Linac-based Stereotactic Body Radiation Therapy Research Articles

LINAC-based SBRT in treating early-stage NSCLC patients-single institution experience and survival data analysis.

Aim: This single institute prospective study aimed to evaluate the feasibility of LINAC-based stereotactic body radiotherapy (SBRT) in treating patients with early-stage non-small cell lung cancer (NSLSC). We focused on the survival data with the local and distant control profiles and the cancer- and non-cancer-specific survival. Treatment-related side effects were also collected and analyzed. Methods: Patients with early-stage NSCLC between January 2018 and October 2021 were included in our prospective study; a total of 77 patients receiving LINAC-based SBRT were analyzed. All patients had pretreatment multidisciplinary tumor board decisions on SBRT. The average patient age was 68.8years (median: 70years, range: 52-82); 70 patients were in ECOG 0 status (91%), while seven patients were in ECOG 1-2 status (9%). 52% of the patients (40) had histologically verified NSCLC, and the other 48% were verified based on PETCT results. We applied the SBRT scheme 8 x 7.5 Gy for central tumors (74%) or 4 x 12 Gy for peripheral tumors (26%). Results: The mean follow-up time was 25.4months (median 23, range 18-50). The Kaplan-Meier estimation for overall survival in patients receiving LINAC-based SBRT was 41.67months. Of the 77 patients treated by SBRT, death was reported for 17 patients (9 cases cancer-specific, 8 cases non-cancer specific reason). The mean local tumor control was 34.25months (range 8.4-41), and the mean systemic control was 24.24months (range 7-25). During the treatments, no Grade I-II were reported; in 30 cases, Grade I non-symptomatic treatment-related lung fibrosis and two asymptomatic rib fractures were reported. Conclusion: In the treatment of early-stage NSCLC, LINAC-based SBRT can be a feasible alternative to surgery. Although we reported worse OS data in our patient cohort compared to the literature, the higher older average age and the initial worse general condition (ECOG1-2) in our patient cohort appear to be the reason for this difference. With the comparable local control and survival data and the favorable side effect profile, SBRT might be preferable over surgery in selected cases.

Electromagnetic Transmitter-Based Prostate Gating for Dose-Escalated Linac-Based Stereotactic Body Radiation Therapy: An Evaluation of Intrafraction Motion.

Stereotactic Body Radiotherapy (SBRT) is as a standard treatment for prostate cancer (PCa). Tight margins and high dose gradients are needed, and the precise localization of the target is mandatory. Our retrospective study reports our experience regarding the evaluation of intrafraction prostate motion during LINAC-based SBRT evaluated with a novel electromagnetic (EM) tracking device. This device consists of an integrated Foley catheter with a transmitter connected to a receiver placed on the treatment table. We analyzed 31 patients who received LINAC-based SBRT using flattening filter-free (FFF) volumetric modulated arc therapy (VMAT). The patients were scheduled to be treated for primary (n = 27) or an intraprostatic recurrent PCa (n = 4). A simulation CT scan was conducted while the patients had a filled bladder (100-150 cc) and an empty rectum, and an EM tracking device was used. The same rectal and bladder conditions were employed during the treatment. The patients received 36.25 Gy delivered over five consecutive fractions on the whole prostate and 40 Gy on the nodule(s) visible via MRI, both delivered with a Simultaneous Integrated Boost approach. The CTV-to-PTV margin was 2 mm for both the identified treatment volumes. Patient positioning was verified with XVI ConeBeam-CT (CBCT) matching before each fraction. When the signals exceeded a 2 mm threshold in any of the three spatial directions, the treatment was manually interrupted. A new XVI CBCT was performed if this offset lasted >20 s. We analyzed data about 155 fractions. The median and mean treatment times, calculated per fraction, were 10 m31 s and 12 m44 s (range: 6 m36 s-65 m28 s), and 95% of the fractions were delivered with a maximum time of 27 m48 s. During treatment delivery, the mean and median number of XVI CBCT operations realized during the treatment were 2 and 1 (range: 0-11). During the treatment, the prostate was outside the CTV-to-PTV margin (2 mm), thus necessitating the stoppage of the delivery +/- a reacquisition of the XVI CBCT for 11.2%, 8.9%, and 3.9% of the delivery time in the vertical, longitudinal, and lateral direction, respectively. We easily integrated an EM-transmitter-based gating for prostate LINAC-based SBRT into our normal daily workflow. Using this system, a 2 mm CTV-to-PTV margin could be safely applied. A small number of fractions showed a motion exceeding the predefined 2 mm threshold, which would have otherwise gone undetected without intrafraction motion management.

