Evaluating stereotactic accuracy with patient-specific MRI distortion corrections for frame-based radiosurgery.

PURPOSE: This study examines how MRI distortions affect frame-based SRS treatments and assesses the need for clinical distortion corrections. METHODS: The study included 18 patients with 80 total brain targets treated using frame-based radiosurgery. Distortion within patients' MRIs were corrected using Cranial Distortion Correction (CDC) software, which utilizes the patient's CT to alter planning MRIs to reduce inherent intra-cranial distortion. Distortion was evaluated by comparing the original planning target volumes (PTVORIG) to targets contoured on corrected MRIs (PTVCORR). To provide an internal control, targets were also re-contoured on uncorrected (PTVRECON) MRIs. Additional analysis was done to assess if 1 mm expansions to PTVORIG targets would compensate for patient-specific distortions. Changes in target volumes, DICE and JACCARD similarity coefficients, minimum PTV dose (Dmin), dose to 95% of the PTV (D95%), and normal tissue receiving 12 Gy (V12Gy), 10 Gy (V10Gy), and 5 Gy (V5Gy) were calculated and evaluated. Student's t-tests were used to determine if changes in PTVCORR were significantly different than intra-contouring variability quantified by PTVRECON. RESULTS: PTVRECON and PTVCORR relative changes in volume were 6.19% ± 10.95% and 1.48% ± 32.92%. PTVRECON and PTVCORR similarity coefficients were 0.90 ± 0.08 and 0.73 ± 0.16 for DICE and 0.82 ± 0.12 and 0.60 ± 0.18 for JACCARD. PTVRECON and PTVCORR changes in Dmin were -0.88% ± 8.77% and -12.9 ± 17.3%. PTVRECON and PTVCORR changes in D95% were -0.34% ± 5.89 and -8.68% ± 13.21%. The 1 mm expanded PTVORIG targets did not entirely cover 14 of the 80 PTVCORR targets. Normal tissue changes (V12Gy, V10Gy, V5Gy) calculated with PTVRECON were (-0.09% ± 7.39%, -0.38% ± 5.67%, -0.08% ± 2.04%) and PTVCORR were (-2.14% ± 7.34%, -1.42% ± 5.45%, -0.61% ± 1.93%). Except for V10Gy, all PTVCORR changes were significantly different (p < 0.05) than PTVRECON. CONCLUSION: MRIs used for SRS target delineation exhibit notable geometric distortions that may compromise optimal dosimetric accuracy. A uniform 1 mm expansion may result in geometric misses; however, the CDC algorithm provides a feasible solution for rectifying distortions, thereby enhancing treatment precision.

Radionecrosis (RN) in patients with brain metastases treated with stereotactic radiosurgery (SRS) and immunotherapy.

OBJECTIVES: Limited data exist regarding radionecrosis (RN) rates when patients receive immunotherapy (IT) and SRS for brain metastases. This study assesses the influence of such treatments on the rate of RN. METHODS: We retrospectively reviewed 352 lesions from 105 patients with metastatic melanoma or NSCLC treated with SRS and IT from 2012 to 2018. Lesions were excluded from analysis if patients had received WBRT or prior GK to the same lesion, if RN occurred before IT, or if IT had been discontinued >6 months pre-SRS or initiated >1 year post-SRS. IT was delivered concurrently (±30 days of SRS) or sequentially. Overall survival and RN rates were assessed with Kaplan-Meier analysis. Univariate analysis and multivariate analysis were performed to identify characteristics predicting RN. RESULTS: Of 195 lesions from 63 patients included in analysis, the median prescription dose, IDL, lesion volume, and maximum tumor dimension (MTD) were 19 Gy, 50%, 0.15 cc and 0.8 cm, respectively. RN rates at 1, 2, and 3 years were 7.3%, 10.4% and 10.4%. On UVA, RN risk increased with, isodose volume (IDV), MTD, and tumor volume (TV) whereas conformity index was associated with a trend toward decreased RN risk. Two-year RN rates increased with TV ≥ 0.3 cc (16% vs 1.1% p = 0.001), MTD ≥ 1.3 cm (19.1% vs 1.8% p < 0.003), and IDV ≥ 1.5 cc (19.6% vs 1.7% p = 0.001). Concurrent vs sequential timing of IT did not predict for RN. CONCLUSIONS: Patients who received IT and SRS had acceptably low rates of RN. Timing of IT did not predict for RN. Further investigation is warranted to define RN risk with combined SRS and IT.

