High-dose Stereotactic Body Radiation Therapy Research Articles

Urinary Outcomes for Men With High Baseline International Prostate Symptom Scores Treated With Prostate SBRT

PurposeThere are limited data regarding high-dose stereotactic body radiation therapy (SBRT) for prostate cancer in patients with poor baseline urinary function. The purpose of this study was to evaluate genitourinary (GU) toxicity and changes in patient-reported symptom severity scores after prostate SBRT in men with a high pretreatment International Prostate Symptom Score (IPSS). Methods and MaterialsSeven hundred fifty-three patients treated with prostate SBRT at our institution from 2012 to 2019 were identified, of whom 72 consecutive patients with baseline IPSS ≥15 were selected for this study. GU toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and IPSS were prospectively documented at each follow-up visit. Univariable logistic regression was used to evaluate for potential predictors of GU toxicity. ResultsMedian follow-up in survivors was 26.8 months. The rates of acute grade 2 and 3 GU toxicity were 20.8% and 1.4%, respectively. The rates of late grade 2 and 3 GU toxicity were 37.5% and 5.6%, respectively. The majority of grade 2+ toxicities resolved by last follow-up, and when toxicities were regraded per CTCAE v5.0, there were no longer any grade 3 adverse events. Total IPSS and individual symptom subscores improved over time. Compared with baseline, median total IPSS at 24 ± 6 months was significantly lower (18 vs 12; P < .001) and the proportion of patients with severe scores (IPSS ≥20) decreased from 29.2% to 13.9%. Pretreatment urinary urgency was associated with late grade 2+ GU toxicity (odds ratio, 2.10; 95% confidence interval, 1.33-3.31; P = .001). ConclusionsIn men with baseline IPSS ≥15 managed with prostate SBRT, the rate of severe GU toxicity was low and patient-reported symptoms generally improved over time. Thus, high pretreatment IPSS should not deter clinicians from offering prostate SBRT.

Radiation therapy for oligometastatic bone disease in breast cancer

Breast cancer (BCa) frequently metastasizes to the bone. BCa patients with oligometastatic bone diseases have much more favorable outcomes than those with metastatic bone disease. Radiation therapy (RT), especially stereotactic body radiation therapy (SBRT), is advised for the treatment of patients with oligometastatic bone disease in other primary sites. This line of treatment provided favorable outcomes in patients and resulted in only mild toxicities. A similar strategy has been suggested for treatment of BCa patients with oligometastatic bone disease. BCa, bone-only, or high radiation dose are reported to have been associated with good outcomes in RT for metastatic disease. Furthermore, based on the guidelines provided by the BCa expert panel of the German Society for Radiation Oncology and members of the Working Party of Gynecologic Oncology Breast Committee and in line of the results obtained in other primary sites, our group supports the use of high-dose RT or SBRT for the treatment of BCa patients with oligometastatic bone disease. Additionally, the use of magnetic resonance imaging (MRI) for proper target volume definition and three-dimensional (3D) treatment planning especially for lesions of the trunk are essential for the treatment planning of RT. Of note, several clinical trials have combined RT with immune checkpoint inhibitors for the treatment of BCa patients with metastatic disease. Based on this, we anticipate that combined RT and ICI may serve as a better treatment modality for BCa patients with oligometastatic bone disease.

Stereotactic Body Radiation Therapy for the Definitive Treatment of Early Stage Kidney Cancer: A Survival Comparison With Surgery, Tumor Ablation, and Observation

PurposePartial nephrectomy is the preferred definitive treatment for early stage kidney cancer, with tumor ablative techniques or active surveillance reserved for patients not undergoing surgery. Stereotactic body radiation therapy (SBRT) has emerged as a potential noninvasive alternative for patients with early stage kidney cancer not amenable to surgery, with early reports suggesting excellent rates of local control and limited toxicity. Methods and MaterialsThe national cancer database from 2004 to 2014 was queried for patients who received a diagnosis of T1N0M0 kidney cancer. Treatments were categorized as surgery (partial or total nephrectomy), tumor ablation (cryoablation or thermal ablation), SBRT (radiation therapy in 5 fractions or less to a total biological effective dose [BED10] of 72 or more), or observation. A propensity score was generated by multinomial logistic regression. A Cox proportional hazards model was fit to determine association between overall survival and treatment group with propensity score adjustments for patient, demographic, and treatment characteristics. ResultsA total of 165,298 received surgery, 17,196 underwent tumor ablation, 104 underwent SBRT, and 18,241 were observed. Median follow-up was 51 months. On multivariable analysis, surgery, tumor ablation, and SBRT were associated with a decreased risk of death compared with observation, with hazard ratios of 0.25 (95% confidence interval, 0.24-0.26, P < .001), 0.36 (0.35-0.38, P < .001), and 0.56 (0.39-0.79, P < .001), respectively. When stratifying by BED10 and compared with observation, hazard ratio for risk of death for patients treated with SBRT to a BED10 ≥100 (n = 62) and a BED10 <100 (n = 42) was 0.34 (0.19-0.60, P < .001) and 0.90 (0.58-1.4, P = .64), respectively. ConclusionsIn this population-based cohort, patients undergoing high-dose SBRT (BED10 ≥100) for early stage kidney cancer demonstrated longer survival compared with patients undergoing observation. This may be a promising noninvasive treatment option for nonsurgical candidates with prospective efficacy and safety assessments meriting study in future clinical trials.