Linac-based versus MR-guided SBRT for localized prostate cancer: a comparative evaluation of acute tolerability.

This study aims to compare acute toxicity of prostate cancer (PCa) stereotactic body radiotherapy (SBRT) delivered by MR-guided radiotherapy (MRgRT) with 1.5-T MR-linac or by volumetric modulated arc (VMAT) with conventional linac. Patients with low-to-favorable intermediate risk class PCa were treated with exclusive SBRT (35Gy in five fractions). Patients treated with MRgRT were enrolled in an Ethical Committee (EC) approved trial (Prot. n° 23,748), while patients treated with conventional linac were enrolled in an EC approved phase II trial (n° SBRT PROG112CESC). The primary end-point was the acute toxicity. Patients were included in the analysis if they had at least 6months of follow-up for the primary end-point evaluation. Toxicity assessment was performed according to CTCAE v5.0 scale. International Prostatic Symptoms Score (IPSS) was also performed. A total of 135 patients were included in the analysis. Seventy-two (53.3%) were treated with MR-linac and 63 (46.7%) with conventional linac. The median initial PSA before RT was 6.1ng/ml (range 0.49-19). Globally, acute G1, G2, and G3 toxicity occurred in 39 (28.8%), 20 (14.5%), and 5 (3.7%) patients. At the univariate analysis, acute G1 toxicity did not differ between MR-linac and conventional linac (26.4% versus 31.8%), as well as G2 toxicity (12.5% versus 17.5%; p = 0.52). Acute G2 gastrointestinal (GI) toxicity occurred in 7% and 12.5% of cases in MR-linac and conventional linac group, respectively (p = 0.06), while acute G2 genitourinary toxicity occurred in 11% and 12.8% in MR-linac and conventional linac, respectively (p = 0.82). The median IPSS before and after SBRT was 3 (1-16) and 5 (1-18). Acute G3 toxicity occurred in two cases in the MR-linac and three cases in the conventional linac group (p = n.s.). Prostate SBRT with 1.5-T MR-linac is feasible and safe. Compared to conventional linac, MRgRT might to potentially reduce the overall G1 acute toxicity at 6months, and seems to show a trend toward a lower incidence of grade 2 GI toxicity. A longer follow-up is necessary to assess the late efficacy and toxicity.