Commissioning cranial single-isocenter multi-target radiosurgery for the Versa HD.

PURPOSE: Brainlab's Elements Multiple Brain Mets SRS (MBMS) is a dedicated treatment planning system for single-isocenter multi-target (SIMT) cranial stereotactic radiosurgery (SRS) treatments. The purpose of this study is to present the commissioning experience of MBMS on an Elekta Versa HD. METHODS: MBMS was commissioned for 6 X, 6 FFF, and 10 FFF. Beam data collected included: output factors, percent depth doses (PDDs), diagonal profiles, collimator transmission, and penumbra. Beam data were processed by Brainlab and resulting parameters were entered into the planning system to generate the beam model. Beam model accuracy was verified for simple fields. MBMS plans were created on previously treated cranial SRS patient data sets. Plans were evaluated using Paddick inverse conformity (ICI), gradient indices (GI), and cumulative volume of brain receiving 12 Gy. Dosimetric accuracy of the MBMS plans was verified using microDiamond, Gafchromic film, and SRS Mapcheck measurements of absolute dose and dose profiles for individual targets. Finally, an end-to-end (E2E) test was performed with a MR-CT compatible phantom to validate the accuracy of the simulation-to-delivery process. RESULTS: For square fields, calculated scatter factors were within 1.0% of measured, PDDs were within 0.5% past dmax, and diagonal profiles were within 0.5% for clinically relevant off-axis distances (<10 cm). MBMS produced plans with ICIs < 1.5 and GIs < 5.0 for targets > 10 mm. Average point doses of the MBMS plans, measured by microDiamond, were within 0.31% of calculated (max 2.84%). Average per-field planar pass rates were 98.0% (95.5% minimum) using a 2%/1 mm/10% threshold relative gamma analysis. E2E point dose measurements were within 1.5% of calculated and Gafchromic film pass rates were 99.6% using a 5%/1 mm/10% threshold gamma analysis. CONCLUSION: The experience presented can be used to aid the commissioning of the Versa HD in the Brainlab MBMS treatment planning system, to produce safe and accurate SIMT cranial SRS treatments.

Long-term follow-up after radiotherapy for prostate cancer with and without rectal hydrogel spacer: a pooled prospective evaluation of bowel-associated quality of life.

OBJECTIVE: To evaluate the long-term bowel-associated quality of life (QOL) in men after radiotherapy (RT) for prostate cancer with and without the use of rectal hydrogel spacer. PATIENTS AND METHODS: The patients' QOL was examined using the Expanded Prostate Cancer Index Composite (EPIC) and mean changes from baseline in EPIC domains were evaluated. A total of 215 patients from a randomised multi-institutional trial of RT, with or without hydrogel spacer, with a QOL endpoint were pooled with 165 non-randomised patients from a single institution with prospective QOL collection in patients with or without hydrogel spacer. The proportions of men with minimally important differences (MIDs) relative to pre-treatment baseline in the bowel domain were tested using repeated measure logistic models with a pre-specified threshold for clinically significant declines (≥5 equivalent to MIDx1 and ≥10 equivalent to MIDx2). RESULTS: A total of 380 men were evaluated (64% with spacer and 36% without) with QOL data being available for 199 men with >24 months of follow-up [median (range) 39.5 (31-71.4) months]. Treatment with spacer was associated with less decline in average long-term bowel QOL (89.4 for control and 94.7 for spacer) with differences at >24 months meeting the threshold of a MID difference between cohorts (bowel score difference from baseline: control = -5.1, spacer = 0.3, difference = -5.4; P < 0.001). When evaluated over time men without spacer were more likely to have MIDx1 (5 points) declines in bowel QOL (P = 0.01). At long-term follow-up MIDx1 was 36% without spacer vs 14% with spacer (P <0.001; odds ratio [OR] 3.5, 95% CI 1.7-6.9) while MIDx2 was seen in 19% vs 6% (P = 0.008; OR 3.6, 95% CI 1.4-9.1). The use of spacer was associated with less urgency with bowel movements (P = 0.002) and fewer loose stools (P = 0.009), as well as less bother with urgency (P = 0.007) and frequency of bowel movements (P = 0.009). CONCLUSIONS: In this pooled analysis of QOL after prostate RT with up to 5 years of follow-up, use of a rectal spacer was associated with preservation of bowel QOL. This QOL benefit was preserved with long-term follow-up.

