Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: 5-Year Toxicity and Biochemical Recurrence Results From a Prospective Trial.

PURPOSE: Stereotactic body radiation therapy (SBRT) is increasingly used as a definitive treatment option for patients with prostate adenocarcinoma. The aim of this study was to assess the late toxicity, patient-reported quality of life outcomes, and biochemical recurrence rates after prostate SBRT with simultaneous integrated boost (SIB) targeting lesions defined by magnetic resonance imaging (MRI). METHODS AND MATERIALS: Patients were eligible if they had biopsy-proven low- or intermediate-risk prostate adenocarcinoma, one or more focal lesions on MRI, and an MRI-defined total prostate volume of <120 mL. All patients received SBRT delivered to the entire prostate to a dose of 36.25 Gy in 5 fractions with an SIB to the lesions seen on MRI to 40 Gy in 5 fractions. Late toxicity was defined as any possible treatment-related adverse event occurring after 3 months from the completion of SBRT. Patient-reported quality of life was ascertained using standardized patient surveys. RESULTS: A total of 26 patients were enrolled. Six patients (23.1%) had low-risk disease and 20 patients had intermediate-risk disease (76.9%). Seven patients (26.9%) received androgen deprivation therapy. Median follow-up was 59.5 months. No biochemical failures were observed. Three patients (11.5%) experienced late grade 2 genitourinary (GU) toxicity requiring cystoscopy, and 7 patients (26.9%) had late grade 2 GU toxicity requiring oral medications. Three patients (11.5%) had late grade 2 gastrointestinal toxicity characterized by hematochezia requiring colonoscopy and steroids per rectum. There were no grade 3 or higher toxicity events observed. The patient-reported quality-of-life metrics at the time of last follow-up were not significantly different than the pre-treatment baseline. CONCLUSIONS: The results of this study support that SBRT to the entire prostate to a dose of 36.25 Gy in 5 fractions with focal SIB to 40 Gy in 5 fractions has excellent biochemical control and is not associated with undue late gastrointestinal or GU toxicity or long-term quality of life decrement. Focal dose escalation with an SIB planning approach may be an opportunity to improve biochemical control while limiting dose to nearby organs at risk.

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: Acute Toxicity and Dosimetry Results From a Prospective Trial.

PURPOSE: This study aimed to report the early toxicity results of a prospective clinical trial of prostate stereotactic body radiation therapy (SBRT) to the entire prostate with a simultaneous integrated boost (SIB) to magnetic resonance imaging (MRI)-defined focal lesions. METHODS AND MATERIALS: Eligible patients included men with biopsy-proven prostate stage T1c to T2c adenocarcinoma, a Gleason score ≤7, and prostate-specific antigen values of ≤20 ng/mL, who had at least 1 focal lesion visible on MRI and a total prostate volume no greater than 120 cm3. SBRT consisted of a dose of 36.25 Gy to the entire prostate with an SIB of 40 Gy to the MRI-defined lesions, delivered in 5 fractions. The primary purpose of the study was to confirm the feasibility of treatment planning/delivery and to estimate the rate of urinary retention requiring placement of a Foley catheter within 90 days of treatment. This study was to be considered successful if urinary retention occurred in no more than 15% of cases, with a planned enrollment of at least 25 patients. RESULTS: A total of 26 men were enrolled, and all underwent SBRT as planned. Twenty patients (77%) had intermediate-risk features, and the remainder were low risk. A treatment plan that met the protocol-defined goals for all cases was developed. Two patients (7.7%) developed acute urinary symptoms that required the temporary placement of a Foley catheter. No grade 3+ toxicity events were observed. CONCLUSIONS: Planning and delivery of prostate SBRT with a whole prostate dose of 36.25 Gy and a focal 40 Gy SIB is feasible. Early follow-up suggests that this treatment is not associated with undue morbidity.

Reduced radiation tolerance of penile structures associated with dose-escalated hypofractionated prostate radiotherapy.