Intrafraction Prostate Motion Management during Dose-Escalated Linac-Based SBRT

<h3>Purpose/Objective(s)</h3> This study reports the first clinical experience worldwide using a novel electromagnetic (EM) tracking device for intrafraction prostate motion management during dose-escalated Linac-based stereotactic body radiation therapy (SBRT). <h3>Materials/Methods</h3> Thirteen patients with organ-confined prostate cancer underwent dose-escalated SBRT using flattening filter-free (FFF) volumetric modulated arc therapy (VMAT). The prescribed dose was 40 Gy in 5 fractions or 38 Gy in 4 fractions. The EM tracking device consisted of an integrated Foley catheter with a transmitter. Patients were simulated and treated with a filled bladder and an empty rectum. Setup accuracy was achieved by ConeBeam-CT (CBCT) matching and the prostate motion was tracked during all the procedure. Treatment was interrupted when the signals exceeded a 2 mm threshold in any of the three spatial directions and, unless the offset was transient, target position was re-defined by repeating CBCT. Moreover, the displacements that would have occurred without any intrafraction organ motion management (i.e., no interruptions and repositionings) were simulated and analyzed. <h3>Results</h3> In 31 out of 56 monitored fractions (55%), no intervention was required to correct the target position as a result of an excessive displacement. In 25 (45%) a correction was mandated, but only in 10 (18%), the beam delivery was interrupted. Total treatment time lasted on average 10.2 minutes, 6.7 minutes for setup, and 3.5 minutes for beam delivery. The prostate was found inside the 2 mm threshold from its initial position in 96% of the treatment time, i.e., in 94% of the time during the setup, and in 98% during the delivery (beam on + interruptions). Without any intrafraction motion management, the overall mean treatment time and the mean delivery time would have been 6.9 minutes and 3.2 minutes, respectively. The prostate would have been found outside the tolerance in 8% of the total session time, in 4% of the time during the setup, and in 14% during the beam-on phase. The probability of motion > 2 mm in the lateral, longitudinal, and vertical direction after 5 minutes was 3.6% (2/56), 8.9% (5/56), and 14.3% (8/56), respectively. The predominant motion pattern was posterior with a mean motion ≤ 2 mm occurring within 10 minutes. Moreover, the analysis of the rotation angles from all patients showed a systematic rotation in the pitch axis which is absent in the yaw axis. Concurrently, the range and standard deviation of rotation angles were larger in the pitch axis. <h3>Conclusion</h3> EM real-time tracking was successfully implemented for intrafraction motion management during dose-escalated prostate SBRT. Results showed that most of the observed displacements were < 2 mm in any direction; however, there were a non-insignificant number of fractions with motion exceeding the predefined threshold, which would have otherwise gone undetected without intrafraction motion management.

Dosimetric Comparison of Supine vs. Prone Position Utilizing Traditional Linac-Based Stereotactic Body Radiation Therapy for Accelerated Partial Breast Irradiation

<h3>Purpose/Objective(s)</h3> Our institution recently completed a pilot trial using stereotactic body radiation therapy (SBRT) for accelerated partial breast irradiation (APBI) on a traditional Linac delivering 30 Gy in 5 fractions. In this study, we compared dosimetry of patients treated in supine versus prone positions. <h3>Materials/Methods</h3> Patients enrolled on our recent pilot trial and additional post-accrual patients using the same SBRT technique were included. All patients had early-stage breast cancer, met the APBI ASTRO suitability criteria, and were treated on a traditional Linac. Treatment position, breast laterality and volume, BMI, and organs at risk (OAR) dosimetry were recorded. Prone treatments were delivered on a prone breast board using sliding window IMRT, and supine plans used either IMRT or partial arcs. All prone and 15 of 18 supine plans used free breathing technique (3 utilized deep inspiration breath-hold). CTV was 1 cm expansion from GTV. PTV was a 3 mm expansion from CTV and excluded skin surface+3 mm. Laterality was controlled for heart dosimetry. A small subset of patients was simulated in both supine and prone positions with associated radiation plans available for comparison. For unpaired data, unadjusted comparisons of means were performed using two-group t-test, and analysis of covariance was used for adjusted comparisons. For paired data, unadjusted comparisons were performed using the paired t-test, and adjusted comparisons used mixed models repeated measures analysis. Statistical tests were two-sided. <h3>Results</h3> This study included 35 patients with 36 treated plans. One patient had bilateral breast cancer. Of the 36 treated plans, 18 were supine (11 right-sided breast cancer, 7 left-sided) and 18 prone (8 right-sided, 10 left-sided). Eight patients had comparison plans in both positions. For patients with left-sided breast cancer, heart mean dose supine vs prone was 0.49 and 1.14 Gy, respectively (p < 0.001), and continued to be significant when controlling for BMI and treated breast volume. Mean heart dose was not different for right-sided patients supine vs prone, 0.36 vs 0.47 Gy, respectively (p = 0.870). Ipsilateral lung V1.5 Gy was higher for supine vs prone, 39.44 vs 29.89% (p=0.017). Max rib dose was higher for supine compared to prone, 28.29 vs 16.12 Gy (p<0.001). For the subset of patients with plans in both positions, mean heart dose continued to be lower for left-sided patients treated supine vs prone (p = 0.001). Ipsilateral lung V1.5 Gy and max dose to ribs were lower for prone with p values of 0.003 and <0.001, respectively. <h3>Conclusion</h3> Supine treatment provided heart dosimetry benefit for left-sided breast cancer patients compared to prone. Benefit was independent of BMI and breast volume. Prone position offered lower dose to ipsilateral lung and ribs. The results from this study can help determine the best treatment position based on patient-specific OAR concerns.