21 Gy single fraction prostate HDR brachytherapy: 5-year results of a single institution prospective pilot study.

PURPOSE: To present the outcome and toxicity results of a prospective trial of 21 Gy single fraction high-dose-rate (HDR) brachytherapy for men with low- or intermediate-risk prostate cancer. METHODS AND MATERIALS: Patients were treated according to an IRB-approved prospective study of single fraction HDR brachytherapy. Eligible patients had low- or intermediate-risk prostate cancer with tumor stage ≤ T2b, PSA ≤ 15, and Gleason score ≤ 7. Patients underwent trans-rectal ultrasound-guided trans-perineal implant of the prostate followed by single fraction HDR brachytherapy to a dose of 21 Gy. The primary endpoint was grade ≥ 2 urinary/GI toxicity rates. RESULTS: Twenty-six patients were enrolled with a median follow up of 5.1 years and median age of 64 years. 88.5% of patients had T1 disease, 15.4% had Gleason score 6 (84.6% Gleason 7), and median pre-treatment PSA was 5.0 ng/mL. Acute and chronic grade ≥ 2 urinary toxicity rates were 38.5% and 38.5%, respectively. There were no grade ≥ 2 acute or chronic GI toxicities. Six (23.1%) patients experienced biochemical failure, six (23.1%) patients experienced radiographic local failure, and five (19.2%) patients had biopsy-proven local failure. No patients developed regional lymph node recurrence or distant metastasis. 5-year overall survival and cause-specific survival were 96.2% and 100%, respectively. CONCLUSIONS: 21 Gy single fraction HDR brachytherapy was associated with modestly higher-than-anticipated chronic urinary toxicity, as well as high biochemical and local failure rates. The results from this prospective pilot study do not support the use of this regimen in standard clinical practice.

A pooled long-term follow-up after radiotherapy for prostate cancer with and without a rectal hydrogel spacer: impact of hydrogel on decline in sexual quality of life.

Purpose: The purpose of this study was to analyze the impact of prostate rectal spacers on sexual quality of life (QOL) following external beam radiation therapy (RT). Methods and materials: Patient- reported QOL was evaluated using the Expanded Prostate Cancer Index Composite (EPIC). Patients were pooled from two sources: a randomized controlled trial and a non-randomized cohort of patients from a single institution. Both cohorts used the same spacing product and QOL instrument. Analysis was limited to those with good baseline pre-treatment sexual QOL (EPIC >/= 60). Differences in QOL summary score and individual items were assessed compared with baseline and between treatment arms. Results: A total of 128 men had good baseline sexual function and were evaluated (64% with spacer and 36% without) with QOL data available for median 33 months (range: 2.5-69.4 months). Men without spacer were more likely to have declines in sexual function (p < 0.0001), bother (p = 0.0002), and sexual summary score (p < 0.0001). A minimally important difference of 10 points (1xMID) and 20 point (2xMID) was more likely without rectal spacer [10 points: odds ratio 3.53, (95% confidence interval 1.11-11.2), p = 0.032; 20 points: odds ratio 3.29, (95% confidence interval 1.16-9.33), p = 0.025]. Seven of 13 QOL items were statistically superior with hydrogel (six of nine functional and one of four bother), while no items were statistically superior for control. At baseline, more men treated with hydrogel had erections sufficient for intercourse; however, when analyzed only by the men with best baseline erectile potential and excluding those with worse function, the benefit of rectal spacing was maintained with a higher likelihood of preservation of erections sufficient for intercourse in those treated with hydrogel. Conclusion: In this pooled analysis of QOL after prostate RT, the utilization of a hydrogel spacer was associated with better sexual QOL, less men with measurable declines in sexual QOL, and higher rates of adequate erectile function.

