Fast transit portal dosimetry using density-scaled layer modeling of aSi-based electronic portal imaging device and Monte Carlo method.

PURPOSE: Fast and accurate transit portal dosimetry was investigated by developing a density-scaled layer model of electronic portal imaging device (EPID) and applying it to a clinical environment. METHODS: The model was developed for fast Monte Carlo dose calculation. The model was validated through comparison with measurements of dose on EPID using first open beams of varying field sizes under a 20-cm-thick flat phantom. After this basic validation, the model was further tested by applying it to transit dosimetry and dose reconstruction that employed our predetermined dose-response-based algorithm developed earlier. The application employed clinical intensity-modulated beams irradiated on a Rando phantom. The clinical beams were obtained through planning on pelvic regions of the Rando phantom simulating prostate and large pelvis intensity modulated radiation therapy. To enhance agreement between calculations and measurements of dose near penumbral regions, convolution conversion of acquired EPID images was alternatively used. In addition, thickness-dependent image-to-dose calibration factors were generated through measurements of image and calculations of dose in EPID through flat phantoms of various thicknesses. The factors were used to convert acquired images in EPID into dose. RESULTS: For open beam measurements, the model showed agreement with measurements in dose difference better than 2% across open fields. For tests with a Rando phantom, the transit dosimetry measurements were compared with forwardly calculated doses in EPID showing gamma pass rates between 90.8% and 98.8% given 4.5 mm distance-to-agreement (DTA) and 3% dose difference (DD) for all individual beams tried in this study. The reconstructed dose in the phantom was compared with forwardly calculated doses showing pass rates between 93.3% and 100% in isocentric perpendicular planes to the beam direction given 3 mm DTA and 3% DD for all beams. On isocentric axial planes, the pass rates varied between 95.8% and 99.9% for all individual beams and they were 98.2% and 99.9% for the composite beams of the small and large pelvis cases, respectively. Three-dimensional gamma pass rates were 99.0% and 96.4% for the small and large pelvis cases, respectively. CONCLUSIONS: The layer model of EPID built for Monte Carlo calculations offered fast (less than 1 min) and accurate calculation for transit dosimety and dose reconstruction.

Combination external beam radiation and brachytherapy boost with androgen deprivation for treatment of intermediate-risk prostate cancer: long-term results of CALGB 99809.

BACKGROUND: Combined transperineal prostate brachytherapy and external beam radiation therapy (EBRT) is widely used for treatment of prostate cancer. Long-term efficacy and toxicity results of a multicenter phase 2 trial assessing combination of EBRT and transperineal prostate brachytherapy boost with androgen deprivation therapy (ADT) for intermediate-risk prostate cancer are presented. METHODS: Intermediate-risk patients per Memorial Sloan-Kettering Cancer Center/National Comprehensive Cancer Network criteria received 6 months of ADT, and 45 grays (Gy) EBRT to the prostate and seminal vesicles, followed by transperineal prostate brachytherapy with I125 (100 Gy) or Pd103 (90 Gy). Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2 and Radiation Therapy Oncology Group late radiation morbidity scoring systems. Disease-free survival (DFS) was defined as time from enrollment to progression (biochemical, local, distant, or prostate cancer death). In addition to the protocol definition of biochemical failure (3 consecutive prostate-specific antigen rises>1.0 ng/mL after 18 months from treatment start), the 1997 American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and Phoenix definitions were also assessed in defining DFS. The Kaplan-Meier method was used to estimate DFS and overall survival. RESULTS: Sixty-one of 63 enrolled patients were eligible. Median follow-up was 73 months. Late grade 2 and 3 toxicity, excluding sexual dysfunction, occurred in 20% and 3% of patients. Six-year DFS applying the protocol definition, 1997 ASTRO consensus, and Phoenix definitions was 87.1%, 75.1%, and 84.9%. Six deaths occurred; only 1 was attributed to prostate cancer. Six-year overall survival was 96.1%. CONCLUSIONS: In a cooperative setting, combination of EBRT and transperineal prostate brachytherapy boost plus ADT resulted in excellent DFS with acceptable late toxicity for patients with intermediate-risk prostate cancer.

Dose reconstruction for intensity-modulated radiation therapy using a non-iterative method and portal dose image.

A straightforward and accurate method was developed to verify the delivery of intensity-modulated radiation therapy (IMRT) and to reconstruct the dose in a patient. The method is based on a computational algorithm that linearly describes the physical relationship between beamlets and dose-scoring voxels in a patient and the dose image from an electronic portal imaging device (EPID). The relationship is expressed in the form of dose response functions (responses) that are quantified using Monte Carlo (MC) particle transport techniques. From the dose information measured by the EPID the received patient dose is reconstructed by inversely solving the algorithm. The unique and novel non-iterative feature of this algorithm sets it apart from many existing dose reconstruction methods in the literature. This study presents the algorithm in detail and validates it experimentally for open and IMRT fields. Responses were first calculated for each beamlet of the selected fields by MC simulation. In-phantom and exit film dosimetry were performed on a flat phantom. Using the calculated responses and the algorithm, the exit film dose was used to inversely reconstruct the in-phantom dose, which was then compared with the measured in-phantom dose. The dose comparison in the phantom for all irradiated fields showed a pass rate of higher than 90% dose points given the criteria of dose difference of 3% and distance to agreement of 3 mm.