Intrafraction Prostate Motion Management During Dose-Escalated Linac-Based Stereotactic Body Radiation Therapy.

BackgroundExtreme hypofractionation requires tight planning margins, high dose gradients, and strict adherence to planning criteria in terms of patient positioning and organ motion mitigation. This study reports the first clinical experience worldwide using a novel electromagnetic (EM) tracking device for intrafraction prostate motion management during dose-escalated linac-based stereotactic body radiation therapy (SBRT).MethodsThirteen patients with organ-confined prostate cancer underwent dose-escalated SBRT using flattening filter-free (FFF) volumetric modulated arc therapy (VMAT). The EM tracking device consisted of an integrated Foley catheter with a transmitter. Patients were simulated and treated with a filled bladder and an empty rectum. Setup accuracy was achieved by ConeBeam-CT (CBCT) matching, and motion was tracked during all the procedure. Treatment was interrupted when the signals exceeded a 2 mm threshold in any of the three spatial directions and, unless the offset was transient, target position was re-defined by repeating CBCT. Moreover, the displacements that would have occurred without any intrafraction organ motion management (i.e. no interruptions and repositionings) were simulated.ResultsIn 31 out of 56 monitored fractions (55%), no intervention was required to correct the target position. In 25 (45%) a correction was mandated, but only in 10 (18%), the beam delivery was interrupted. Total treatment time lasted on average 10.2 minutes, 6.7 minutes for setup, and 3.5 minutes for beam delivery. Without any intrafraction motion management, the overall mean treatment time and the mean delivery time would have been 6.9 minutes and 3.2 minutes, respectively. The prostate would have been found outside the tolerance in 8% of the total session time, in 4% of the time during the setup, and in 14% during the beam-on phase. Predominant motion pattern was posterior and its probability increased with time, with a mean motion ≤ 2 mm occurring within 10 minutes.ConclusionsEM real-time tracking was successfully implemented for intrafraction motion management during dose-escalated prostate SBRT. Results showed that most of the observed displacements were < 2 mm in any direction; however, there were a non-insignificant number of fractions with motion exceeding the predefined threshold, which would have otherwise gone undetected without intrafraction motion management.

Association of pretreatment CA19-9 with survival after 3-fraction SBRT for locally advanced pancreatic cancer: Results from a phase I dose-escalation trial.