Patient reported outcomes for quality of life (QOL) by Expanded Prostate Cancer Index (EPIC) on average 15 years post treatment.

Objective/purpose: Previously patient reported quality of life (QOL) was reported in men with prostate cancer a mean 2 and 6 years post treatment with open radical prostatectomy (RP), 3D conformal radiation therapy (3D CRT), or 125I low dose rate (LDR) brachytherapy (BT). Herein we update the results 15 years post-treatment QOL. Materials/methods: The Expanded Prostate Cancer Index (EPIC) domains were scored with differences evaluated at a median 15.8 years follow up based upon mean EPIC summary domains by ANOVA with pairwise post-hoc comparisons adjusted for age. Patient differences of current survey from first cross-section are reported as median change in summary score for each treatment group at median of 2.2 and 6.0, and 15.8 years. Results: Among men still alive response rate was 52% in BT, 60% in 3D CRT, and 62% in RP resulting in 30, 41, and 330 QOL questionnaires to evaluate for each corresponding modality at median follow up of 15.8 years. Men were a mean 75.3, 83.6, and 79.3 years of age after RP, 3DCRT, and BT, respectively.At a median of 15.8 years, there were largely persistent differences in EPIC domains without substantial evolution in QoL from middle time points. Persistent worsening in urinary irritative and bowel domain with 3DRT or BT compared to RP. Trend towards worse urinary incontinence with RP were noted without statistical differences within radiotherapy options. Conclusion: As the EPIC patient reported outcomes with the longest follow-up, these data uniquely reveal temporal trends from 2 to 15 years post treatment. However, the treatment modalities of open RP, 3D CRT without image guidance or intensity modulation, and BT without peripheral loading or MRI guidance may not reflect modern techniques.

Adverse radiation effects in volume-staged radiosurgery for large arteriovenous malformations: a multiinstitutional study.

OBJECTIVE: The optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. One approach is volume-staged stereotactic radiosurgery (VS-SRS). The authors previously reported efficacy of VS-SRS for large AVMs in a multiinstitutional cohort; here they focus on risk of symptomatic adverse radiation effects (AREs). METHODS: This is a multicentered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM, with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. The authors evaluated permanent, transient, and total ARE events that were symptomatic. RESULTS: Patients received 2-4 total volume stages. The median age was 33 years at the time of the first SRS volume stage, and the median follow-up was 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cm3 (range 7.7-94.4 cm3), with a median margin dose per stage of 17 Gy (range 12-20 Gy). A total of 64 patients (25%) experienced an ARE, of which 19 were permanent. Rather than volume, maximal linear dimension in the Z (craniocaudal) dimension was associated with toxicity; a threshold length of 3.28 cm was associated with an ARE, with a 72.5% sensitivity and a 58.3% specificity. In addition, parietal lobe involvement for superficial lesions and temporal lobe involvement for deep lesions were associated with an ARE. CONCLUSIONS: Size remains the dominant predictor of toxicity following SRS, but overall rates of AREs were lower than anticipated based on baseline features, suggesting that dose and size were relatively dissociated through volume staging. Further techniques need to be assessed to optimize outcomes.

Hallux Valgus Deformities: Preferred Surgical Repair Techniques and All-Cause Revision Rates.