Investigation of Radiation Oncologists' Awareness of Online Reputation Management.

BACKGROUND: Online reputation management (ORM) is an emerging practice strategy that emphasizes the systematic and proactive monitoring of online reviews relating to one's professional reputation. OBJECTIVE: We developed this survey project to assess whether radiation oncologists are aware of ORM and how it is utilized in their practices. We hypothesized that ORM is largely unknown by most practicing radiation oncologists and that little time is spent actively managing their reputations. METHODS: An online survey was submitted to 1222 radiation oncologists using the Qualtrics research platform. Physician emails were gathered from the American Society for Radiation Oncology member directory. A total of 85 physicians initiated the survey, whereas 76 physicians completed more than or equal to 94% (15/16) of the survey questions and were subsequently used in our analyses. The survey consisted of 15 questions querying practice demographics, patient satisfaction determination, ORM understanding, and activities to address ORM and 1 question for physicians to opt-in to a US $50 Amazon gift card raffle. The survey data were summarized using a frequency table, and data were analyzed using the Chi-square test, Fisher exact test, and Spearman correlation coefficients. RESULTS: We calculated a 7% (85/1222) response rate for our survey, with a completion rate of 89% (76/85). A majority of respondents (97%, 74/76) endorsed being somewhat or strongly concerned about patient satisfaction (P<.001). However, 58% (44/76) of respondents reported spending 0 hours per week reviewing or managing their online reputation and 39% (30/76) reported spending less than 1 hour per week (P<.001). A majority of physicians (58%, 44/76) endorsed no familiarity with ORM (P<.001) and 70% (53/76) did not actively manage their online reputation (P<.001). Although 83% (63/76) of respondents strongly or somewhat believed that patients read online reviews (P<.001), 57% (43/76) of respondents did not check their online reviews (P=.25) and 80% (61/76) endorsed never responding to online reviews (P<.001). Moreover, 58% (44/76) of the respondents strongly or somewhat supported the idea of managing their online reputation going forward (P=.001). In addition, 11 out of the 28 pairs of questions asked in our correlation studies reached statistical significance. Degree of concern for patient satisfaction and the notion of managing one's ORM going forward were the 2 most frequently correlated topics of statistical significance in our analyses. CONCLUSIONS: ORM is presently under-recognized in radiation oncology. Although most practitioners are concerned about patient satisfaction, little effort is directed toward the internet on this matter. ORM offers an area of practice improvement for many practicing radiation oncologists.

Regional Differences in the Treatment of Localized Prostate Cancer: An Analysis of Surgery and Radiation Utilization in the United States.

PURPOSE: Men with localized prostate cancer have various treatment options available in their management. The optimal approach is controversial and can be influenced by multiple factors. This study aimed to investigate the influence of geographic region on the selection of treatment for prostate cancer. METHODS AND MATERIALS: Using the National Cancer Database, we identified men diagnosed with localized prostate cancer between 2010 and 2014. The United States was divided into 11 regions per the American Cancer Society Divisions. The first course of treatment was recorded as radiation therapy (RT), radical prostatectomy (RP), or active surveillance (AS). The RT subgroup consisted of patients receiving all forms of RT, including external beam and brachytherapy, or RT plus androgen deprivation therapy. The RP subgroup consisted of patients receiving RP alone or combined with RT or androgen deprivation therapy. A χ2 test was performed to assess the association between region and frequency of RT and RP. RESULTS: This study included 462,811 men with localized prostate cancer who were treated in the United States, of whom 63.46% underwent RP, 31.54% underwent RT, and 5.00% underwent AS. Significant regional differences in RP and RT were observed (P ≤ .0001). RP was used most commonly in the Midwest (75.07%) and High Plains (73.37%) regions, whereas RP was least used in the South Atlantic (59.04%) region. Similarly, RT was used most commonly in South Atlantic (40.96%) and New England (38.98%) regions and least commonly in the Midwest (24.93%) region. AS was used most in the New England (7.27%) and Midwest (6.8%) regions and least used in the High Plains (2.57%) and Mid-South (2.84%) regions. CONCLUSIONS: Regional differences exist in the United States with regard to the definitive treatment of localized prostate cancer. The etiology for these regional differences is likely multifactorial.

Deformable image registration for the use of magnetic resonance spectroscopy in prostate treatment planning.

