Allan F. deGuzman

Cavity-directed radiosurgery as adjuvant therapy after resection of a brain metastasis

OBJECT As a strategy to delay or avoid whole-brain radiotherapy (WBRT) after resection of a brain metastasis, the authors used high-resolution MR imaging and cavity-directed radiosurgery for the detection and treatment of further metastases. METHODS Between April 2001 and October 2009, 112 resection cavities in 106 patients with no prior WBRT were treated using radiosurgery directed to the tumor cavity and for any synchronous brain metastases detected on high-resolution MR imaging at the time of radiosurgical planning. A median dose of 17 Gy to the 50% isodose line was prescribed to the gross tumor volume, defined as the rim of enhancement around the resection cavity. Patients were followed up via serial imaging, and new brain metastases were generally treated using additional radiosurgery, with salvage WBRT typically reserved for local treatment failure at a resection cavity, numerous failures, or failures occurring at short time intervals. Local and distant treatment failures were determined based on imaging results. Kaplan-Meier curves were generated to estimate local and distant treatment failure rates, overall survival, neurological cause-specific survival, and time delay to salvage WBRT. RESULTS Radiosurgery was delivered to the resection cavity alone in 57.5% of patients, whereas 24.5% of patients also received treatment for 1 synchronous metastasis, 11.3% also received treatment for 2 synchronous metastases, and 6.6% also received treatment for 3-10 additional lesions. The median overall survival was 10.9 months. Overall survival at 1 year was 46.8%. The local tumor control rate at 1 year was 80.3%. The disease control rate in distant regions of the brain at 1 year was 35.4%, with a median time of 6.9 months to distant failure. Thirty-nine of 106 patients eventually received salvage WBRT, and the median time to salvage WBRT was 12.6 months. Kaplan-Meier estimates showed that the rate of requisite WBRT at 1 year was 45.9%. Neurological cause-specific survival at 1 year was 50.1%. Leptomeningeal failure occurred in 8 patients. One patient had treatment failure within the resection tract. Seven patients required reoperation: 2 for resection cavity recurrence, 3 for radiation necrosis, 1 for hydrocephalus, and 1 for a CSF cutaneous fistula. On multivariate analysis, a preoperative tumor diameter > 3 cm was predictive of local treatment failure. CONCLUSIONS Cavity-directed radiosurgery combined with high-resolution MR imaging detection and radiosurgical treatment of synchronous brain metastases is an effective strategy for delaying and even foregoing WBRT in most patients. This technique provides acceptable local disease control, although distant treatment failure remains significant.

Postimplant analysis of transperineal interstitial permanent prostate brachytherapy: evidence for a learning curve in the first year at a single institution.

PURPOSE The utilization of transperineal interstitial permanent prostate brachytherapy (TIPPB) is increasing in the United States. Quality assessment of TIPPB is in its infancy, and to date, dosimetric analyses have only been reported from centers with a large experience in prostate brachytherapy. The purpose of this report is to critically analyze the dosimetric coverage achieved following TIPPB in the first 63 cases performed by a multidisciplinary group of investigators with no prior experience with TIPPB. METHODS AND MATERIALS The information in this report concerns the first 63 men treated with TIPPB alone at our institution between September 1997 and September 1998. All men were treated similarly, adapting the methods described by Blasko and Grimm. All men were treated with 125I. The prescription dose was 144 Gy according to the TG43 formalism. TIPPB was performed jointly by a radiation oncologist and a urologist. One month following TIPPB, all men underwent a computed tomography (CT) scan of the pelvis according to a protocol using 3-mm abutting slices. CT images were transferred by a local area network to a commercially available treatment planning system and dose-volume histograms were calculated with 0.5-mm pixel spacing. A variety of dosimetric endpoints were examined. A single measure of dose homogeneity, the dose-homogeneity index (DHI), is defined as the volume within the prostate that receives 100-150% of the prescription dose (144-216 Gy) divided by the volume within the prostate that receives 100% of the prescription dose (144 Gy). Three measures of target (prostate) dosimetric coverage are provided. C100 is defined as the percentage of the prostate volume defined on postimplant CT that receives at least 100% of the prescription dose. C90 and C80 are similar but represent the percentage of the prostate volume that receive 90% and 80% of the prescription dose, respectively. Statistical analyses were performed using commercially available computer software. To investigate any changes with time the first 30 cases (group 1) are compared to cases 31-63 (group 2). All p-values are two-sided. RESULTS The mean C100, C90, and C80 for all 63 patients were 80.7% (SD 10.1), 85.1% (SD 10.2), and 89.3% (SD 9.5). The quantifiers of implant adequacy were all improved in the most recent 33 patients compared to the first 30 patients, (group 1: C100, 75.8% [SD 12.2], C90 79.9% [SD 11.4], C80 84.3% [SD 11.1]; group 2: C100, 85.2 [SD 7.0], C90 89.9% [SD 5.8], C80 93.8% [SD 4.2]; p<0.001). The mean DHI was 0.538 SD (0.124). A multivariate model incorporating a number of variables (ultrasound volume, CT volume, total activity, activity/ seed, implant number) with C100 as the dependent variable found that the implant number was the only statistically significant predictor of C100 (p = 0.0001). Using C90 and C80 as the dependent variable produced similar results (C90, p = 0.0001; C80, p = 0.0001). CONCLUSION In this single institution experience with the first 63 men receiving TIPPB by a multidisciplinary group of investigators, there is evidence for a learning curve. All quantifiers of implant adequacy improved as clinicians gained experience. In the most recent group of patients, quantifiers of implant adequacy are similar to those reported from other groups with significantly more experience with TIPPB.