Long term results of single high dose Stereotactic Body Radiotherapy in the treatment of primary lung tumors

Stereotactic body radiotherapy (SBRT) is a standard treatment for inoperable early-stage NSCLC, with local control rates comparable to surgical series. Promising results have been achieved utilizing a high single-dose schedule. The aim of our study was to evaluate long-term local control and toxicity in a series of patients treated with SBRT delivered in a single dose of 30 Gy. 44 patients affected by early stage NSCLC were treated with SBRT delivered in a single dose of 30 Gy. Survival and prognostic factors were retrospectively evaluated. Median follow-up was 34 months (range 3–81). Three- and 5-year local progression-free survival (LPFS) were 87.8% and 87.8% respectively (median 30 months; range 6–81 months), 3- and 5-year OS and CSS were 64.9% and 36.9%, 80.9% and 65.5%, respectively. Two (4.6%) cases of grade 3 pneumonitis occurred. At the univariate analysis lesion diameter ≤ 25 mm was predictive of better 5-year LPFS (95.8% versus 56.3%; p = 0.003) and 5-year PFS (69.8% versus 27.8%; p = 0.002). The results of our study indicated a high local control, survival and tolerability after a long-term follow-up with the use of SBRT 30 Gy single dose. Further prospective studies could better define the role of this regimen.

Early Tolerance and Tumor Control Outcomes with High-dose Ultrahypofractionated Radiation Therapy for Prostate Cancer

BackgroundStudies using stereotactic body radiotherapy (SBRT) dose escalation in in low- and intermediate-risk prostate cancer patients have indicated favorable outcomes. ObjectiveTo evaluate tolerance and tumor control outcomes in low- and intermediate-risk prostate cancer patients treated with high-dose SBRT following our phase 1 trial. Design, setting, and participantsA total of 551 patients with low- or intermediate-risk prostate cancer were treated with SBRT. InterventionTreatment with 37.5–40Gy SBRT in five fractions directed to the prostate and seminal vesicles. Outcome measurements and statistical analysisOutcome measurements included acute toxicities (<3 mo after radiotherapy [RT]) and late toxicities (>3 mo after RT) and tumor control evaluation (prostate-specific antigen [PSA] levels at 3–6-mo intervals and post-treatment prostate biopsy at 2yr). Results and limitationsAcute grade 2 gastrointestinal (GI) toxicities occurred in 1.8% of patients, and late grade 2 and 3 GI toxicities were observed in 3.4% and 0.4% of patients, respectively. Acute grade 2 genitourinary (GU) toxicities occurred in 10% of patients, and grade 3 acute GU toxicities were observed in 0.7% of patients. Late grade 2 and 3 GU toxicities were observed in 21.1% and 2.5% of patients, respectively. The use of a hydrogel rectal spacer was significantly associated with reduced late GI toxicity and lower odds of developing late GU toxicity. The median follow-up was 17 mo, and 53% of those with at least 2yr of follow-up (103/193) had a biopsy performed. The 5-yr cumulative incidence of PSA failure was 2.1%, and the incidence of a positive 2-yr treatment biopsy was 12%. Limitations to this report include its retrospective nature and short follow-up time. ConclusionsFavorable short-term outcomes were achieved with high-dose SBRT for low- and intermediate-risk disease. Severe late toxicities were observed and favorable tumor control was found. Patient summaryWe utilized stereotactic body radiotherapy, a form of external beam radiotherapy that delivers highly targeted high-dose treatment to the prostate, to treat over 500 localized prostate cancer patients in five sessions over 1.5 wk. Treatments were well tolerated without significant urinary or rectal side effects. Nearly 90% of those who underwent biopsies after treatment did not demonstrate residual active disease.

