., Conclusion: Concomitant chemoradiotherapy was well tolerated, resulted in a high rate of local control, and in a survival benefit for patients demonstrating a complete response or going on to surgical resection. The incidence of distant metastases continues to be high and future strategies should be directed at improving systemic therapy.