Russell Fuhrer

Stereotactic radiosurgery boost to the resection bed for oligometastatic brain disease: challenging the tradition of adjuvant whole-brain radiotherapy.

OBJECTnWhole-brain radiation therapy (WBRT) has been the traditional approach to minimize the risk of intracranial recurrence following resection of brain metastases, despite its potential for late neurotoxicity. In 2007, the authors demonstrated an equivalent local recurrence rate to WBRT by using stereotactic radiosurgery (SRS) to the operative bed, sparing 72% of their patients WBRT. They now update their initial experience with additional patients and more mature follow-up.nnnMETHODSnThe authors performed a retrospective review of all cases involving patients with limited intracranial metastatic disease (< or = 4 lesions) treated at their institution with SRS to the operative bed following resection. No patient had prior cranial radiation and WBRT was used only for salvage.nnnRESULTSnFrom November 2000 to June 2009, 52 patients with a median age of 61 years met inclusion criteria. A single metastasis was resected in each patient. Thirty-four of the patients each had 1 lesion, 13 had 2 lesions, 3 had 3 lesions, and 2 had 4 lesions. A median dose of 1500 cGy (range 800-1800 cGy) was delivered to the resection bed targeting a median volume of 3.85 cm(3) (range 0.08-22 cm(3)). With a median follow-up of 13 months, the median survival was 15.0 months. Four patients (7.7%) had a local recurrence within the surgical site. Twenty-three patients (44%) ultimately developed distant brain recurrences at a median of 16 months postresection, and 16 (30.7%) received salvage WBRT (8 for diffuse disease [> 3 lesions], 4 for local recurrence, and 4 for diffuse progression following salvage SRS). The median time to WBRT administration postresection was 8.7 months (range 2-43 months). On univariate analysis, patient factors of a solitary tumor (19.0 vs 12 months, p = 0.02), a recursive partitioning analysis (RPA) Class I (21 vs 13 months, p = 0.03), and no extracranial disease on presentation (22 vs 13 months, p = 0.01) were significantly associated with longer survival. Cox multivariate analysis showed a significant association with longer survival for the patient factors of no extracranial disease on presentation (p = 0.01) and solitary intracranial metastasis (p = 0.02). Among patients with no extracranial disease, a solitary intracranial metastasis conferred significant additional survival advantage (43 vs 10.5 months, p = 0.05, log-rank test). No factor (age, RPA class, tumor size or histological type, disease burden, extent of resection, or SRS dose or volume) was related to the need for salvage WBRT.nnnCONCLUSIONSnAdjuvant SRS to the metastatic intracranial operative bed results in a local recurrence rate equivalent to adjuvant WBRT. In combination with SRS for unresected lesions and routine imaging surveillance, this approach achieves robust overall survival (median 15 months) while sparing 70% of the patients WBRT and its potential acute and chronic toxicity.

IMRT planning and delivery incorporating daily dose from mega-voltage cone-beam computed tomography imaging.

The technology of online mega-voltage cone-beam (CB) computed tomography (MV-CBCT) imaging is currently used in many institutions to generate a 3D anatomical dataset of a patient in treatment position. It utilizes an accelerator therapy beam, delivered with 200 degrees gantry rotation, and captured by an electronic portal imager to account for organ motion and setup variations. Although the patient dose exposure from a single volumetric MV-CBCT imaging procedure is comparable to that from standard double-exposure orthogonal portal images, daily image localization procedures can result in a significant dose increase to healthy tissue. A technique to incorporate the daily dose, from a MV-CBCT imaging procedure, in the IMRT treatment planning optimization process was developed. A composite IMRT plan incorporating the total dose from the CB was optimized with the objective of ensuring uniform target coverage while sparing the surrounding normal tissue. One head and neck cancer patient and four prostate cancer patients were planned and treated using this technique. Dosimetric results from the prostate IMRT plans optimized with or without CB showed similar target coverage and comparable sparing of bladder and rectum volumes. Average mean doses were higher by 1.6 +/- 1.0 Gy for the bladder and comparable for the rectum (-0.3 +/- 1.4 Gy). In addition, an average mean dose increase of 1.9 +/- 0.8 Gy in the femoral heads and 1.7 +/- 0.6 Gy in irradiated tissue was observed. However, the V65 and V70 values for bladder and rectum were lower by 2.3 +/- 1.5% and 2.4 +/- 2.1% indicating better volume sparing at high doses with the optimized plans incorporating CB. For the head and neck case, identical target coverage was achieved, while a comparable sparing of the brain stem, optic chiasm, and optic nerves was observed. The technique of optimized planning incorporating doses from daily online MV-CBCT procedures provides an alternative method for imaging IMRT patients. It allows for daily treatment modifications where other volumetric tomographic imaging techniques may not be feasible and/or available and where accurate patient localization with a high degree of precision is required.