PURPOSE: There is now convincing evidence that prostate cancer cells lack the ability to produce and accumulate citrate. Using magnetic resonance spectroscopy imaging (MRSI), regions of absent or low citrate concentration in the prostate can be visualized at a resolution of a few mm. This new advancement provides not only a tool for early diagnosis and screening but also the opportunity for preferential targeting of radiation to regions of high tumor burden in the prostate. The differences in the shape and location of the prostate between MRSI imaging and treatment have been the major obstacle in integrating MRSI in radiation therapy treatment planning. The purpose of this study is to develop a reliable method for deforming the prostate and surrounding regions from the geometry of MRSI imaging to the geometry of treatment planning, so that the regions of high tumor burden identified by the MRSI study can be faithfully transferred to the images used for treatment planning. METHODS AND MATERIALS: Magnetic resonance spectroscopy imaging studies have been performed on 2 prostate cancer patients using a commercial MRSI system with an endorectal coil and coupling balloon. At the end of each study, we also acquired the MRI of the pelvic region at both the deformed state where the prostate is distorted by the endorectal balloon and the resting state with the endorectal balloon deflated and removed. The task is to find a three-dimensional matrix of transformation vectors for all volume elements that links the two image sets. We have implemented an optimization method to iteratively optimize the transformation vectors using a Newton-Ralphson algorithm. The objective function is based on the mutual information. The distorted images using the transformation vectors are compared with the images acquired at the resting conditions. RESULTS AND DISCUSSION: The algorithm is capable of performing the registration automatically without the need for intervention. It does not require manual contouring of the organs. By applying the algorithm to multiple image sets of different patients, we found a good agreement between the images transformed from those acquired at the deformed state and those acquired at resting conditions. The computation time required for achieving the registration is in the range of a half-hour (for image size: 256 pixels x 256 pixels x 25 slices). However, the space of registration can be restricted to speed up the process. CONCLUSION: In this article, we described a three-dimensional deformable image registration method to automatically transform images from the deformed imaging state to resting state. Our examples show that this method is feasible and useful to the treatment planning system.

The low alpha/beta ratio for prostate cancer: what does the clinical outcome of HDR brachytherapy tell us?

PURPOSE: Accumulating evidence demonstrates that prostate cancer has a low alpha/beta ratio. However, several challenging issues have been raised from previous studies, including the biologic equivalence between external beam radiotherapy (EBRT) and brachytherapy, the effect of relative biologic effectiveness (RBE) for permanent implantation, and the systematic uncertainties of multi-institutional and multi-modality clinical data. The purpose of this study is to address these issues by reexamining a reported clinical outcome of high-dose-rate (HDR) brachytherapy and to confirm the low alpha/beta ratio for prostate cancer. METHODS AND MATERIALS: The generalized linear-quadratic (LQ) model with considerations of sublethal damage repair and clonogen repopulation was used to calculate the cell-killing efficiency of radiotherapy treatments for prostate cancer. Standard models of tumor cure based on Poisson statistics were used to bridge cell killing to treatment outcome. The data collected in a clinical trial using EBRT plus HDR brachytherapy boost for prostate cancer at William Beaumont Hospital (WBH) were reanalyzed. A 4-year post-treatment time endpoint was chosen as compared to the 3-year endpoint used in the previous study because of better maturity and stability of the data. The least chi-square method was employed to fit the clinical data to estimate the LQ parameters as well as their confidence intervals. The number of clonogens for prostate tumors derived in a separate study was used as a constraint for the data modeling to improve the confidence level. RESULTS: Our analysis demonstrates that only relationships among the LQ parameters, not their definitive and unique values, can be derived from the WBH data set alone. This is due to the large statistical uncertainties, i.e., the small numbers of sampled patients. By combining with the results obtained with the clinical data from Memorial Sloan-Kettering Cancer Center (MSKCC), a new set of LQ parameters (alpha = 0.14 +/- 0.05 Gy(-1), alpha/beta = 3.1(-1.6)(+2.6) Gy) was obtained from the current analysis of the WBH data without dealing with data from permanent implants. The results are consistent with a previous study based on the biologic equivalence between EBRT and permanent implants with a consideration of tumor repopulation. This set of LQ parameters provides a consistent interpretation of clinical data currently available for prostate cancer. CONCLUSIONS: This study provides further evidence to support that prostate cancer has a low alpha/beta ratio of about 3.1 Gy. This study shows that the RBE effect in permanent implantation may not be clinically significant for prostate cancer. The consistency found between this analysis and the previous reported study supports the general biologic equivalence between EBRT and brachytherapy treatments for prostate cancer. The low alpha/beta ratio opens the door to search for more effective radiotherapeutic approaches for prostate cancer, e.g., hypofractionation radiotherapy.

Radiosurgical treatment of trigeminal neuralgia: evaluating quality of life and treatment outcomes.