Early quality of life assessment in men treated with permanent source interstitial brachytherapy for clinically localized prostate cancer.

PURPOSE We prospectively assessed quality of life changes with time using validated instruments in men with clinically localized prostate cancer treated with permanent source interstitial brachytherapy. MATERIALS AND METHODS A total of 46 men consecutively treated with permanent source interstitial brachytherapy between September 1997 and June 1998 completed quality of life (Functional Assessment of Cancer Therapy-Prostate [FACT-P]) and urinary symptom (International Prostate Symptom Score [I-PSS]) questionnaires before (T0), and 1 (T1) and 3 (T3) months after treatment. All participants were treated with 125iodine alone. Repeated measures analyses of variance were conducted on all quality of life and urinary outcome measures for 44 patients with data at all 3 time points. RESULTS Median patient age was 68 years (range 51 to 80). All men had clinical T1c to T2b prostate cancer, Gleason score was 6 or less in 36 (78%) and median pretreatment prostate specific antigen was 7 ng./ml. (range 1.1 to 20.6). Mean score (and standard deviation) at T0, T1 and T3 for each questionnaire was FACT-P 138.9 (14.4), 128.6 (19.4) and 136.7 (17.4), TO versus T1 p = 0.0005 and T0 versus T3 p = 0.6612, and I-PSS 8.3 (5.4), 19.7 (9.0) and 15.7 (7.2), T0 versus T1 p = 0.0001 and T0 versus T3 p = 0.0001. For the global test across time statistically significant differences were observed for the cumulative scores of FACT-P, I-PSS, physical well-being and prostate cancer subscales of the FACT-P and the Trial Outcome Index. By 3 months all quality of life measures had returned to baseline. Urinary symptoms as measured by I-PSS persisted for at least 3 months. CONCLUSIONS Clinically meaningful decreases in quality of life, as measured by the FACT-P instrument, were evident within weeks after permanent source interstitial brachytherapy. However, by 3 months FACT-P scores returned to near baseline levels. A validated instrument designed to measure urinary symptoms (I-PSS) demonstrated that moderate to severe urinary symptoms persisted for at least 3 months following permanent source interstitial brachytherapy. An instrument specifically designed to measure urinary symptoms can provide additional clinical information when combined with FACT-P.

Radioactive sources embedded in suture are associated with improved postimplant dosimetry in men treated with prostate brachytherapy

BACKGROUND AND PURPOSE Reports using the retropubic and transperineal technique of prostate brachytherapy suggest that adequate radiation doses are required for good clinical results with I-125. After 3 years of using loose sources (LS), radioactive sources embedded in suture (SES) were introduced into our prostate brachytherapy technique. The purpose of the present report is to determine whether dosimetric quantifiers of implant adequacy were affected by the use of SES. MATERIALS AND METHODS Between September 1999 and April 2000, 20 patients were treated with prostate brachytherapy alone with a preplanned, preloaded needle technique using LS. Between May 2000 and February 2001, 20 patients were treated with prostate brachytherapy alone with a preplanned, preloaded needle technique using SES. Dosimetric quantifiers (DQ) of implant adequacy were calculated using a computed tomography scan performed 1 month following prostate brachytherapy. DQ were compared between patients treated with LS and patients treated with SES. RESULTS The demographic characteristics were similar for each group. Men treated with SES had slightly smaller prostate glands compared to men treated with LS. The mean total activity and activity per seed were similar for each group but the activity per unit volume was slightly higher for the SES group. Patients treated with SES were found to have significantly improved DQ compared to patients treated with LS. The mean V100 for patients treated with SES was 94.10% compared to 86.54% in those patients treated with LS (P<0.001). CONCLUSIONS In our experience using preplanning and preloaded needles, the use of SES is associated with improved postimplant DQ.