INTRODUCTION: Hallux valgus is a commonly treated condition by foot and ankle surgeons with more than 200 different described correction techniques. Recurrence rates range from 5% to 50%, with increasing support of the theory that arthrodesis procedures may have a lower recurrence rate than osteotomies. Arthrodesis procedures to the first metatarsophalangeal (MTP) joint or tarsometatarsal (TMT) joint for correction of hallux valgus deformity are becoming more commonly utilized. The purpose of this study is to investigate the surgical incidence and revision rates of hallux valgus deformities corrected by arthrodesis compared to osteotomy in the state of South Carolina. METHODS: The South Carolina Revenue and Fiscal Affairs Office was queried from 2000 to 2017 to identify all surgically treated hallux valgus deformities. Data extraction included patient demographics, ICD-9 diagnoses, CPT procedure codes, and dates of surgery. A logistic regression model was used for statistical inference. RESULTS: A total of 22 199 feet had surgical treatment for hallux valgus during this time period, with 20 422 (92.0%), 592 (2.7%), and 1185(5.3%) receiving an osteotomy, arthrodesis, or other procedure at initial treatment, respectively. There was an all-cause revision rate of 5.6% in the osteotomy group and 6.4% in the arthrodesis group. Demographic factors such as female sex, white race, and surgery pre-2010 were associated with higher revision rates. Multiple comorbidities were correlated with higher revision rates such as tobacco use, hypothyroidism, osteoarthritis, recurrent dislocations, hallux rigidus, lesser toe deformities, metatarsus varus, and talipes cavus. CONCLUSION: Despite the recent increase in arthrodesis procedures for the treatment of hallux valgus deformity, our results suggest that osteotomy procedures are more commonly performed and there is no difference in all-cause revision surgery. However, there are multiple patient demographics and comorbidities that are associated with higher rates of revision surgery and should be considered and discussed during the preoperative planning period. LEVEL OF EVIDENCE: Level IV.

Dose response and architecture in volume staged radiosurgery for large arteriovenous malformations: A multi-institutional study.

BACKGROUND: Optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. Volume-staged stereotactic radiosurgery (VS-SRS) provides an effective option for these high-risk lesions, but optimizing treatment for these recalcitrant and rare lesions has proven difficult. METHODS: This is a multi-centered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. We evaluated near complete response (nCR), obliteration, cure, and overall survival. RESULTS: With a median age of 33 years old at the time of first SRS volume stage, patients received 2-4 total volume stages and a median follow up of 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cc (range: 7.7-94.4 cc) with a median margin dose per stage of 17 Gy (range: 12-20 Gy). Total AVM volume, margin dose per stage, compact nidus, lack of prior embolization, and lack of thalamic location involvement were all associated with improved outcomes. Dose >/= 17.5 Gy was strongly associated with improved rates of nCR, obliteration, and cure. With dose >/= 17.5 Gy, 5- and 10-year cure rates were 33.7% and 76.8% in evaluable patients compared to 23.7% and 34.7% of patients with 17 Gy and 6.4% and 20.6% with <17 Gy per volume-stage (p = 0.004). Obliteration rates in diffuse nidus architecture with <17 Gy were particularly poor with none achieving obliteration compared to 32.3% with doses >/= 17 Gy at 5 years (p = 0.007). Comparatively, lesions with a compact nidus architecture exhibited obliteration rates at 5 years were 10.7% vs 9.3% vs 26.6% for dose >17 Gy vs 17 Gy vs >/=17.5 Gy. CONCLUSION: VS-SRS is an option for upfront treatment of large AVMs. Higher dose was associated with improved rates of nCR, obliteration, and cure suggesting that larger volumetric responses may facilitate salvage therapy and optimize the chance for cure.

Evolution of techniques for the resection of vestibular schwannomas: from saving life to saving function.

The current state of surgery for vestibular schwannomas (VSs) is the result of a century of step-by-step technical progress by groundbreaking surgeons who transformed the procedure from its hazardous infancy and high mortality rate to its current state of safety and low morbidity rate. Harvey Cushing advocated bilateral suboccipital decompression and developed the method of intracapsular tumor enucleation. Walter Dandy supported the unilateral suboccipital approach and developed the technique of gross-total tumor resection. Microsurgical techniques revolutionized VS surgery to its current status. In this article, the authors review the early history of surgery for VSs with an emphasis on contributions from pioneering surgeons. The authors examined the Cushing Brain Tumor Registry for clues regarding the bona fide intention of Cushing for the resection of these tumors.

Receiver operating curves and dose-volume analysis of late toxicity with stereotactic body radiation therapy for prostate cancer.