Initial Dosimetric Outcomes and Treatment Related Toxicities Using Stereotactic MRI-Guided Radiation Therapy (SMART) for Unresectable Pancreatic Cancer at a Single Institution

High dose stereotactic body radiotherapy (SBRT) may offer improved disease outcomes for locally advanced pancreatic cancer but treatment delivery remains a challenge due to tumor proximity to organs-at-risk (OAR) and daily, anatomic variability. Stereotactic MRI-guided adaptive radiation therapy (SMART) with real-time tumor tracking allows for improved dose delivery to disease targets and OAR sparing by accounting for anatomic changes with each treatment. This study reports initial dosimetric outcomes and treatment related toxicities in unresectable pancreatic cancer patients treated using SMART. Ten patients with unresectable, locally advanced pancreatic cancer were treated on a MR-guided linear accelerator using real-time tumor tracking and motion management. A plan was generated for each patient after initial CT and MR-simulation. At each treatment, MR imaging was obtained for the daily anatomy and the initial (unadapted) plan was compared to obtain a predicted dose coverage of tumor volumes and OAR constraints using a prescribed dose of 50 Gy in 5 fractions. If OAR constraints were not met or PTV coverage was inadequate, an adaptive plan was generated based on the anatomy imaged on the day of treatment. Goal PTV coverage was 95% of the volume at 100% of prescription dose, however, this was subject to hard OAR constraints and plans were optimized for best PTV coverage within an acceptable OAR dose. For each adaptive plan generated, the delivered dose for that fraction was compared to the predicted dose from the initial plan. Only toxicities grade 3 or higher were considered for inclusion. At time of analysis, from June 2018 to February 2019, a total of 46 fractions were delivered to ten patients. Of the 46 treatments, 5 were with the initial, unadapted plan and 41 were adaptive. Due to intra-fraction adjustments that occurred during 6 treatments, only 35 adaptive plans were included for analysis. When comparing the performance of the initial plan on the daily updated MR anatomy, adaptive planning led to improved coverage of both PTV (86.36% vs. 73.15% at 100% of prescribed dose) and CTV (95.97% vs 89.59% at 95% of prescribed dose). Unadapted plans were much more likely to exceed OAR constraints, with 27 of 35 (77%) unadapted fractions predicted to violate prescribed duodenal, stomach, or small bowel constraints compared to 2 of 35 (6%) of adapted fractions. Moreover, 16/35 (46%) of unadapted fractions violated constraints for 2 of 3 abdominal OARs and 5/35 (14%) violated constraints for all 3 compared to none for adapted fractions. No grade 3 toxicities were reported in any of the treated patients. Stereotactic adaptive MRI-guided radiotherapy led to improved tumor volume coverage and reduced dose to abdominal OARs in patients with locally advanced pancreatic cancer with no grade 3 or higher toxicities. Prospective studies examining disease outcomes and treatment related toxicities are ongoing.

Stereotactic body radiation therapy for benign spine tumors: is dose de-escalation appropriate?

OBJECTIVE Akin to the nonoperative management of benign intracranial tumors, stereotactic body radiation therapy (SBRT) has emerged as a nonoperative treatment option for noninfiltrative primary spine tumors such as meningioma and schwannoma. The majority of initial series used higher doses of 16-24 Gy in 1-3 fractions. The authors hypothesized that lower doses (such as 12-13 Gy in 1 fraction) might provide an efficacy similar to that found with the dose de-escalation commonly used for intracranial radiosurgery to treat acoustic neuroma or meningioma and with a lower risk of toxicity. METHODS The authors identified 38 patients in a prospectively maintained institutional radiosurgery database who were treated with definitive SBRT for a total of 47 benign primary spine tumors between 2004 and 2016. SBRT consisted of 9-21 Gy in 1-3 fractions using the CyberKnife (n = 11 [23%]), Synergy S (n = 21 [45%]), or TrueBeam (n = 15 [32%]) radiosurgery platform. For a comparison of SBRT doses, patients were dichotomized into 1 of 2 groups (low-dose or high-dose SBRT) using a cutoff biologically effective dose (BED10Gy) of 30 Gy. Tumor control was calculated from the date of SBRT to the last follow-up using Kaplan-Meier survival analysis, with comparisons between groups completed using a log-rank method. To account for potential indication bias, a propensity score analysis was completed based on the conditional probabilities of SBRT dose selection. Toxicity was graded using Common Terminology Criteria for Adverse Events version 4.0 with a focus on grade 3+ toxicity and the incidence of pain flare. RESULTS For the 38 patients, the most common histological findings were meningioma (15 patients), schwannoma (13 patients), and hemangioblastoma (7 patients). The median age at SBRT was 58 years (range 25-91 years). The 47 treated lesions were located in the cervical (n = 18), thoracic (n = 19), or lumbosacral (n = 10) spine. Five (11%) lesions were lost to follow-up after SBRT. The median follow-up duration for the remaining 42 lesions was 54 months (range 1.2-133 months). Six (16%) patients (with a total of 8 lesions) experienced pain flare after SBRT; no significant predictor of pain flare was identified. No grade 3+ acute- or late-onset complication was noted. The 5-year local control rate was 76% (95% CI 61%-91%). No significant difference in local control according to dose, fractionation, previous radiation, surgery, tumor histology, age, treatment platform, planning target volume, or spine level treated was found. The 5-year local control rates for low- and high-dose treatments were 73% (95% CI 53%-93%) and 83% (95% CI 61%-100%) (p = 0.52). In propensity score-adjusted multivariable analysis, no difference in local control was identified (HR 0.30, 95% CI 0.02-5.40; p = 0.41). CONCLUSIONS Long-term follow-up of patients treated with SBRT for benign spinal lesions revealed no significant difference between low-dose (BED10Gy ≤ 30) and high-dose SBRT in local control, pain-flare rate, or long-term toxicity.