PURPOSE: To assess the safety, efficacy, and quality of life (QOL) associated with radiosurgical treatment for trigeminal neuralgia (TN). METHODS AND MATERIALS: Between June 1996 and June 2001, 112 patients with TN refractory to medical or surgical management were treated with gamma knife radiosurgery (GKRS) at the University of Maryland Medical Center. A median prescription dose of 75 Gy (range: 70-80 Gy) was delivered to the involved trigeminal nerve root entry zone. Treatment outcomes were assessed through patient self-reports of pain control and medication usage during follow-up visits. In addition, patients responded to a standard questionnaire containing the Barrow Neurologic Institute Pain Scale (BNI) and selected sections of the McGill Pain Scale. Treatment outcomes and objective quality of life measures were also addressed. RESULTS: Ninety-six patients (86%) completed questionnaires for a median follow-up of 30 months (range: 8-66 months). Seventy-four patients (77%) reported pain relief occurring after a median of 3 weeks (range: 0-24 weeks) after GKRS. A decrease in medication usage was noted in 66% of patients. Actuarial analysis demonstrated 1-year, 2-year, and 3-year recurrence rates of 23%, 33%, and 39%, respectively. Response to treatment was associated with lack of prior surgical treatment (p = 0.03) and less than 50 months' pain duration before GKRS (p = 0.04). Patients who described their TN pain as more severe than their worst non-TN headache pain (McGill Pain Scale IV-V vs. I-III) were also more likely to respond to treatment (p < 0.001). Seven (7.3%) patients reported new or increased trigeminal dysfunction; however, only 3.1% reported these symptoms as bothersome (BNI III-IV). Patients with sustained pain relief reported an average of 100% improvement in their QOL as a direct result of pain relief after GKRS, and 100% believed that the procedure was successful. Furthermore, among those patients with temporary pain relief and subsequent recurrence, 65% felt their treatment was a success with an average of 80% improvement in their QOL. CONCLUSIONS: GKRS provides significant pain relief and improves QOL in the majority of patients treated for TN, with few bothersome side effects. Patients with both temporary and sustained responses to treatment realized significant improvements in QOL after GKRS, and considered their treatment successful. Longer follow-up of these patients may reveal additional recurrences highlighting the importance of studies evaluating repeat GKRS and optimization of current treatment techniques and patient selection.

Risk group stratification in patients undergoing permanent (125)I prostate brachytherapy as monotherapy.

PURPOSE: Patients undergoing prostate brachytherapy (PB) as monotherapy are often selected on the basis of favorable pretreatment factors. However, intermediate and high-risk prostate cancer patients are commonly offered PB as monotherapy without the addition of external beam radiotherapy (EBRT) or hormonal therapy. This series reports the outcome of patients undergoing PB as monotherapy who were stratified into low, intermediate, and high-risk groups with extended follow-up. METHODS AND MATERIALS: A total of 102 patients with clinically localized prostate cancer underwent PB alone as monotherapy. EBRT or hormonal therapy was not part of their initial treatment. Prostate-specific antigen (PSA) relapse-free survival (PRFS) was determined in accordance with the American Society for Therapeutic Radiology and Oncology consensus statement. Patients were stratified as at favorable risk (Stage T1-2a, pretreatment PSA < or =10.0 ng/mL, and Gleason score < or =6), intermediate risk (one prognostic indicator with a higher value), or unfavorable risk (> or =2 indicators with higher values). The median follow-up period for patients in this series was 7 years (range 2.1-9.7). The median age at treatment was 71 years (range 54-80), and the median prescribed dose of (125)I was 145 Gy. RESULTS: Forty patients experienced a biochemical relapse at a median of 1.9 years (range 0.4-4.2). The 5-year actuarial PRFS rate for patients with favorable, intermediate, and unfavorable risk was 85%, 63%, and 24%, respectively (p <0.0001). All but 1 patient had the relapse within the first 5 years of treatment. When stratifying patients on the basis of their pretreatment PSA level, the 5-year PRFS rate for men with a PSA < or =10 ng/mL vs. >10 ng/mL was 78% vs. 35%, respectively (p = 0.0005). Furthermore, the 5-year PRFS rate for men with a Gleason score of < or =6 vs. > or =7 was 74% vs. 33%, respectively (p = 0.0001). No difference was found between Stage T1-T2a and Stage T2b or higher (64% vs. 54%, respectively; p = 0.353). CONCLUSION: On the basis of risk stratification, PB as monotherapy produces comparable PRFS to EBRT and surgery at 7 years of follow-up. PB as monotherapy is particularly ineffective in patients with unfavorable risk factors, and additional therapy is warranted.

Influence of radiation dose on positive surgical margins in women undergoing breast conservation therapy.

PURPOSE: Positive surgical margins adversely influence local tumor control in breast conservation therapy (BCT). However, reports have conflicted regarding whether an increased radiation dose can overcome this poor prognostic factor. In this study, we evaluated the influence of an increased radiation dose on tumor control in women with positive surgical margins undergoing BCT. METHODS AND MATERIALS: Between 1978 and 1994, 733 women with pathologic Stage I-II breast cancer and known surgical margin status were treated at Thomas Jefferson University Hospital with BCT. Of these 733 patients, 641 women had a minimal tumor bed dose of 60 Gy and had documentation of their margin status; 509 had negative surgical margins, and 132 had positive surgical margins before definitive radiotherapy. Complete gross excision of the tumor and axillary lymph node sampling was obtained in all patients. The median radiation dose to the primary site was 65.0 Gy (range 60-76). Of the women with positive margins (n = 132), the influence of higher doses of radiotherapy was evaluated. The median follow-up time was 52 months. RESULTS: The local tumor control rate for patients with negative margins at 5 and 10 years was 94% and 88%, respectively, compared with 85% and 67%, respectively, for those women with positive margins (p = 0.001). The disease-free survival rate for the negative margin group at 5 and 10 years was 91% and 82%, respectively, compared with 76% and 71%, respectively, for the positive margin group (p = 0.001). The overall survival rate of women with negative margins at 5 and 10 years was 95% and 90%, respectively. By comparison, for women with positive surgical margins, the overall survival rate at 5 and 10 years was 86% and 79%, respectively (p = 0.008). A comparison of the positive and negative margin groups revealed that an increased radiation dose (whether entered as a dichotomous or a continuous variable) >65.0 Gy did not improve local tumor control (p = 0.776). On Cox multivariate analysis, margin status and menopausal status had prognostic significance for local tumor control and DFS. CONCLUSION: Patients with positive surgical margins have a higher risk of local tumor recurrence and worse survival when undergoing BCT. Higher doses of radiation are unable to provide an adequate level of local control in patients with positive margins.