OBJECTIVE: To investigate the effect of hypofractionated external beam radiation therapy (RT) on sexual function in patients treated for localized prostate cancer, and also to determine the effect of radiation dose to the penile bulb or crura of the corpus cavernosum on sexual function outcome. MATERIALS AND METHODS: Forty-one patients treated with hypofractionated RT without androgen deprivation were prescribed 67.6-70.2 Gy to the prostate, delivered in 26-28 fractions. The primary endpoint was erectile dysfunction (ED) category based on the Sexual Health Inventory for Men (SHIM) score closest to 2 years from RT. The penile bulb and crura were contoured and mean radiation dose calculated for each structure. RESULTS: The mean pretreatment SHIM score was 19.8, and the mean posttreatment SHIM score was 15.1. The ED category was decreased by ≥ 2 in 50% of patients with a mean penile bulb of >20 Gy compared with that in 9% of patients with a mean penile bulb dose of ≤ 20 Gy (P = .003). Mean dose to the crura was highly correlated with mean dose to the penile bulb (Pearson correlation = 0.842; P <.001) but did not reach statistical significance as a predictor of ED after radiation. CONCLUSION: Radiation dose to the penile bulb is predictive of posttreatment ED in patients treated with dose-escalated hypofractionated prostate RT. The cutpoint at which this effect was observed with this treatment is substantially lower than the previous reports.

Comparison of plan quality and delivery time between volumetric arc therapy (RapidArc) and Gamma Knife radiosurgery for multiple cranial metastases.

BACKGROUND: Volumetric modulated arc therapy (VMAT) has been shown to be feasible for radiosurgical treatment of multiple cranial lesions with a single isocenter. OBJECTIVE: To investigate whether equivalent radiosurgical plan quality and reduced delivery time could be achieved in VMAT for patients with multiple intracranial targets previously treated with Gamma Knife (GK) radiosurgery. METHODS: We identified 28 GK treatments of multiple metastases. These were replanned for multiarc and single-arc, single-isocenter VMAT (RapidArc) in Eclipse. The prescription for all targets was standardized to 18 Gy. Each plan was normalized for 100% prescription dose to 99% to 100% of target volume. Plan quality was analyzed by target conformity (Radiation Therapy Oncology Group and Paddick conformity indices [CIs]), dose falloff (area under the dose-volume histogram curve), as well as the V4.5, V9, V12, and V18 isodose volumes. Other end points included beam-on and treatment time. RESULTS: Compared with GK, multiarc VMAT improved median plan conformity (CIVMAT = 1.14, CIGK = 1.65; P < .001) with no significant difference in median dose falloff (P = .269), 12 Gy isodose volume (P = .500), or low isodose spill (P = .49). Multiarc VMAT plans were associated with markedly reduced treatment time. A predictive model of the 12 Gy isodose volume as a function of tumor number and volume was also developed. CONCLUSION: For multiple target stereotactic radiosurgery, 4-arc VMAT produced clinically equivalent conformity, dose falloff, 12 Gy isodose volume, and low isodose spill, and reduced treatment time compared with GK. Because of its similar plan quality and increased delivery efficiency, single-isocenter VMAT radiosurgery may constitute an attractive alternative to multi-isocenter radiosurgery for some patients.

Hypofractionated stereotactic radiosurgery with concurrent bevacizumab for recurrent malignant gliomas: the University of Alabama at Birmingham experience.