613 Background: The optimal dose and fractionation scheme for stereotactic body radiotherapy (SBRT) is unknown. The biologic effects of ultra-high doses per fraction (&gt;8Gy) are theoretical, but may include eliciting an effect on the endothelial cells of the tumor vasculature which could improve treatment response. This study aimed to determine the safety and maximally tolerated dose of 3-fraction SBRT for locally advanced pancreatic cancer (LAPC). Methods: A multi-site phase 1 dose escalation trial was conducted from March 2016 to April 2019 at Memorial Sloan Kettering Cancer Center (NCT02643498) and University of Colorado (NCT02873598). Patients with localized histologically confirmed pancreatic adenocarcinoma deemed unresectable on multidisciplinary review without distant progression following induction chemotherapy for ≥ 2 months were eligible. Patients received 3-fraction LINAC-based SBRT at 3 dose levels, 27Gy, 30Gy and 33Gy following a modified 3+3 design, allowing for enrollment of additional patients at the last dose level during the 90-day observation period, provided no dose-limiting toxicities (DLTs) were observed. DLTs were defined as ≥ Grade 3 treatment-related GI toxicity within 90 days of RT by CTCAE v.4. The secondary endpoints were overall survival (OS), local progression-free and distant metastasis-free survival (LPFS and DMFS, respectively). Univariate analysis using log-rank test was performed to identify factors associated with OS. Results: Twenty-three evaluable patients were enrolled, including 8 patients at 27Gy, 8 patients at 30Gy and 7 patients at 33Gy. The median age was 67 years (range 52 - 79), 9 patients (39%) were male, all were stage IIIwith a median tumor size of 3.5cm (range, 1.0 - 6.4) and CA19-9 of 60U/mL (range, &lt;1 - 4880). All received chemotherapy for a median of 4.0 months (range 2.5 -11.4). There were no grade ≥ 3 abdominal pain, dyspepsia, diarrhea, nausea, vomiting, or gastrointestinal hemorrhage. Four patients underwent resections (pancreaticoduodenectomy=3, Appleby=1). Twelve-month rates of OS, DMFS and LPFS were 45.8 %, 37.7% and 53.0%, respectively. On univariate analysis, CA19-9 (HR=0.2365, 95%CI 0.07999 to 0.6990), but not dose level, size, N stage, tumor location, duration of chemotherapy were associated with OS. Twelve-month OS for patients with CA19-9 ≤ 60U/mL vs &gt; 60U/mL were 80% vs 27% (p=0.0023). Conclusions: For select LAPC patients, dose escalation to the target dose of 33Gy in 3 fractions resulted in no DLTs and disease outcomes comparable to conventional RT. Lower pre-SBRT CA19-9 values were associated with improved OS and could help identify patients most likely to benefit from local therapies. Continued exploration of (ultra)hypofractionated schemes to maximize tumor control while enabling efficient integration of RT with systemic therapy is warranted. Clinical trial information: NCT02643498/NCT02873598.

Phase I Dose Escalation Trial Using 3-Fraction SBRT for Locally Advanced Pancreatic Cancer

This prospective multi-institutional study aimed to determine the safety and maximally tolerated dose of 3-fraction stereotactic body radiotherapy (SBRT) for locally advanced pancreatic cancer (LAPC).Patients with localized, histologically confirmed pancreatic adenocarcinoma deemed unresectable on radiographic multidisciplinary review without distant progression following induction chemotherapy for at least 2 months were eligible. Patients received 3-fraction LINAC-based SBRT at 3 dose levels, 27Gy, 30Gy and 33Gy following a modified 3+3 design, allowing for enrollment of additional patients at the last dose level during the 90-day observation period, provided no dose-limiting toxicities (DLTs) were observed. DLTs were defined as ≥ Grade 3 treatment-related GI toxicity within 90 days of RT as scored by CTCAE v.4. The secondary endpoints were overall survival (OS), local progression-free and distant metastasis-free survival (LPFS and DMFS, respectively), treatment-related toxicity and quality of life.Between 3/2016 and 4/2019, 23 consecutive evaluable LAPC patients were enrolled at two academic hospitals (14 and 9 patients, respectively), including 8 patients at 27Gy, 8 patients at 30Gy and 7 patients at 33Gy. The median age was 67 years (range 52 - 79 years), 9 patients (39%) were male, all were stage III, 12 (52%) had a head/uncinate tumor location, with a median tumor size of 3.5cm (range, 1.0 - 6.4cm) and a median CA19-9 of 60U/mL (range, < 1 - 4880U/mL). All received chemotherapy for a median of 4.0 months (range 2.5 -11.4 months). There was no grade ≥ 3 abdominal pain, dyspepsia, diarrhea, nausea, vomiting, or gastrointestinal hemorrhage. Four patients experienced grade ≥3 hematologic or metabolic adverse events not related to RT. Four patients underwent resections (pancreaticoduodenectomy = 3, Appleby = 1). Two-year rates of LPFS, DMFS and OS were 26.5%, 25.1% and 29.2%, respectively.For select LAPC patients, dose escalation to the target dose of 33Gy in 3 fractions resulted in no DLTs and disease outcomes comparable to conventional RT. These results warrant further exploration of hypofractionated SBRT schemes to maximize tumor control while enabling efficient integration of RT with systemic therapy for more expedient treatment options for these high-risk LAPC patients.