Clinical implementation of an automated planning system for gamma knife radiosurgery.

PURPOSE: To evaluate an automated treatment planning system for gamma knife radiosurgery. This planning system was developed in our clinic and is now in routine clinical use. The system simultaneously optimizes the shot sizes, locations, and weights. It also guides the user in selecting the total number of radiation shots. METHODS AND MATERIALS: We assessed the clinical significance of the automated system by comparing an optimized plan with a manual plan for 10 consecutive patients treated at our gamma knife facility. Each treatment plan was analyzed using dose-volume histograms in conjunction with the conformity index, the minimum target dose, and the integral normal tissue dose. RESULTS: On average, the treatment plan produced by the inverse planning tool provided an improved conformity index, a higher minimum target dose, and a reduced volume of the 30% isodose line as compared to the corresponding plan developed by an experienced physician. An optimized treatment plan can typically be produced in 10 min or less. CONCLUSIONS: The automated planning system consistently provides a high-quality treatment plan while reducing the time required for gamma knife treatment planning.

Magnetic resonance spectroscopic imaging-guided brachytherapy for localized prostate cancer.

PURPOSE: Prostate brachytherapy (PB) entails the placement of radioactive sources throughout the entire prostate gland to treat localized cancer. Typically, the target volume in PB encompasses the entire prostate gland because of the inability to localize the cancer and the multifocal nature of this malignancy. However, because of the unique biochemical nature of the prostate gland, recent advances in magnetic resonance spectroscopic imaging (MRSI) of the prostate have allowed precise delineation of the cancer location within the prostate gland. This report reveals our initial experience of MRSI-guided PB. METHODS: A MRSI study was obtained in 15 localized prostate cancer patients before their scheduled PB. The results of this study were used to internally map 7 x 7 x 9-mm volumes of prostate tissue to assign cancerous areas a higher dose of radiation. Such tumor-bearing areas had a low citrate/(choline+creatine) ratio consistent with cancer. On the basis of the anatomic MRI and MRSI correlation, three-dimensional coordinates were assigned to the locations of MRSI-defined cancer. The entire target volume was treated to a standard prescription dose using I-125 or Pd-103. Abnormal citrate regions, termed the biologic tumor volume, were prescribed a dose of 130% of the target volume dose to dose escalate in the abnormal citrate regions while respecting the normal radiation tolerances of the surrounding areas. Three-dimensional treatment planning was used to perform the implant. RESULTS: Of the 15 prostate cancer patients evaluated, all had successful three-dimensional MRSI acquisition before their scheduled PB procedure. In 14 of the 15 patients planned with MRSI, the data were successfully incorporated into their treatment planning and were used to increase the radiation dose prescription to 130% in the MRSI-defined volumes. In 1 patient, MRSI revealed significant background artifact that made a focal boost impractical. Postimplant dosimetry confirmed a median V100 of 95% (range 72%-100%) in the 15 evaluated patients for the prescription dose. Furthermore, the median BTV100 for the abnormal citrate region was 90% (range 80-100%) as determined by postimplant dosimetry. Urethral and rectal dose-volume histograms were within normal limits. Morbidity was comparable with that for conventionally treated patients. CONCLUSION: MRSI offers a promising new approach for the delivery of ionizing radiation in PB. Although this series was small and with a short follow-up, MRSI-guided implants are feasible and warrant further investigation as a means of improving the therapeutic ratio in PB [corrected].

Factors predicting local tumor control after gamma knife stereotactic radiosurgery for benign intracranial meningiomas.