Surgical strategy of metastatic spine disease and progress of separation surgery

Spinal metastases may cause pain, pathological fracture and/or neurological symptoms. The most common treatment of spinal metastases is conservative therapy. Surgical intervention is necessary when there are pathological and/or neurological deficits. Total en bloc spondylectomy (TES) has lower local recurrence rate and may be applicable to a patient with single metastatic tumor and a long survival expectancy. While debulking surgery is less risky and higher recurrence rate. Conventional radiotherapy is a kind of effective supplement to reduce the local recurrence rate in spinal metastases. However, the local dose is often failed to reach the effective dose because of the close connection of tumor and spinal cord and it is less effective for relatively radioresistant histologies. With the development of radiotherapy technology, spinal radiotherapy has become increasingly accurate to avoid of spinal cord injury. In addition, conventional radioresistant tumors has become treatable with high-dose stereotactic body radiotherapy (SBRT). At the same time, SBRT is also an important basis for the implementation of separation surgery of spinal metastases. Separation surgery is to separate the tumor and dura and achieve circumferential decompression and stabilization through posterior approach. As a result, a high-dose SBRT can be performed because of the small interspace to protect the spinal cord, which greatly reduces the local recurrence rate. Compared with TES, separation surgery combined with high-dose radiotherapy not only reduces the difficulty of surgery, but also has a good local control rate, which is a relatively minimally invasive strategy. Separation surgery is particularly suitable for patients with high-grade epidural spinal cord compression and moderately sensitive or insensitive to radiotherapy. Although the concept of separation surgery has been proposed for several years, only a few applications have been reported in foreign literature and fewer in domestic literature. This article aims to summarize the relevant concepts and clinical applications of separation surgery in spine metastases and to provide a reference for the treatment of spinal metastases.

Early Tissue Effects of Stereotactic Body Radiation Therapy for Spinal Metastases

Stereotactic body radiation therapy (SBRT) is a highly effective and potentially ablative treatment for complex spinal metastases. Recent data have suggested radiobiologic effects of SBRT that expand beyond the traditional concept of DNA damage. Antitumor immunity, vascular damage leading to tumor necrosis, and increased rates of tumor apoptosis have been implied; however, in-human evidence remains scarce. The present study reports unique pathologic confirmation of SBRT-induced biological effects within spinal metastases treated with preoperative SBRT. Ten patients with spinal metastases secondary to various solid tumors were treated with preoperative single-fraction SBRT (18Gy) to the magnetic resonance imaging-defined macroscopic metastasis, followed by spinal stabilization within 24hours. Perioperative samples of spinal metastases were obtained, and 6 patients also had a pre-SBRT biopsy specimen available for a matched comparison. The samples were stained for tumor necrosis on routine hematoxylin-eosin-stained slices and, subsequently, immunohistochemical staining for T cells (CD3+, CD4+, CD8+), natural killer cells (CD56+), endothelium (CD31+), and apoptotic activity (caspase-3). Perioperative biopsy specimens were obtained ∼6hours (range 4.5-7.5) or 21hours (range 18.5-22.5) after SBRT. Necrosis was observed in 83% of the 21-hour post-SBRT samples (5 of 6) compared with 0% of pre-SBRT biopsies (0 of 6) and 6-hour post-SBRT biopsies (0 of 4). Tumor cell apoptosis had increased greatly in the 21-hour post-SBRT samples compared with before and 6hours after SBRT. The CD31+vessel counts decreased after SBRT, as did mitotic activity. Both of the renal cell metastases displayed major decreases in vessel density. Desmoplastic reaction was visible in 67% (4 of 6) of the pre-SBRT samples compared with 100% (10 of 10) the post-SBRT samples. The T-cell and natural killer cell counts were relatively unaffected. High-dose single-fraction SBRT induced tumor necrosis, desmoplasia, and tumor apoptosis and decreased tumor vessel density within 24hours, even in renal cell metastases. The role of immune cells seems limited in this early phase. These first-in-human results imply direct vascular and DNA damage mechanisms important in the clinical efficacy specific to spinal SBRT.