PO-1256: Feasibility and initial results of Linac-based Stereotactic Body Radiotherapy in spinal metastases

PO-1256: Feasibility and initial results of Linac-based Stereotactic Body Radiotherapy in spinal metastases

Thoracic Reirradiation with Stereotactic Body Radiation Therapy (SBRT) for Recurrent Advanced Non-Small Cell Lung Cancer (NSCLC)

Locoregional failure is common among patients with advanced non-small cell lung cancer (NSCLC) treated with definitive chemoradiation +/- immunotherapy, and palliative systemic therapy is the most common treatment for locoregional failure. SBRT with ≤5 fractions have been described for small volume local recurrences, but may not be amenable to recurrences that are large or centrally located near critical structures. The purpose of this study is to evaluate the safety and efficacy of hypofractionated RT with 60 Gy in 8 using SBRT treatment techniques as salvage therapy for local failure for patients with advanced NSCLC previously treated with external beam radiation therapy (EBRT). Between July 2013 and February 2020, 5 patients were re-irradiated with SBRT of 60 Gy in 8 fractions for recurrence in the lung parenchyma after previous EBRT delivered to the same site. Patients with lymph node recurrence were excluded from analysis. Internal target volume (ITV) was created on 4D-CT with +0.5cm uniform margin to create the planning target volume (PTV). LINAC-based SBRT was delivered on non-consecutive days. Toxicity was assessed by CTCAE v5.0. Median follow-up from re-irradiation was 36 months (5.9 – 55.3 months). Median age was 67 years (range, 63 – 80 years), with KPS > 70. Patients were previously treated with a median dose of 60 Gy in median number of 30 fractions (59.4 – 66 Gy in 30 – 33 fractions). Median time to re-irradiation was 15 months (7.3 – 28.6 months). Median re-treated tumor size was 4.8 cm, with median re-treated ITV of 58.3 cc (18.3 – 344.6 cc) and median re-treated PTV of 121.3 cc (44.3 – 506.9 cc). Local control was 100%, and 60% patients remained free of any progression of disease at time of analysis. All patients remain alive at follow-up. One patient experienced grade 3 rib fracture as late toxicity for a chest wall invasive recurrence. Our institutional experience shows that SBRT-like 60 Gy in 8 fractions appears to be a safe and effective means of salvaging recurrent advanced NSCLC that was previously irradiated.Abstract 2415; TablePatient NumberInitial StageTime to re-irradiation (months)ITV of re-irradiation (cc)PTV of re-irradiation (cc)Follow-up after re-irradiation (months)Disease StatusAdditional treatment rendered1IIB, T3 N0 M07.3133.822918.1Locally controlled but metastatic disease in spinePembrolizumab and SBRT to oligometastatic adrenal gland2IIIA, T4 N0 M011.657.9113.655.3No evidence of diseaseNone3Recurrence at suture line after wedge resection for IA128.658.3121.350.3Locally controlled but metastatic disease in bilateral lungs, adrenal, and ribCarboplatin, Pemetrexed, and Pembrolizumab followed by SBRT to 3 oligoprogressive lung metastases and maintenance Pemetrexed/Pembrolizumab4IIIA, T2a N2 M018.3344.6506.936.0No evidence of diseaseNone5IIIB, T3 N2 M015.018.344.35.9No evidence of diseaseNone Open table in a new tab

Linac-based stereotactic body radiation therapy for low and intermediate-risk prostate cancer : Long-term results and factors predictive for outcome and toxicity.