PURPOSE: The purpose of this study was to evaluate a receiver operating characteristic (ROC) curve method to determine dose thresholds with late genitourinary (GU) toxicity after stereotactic body radiation therapy for prostate cancer. METHODS AND MATERIALS: Seventy-eight patients diagnosed with low- to intermediate-risk prostate cancer and treated with stereotactic body radiation therapy alone were reviewed retrospectively. All patients received a total dose of 38 Gy in 4 fractions with a planning target volume expansion of 2 mm. GU toxicity was documented according to the Common Terminology Criteria for Adverse Events, version 4. ROC analysis applied on a logistic regression model was used to determine optimal dosimetric parameters for GU toxicity. RESULTS: The median age at treatment was 69 years with a median prostate volume of 46.2 mL. The median prescription isodose line was 67% (interquartile range, 65, 70). The median clinical follow-up was 35.49 months. Late grade 1, 2, and 3 GU toxicity occurred in 21.8%, 19.2%, and 2.6% of cases, respectively. Late grade 2+ GU toxicity was associated with prescription to isodose line (P = .009) and normalized volumes for heterogeneity ≥46 Gy. The ROC method successfully produced thresholds for dose-volume recommendations for both prostate and urethra, including normalized prostate volumes from 46 to 50 Gy, such as volume of target tissue receiving 46% of the prescribed dose (V46) Gy of 36.7% (sensitivity, 71%; specificity, 61%; area under the curve, 0.67) with an associated probability of late GU grade 2+ toxicity of 21%. CONCLUSIONS: Intraprostatic heterogeneity should be controlled with potential thresholds at V46 Gy <36.7%, V48 Gy <21%, and V50 Gy <9.5% of the normalized prostate volume to keep late grade 2+ GU toxicity ≤20% with 4-fraction schemes. This may be facilitated with a higher prescription isodose line (>69%).

Resection and brain brachytherapy with permanent iodine-125 sources for brain metastasis.

OBJECTIVE Stereotactic radiosurgery (SRS) with or without whole-brain radiotherapy can be used to achieve local control (> 90%) for small brain metastases after resection. However, many brain metastases are unsuitable for SRS because of their size or previous treatment, and whole-brain radiotherapy is associated with significant neurocognitive morbidity. The purpose of this study was to investigate the efficacy and toxicity of surgery and iodine-125 (125I) brachytherapy for brain metastases. METHODS A total of 95 consecutive patients treated for 105 brain metastases at a single institution between September 1997 and July 2013 were identified for this analysis retrospectively. Each patient underwent MRI followed by craniotomy with resection of metastasis and placement of 125I sources as permanent implants. The patients were followed with serial surveillance MRIs. The relationships among local control, overall survival, and necrosis were estimated by using the Kaplan-Meier method and compared with results of log-rank tests and multivariate regression models. RESULTS The median age at surgery was 59 years (range 29.9-81.6 years), 53% of the lesions had been treated previously, and the median preoperative metastasis volume was 13.5 cm3 (range 0.21-76.2 cm3). Gross-total resection was achieved in 81% of the cases. The median number of 125I sources implanted per cavity was 28 (range 4-93), and the median activity was 0.73 mCi (range 0.34-1.3 mCi) per source. A total of 476 brain MRIs were analyzed (median MRIs per patient 3; range 0-22). Metastasis size was the strongest predictor of cavity volume and shrinkage (p < 0.0001). Multivariable regression modeling failed to predict the likelihood of local progression or necrosis according to metastasis volume, cavity volume, or the rate of cavity remodeling regardless of source activity or previous SRS. The median clinical follow-up time in living patients was 14.4 months (range 0.02-13.6 years), and crude local control was 90%. Median overall survival extended from 2.1 months in the shortest quartile to 62.3 months in the longest quartile (p < 0.0001). The overall risk of necrosis was 15% and increased significantly for lesions with a history of previous SRS (p < 0.05). CONCLUSIONS Therapeutic options for patients with large or recurrent brain metastases are limited. Data from this study suggest that resection with permanent 125I brachytherapy is an effective strategy for achieving local control of brain metastasis. Although metastasis volume significantly influences resection cavity size and remodeling, volumetric parameters do not seem to influence local control or necrosis. With careful patient selection, this treatment regimen is associated with minimal toxicity and can result in long-term survival for some patients. ▪ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: retrospective case series; evidence: Class IV.

Outcomes of hypofractionated stereotactic body radiotherapy boost for intermediate and high-risk prostate cancer.