Thoracic reirradiation with SBRT for residual/recurrent and new primary NSCLC within or immediately adjacent to a prior high-dose radiation field

PurposeLocal failure following concurrent chemoradiation and in-lobe failures following stereotactic body radiation therapy (SBRT) are common. We evaluated our institutional experience using SBRT as salvage in this setting. Methods and materialsSeventy-two patients were reirradiated with SBRT for residual, locally recurrent, or new primary non-small cell lung cancer within or adjacent to a high-dose external beam radiation therapy or SBRT field. Kaplan-Meier analysis with log-rank test were used to estimate endpoints and differentiate cohorts. ResultsMedian follow-up was 17.9 months. Patients had residual or recurrent disease (54.2%); 45.8% had new lung primaries. Median reirradiated T size was 2.5 cm (range, 0.8-7.8 cm). Median pre-retreatment maximum standardized uptake value (SUVmax) was 7.15 (range, 1.2-37.6). The most common SBRT reirradiation regimen was 48 Gy in 4 fractions (range, 17-60 Gy in 1-5 fractions). Median progression-free survival was 15.2 months, and median overall survival was 20.8 months. Two-year local failure was 21.6%. Patients with SUVmax at reirradiation <7.0 had a 2-year local control of 93.1% versus 61.1% above the median (P < .001). The 2-year rate of distant metastases was 10.4% versus 54.1% in patients treated for a new primary versus residual or recurrent disease (P < .001). Median progression-free survival was 31.9 months versus 8.4 months, respectively (P = .037). Median survival of patients treated for new primary was 25.2 months versus 16.2 months with residual or recurrent disease (P = .049), and median survival for patients with reirradiation SUVmax below the median was 42.0 months versus 9.8 months above the median (P < .001). Acute any-grade toxicity was seen in 29.2% of patients, acute grade 3 toxicity in 11.1%, and late grade 3 toxicity in 1.4% with no treatment-related deaths. ConclusionsSBRT appears to be a safe and effective means of salvaging recurrent, residual, or new primary NSCLC in or adjacent to a previous high-dose radiation field.

Multi-Institutional Phase 2 Trial of High-Dose Stereotactic Body Radiation Therapy with Temporary Hydrogel Spacer for Low- and Intermediate-Risk Prostate Cancer

High-dose stereotactic body radiation therapy (SBRT) yields very high rates of biochemical control for low- (LR) and intermediate-risk (IR) prostate cancer (PCa), but in our prior Phase 1/2 trial of SBRT for LR and IR PCa a degree of rectal injury (e.g., mucosal erosion or ulcer) was observed in all cases, with potential high grade toxicity associated with incidental dose to the rectal wall. We report outcomes of a multi-institutional phase 2 clinical trial of high-dose SBRT for LR and IR PCa patients following placement of a peri-rectal hydrogel spacer.

Stereotactic body radiotherapy (SBRT) for pulmonary metastases from renal cell carcinoma-a multicenter analysis of the German working group "Stereotactic Radiotherapy".