PURPOSE: To determine the long-term outcomes and prognostic factors in benign intracranial meningiomas treated with gamma knife stereotactic radiosurgery (GK-SRS). METHODS AND MATERIALS: Between 1992 and 2000, 162 patients with benign meningiomas were treated with GK-SRS at the University of Maryland Medical Center. Complete follow-up was available in 137 patients. All patients underwent magnetic resonance imaging (MRI)-based treatment planning. Serial MRIs and clinical exams were performed to assess tumor response. GK-SRS was the primary treatment in 85 patients (62%), whereas 52 patients (48%) had prior surgical resections. The median prescribed dose was 14 Gy (range, 4-25 Gy) to the 50% isodose line. The median tumor volume, treatment volume, and conformity index were 4.5 cc (range, 0.32-80.0 cc), 6.3 cc (range, 1.0-75.2 cc), and 1.34 (range, 0.65-3.16), respectively. The median follow-up for the entire cohort was 4.5 years (range, 0.33-10.5 years). The following factors were included in the statistical analysis for disease-free survival (DFS) and overall survival (OS): sex, age, dose, gross tumor volume (GTV), conformity index (CI), and dural tail coverage. RESULTS: Serial MRI analysis was available in 121 patients (88.3%). Decrease in tumor size was observed in 34 patients (28.1%), whereas there was no change in 77 patients (63.6%), for a crude radiographic control rate of 91.7%. Increase in tumor size was seen in 10 patients (8.3%). New neurologic deficits attributed to the treatment developed in 10 patients (8.3%). The mean DFS and OS for the entire cohort are 4.6 years and 5.0 years, respectively. The 5-year actuarial DFS and OS were 86.2% and 91.0%, respectively. Univariate analysis revealed GTV, sex, CI, and dural tail treatment to be significant prognostic factors. Patients with GTV < or =10 cc also had longer survivals, with the 5-years DFS and OS of 91.9% vs. 68.0% (p = 0.038) and 100% vs. 59.7% (p = 0.0001), respectively. The 5-years actuarial DFS and OS for females vs. males were 90.2% vs. 74.2% (p = 0.0094) and 91.6% vs. 89.1% (p = 0.016), respectively. Patients with CI > or =1.4 achieved a longer DFS, with a 5-year DFS of 95.2% vs. 77.3% (p = 0.01). Patients who had the dural tail treated also had higher 5-year DFS (96.0% vs. 77.9%, p = 0.038). Patients with lower conformity (i.e., CI > or =1.4) tended to have the dural tail covered in the prescription isodose line (p = 0.04). The only factor significant in the multivariate analysis was for patients with GTV >10 cc, who had a worse DFS (hazard ratio 4.58, p = 0.05). CONCLUSIONS: This report adds to the literature that supports the efficacy and safety of GK-SRS in the management of patients with benign intracranial meningiomas. Our report identified male patients, patients with a CI <1.4, and tumor size greater than 10 cc to have a worse prognosis. Patients who were treated with less conformal plans to cover the dural tail had better outcomes. Our data clearly demonstrate the need to adequately cover the dural tail in patients treated with GK-SRS for benign intracranial meningiomas.

Stereotactic radiosurgery for benign neoplasms.

Over the last decade, the use of stereotactic radiosurgery (SRS) for the treatment of intracranial lesions has grown significantly. In addition to malignant brain tumors and vascular malformations, benign tumors have also been treated with SRS. Although surgical resection has long been considered the gold standard in the management of such benign lesions, the outcomes of SRS in various benign neoplasms appears to be comparable. In this review, we will examine the literature as it pertains to the treatment of benign brain tumors with SRS. Of particular note, we will examine the results of SRS in acoustic neuromas, meningiomas, pituitary adenomas, and other benign tumors.

Gamma knife stereotactic radiosurgery for patients with glioblastoma multiforme.

OBJECTIVE: Stereotactic radiosurgery (SRS) has become an effective therapeutic modality for the treatment of patients with glioblastoma multiforme (GBM). This retrospective review evaluates the impact of SRS delivered on a gamma knife (GK) unit as an adjuvant therapy in the management of patients with GBM. METHODS: Between August 1993 and December 1998, 82 patients with pathologically confirmed GBM received external beam radiotherapy (EBRT) at the University of Maryland Medical Center. Of these 82 patients, 64 with a minimum follow-up duration of at least 1 month are the focus of this analysis. Of the 64 assessable patients, 33 patients were treated with EBRT alone (Group 1), and 31 patients received both EBRT plus a GK-SRS boost (Group 2). GK-SRS was administered to most patients within 6 weeks of the completion of EBRT. The median EBRT dose was 59.7 Gy (range, 28-070.2 Gy), and the median GK-SRS dose to the prescription volume was 17.1 Gy (range, 10-28 Gy). The median age of the study population was 50.4 years, and the median pretreatment Karnofsky performance status was 80. Patient-, tumor-, and treatment-related variables were analyzed by Cox regression analysis, and survival curves were generated by the Kaplan-Meier product limit. RESULTS: Median overall survival for the entire cohort was 16 months, and the actuarial survival rate at 1, 2, and 3 years were 67, 40, and 26%, respectively. When comparing age, Karnofsky performance status, extent of resection, and tumor volume, no statistical differences where discovered between Group 1 versus Group 2. When comparing the overall survival of Group 1 versus Group 2, the median survival was 13 months versus 25 months, respectively (P = 0.034). Age, Karnofsky performance status, and the addition of GK-SRS were all found to be significant predictors of overall survival via Cox regression analysis. No acute Grade 3 or Grade 4 toxicity was encountered. CONCLUSION: The addition of a GK-SRS boost in conjunction with surgery and EBRT significantly improved the overall survival time in this retrospective series of patients with GBM. A prospective, randomized validation of the benefit of SRS awaits the results of the recently completed Radiation Therapy Oncology Group's trial RTOG 93-05.

Dose escalation in permanent brachytherapy for prostate cancer: dosimetric and biological considerations.

