Steven J. DiBiase
University of Maryland, Baltimore
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Neurosurgery | 2002
Emmanuel C. Nwokedi; Steven J. DiBiase; Salma K Jabbour; Joseph Herman; Pradip Amin; Lawrence S. Chin
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, 28–70.2 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.
International Journal of Radiation Oncology Biology Physics | 2003
Jian Z. Wang; X. Allen Li; C Yu; Steven J. DiBiase
Abstract Purpose Accumulating evidence demonstrates that prostate cancer has a low α/β 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 α/β 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 (α = 0.14 ± 0.05 Gy −1 , α/β = 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 α/β 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 α/β ratio opens the door to search for more effective radiotherapeutic approaches for prostate cancer, e.g., hypofractionation radiotherapy.
International Journal of Radiation Oncology Biology Physics | 2000
Steven J. DiBiase; Kent E. Wallner; Kevin Tralins; Steven Sutlief
PURPOSE To investigate the role of radiation dose to the neurovascular bundles (NVB) in brachytherapy-related impotence. METHODS AND MATERIALS Fourteen Pd-103 or I-125 implant patients were studied. For patients treated with implant alone, the prostate and margin (clinical target volume [CTV]) received a prescription dose of 144 Gy for I-125 or 115 Gy for Pd-103. Two patients received Pd-103 (90 Gy) with 46 Gy supplemental external beam radiation (EBRT). Axial CT images were acquired 2 to 4 hours postoperatively for postimplant dosimetry. Because the NVBs cannot be visualized on CT, NVB calculation points were determined according to previously published anatomic descriptions. Bilateral NVB points were considered to lie posterior-laterally, approximately 2 mm from the prostatic capsule. NVB doses were recorded bilaterally, at 0.5-cm intervals from the prostatic base. RESULTS For Pd-103, the average NVB doses ranged from 150 Gy to 260 Gy, or 130% to 226% of the prescription dose. For I-125, the average NVB dose ranged from 200 Gy to 325 Gy, or 140% to 225% of the prescription dose. These was no consistent relationship between the NVB dose and the distance from the prostatic base. To examine the possible effect of minor deviations of our calculation points from the true NVB location, we performed NVB calculations at points 2 mm medial or lateral from the NVB calculation point in 8 patients. Doses at these alternate calculation points were comparable, although there was greater variability with small changes in the calculation point if sources were located outside the capsule, near the NVB calculation point. Three patients who developed early postimplant impotence had maximal NVB doses that far exceeded the average values. CONCLUSIONS In the next few years, we hope to clarify the role of high NVB radiation doses on potency, by correlating NVB dose calculations with a large number of patients enrolled in an ongoing I-125 versus Pd-103 trial for early-stage patients, for whom detailed dosimetric and potency data are being collected prospectively. In the future, we anticipate that NVB doses may be incorporated into dosimetry guidelines to maximize tumor control and minimize treatment-related morbidity.
International Journal of Cancer | 2001
Lijun Ma; C Yu; M Earl; Tim Holmes; Mehrdad Sarfaraz; X. Allen Li; D Shepard; Pradip Amin; Steven J. DiBiase; Mohan Suntharalingam; Carl M. Mansfield
We recently implemented intensity‐modulated arc therapy (IMAT) at our institution. In this study, we evaluate the dosimetric merits of the application of this technique to the treatment of prostate cancer. Each IMAT treatment plan incorporated bilateral overlapping arcs. The dose from each beam segment was computed using the three‐dimensional dose model of a clinical treatment planning system (Render Plan 3.5, Precision Therapy). The weights assigned to the individual arc segments were optimized using a gradient search method. For 12 patients, comparisons were made between the IMAT treatment plans and corresponding plans using fixed cone‐beam intensity‐modulated radiotherapy (IMRT) from a commercial inverse planning system (CORVUS, NOMOS Corp.). We found that the optimized IMAT treatments produced similar dose distributions to the IMRT deliveries. Compared with the IMRT treatments, the IMAT treatments produced slightly less target dose homogeneity with consistently greater sparing of the rectum in regions of lower dose. The trade‐off between target dose conformity and rectum sparing can be adjusted in both optimization procedures. Because the total beam‐on time for IMAT delivery is 1 to 2 minutes with approximately 5–6 minutes of patient setup time, the delivery efficiency of the IMAT treatment was significantly better than the multiple‐beam IMRT treatment.
International Journal of Radiation Oncology Biology Physics | 2002
Steven J. DiBiase; Lydia Komarnicky; Dwight E. Heron; Gordon F. Schwartz; Carl M. Mansfield
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.
Physics in Medicine and Biology | 2003
X. Allen Li; Jian Z. Wang; Robert D. Stewart; Steven J. DiBiase
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.
International Journal of Radiation Oncology Biology Physics | 2002
Young Kwok; Steven J. DiBiase; Pradip Amin; Michael Naslund; Geoffrey N. Sklar; Stephen C. Jacobs
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.
American Journal of Clinical Oncology | 2002
Steven J. DiBiase; Lawrence S. Chin; Lijun Ma
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.
International Journal of Radiation Oncology Biology Physics | 2003
D Shepard; Lawrence S. Chin; Steven J. DiBiase; S Naqvi; Jinho Lim; Michael C. Ferris
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.
Journal of Surgical Oncology | 1997
Steven J. DiBiase; Jeffrey G. Rosenstock; Leonard Shabason; Benjamin W. Corn
Locally advanced and recurrent malignancies often require adjuvant radiotherapy to achieve tumor control. We report our experience with a technique that uses an intraoperatively placed mesh template for the delivery of radiotherapy.