BACKGROUND: Nearly all patients with malignant glioma will have disease recurrence. Our purpose was to define the treatment toxicity and efficacy of concurrent bevazicumab (BVZ) with hypofractionated stereotactic radiosurgery (SRS) of relatively larger targets for patients with recurrent MG. METHODS: A retrospective review of 21 patients with recurrent malignant glioma (18 glioblastoma, 3 WHO grade III glioma), treated at initial diagnosis with surgery and standard chemoradiation, was performed. All patients had concurrent BVZ with hypofractionatedSRS, 30 Gy in 5 fractions, with or without concurrent chemotherapy (temozolomide or CCNU). RESULTS: Median patient age was 54 years, median Karnofsky Performance Status was 80, and median target size was 4.3 cm (range, 3.4-7.5 cm). Eleven patients (52%) had previously failed BVZ. One patient had grade 3 toxicities (seizures, dysphasia), which resolved with inpatient admission and intravenous steroids/antiepileptics. Treatment-related toxicities were grade 3 (n = 1), grade 2 (n = 9), and grade 0-1 (n = 11). Kaplan-Meier median progression-free survival and overall survival estimates (calculated from start of SRS) for GBM patients (n = 18) were 11.0 and 12.5 months, respectively. Concurrent chemotherapy did not appear to show any statistically significant efficacy benefit or have any propensity for toxicity. CONCLUSION: BVZ concurrent with hypofractionated SRS was well tolerated by this cohort of patients with relatively larger targets. Ongoing randomized trials with more moderate radiotherapy dosing may help establish the efficacy of this regimen, though intricacies of this approach, including patient selection, radiation target volume delineation/size, and optimal radiation dose, will need further evaluation.

Effects of flattening filter-free and volumetric-modulated arc therapy delivery on treatment efficiency.

Flattening filter-free (FFF) beams are available on an increasing number of commercial linear accelerators. FFF beams have higher dose rates than flattened beams of equivalent energy which can lead to increased efficiency of treatment delivery, especially in conjunction with increased FFF beam energy and arc-based delivery configurations. The purpose of this study is to quantify and assess the implications of improved treatment efficiency for several FFF delivery options on common types of linac applicable radiotherapy. Eleven characteristic cases representative of a variety of clinical treatment sites and prescription doses were selected from our patient population. Treatment plans were generated for a Varian TrueBeam linear accelerator. For each case, a reference plan was created using DMLC IMRT with 6MV flat beams. From the same initial objectives, plans were generated using DMLC IMRT and volumetric-modulated arc therapy (VMAT) with 6 MV FFF and 10 MV FFF beams (max. dose rates of 1400 and 2400 MU/min, respectively). The plans were delivered to a phantom; beam-on time, total treatment delivery time, monitor units (MUs), and integral dose were recorded. For plans with low dose fractionations (1.8-2.0 & 3.85 Gy/fraction), mean beam-on time difference between reference plan and most efficient FFF plan was 0.56 min (41.09% decrease); mean treatment delivery time difference between the reference plan and most efficient FFF plan was 1.54 min (range: 0.31-3.56 min), a relative improvement of 46.1% (range: 29.2%-59.2%). For plans with high dose fractionations (16-20 Gy/fraction), mean beam-on time difference was 6.79 min (74.9% decrease); mean treatment delivery time difference was 8.99 min (range: 5.40-13.05 min), a relative improvement of 71.1% (range: 53.4%- 82.4%). 10 MV FFF VMAT beams generated the most efficient plan, except in the spine SBRT case. The distribution of monitor unit counts did not vary by plan type. In cases where respiratory motion management would be applicable, 10 MV FFF DMLC IMRT reduced beam-on time/field to less than 12 sec. FFF beams significantly reduced treatment delivery time. For radiosurgical doses, the efficiency improvement for FFF beams was clinically significant. For conventional fractionation, a large improvement in relative treatment delivery time was observed, but the absolute time savings were not likely to be of clinical value. In cases that benefit from respiratory motion management, beam-on/field was reduced to a time for which most patients can comfortably maintain deep inspiratory breath hold.

Flattening filter-free linac improves treatment delivery efficiency in stereotactic body radiation therapy.