No prospective dose escalation study for prostate brachytherapy (PB) with permanent implants has been reported. In this work, we have performed a dosimetric and biological analysis to explore the implications of dose escalation in PB using 125I and 103Pd implants. The concept of equivalent uniform dose (EUD), proposed originally for external-beam radiotherapy (EBRT), is applied to low dose rate brachytherapy. For a given 125I or 103Pd PB, the EUD for tumour that corresponds to a dose distribution delivered by EBRT is calculated based on the linear quadratic model. The EUD calculation is based on the dose volume histogram (DVH) obtained retrospectively from representative actual patient data. Tumour control probabilities (TCPs) are also determined in order to compare the relative effectiveness of different dose levels. The EUD for normal tissue is computed using the Lyman model. A commercial inverse treatment planning algorithm is used to investigate the feasibility of escalating the dose to prostate with acceptable dose increases in the rectum and urethra. The dosimetric calculation is performed for five representative patients with different prostate sizes. A series of PB dose levels are considered for each patient using 125I and 103Pd seeds. It is found that the PB prescribed doses (minimum peripheral dose) that give an equivalent EBRT dose of 64.8, 70.2, 75.6 and 81 Gy with a fraction size of 1.8 Gy are 129, 139, 150 and 161 Gy for 125I and 103, 112, 122 and 132 Gy for 103Pd implants, respectively. Estimates of the EUD and TCP for a series of possible prescribed dose levels (e.g., 145, 160, 170 and 180 Gy for 125I and 125, 135, 145 and 155 for 103Pd implants) are tabulated. The EUD calculation was found to depend strongly on DVHs and radiobiological parameters. The dosimetric calculations suggest that the dose to prostate can be escalated without a substantial increase in both rectal and urethral dose. For example, increasing the PB prescribed dose from 145 to 180 Gy increases EUD for the rectum by only 3%. Our studies indicate that the dose to urethra can be kept within 100-120% of the prescription dose for all the dose levels studied. In conclusion, dose escalation in permanent implant for localized prostate cancer may be advantageous. It is dosimetrically possible to increase dose to prostate without a substantial increase in the dose to the rectum and urethra. Based on the results of our studies, a prospective dose escalation trial for prostate permanent implants has been initiated at our institution.

Influence of gamma knife radiosurgery on the quality of life in patients with brain metastases.

Quality of life (QOL) is an important issue in the treatment of patients with brain metastases. With median survival times often less than 4 months, less invasive treatment options that maximize QOL parameters are essential. In recent years, stereotactic radiosurgery (SRS) has been commonly used as a noninvasive alternative to surgical resection for such patients. This prospective study was undertaken to evaluate QOL in patients undergoing SRS for brain metastases. Between 1999 and 2000, 20 patients with metastatic disease to the brain were evaluated and treated in our Gamma Knife unit. All patients performed the Spitzer QOL survey (10-point scale) both before stereotactic radiosurgery and at each follow-up visit. Primary sites of disease included lung (n = 10), breast (n = 5), melanoma (n = 2), thyroid (n = 1), uterine (n = 1), and kidney (n = 1). Fifteen (75%) had prior whole brain radiotherapy (median dose: 35 Gy). The median age and Karnofsky Performance Status were 58 years and 80, respectively. The median Spitzer score before SRS was 9 (range: 7-10), and the median follow-up time of the patients in this series was 7 months. The median posttreatment Spitzer score at 1 and 3 months after SRS was 9 (range: 5-10) and 8 (range: 4-10), respectively. Crude intracranial tumor control in this cohort of patients was 90%. Extracranial tumor progression was noted in 8 patients (40%), and in these patients, Spitzer scores tended to decrease in value. In those patients who had no evidence of intracranial or extracranial tumor progression, Spitzer scores remained either unchanged or improved. Gamma knife SRS is an appropriate treatment modality for maintaining QOL parameters in patients with brain metastases. Tumor progression both intracranially and extracranially influences QOL parameters. Confirmation of this finding will require further investigation.

Long-term follow-up of a prospective trial of trimodality therapy of weekly paclitaxel, radiation, and androgen deprivation in high-risk prostate cancer with or without prior prostatectomy.

PURPOSE: Weekly paclitaxel, concurrent radiation, and androgen deprivation (ADT) were evaluated in patients with high-risk prostate cancer (PC) with or without prior prostatectomy (RP). METHODS AND MATERIALS: Eligible post-RP patients included: pathological T3 disease, or rising prostate-specific antigen (PSA) ≥ 0.5 ng/mL post-RP. Eligible locally advanced PC (LAPC) patients included: 1) cT2b-4N0N+, M0; 2) Gleason score (GS) 8-10; 3) GS 7 + PSA 10-20 ng/mL; or 4) PSA 20-150 ng/mL. Treatment included ADT (4 or 24 months), weekly paclitaxel (40, 50, or 60 mg/m(2)/wk), and pelvic radiation therapy (total dose: RP = 64.8 Gy; LAPC = 70.2 Gy). RESULTS: Fifty-nine patients were enrolled (LAPC, n = 29; RP, n = 30; ADT 4 months, n = 29; 24 months, n = 30; whites n = 29, African Americans [AA], n = 28). Baseline characteristics (median [range]) were: age 67 (45-86 years), PSA 5.9 (0.1-92.1 ng/mL), GS 8 (6-9). At escalating doses of paclitaxel, 99%, 98%, and 95% of doses were given with radiation and ADT, respectively, with dose modifications required primarily in RP patients. No acute Grade 4 toxicities occurred. Grade 3 toxicities were diarrhea 15%, urinary urgency/incontinence 10%, tenesmus 5%, and leukopenia 3%. Median follow-up was 75.3 months (95% CI: 66.8-82.3). Biochemical progression occurred in 24 (41%) patients and clinical progression in 11 (19%) patients. The 5- and 7-year OS rates were 83% and 67%. There were no differences in OS between RP and LAPC, 4- and 24-month ADT, white and AA patient categories. CONCLUSIONS: In addition to LAPC, to our knowledge, this is the first study to evaluate concurrent chemoradiation with ADT in high-risk RP patients. With a median follow-up of 75.3 months, this trial also represents the longest follow-up of patients treated with taxane-based chemotherapy with EBRT in high-risk prostate cancer. Concurrent ADT, radiation, and weekly paclitaxel at 40 mg/m(2)/week in RP patients and 60 mg/m(2)/week in LAPC patients is feasible and well-tolerated.