Radiation dose to the neurovascular bundles or penile bulb does not predict erectile dysfunction after prostate brachytherapy

PURPOSE To examine the relationship between calculated doses to the neurovascular bundles (NVBs) and the penile bulb (PB) and the development of erectile dysfunction (ED) after low-dose-rate prostate brachytherapy (LDRPB) alone. METHODS AND MATERIALS Between September 1997 and June 1999, 84 men were treated with LDRPB alone. Inclusion criteria for this study were (1) no ED according to a self-administered questionnaire before PB, (2) treatment with PB alone (125I; 144 Gy), (3) postimplant CT scan of the prostate 1 month after PB, and (4) minimum of 24 months of continuous follow-up. Fifty men met all inclusion criteria. ED was assessed by a self-administered questionnaire completed before and at each follow-up visit after LDRPB. Radiation doses to the NVB and PB were calculated on the basis of axial postimplant CT images. Multiple variables (patient-related and dosimetric quantifiers) that may predict for the development of ED were examined by univariate analysis. RESULTS Thirty of the 50 men (60%) were potent at last follow-up. The only patient-related variable that predicted for the development of ED was patient age (<65 vs. >65 years; p=0.03). The calculated mean maximum doses to the NVB and PB were 684 Gy (range, 195-1277 Gy) and 498 Gy (range, 44-971 Gy), respectively. The mean calculated doses to 50% of the NVB and PB were 158 Gy (range, 76-240 Gy) and 43 Gy (range, 19-101 Gy), respectively. The calculated mean maximum, mean minimum, and mean doses to 50% of the NVB or PB did not differ between those men who developed ED and those men who did not develop ED. None of the dosimetric variables examined predicted the development of ED after LDRPB. CONCLUSIONS In our experience, higher calculated doses to the NVB or PB are not associated with ED after LDRPB.

Predictive Variables for the Successful Treatment of Trigeminal Neuralgia With Gamma Knife Radiosurgery

BACKGROUND Gamma Knife radiosurgery (GKRS) has been reported to be an effective modality to treat trigeminal neuralgia. OBJECTIVE To determine predictive factors for the successful treatment of trigeminal neuralgia with GKRS. METHODS Between 1999 and 2008, 777 GKRS procedures for patients with trigeminal neuralgia were performed at our institution. Evaluable follow-up data were obtained for 448 patients. Median follow-up time was 20.9 months (range, 3-86 months). The mean maximum prescribed dose was 88 Gy (range, 80-97 Gy). Dosimetric variables recorded included dorsal root entry zone dose, pons maximum dose, dose to the petrous dural ridge, and cisternal nerve length. RESULTS By 3 months after GKRS, 86% of patients achieved Barrow Neurologic Institute I to III pain scores, with 43% of patients achieving a Barrow Neurologic Institute I pain score. Twenty-six percent of patients reported posttreatment facial numbness; 28% of patients reported a post-GKRS procedure for relapsed pain, and median time to next procedure was 4.4 years. Multivariate analysis revealed that the development of postsurgical numbness (odds ratio [OR], 2.76; P = .006) was the dominant factor predictive of efficacy. Longer cisternal nerve length (OR, 0.85; P = .005), prior radiofrequency ablation (OR, 0.35; P = .028), and diabetes mellitus (OR, 0.38; P = .013) predicted decreased efficacy. The mean dose delivered to the dorsal root entry zone dose in patients who developed facial numbness (57.6 Gy) was more than the mean dose (47.3 Gy) given to patients who did not develop numbness (P = .02). CONCLUSION The development of post-GKRS facial numbness is a dominant factor that predicts for efficacy of GKRS. History of diabetes mellitus or previous radiofrequency ablation may portend worsened outcome.

Repeat gamma knife radiosurgery for trigeminal neuralgia.