Renal cell carcinoma (RCC) is traditionally considered to be radioresistant. Radiotherapy response rates are believed to improve with hypofractionated, high dose stereotactic body radiotherapy (SBRT). However, limited data exist regarding the role of SBRT in the treatment of pulmonary metastases. The working group "Stereotactic Radiotherapy" of the German Society of Radiation Oncology analyzed its multi-institutional database of more than 700 patients who received SBRT for pulmonary metastases. Treatment was performed at 10 centers between 2001 and 2016. Patients with metastatic RCC were included in the study. Tumor characteristics, treatment details, and follow-up data including survival, local control (LC), distant metastases, and toxicity were evaluated. A total of 46 RCC patients treated with SBRT for 67 lung metastases were identified, who received a median total biologically effective dose (BEDiso) at planning target volume (PTV) isocenter of 117.0 Gy (range, 48.0-189.0 Gy). A median fractional dose of 20.8 Gy at isocenter (range, 6.0-37.9 Gy) was administered in a median number of 3 fractions (1-8 fractions). After a median follow-up time of 28.3 months for all patients, 1- and 3-year LC rates were 98.1% and 91.9%, with corresponding 1- and 3-year overall survival (OS) of 84.3% and 43.8%, respectively. Pulmonary metastases treated with BEDiso ≥130 Gy showed a trend for superior LC (P=0.054). OS was significantly improved in both uni- and multivariate analysis for patients with higher Karnofsky performance scale, lower maximum pulmonary metastasis diameter and lack of post-SBRT systemic therapy due to progression (P=0.014; P=0.049; P=0.006). Only mild acute and late toxicity was reported. SBRT for pulmonary metastases from RCC was associated with low treatment-associated toxicity, promising survival, and excellent LC, especially in those patients receiving a BEDiso ≥130 Gy.

Five-fraction SBRT for ultra-central NSCLC in-field recurrences following high-dose conventional radiation

Purpose/objectiveLocal treatment options for patients with in-field non-small cell lung cancer (NSCLC) recurrence following conventionally fractionated external beam radiation therapy (CF-EBRT) are limited. Stereotactic body radiation therapy (SBRT) is a promising modality to achieve reasonable local control, although toxicity remains a concern.Materials/methodsPatients previously treated with high-dose CF-EBRT (≥59.4 Gy, ≤3 Gy/fraction) for non-metastatic NSCLC who underwent salvage SBRT for localized ultra-central in-field recurrence were included in this analysis. Ultra-central recurrences were defined as those abutting the trachea, mainstem bronchus, or esophagus and included both parenchymal and nodal recurrences. The Kaplan-Meier method was used to estimate local control and overall survival. Durable local control was defined as ≥12 months. Toxicity was scored per the CTC-AE v4.0.ResultsTwenty patients were treated with five-fraction robotic SBRT for ultra-central in-field recurrence following CF-EBRT. Fifty percent of recurrences were adenocarcinoma, while 35% of tumors were classified as squamous cell carcinoma. The median interval between the end of CF-EBRT and SBRT was 23.3 months (range: 2.6 – 93.6 months). The median CF-EBRT dose was 63 Gy (range: 59.4 – 75 Gy), the median SBRT dose was 35 Gy (range: 25 – 45 Gy), and the median total equivalent dose in 2 Gy fractions (EQD2) was 116 Gy (range: 91.3 – 136.7 Gy). At a median follow-up of 12 months for all patients and 37.5 months in surviving patients, the majority of patients (90%) have died. High-dose SBRT was associated with improved local control (p < .01), and the one-year overall survival and local control were 77.8% and 66.7% respectively in this sub-group. No late esophageal toxicity was noted, although a patient who received an SBRT dose of 45 Gy (total EQD2: 129.7 Gy) experienced grade 5 hemoptysis 35 months following treatment.ConclusionsAlthough the overall prognosis for patients with in-field ultra-central NSCLC recurrences following CF-EBRT remains grim, five-fraction SBRT was well tolerated with an acceptable toxicity profile. Dose escalation above 35 Gy may offer improved local control, however caution is warranted when treating high-risk recurrences with aggressive regimens.

Optimal Patient Selection for Stereotactic Body Radiation Therapy: A Practical Approach in a High-Volume Community-Based Private Setting

Establishment of an objective and documentable selection process of patients for free-breathing stereotactic body radiation therapy (SBRT) in a high-volume community-based private setting. A vendor-based respiratory gating system and wide-bore multi-slice CT simulation acquire 4-dimensional image data sets throughout full respiratory cycles. SBRT is delivered on modern linear accelerators including SBRT-dedicated systems, with respiratory gating control and multiple volumetric modulated arc therapy (VMAT) techniques. Flattening Filter Free (FFF) mode of RT delivery is available as needed. Use of cone-beam CT image guidance and 6 degrees of freedom patient repositioning are also available to optimize target alignment. Patients were observed closely at time of CT simulation to select those with optimal and stable respiratory patterns with or without the need for supplemental oxygen. Selection of appropriate patients for SBRT is needed to assure optimal CT simulation image capture, prediction for subsequent treatment deliverability, and reproducibility of high dose SBRT. Typical SBRT is up to 10 Gy per fraction for 5 fractions. Through real-time evaluation of respiratory patterns, appropriate patients can be selected for SBRT. Compliance rate of selected patients during simulation and subsequent SBRT is 100% without significant interruption during SBRT delivery. Use of respiratory gating control effectively prevents out-of-range SBRT delivery during fits of coughing and dyspnea. Use of FFF mode and VMAT via multiple arcs significantly reduces SBRT delivery time and optimizes normal tissue protection. The selection ”process“ is also recorded via screen capture of the respiratory cycles with a corresponding graphical representation of steady breathing patterns. These graphics can then be inserted into the CT simulation documentation as part of the permanent electronic health record. Appropriate selection of patients for SBRT via objective analysis and recorded respiratory patterns ensures optimal conditions for clinical setup, tumor targeting, and reproducible delivery of SBRT. This process is also recorded in the electronic health records of each patient for permanent documentation, future reference, and chart review.