BACKGROUND AND PURPOSE: Treatment of intermediate and high-risk prostate cancer with a high BED has been shown to increase recurrence free survival (RFS). While high dose rate (HDR) brachytherapy, given as a boost is effective in delivering a high BED, many patients are not candidates for the procedure or wish to avoid an invasive procedure. We evaluated the use of stereotactic body radiotherapy (SBRT) as a boost, with dosimetry modeled after HDR-boost. MATERIAL AND METHODS: Fifty patients were treated with two fractions of SBRT (9.5-10.5 Gy/fraction) after 45 Gy external-beam radiotherapy, with 48 eligible for analysis at a median follow-up of 42.7 months. RESULTS: The Kaplan-Meier estimates of biochemical control post-radiation therapy (95 % Confidence Interval) at 3, 4 and 5 years were 95 % (81-99 %), 90 % (72-97 %) and 90 % (72-97 %), respectively (not counting 2 patients with a PSA bounce as failures). RFS (defined as disease recurrence or death) estimates at 3, 4 and 5 years were 92 % (77-97 %), 88 % (69-95 %) and 83 % (62-93 %) if patients with PSA bounces are not counted as failures, and were 90 % (75-96 %), 85 % (67-94 %) and 75 % (53-88 %) if they were. The median time to PSA nadir was 26.2 months (range 5.8-82.9 months), with a median PSA nadir of 0.05 ng/mL (range <0.01-1.99 ng/mL). 2 patients had a "benign PSA bounce", and 4 patients recurred with radiographic evidence of recurrence beyond the RT fields. Treatment was well tolerated with no acute G3 or higher GI or GU toxicity and only a single G3 late GU toxicity of urinary obstruction. CONCLUSIONS: SBRT boost is well-tolerated for intermediate and high-risk prostate cancer patients with good biochemical outcomes and low toxicity.

Volume-staged radiosurgery for large arteriovenous malformations: an evolving paradigm.

OBJECT Large arteriovenous malformations (AVMs) remain difficult to treat, and ideal treatment parameters for volume-staged stereotactic radiosurgery (VS-SRS) are still unknown. The object of this study was to compare VS-SRS treatment outcomes for AVMs larger than 10 ml during 2 eras; Era 1 was 1992-March 2004, and Era 2 was May 2004-2008. In Era 2 the authors prospectively decreased the AVM treatment volume, increased the radiation dose per stage, and shortened the interval between stages. METHODS All cases of VS-SRS treatment for AVM performed at a single institution were retrospectively reviewed. RESULTS Of 69 patients intended for VS-SRS, 63 completed all stages. The median patient age at the first stage of VS-SRS was 34 years (range 9-68 years). The median modified radiosurgery-based AVM score (mRBAS), total AVM volume, and volume per stage in Era 1 versus Era 2 were 3.6 versus 2.7, 27.3 ml versus 18.9 ml, and 15.0 ml versus 6.8 ml, respectively. The median radiation dose per stage was 15.5 Gy in Era 1 and 17.0 Gy in Era 2, and the median clinical follow-up period in living patients was 8.6 years in Era 1 and 4.8 years in Era 2. All outcomes were measured from the first stage of VS-SRS. Near or complete obliteration was more common in Era 2 (log-rank test, p = 0.0003), with 3- and 5-year probabilities of 5% and 21%, respectively, in Era 1 compared with 24% and 68% in Era 2. Radiosurgical dose, AVM volume per stage, total AVM volume, era, compact nidus, Spetzler-Martin grade, and mRBAS were significantly associated with near or complete obliteration on univariate analysis. Dose was a strong predictor of response (Cox proportional hazards, p < 0.001, HR 6.99), with 3- and 5-year probabilities of near or complete obliteration of 5% and 16%, respectively, at a dose < 17 Gy versus 23% and 74% at a dose ≥ 17 Gy. Dose per stage, compact nidus, and total AVM volume remained significant predictors of near or complete obliteration on multivariate analysis. Seventeen patients (25%) had salvage surgery, SRS, and/or embolization. Allowing for salvage therapy, the probability of cure was more common in Era 2 (log-rank test, p = 0.0007) with 5-year probabilities of 0% in Era 1 versus 41% in Era 2. The strong trend toward improved cure in Era 2 persisted on multivariate analysis even when considering mRBAS (Cox proportional hazards, p = 0.055, HR 4.01, 95% CI 0.97-16.59). The complication rate was 29% in Era 1 compared with 13% in Era 2 (Cox proportional hazards, not significant). CONCLUSIONS VS-SRS is an option to obliterate or downsize large AVMs. Decreasing the AVM treatment volume per stage to ≤ 8 ml with this technique allowed a higher dose per fraction and decreased time to response, as well as improved rates of near obliteration and cure without increasing complications. Reducing the volume of these very large lesions can facilitate a surgical approach for cure.