Phase I clinical trial assessing temozolomide and tamoxifen with concomitant radiotherapy for treatment of high-grade glioma.

PURPOSE: The new standard treatment of glioblastoma multiforme is concurrent radiotherapy (RT) and temozolomide. The proliferation of high-grade gliomas might be partly dependent on protein kinase C-mediated pathways. Tamoxifen has been shown in vitro to inhibit protein kinase C through estrogen receptor-independent antineoplastic effects. This Phase I trial was designed to determine the maximal tolerated dose (MTD) of tamoxifen when given with temozolomide and concurrent RT to patients with high-grade gliomas. METHODS AND MATERIALS: A total of 17 consecutive patients in four cohorts with World Health Organization Grade 3 (n = 2) and 4 (n = 15) gliomas were given tamoxifen twice daily during 6 weeks of concurrent RT and temozolomide. Eligibility included histologic diagnosis, age >18 years old, Karnofsky performance status ≥ 60, and no previous brain RT or chemotherapy. The starting dose was 50 mg/m(2) divided twice daily. If no dose-limiting toxicities (DLTs) occurred in 3 patients, the dose was escalated in 25-mg/m(2) increments until the MTD was reached. When ≥ 2 patients within a cohort experienced a DLT, the MTD had been exceeded. Temozolomide was given with RT at 75 mg/m(2). A dose of 60 Gy in 2 Gy/d fractions to a partial brain field was delivered. RESULTS: A total of 6 patients in Cohort 4 had received tamoxifen at 125 mg/m(2). One patient was excluded, and the fourth patient developed Grade 4 thrombocytopenia (DLT). Thus, 3 more patients needed to be enrolled. A deep venous thrombosis (DLT) occurred in the sixth patient. Thus, the MTD was 100 mg/m(2). CONCLUSIONS: The MTD of tamoxifen was 100 mg/m(2) when given concurrently with temozolomide 75 mg/m(2) and RT. Tamoxifen might have a role in the initial treatment of high-grade gliomas and should be studied in future Phase II trials building on the newly established platform of concurrent chemoradiotherapy.

Long-term results of a prospective, Phase II study of long-term androgen ablation, pelvic radiotherapy, brachytherapy boost, and adjuvant docetaxel in patients with high-risk prostate cancer.

PURPOSE: We report the long-term results of a prospective, Phase II study of long-term androgen deprivation (AD), pelvic radiotherapy (EBRT), permanent transperineal prostate brachytherapy boost (PB), and adjuvant docetaxel in patients with high-risk prostate cancer. METHODS AND MATERIALS: Eligibility included biopsy-proven prostate adenocarcinoma with the following: prostate-specific antigen (PSA) > 20 ng/ml; or Gleason score of 7 and a PSA >10 ng/ml; or any Gleason score of 8 to 10; or stage T2b to T3 irrespective of Gleason score or PSA. Treatment consisted of 45 Gy of pelvic EBRT, followed 1 month later by PB with either iodine-125 or Pd-103. One month after PB, patients received three cycles of docetaxel chemotherapy (35 mg/m(2) per week, Days 1, 8, and 15 every 28 days). All patients received 2 years of AD. Biochemical failure was defined as per the Phoenix definition (PSA nadir + 2). RESULTS: From August 2000 to March 2004, 42 patients were enrolled. The median overall and active follow-ups were 5.6 years (range, 0.9-7.8 years) and 6.3 years (range, 4-7.8 years), respectively. Grade 2 and 3 acute genitourinary (GU) and gastrointestinal (GI) toxicities were 50.0% and 14.2%, respectively, with no Grade 4 toxicities noted. Grade 3 and 4 acute hematologic toxicities were 19% and 2.4%, respectively. Of the patients, 85.7% were able to complete the planned multimodality treatment. The 5- and 7-year actuarial freedom from biochemical failures rates were 89.6% and 86.5%, and corresponding rates for disease-free survival were 76.2% and 70.4%, respectively. The 5- and 7-year actuarial overall survival rates were 83.3% and 80.1%, respectively. The 5- and 7-year actuarial rates of late Grade 2 GI/GU toxicity (no Grade 3-5) was 7.7%. CONCLUSIONS: The trimodality approach of using 2 years of AD, external radiation, brachytherapy, and upfront docetaxel in high-risk prostate cancer is well tolerated, produces encouraging long-term results, and should be validated in a multi-institutional setting.