Current Role of Radiotherapy for Renal-Cell Carcinoma: Review.

Surgery is the standard of care for patients with renal-cell carcinoma (RCC). Radiotherapy (RT) can decrease the risk of local recurrence after surgery and can lead to excellent outcomes in patients unfit for surgery. We reviewed clinical experience with various forms of RT, including conventional fractionated RT and intraoperative radiotherapy (IORT) as adjunct to surgery, hypofractionated high-dose stereotactic body radiotherapy (SBRT), and particle therapy in unresectable RCC. We discuss future directions for using RT in the treatment of RCC. We encourage clinicians to incorporate RT modalities in prospective clinical trials.

Stereotactic body radiotherapy for patients with oligometastases from colorectal cancer: risk-adapted dose prescription with a maximum dose of 83-100 Gy in five fractions.

We previously reported that the local control of pulmonary metastases from colorectal cancer (CRC) following stereotactic body radiotherapy (SBRT) with moderate prescription dose was relatively worse. We investigated the treatment outcomes and toxicities of patients with oligometastases from CRC treated by SBRT using risk-adapted, very high- and convergent-dose regimens. Among patients referred for SBRT from August 2011 to January 2015, those patients were extracted who had liver or pulmonary metastases from CRC, and they were treated with a total dose of 50–60 Gy in five fractions prescribed to the 60% isodose line of the maximum dose covering the surface of the planning target volume. Concurrent administration of chemotherapy was not admitted during SBRT, while neoadjuvant or adjuvant chemotherapy was allowed. A total of 21 patients (12 liver, 9 lung) with 28 oligometastases were evaluated. The median follow-up duration was 27.5 months (range: 6.5–43.3 months). Four patients were treated with SBRT as a series of initial treatments, and 17 patients were treated after recurrent oligometastases. The local control rates at 1 and 2 years from the start of SBRT were 100%. The disease-free and actuarial overall survival rates were 62% and 55%, and 79% and 79%, respectively. No severe toxicities (≥grade 3) occurred during follow-up. The outcomes following high-dose SBRT were excellent. This treatment can provide an alternative to the surgical resection of oligometastases from CRC. Prospective studies are needed to validate the effectiveness of SBRT.

Early and multiple PSA bounces can occur following high-dose prostate stereotactic body radiation therapy: Subset analysis of a phase 1/2 trial

PurposeWe hypothesized that high-dose stereotactic body radiation therapy (SBRT) would lead to faster time to nadir and lower nadir values compared with conventional radiation therapy experiences. We now report prostate-specific antigen (PSA) kinetics following high-dose SBRT in patients treated with radiation alone. Methods and materialsNinety-one patients were enrolled on the phase 1/2 dose escalation study of SBRT for localized prostate cancer. All patients with at least 36 months of follow-up and without hormone therapy were included in this analysis (n = 47). Treatment response parameters evaluated include time to nadir, nadir value, occurrence of PSA bounces (rise of ≥0.2 ng/mL followed by a subsequent fall), magnitude of bounces, duration of bounces, and correlation of bounces with clinical outcomes. ResultsMedian follow-up was 42 months (range, 36-78 months). Treatment dose levels were 45 Gy (n = 10), 47.5 Gy (n = 8), and 50 Gy (n = 29) in 5 fractions. Biochemical control rate was 98%. Median PSA at follow-up was 0.10 ± 0.20 ng/mL. Median time to nadir was 36 ± 11 months. A total of 24/47 (51.1%) patients had ≥1 PSA bounce. Median magnitude of PSA rise during bounce was 0.50 ± 1.2 ng/mL. Median time to first bounce was 9 ± 7.0 months. Median bounce duration was 3 ± 2.3 months for the first bounce and 6 ± 5.2 months for subsequent bounces. Prostate volumes <30 mL were associated with a decreased likelihood of bounce (P = .0202), and increasing prostate volume correlated with increasingly likelihood of having ≥2 bounces (P = .027). Patients reaching PSA nadir of ≤0.1 ng/mL were less likely to experience any bounce (P = .0044). ConclusionsCompared with other SBRT experiences, our study demonstrated a higher PSA bounce rate, a similar or shorter median time to bounce, and a very low nadir. Prostate volume appears correlated with bounce.