Audiometric Outcomes for Acoustic Neuroma Patients After Single Versus Multiple Fraction Stereotactic Irradiation

Objective: To compare tumor control and changes in audiometric parameters of acoustic neuroma patients treated with either linac-based stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) at Allegheny General Hospital. Study Design: Twenty-three patients with acoustic neuroma were treated between February 2003 and April 2009 with either SRS (n = 13) or SRT (n = 10). The median age for all patients was 69 years and the median size of lesions was 1.2 cm (range 0.5-2.2 cm). The prescribed dose was a single dose of 1250 cGy for all SRS patients compared to 2500 cGy in 5 daily fractions for SRT patients. All patients had pre- and post-procedure audiometry including hearing acuity assessed using pure tone average (PTA), speech discrimination score (SDS), and speech reception threshold (SR). The results of treatment type and tumor variables resulting in hearing degradation were evaluated and compared. Results: At a median follow-up of 13 months (range 3-36 months), only 1 of 13 patients treated with SRS and 2 of 10 patients treated with SRT develped progression of disease. However; all patients developed deterioration in PTA, SDS, or SR on the treated side. There were no statistically significant audiometric differences between patients treated with SRT or SRS and tumor response was similar regardless of irradiation technique. Conclusion: Both SRS and SRT provide excellent local control rates for the treatment of acoustic neuroma. While SRS demonstrated a trend toward worsening of SDS and the treatment of lesions >1.2 cm demonstrated a trend toward worsening of PTA, neither reached statistical significance. Our data suggest that single dose irradiation using the SRS technique should be considered primarily for patient convenience. All patients treated with radiotherapy for acoustic neuromas should undergo formal hearing testing before and after treatment.

Combination of IG-IMRT and permanent source prostate brachytherapy in patients with organ-confined prostate cancer: GU and GI toxicity and effect on erectile function

PURPOSEnTo assess toxicity outcomes of image-guided intensity-modulated radiation therapy (IG-IMRT) combined with permanent prostate seed implant in a cohort of patients with localized prostate cancer.nnnMETHODS AND MATERIALSnA retrospective analysis was performed on 67 patients with the median pretreatment prostate-specific antigen level of 5.4. The Gleason score was less than 7 in 7 patients, 7 in 52 patients, and greater than 7 in 8 patients. The median followup was 28.2 months (range, 12-89.5 months). Treatment consisted of 45 (n=65) or 50.4 Gy (n=2) at 1.8 Gy/fraction of IG-IMRT to the prostate and seminal vesicles. Eight patients had simultaneous irradiation of pelvic lymph nodes to 45 (n=65) or 50.4 Gy (n=2). After IG-IMRT, patients received transperineal prostate implant boost with either (103)Pd (n=65, the prescribed D(90) of 100 Gy) or (125)I (n=2, D(90) of 110 Gy). Eleven patients received androgen deprivation therapy with radiotherapy.nnnRESULTSnToxicity higher than Grade 3 was not observed. The combined incidence of acute and late Grade 3 genitourinary toxicity was 6%. The combined incidence of acute and late Grade 3 gastrointestinal toxicity was 3%. At least one episode of gastrointestinal bleeding on followup, which could be attributed to radiation, was recorded in 14.9% of patients. For patients achieving erections before radiation, the 3-year Kaplan-Meier potency preservation rate was 66.5%.nnnCONCLUSIONSnThe early toxicity of the combination of IG-IMRT and low-dose rate brachytherapy boost in this study was favorable.

Implant R100 Predicts Rectal Bleeding in Prostate Cancer Patients Treated with IG-IMRT to 45 Gy and Pd-103 Implant

Purpose. To define factors associated with rectal bleeding in patients treated with IG-IMRT followed by Pd-103 seed implant. Methods and Materials. We retrospectively reviewed 61 prostate adenocarcinoma patients from 2002 to 2008. The majority (85.2%) were of NCCN intermediate risk category. All received IG-IMRT to the prostate and seminal vesicles followed by Pd-103 implant delivering a mean D90 of 100.7u2009Gy. Six patients received 45u2009Gy to the pelvic nodes and 10 received androgen deprivation. Results. Ten patients (16.4%) developed rectal bleeding: 4 were CTCAE v.3 grade 1, 5 were grade 2, and 1 was grade 3. By univariate analysis, age, stage, Gleason sum, PSA, hormonal therapy, pelvic radiation, postoperative prostate volume, D9, V100, individual source activity, total implanted activity per cm3, and duration of interval before implant did not impact rectal bleeding. Implant R100 was higher in patients with rectal bleeding: on average, 0.885 versus 0.396u2009cm3, , odds ratio of 2.26 per .5u2009cm3 (95% CI, 1.16–4.82). A trend for significance was seen for prostate V200 and total implanted activity. Conclusion. Higher implant R100 was associated with development of rectal bleeding in patients receiving IG-IMRT to 45u2009Gy followed by Pd-103 implant. Minimizing implant R100 may reduce the rate of rectal bleeding in similar patients.