Interval From Imaging to Treatment Delivery in the Radiation Surgery Age: How Long Is Too Long?

PURPOSE: The purpose of this study was to evaluate workflow and patient outcomes related to frameless stereotactic radiation surgery (SRS) for brain metastases. METHODS AND MATERIALS: We reviewed all treatment demographics, clinical outcomes, and workflow timing, including time from magnetic resonance imaging (MRI), computed tomography (CT) simulation, insurance authorization, and consultation to the start of SRS for brain metastases. RESULTS: A total of 82 patients with 151 brain metastases treated with SRS were evaluated. The median times from consultation, insurance authorization, CT simulation, and MRI for treatment planning were 15, 7, 6, and 11 days to SRS. Local freedom from progression (LFFP) was lower in metastases with MRI ≥ 14 days before treatment (P = .0003, log rank). The 6- and 12-month LFFP rate were 95% and 75% for metastasis with interval of <14 days from MRI to treatment compared to 56% and 34% for metastases with MRI ≥ 14 days before treatment. On multivariate analysis, LFFP remained significantly lower for lesions with MRI ≥ 14 days at SRS (P = .002, Cox proportional hazards; hazard ratio: 3.4, 95% confidence interval: 1.6-7.3). CONCLUSIONS: Delay from MRI to SRS treatment delivery for brain metastases appears to reduce local control. Future studies should monitor the timing from imaging acquisition to treatment delivery. Our experience suggests that the time from MRI to treatment should be <14 days.

Dose-volume analysis and the temporal nature of toxicity with stereotactic body radiation therapy for prostate cancer.

PURPOSE: The purpose of this study was to evaluate the dose-volume relationships of genitourinary toxicity after stereotactic body radiation therapy (SBRT) monotherapy for prostate cancer. METHODS AND MATERIALS: Fifty-six patients diagnosed with low- to intermediate-risk prostate cancer treated with SBRT alone were reviewed retrospectively. All patients received a total dose of 38 Gy in 4 fractions with a planning target volume expansion of 2 mm. Overall, acute, and late genitourinary toxicity were documented according to the Common Terminology Criteria for Adverse Events (version 4) and International Prostate Symptom Scores (IPSS). RESULTS: The median age at treatment was 68 years, and the median prostate volume was 45.5 mL, with a median baseline IPSS of 9.95. The median prescription isodose line was 68%. The median clinical follow-up was 35.49 months. Acute grade 1, 2, and 3 genitourinary toxicities occurred in 41.1%, 35.7%, and 0% of patients. All acute genitourinary toxicities resolved except 1 patient with grade 2 toxicity that progressed to grade 3 late toxicity. No dose-volume relationships were associated with acute genitourinary grade 2+ toxicity. Late grade 1, 2, and 3 genitourinary toxicity occurred in 19.6%, 19.6%, and 3.6% of cases, respectively. Of the cases with late toxicities, 16.7% were persistent. Late grade 2+ genitourinary toxicity was associated with prostate volume ≥50 mL, lower homogeneity index, and urethral maximum point dose ≥47 Gy. The overall risk of any grade 2+ genitourinary toxicity was associated with baseline IPSS >7, prostate volume ≥50 mL, urethral volume receiving 44 Gy, and bladder volume receiving 19 Gy. CONCLUSIONS: SBRT for prostate cancer appears well tolerated, with mostly transient low-grade toxicity. Urethral sparing should be used with a maximum point dose <47 Gy, volume receiving 120 Gy <50% of the prostate, and bladder volume receiving 19 Gy <15 mL in 4 fraction treatments. Patients with prostate volumes ≥50 mL should be counseled regarding the increased risk of moderate-grade genitourinary toxicity.