TH‐EF‐BRB‐04: 4π Dynamic Conformal Arc Therapy Dynamic Conformal Arc Therapy (DCAT) for SBRT

Purpose:To develop an efficient and effective trajectory optimization methodology for 4π dynamic conformal arc treatment (4π DCAT) with synchronized gantry and couch motion; and to investigate potential clinical benefits for stereotactic body radiation therapy (SBRT) to breast, lung, liver and spine tumors.Methods:The entire optimization framework for 4π DCAT inverse planning consists of two parts: 1) integer programming algorithm and 2) particle swarm optimization (PSO) algorithm. The integer programming is designed to find an optimal solution for arc delivery trajectory with both couch and gantry rotation, while PSO minimize a non‐convex objective function based on the selected trajectory and dose‐volume constraints. In this study, control point interaction is explicitly taken into account. Beam trajectory was modeled as a series of control points connected together to form a deliverable path. With linear treatment planning objectives, a mixed‐integer program (MIP) was formulated. Under mild assumptions, the MIP is tractable. Assigning monitor units to control points along the path can be integrated into the model and done by PSO. The developed 4π DCAT inverse planning strategy is evaluated on SBRT cases and compared to clinically treated plans.Results:The resultant dose distribution of this technique was evaluated between 3D conformal treatment plan generated by Pinnacle treatment planning system and 4π DCAT on a lung SBRT patient case. Both plans share the same scale of MU, 3038 and 2822 correspondingly to 3D conformal plan and 4π DCAT. The mean doses for most of OARs were greatly reduced at 32% (cord), 70% (esophagus), 2.8% (lung) and 42.4% (stomach).Conclusion:Initial results in this study show the proposed 4π DCAT treatment technique can achieve better OAR sparing and lower MUs, which indicates that the developed technique is promising for high dose SBRT to reduce the risk of secondary cancer.

Decision analysis model evaluating the cost of a temporary hydrogel rectal spacer before prostate radiation therapy to reduce the incidence of rectal complications

PurposeWe conducted a decision analysis to evaluate the cost effectiveness of a newly Food and Drug Administration approved rectal spacer gel (SpaceOAR, Augmenix) for the reduction of rectal toxicity of prostate radiation therapy (RT). MethodsA decision tree model (TreeAge Pro) was used to compare the strategy of pretherapy placement of a spacing hydrogel before RT to RT alone. The model compared costs associated with rectal complications because of rectal toxicity over a 10-year period across 3 different RT modalities. Rectal toxicity rates were estimated from studies on conformal RT dose escalation, high-dose stereotactic body radiotherapy (SBRT) and low-dose SBRT. Rectal toxicity reduction rates (baseline reduction 70%) were estimated from recently published 15 month data using a rectal spacer. Direct and indirect cost estimates for established grades of rectal toxicity were based on national and institutional costs. Reduction in short-term complications were assumed to carry forward to a reduction in long-term toxicity. One-way and two-way sensitivity analyses were performed. ResultsThe overall standard management cost for conformal RT was $3,428 vs. $3,946 with rectal spacer for an incremental cost of $518 over 10 years. A 1-way sensitivity analyses showed the breakeven cost of spacer at $2,332 or a breakeven overall risk reduction of 86% at a cost of $2,850. For high-dose SBRT, spacer was immediately cost effective with a savings of $2,640 and breakeven risk reduction at 36%. However, 2-way spacer cost to risk reduction sensitivity analyses were performed. ConclusionThe use of a rectal spacer for conformal RT results in a marginal cost increase with a significant reduction in rectal toxicity assuming recently published 15 month rectal toxicity reduction is maintained over 10 years. For high-dose SBRT it was cost effective. Further studies would be necessary to validate the long-term benefits of rectal spacers.

Determining radiographic outcome after spine radiosurgery—not as straightforward as one might think

Spratt DE, Arevalo-Perez J, Leeman JE, Gerber NK, Folkert M, Taunk NK, et al. Early magnetic resonance imaging biomarkers to predict local control after high dose stereotactic body radiotherapy for patients with sarcoma spine metastases. Spine J 2016:16:291-98 (in this issue).