PURPOSE Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. METHODS AND MATERIALS Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. RESULTS Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). CONCLUSION Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

Clinical Experience With Radiation Therapy in the Management of Neurofibromatosis-Associated Central Nervous System Tumors

PURPOSE Patients with neurofibromatosis (NF) develop tumors of the central nervous system (CNS). Radiation therapy (RT) is used to treat these lesions. To better define the efficacy of RT in these patients, we reviewed our 20-year experience. METHODS AND MATERIALS Eighteen patients with NF with CNS tumors were treated from 1986 to 2007. Median follow-up was 48 months. Progression was defined as growth or recurrence of an irradiated tumor on serial imaging. Progression-free survival (PFS) was measured from the date of RT completion to the date of last follow-up imaging study. Actuarial rates of overall survival (OS) and PFS were calculated according to the Kaplan-Meier method. RESULTS Eighty-two tumors in 18 patients were irradiated, with an average of five tumors/patient. Median age at treatment was 25 years (range, 4.3-64 years). Tumor types included acoustic neuroma (16%), ependymoma (6%), low-grade glioma (11%), meningioma (60%), and schwanomma/neurofibroma (7%). The most common indication for treatment was growth on serial imaging. Most patients (67%) received stereotactic radiosurgery (median dose, 1,200 cGy; range, 1,000-2,400 cGy). The OS rate at 5 years was 94%. Five-year PFS rates were 75% (acoustic neuroma), 100% (ependymoma), 75% (low-grade glioma), 86% (meningioma), and 100% (schwanomma/neurofibroma). Thirteen acoustic neuromas had a local control rate of 94% with a 50% hearing preservation rate. CONCLUSIONS RT provided local control, OS, and PFS rates similar to or better than published data for tumors in non-NF patients. Radiation therapy should be considered in NF patients with imaging progression of CNS tumors.

Use of 3.0-T MRI for Stereotactic Radiosurgery Planning for Treatment of Brain Metastases: A Single-Institution Retrospective Review

PURPOSE To investigate the efficacy of 3.0-T magnetic resonance imaging (MRI) for detecting brain metastases for stereotactic radiosurgery (SRS) planning. METHODS AND MATERIALS All adult patients scheduled for SRS treatment for brain metastases at our institution between October 2005 and January 2008 were eligible for analysis. All patients underwent radiosurgery treatment planning 3.0-T MRI on the day of scheduled radiosurgery and a diagnostic 1.5-T MRI in the days or weeks prior to radiosurgery for comparison. Both scans were interpreted by neuroradiologists who reported their findings in the radiology reports. We performed a retrospective review of the radiology reports to determine the number of brain metastases identified using each MRI system. RESULTS Of 254 patients scheduled for treatment from October 2005 to January 2008, 138 patients had radiology reports that explicitly described the number of metastases identified on both scans. With a median interval of 17 days (range, 1-82) between scans, the number of metastases detected using 1.5-T MRI system ranged from 1 to 5 and from 1 to 8 using the 3.0 T-MRI system. Twenty-two percent of patients were found to have a greater number of metastases with the 3.0 T-MRI system. The difference in number of metastases detected between the two scans for the entire cohort ranged from 0 to 6. Neither histology (p = 0.52 by chi-sq test) nor time between scans (p = 0.62 by linear regression) were significantly associated with the difference in number of metastases between scans. CONCLUSIONS The 3.0-T MRI system appears to be superior to a 1.5-T MRI system for detecting brain metastases, which may have significant implications in determining the appropriate treatment modality. Our findings suggest the need for a prospectively designed study to further evaluate the use of a 3.0 T-MRI system for stereotactic radiosurgery planning in the treatment of brain metastases.

Single-Institution Retrospective Series of Gamma Knife Radiosurgery in the Treatment of Multiple Sclerosis-Related Trigeminal Neuralgia: Factors that Predict Efficacy

Background: Gamma knife radiosurgery (GKRS) has been reported as a treatment option for multiple sclerosis (MS)-related trigeminal neuralgia. Objective: To report the outcomes of a single-institution retrospective series of MS-related trigeminal neuralgia. Methods: Between 2002 and 2010, 35 patients with MS-related trigeminal neuralgia were treated with GKRS. The median maximum dose was 90 Gy. Data were analyzed to determine the response to GKRS and factors that may predict for efficacy. Results: Of the 35 patients, 88% experienced a Barrow Neurological Institute (BNI) pain score of I-III at 3 months after GKRS. Kaplan-Meier estimates of 1-, 2- and 5-year freedom from BNI IV-V pain relapse were 57, 57 and 52%, respectively. Numbness was experienced by 39% of patients after GKRS, though no patients reported bothersome numbness. Several differences were noted between how the MS-related variant responded to GKRS and what has previously been reported for idiopathic trigeminal neuralgia. These include the observations that development of post-GKRS numbness did not predict for treatment response (p = 0.62) and that dorsal root entry zone dose did not predict for freedom from pain relapse (odds ratio 1.01, p = 0.1). Active smoking predicted for freedom from pain relapse (odds ratio 67.4, p = 0.04). Conclusion: GKRS is a viable noninvasive treatment option for MS-related trigeminal neuralgia.