Stereotactic body radiation therapy (SBRT) employs precision target tracking and image-guidance techniques to deliver ablative doses of radiation to localized malignancies; however, treatment with conventional photon beams requires lengthy treatment and immobilization times. The use of flattening filter-free (FFF) beams operating at higher dose rates can shorten beam-on time, and we hypothesize that it will shorten overall treatment delivery time. A total of 111 lung and liver SBRT cases treated at our institution from July 2008 to July 2011 were reviewed and 99 cases with complete data were identified. Treatment delivery times for cases treated with a FFF linac versus a conventional dose rate linac were compared. The frequency and type of intrafraction image guidance was also collected and compared between groups. Three hundred and ninety-one individual SBRT fractions from 99 treatment plans were examined; 36 plans were treated with a FFF linac. In the FFF cohort, the mean (± standard deviation) treatment time (time elapsed from beam-on until treatment end) and patient's immobilization time (time from first alignment image until treatment end) was 11.44 (± 6.3) and 21.08 (± 6.8) minutes compared to 32.94 (± 14.8) and 47.05 (± 17.6) minutes for the conventional cohort (p < 0.01 for all values). Intrafraction-computed tomography (CT) was used more often in the conventional cohort (84% vs. 25%; p < 0.05), but use of orthogonal X-ray imaging remained the same (16% vs. 19%). For lung and liver SBRT, a FFF linac reduces treatment and immobilization time by more than 50% compared to a conventional linac. In addition, treatment with a FFF linac is associated with less physician-ordered image guidance, which contributes to further improvement in treatment delivery efficiency.

Plan quality and treatment planning technique for single isocenter cranial radiosurgery with volumetric modulated arc therapy.

PURPOSE: To demonstrate plan quality and provide a practical, systematic approach to the treatment planning technique for single isocenter cranial radiosurgery with volumetric modulated arc therapy (VMAT; RapidArc, Varian Medical systems, Palo Alto, CA). METHODS AND MATERIALS: Fifteen patients with 1 or more brain metastases underwent single isocenter VMAT radiosurgery. All plans were normalized to deliver 100% of the prescription dose to 99%-100% of the target volume. All targets per plan were treated to the same dose. Plans were created with dose control tuning structures surrounding targets to maximize conformity and dose gradient. Plan quality was evaluated by calculation of conformity index (CI = 100% isodose volume/target volume) and homogeneity index (HI = maximum dose/prescription dose) scores for each target and a Paddick gradient index (GI = 50% isodose volume/100% isodose volume) score for each plan. RESULTS: The median number of targets per patient was 2 (range, 1-5). The median number of non-coplanar arcs utilized per plan was 2 (range, 1- 4). Single target plans were created with 1 or 2 non-coplanar arcs while multitarget plans utilized 2 to 4 non-coplanar arcs. Prescription doses ranged from 5-16 Gy in 1-5 fractions. The mean conformity index was 1.12 (± SD, 0.13) and the mean HI was 1.44 (± SD, 0.11) for all targets. The mean GI per plan was 3.34 (± SD, 0.42). CONCLUSIONS: We have outlined a practical approach to cranial radiosurgery treatment planning using the single isocenter VMAT platform. One or 2 arc single isocenter plans are often adequate for treatment of single targets, while 2-4 arcs may be more advantageous for multiple targets. Given the high plan quality and extreme clinical efficiency, this single isocenter VMAT approach will continue to become more prevalent for linac-based radiosurgical treatment of 1 or more intracranial targets and will likely replace multiple isocenter techniques.

Improved clinical efficiency in CNS stereotactic radiosurgery using a flattening filter free linear accelerator.

Linear accelerator (linac) based CNS stereotactic radiosurgery (SRS) requires significant time resources. We hypothesized that CNS SRS using a flattening filter free (FFF) linac would reduce treatment time and improve clinical efficiency. A FFF linac was recently commissioned for CNS radiosurgery at the University of Alabama at Birmingham. The efficiency of this linac for CNS SRS was retrospectively reviewed. Beam on time (BOT), time in room (TIR), and clinical dose rate (CDR) were calculated using an integrated treatment planning, record, and verification software platform and are proposed as surrogates for treatment efficiency. Twenty-seven eligible CNS SRS cases consisting of 1-5 fractions of 5 Gy or more per fraction were reviewed. Mean BOT was 1:21 (minutes:seconds; range: 00:36-2:52) and mean TIR was 10:42 (minutes:seconds; range: 6:05-22:56). The mean CDR was 1820 MU/ min (range: 872-2396). On regression analysis the number of alignment images, treatment arcs, targets, monitor units, and presence of intra-fraction imaging were factors significantly (p < 0.05) associated with prolonged TIR. Use of FFF mode in CNS SRS more than triples the CDR and results in shortened BOT and TIR compared to treatment at conventional dose rates. Reduction in clinical treatment times may translate to better target localization due to reduced opportunity for intrafraction motion. Linac-based CNS SRS can be completed in a normal time slot with a high output FFF linac.