The Allegheny Prostate Center: Comprehensive Evaluation and Unbiased Counseling on Treatment Options

a leader in innovative approaches to the delivery of healthcare. In the early 1990s, researchers began investigating cryosurgery for the treatment of tumors. Jeffrey Cohen, MD, and Ralph Miller, Jr., MD, urologists at Allegheny General Hospital, saw the potential for adapting this technology to treat their prostate cancer patients. These physician leaders then developed and pioneered a program for the treatment of prostate cancer with cryosurgery. As the technology developed and was described in medical and popular literature, the number of patients seeking cryosurgery at Allegheny General Hospital soon increased rapidly. For a variety of reasons, however, many men who presented with the intent of undergoing cryosurgery were not candidates for this procedure and instead were sent to see a radiation oncologist. It became obvious to both specialties that patients were presenting intent on cryosurgery but were not well informed about the myriad of other treatment options for prostate cancer. The urologists and radiation oncologists soon came to agree that the best way for patients to be fully informed about all the options for prostate cancer treatment was to talk with both specialties—ideally in a multidisciplinary clinic setting. The Allegheny Prostate Center

SU‐FF‐J‐46: Dosimetric Effects of Daily Localization for Prostate Cancer Patients Using MV‐CBCT

Purpose: To evaluate the effect of daily shifts observed with mega‐voltage cone beam CT (MV‐CBCT) localization on the IMRT dose distribution received by prostate cancer patients. Method and Materials: Eight patients who received a dose of 77.4 Gy to the PTV, which included the prostate and the seminal vesicles with a 1 cm margin, were selected for this retrospective study. Prior to each daily treatment fraction, the prostate was localized using MV‐CBCT, and the treatment couch position was corrected accordingly in the lateral (RL), longitudinal (SI) and vertical (AP) directions. The shifts for each of the 308 fractions were recorded, and the 308 corresponding dose distributions that the patients would have received if the shifts were not applied were calculated. Dose volume histograms (DVH) and mean dose for target and organs‐at‐risk were derived from these dose distributions, and compared to the treatment plan. Results: The average shifts for each patient were less than 6, 5 and 5 mm in the RL, SI and AP directions, respectively, with standard deviations ranging from 2 to 7 mm. The relative mean dose difference for the prostate was less that 1%, however effects as large as 15% and 20% were observed for the rectum and bladder, respectively. Rectum dose differences were correlated to AP shifts, while the bladder dose was affected by the SI shifts. Conclusion: For IMRT plans with a 1 cm margin, daily localization of the prostate is necessary to reduce the risk of bladder and rectum complication. The dose to these organs is very sensitive to systematic errors, while the effects of random errors cancel each other due to the essentially spherical shape of the dose distribution. Our results show that accurate patient positioning is an important step in any dose‐escalation and/or margin reduction strategy to further improve the therapeutic ratio.

TU‐EE‐A3‐06: Comparison of Prostate Localization with Online Ultrasound and Mega‐Voltage Cone‐Beam Computed Tomography

Purpose: To analyze the online image‐guided localization data from 846 ultrasound (US)and 350 MV‐CBCT couch alignments for patients undergoing IMRT of the prostate. Method and Materials: Daily volumetric MV‐CBCT and USimages were acquired for 11 and 23 patients, respectively, after each patient was immobilized in a vacuum cradle and setup to skin markers as the center‐of‐mass. The couch shifts applied in the lateral (left‐right/LR), vertical (anterior‐posterior/AP), and longitudinal (superior‐inferior/SI) directions, along with the magnitude of the three‐dimensional (3D) shift vector, were analyzed and compared for both methods. The percentage of shifts larger than 5 mm in all directions was also compared. CTV‐to‐PTV expansion margins were estimated based on the localization data with US and CB image‐guidance.Results: Systematic and random shifts from CB versus US were: laterally, 1.6 ± 3.8 mm vs. − 0.7 ± 6.9 mm; vertically, − 0.9 ± 5.4 mm vs. − 0.2 ± 6.4 mm; longitudinally, −1.4 ± 2.9 mm vs. −2.9 ± 5.2 mm. The mean 3D shift distance was smaller using CB (6.6 ± 3.6 mm vs. 9.1 ± 6.5 mm) with a p‐value < 0.05. The US data show greater variability. The percentage of US shifts larger than 5 mm were 33%, 40%, and 31% in the LR, AP, and SI directions, respectively, compared to 17%, 31%, and 7% for CB. Conclusion: MV‐CBCT localization data suggest a different distribution of prostate center‐of‐mass shifts with smaller variability, compared to US. The online MV‐CBCT image‐guidance data show that for treatments that do not include daily prostate localization,one can use a CTV‐to‐PTV margin that is 2.5 mm smaller than the one suggested by US data,hence allowing more rectum and bladder sparing and potentially improving the therapeutic ratio.