Early clinical outcomes for 3 radiation techniques for brain metastases: focal versus whole-brain.

PURPOSE: To present our novel technique for brain metastases (low-dose whole brain radiation therapy [WBRT] with simultaneous integrated boost (SIB) and focal, frameless stereotactic intensity modulated radiotherapy [IMRT]) in the context of patterns of failure, dosimetry, acute toxicity, and overall survival for 3 different radiation techniques. METHODS AND MATERIALS: We retrospectively reviewed 92 patients undergoing radiation for brain metastases via the following: (1) "prophylactic" WBRT to a low dose (median 30 Gy) with an SIB to the gross tumor volume plus 2-3 mm margin (median dose 45 Gy) in 10-15 fractions; (2) focal, frameless image-guided stereotactic IMRT (S-IMRT) in 5 fractions to tumor only (median 30 Gy); or (3) conventional (c)WBRT using 2 lateral opposed beams in 10-15 fractions (30-37.5 Gy). The primary endpoints were local (LBC), distant (DBC), and total brain control (TBC) for each of the 3 types of brain radiation. Survival, toxicity, and dosimetry were reported as secondary endpoints. RESULTS: LBC was achieved in 72%, 78%, and 56% for SIB, S-IMRT, and cWBRT, respectively. DBC (ie, no new brain metastases) was observed in 92%, 67%, and 81% for SIB, S-IMRT, and cWBRT, respectively. TBC (LBC + DBC) was 72%, 67%, and 56% for SIB, S-IMRT, and cWBRT, respectively. No statistical difference in overall survival was observed (P = .067), and only 1 patient experienced biopsy proven radionecrosis. CONCLUSIONS: TBC after low-dose WBRT with SIB was acceptable and at least comparable to S-IMRT and cWBRT. SIB seems to be a safe and effective treatment strategy for patients with brain metastases and may efficiently combine the benefits of cWBRT and stereotactic radiosurgery.

Feasibility of single-isocenter volumetric modulated arc radiosurgery for treatment of multiple brain metastases.

PURPOSE: To evaluate the relative plan quality of single-isocenter vs. multi-isocenter volumetric modulated arc therapy (VMAT) for radiosurgical treatment of multiple central nervous system metastases. METHODS AND MATERIALS: VMAT plans were created using RapidArc technology for treatment of simulated patients with three brain metastases. The plans consisted of single-arc/single-isocenter, triple-arc (noncoplanar)/single-isocenter, and triple-arc (coplanar)/triple-isocenter configurations. All VMAT plans were normalized to deliver 100% of the 20-Gy prescription dose to all lesions. The plans were evaluated by calculation of Paddick and Radiation Therapy Oncology Group conformity index scores, Paddick gradient index scores, and 12-Gy isodose volumes. RESULTS: All plans were judged clinically acceptable, but differences were observed in the dosimetric parameters, with the use of multiple noncoplanar arcs showing small improvements in the conformity indexes compared with the single-arc/single-isocenter and triple-arc (coplanar)/triple-isocenter plans. Multiple arc plans (triple-arc [noncoplanar]/single-isocenter and triple-arc [coplanar]/triple-isocenter) showed smaller 12-Gy isodose volumes in scenarios involving three metastases spaced closely together, with only small differences noted among all plans involving lesions spaced further apart. CONCLUSION: Our initial results suggest that single-isocenter VMAT plans can be used to deliver conformity equivalent to that of multiple isocenter VMAT techniques. For targets that are closely spaced, multiple noncoplanar single-isocenter arcs might be required. VMAT radiosurgery for multiple targets using a single isocenter can be efficiently delivered, requiring less than one-half the beam time required for multiple isocenter set ups. VMAT radiosurgery will likely replace multi-isocenter techniques for linear accelerator-based treatment of multiple targets.