Stereotactic body radiation therapy (SBRT) is considered an effective and safe treatment in patients with low- and intermediate-risk prostate cancer (PC). However, due to alack of long-term follow-up and late toxicity data, this treatment is not universally accepted. The present study aimed to evaluate outcome and early and late toxicity in acohort of patients with low- and intermediate-risk PC treated prospectively with linear accelerator (linac)-based SBRT. Patients with low- or intermediate-risk (NCCN criteria) PC were included. All patients received linac-based SBRT to 35 Gy in 5fractions delivered on alternate days. Endpoints were toxicity, biochemical relapse-free survival (BRFS), metastatic progression-free survival (mPFS), and overall survival (OS). From 2012 to 2018, 178 patients were treated. Median baseline prostate-specific antigen (iPSA) was 6.37 ng/ml (range 1.78-20). Previous transurethral resection of the prostate (TURP) was present in 23 (12.9%) patients. Median follow-up was 58.9 months (range 9.7-89.9). BRFS rates at 1, 3, and 5years were 98.3 (95% confidence interval, CI, 94.7-99.4%), 94.4 (95%CI 89.4-97), and 91.6% (95%CI 85.4-95.2), respectively. In univariate analysis, performance status (PS), iPSA, and nadir PSA (nPSA) were correlated with BRFS. In multivariable analysis iPSA and nPSA remained significant. BRFS rates at 5years were 94.9% (95%CI 86.8-98) for International Society of Urological Pathology (ISUP) grade group1, 93.2% (95%CI 80.5-97.7) for ISUP group2, and 74.8% (95%CI 47.1-89.5) for ISUP group3. At 1, 3, and 5years, mPFS rates were 98.8 (95%CI 95.5-99.7), 96.2 (95%CI 91.9-98.3), and 92.9% (95%CI 87.2-96.2), respectively; OS rates were 100, 97.2 (95%CI 92.9-98.9), and 95.1% (95%CI 90-97.6), respectively. One (0.56%) case of grade3 acute genitourinary (GU), one case of acute gastrointestinal (GI), and one case of grade3 late GU toxicity were observed. GI toxicity positively correlated with prostate volume. At long-term follow-up, linac-based SBRT continues to be avalid option for the management localized PC. Biochemical control remains high at 5years, albeit with some concerns regarding the optimal schedule for unfavorable intermediate-risk PC. Considering the excellent prognosis, patient selection is crucial for prevention of severe late toxicity.

The Use of High-Volume Endorectal Balloon is Effective to Reduce Doses of Rectum and Bladder in Prostate Cancer Patients Treated with Linac-Based Stereotactic Body Radiotherapy

The Use of High-Volume Endorectal Balloon is Effective to Reduce Doses of Rectum and Bladder in Prostate Cancer Patients Treated with Linac-Based Stereotactic Body Radiotherapy

The First Linac-based Stereotactic Body Radiation Therapy (SBRT) in Iran: A Case Study

Introduction: In this paper, we present the first experience of linac-based stereotactic body radiation therapy (SBRT) in Iran to treat a single liver metastasis. Case Presentation: A 23-year-old girl with a history of visceral melanoma of the uterine was treated for liver metastasis. Stereotactic body radiotherapy was selected as the treatment of choice after tumor recurrence following surgical removal and radiofrequency ablation. The treatment was delivered in five fractions to a total dose of 50 Gy. The patient tolerated the treatment without any considerable side effect and the lesion remained progression-free twelve months after treatment. Conclusions: It can be presumed that SBRT can be safely applied using IGRT-equipped conventional linear accelerators with a few but no adverse events if it is delivered with due consideration.

Feasibility and preliminary clinical results of linac-based Stereotactic Body Radiotherapy for spinal metastases using a dedicated contouring and planning system

BackgroundStereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) are well established local treatment approaches in several cancer settings. Although SBRT is still under investigation for spinal metastases, promising results in terms of a high effectiveness and optimal tolerability have been recently published on this topic. For spinal SBRT, one of the most relevant issues is represented by the inter-observer variability in target definition. Recently, several technological innovations, including specific tools such as multimodality-imaging (computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET-CT), automated volumes contouring and planning, could allow clinicians to minimize the uncertainties related to spinal SBRT workflow. Aim of this study is to report the feasibility of the clinical application of a dedicated software (Element®, Brainlab™ Germany) for spinal metastases SBRT.Material and methodThe patient selection criteria for SBRT in spinal metastases were the following: age > 18 years, diagnosis of spinal metastases (n ≤ 3), life expectancy > 3 months, controlled primary tumor or synchronous diagnosis and Spinal Instability Neoplastic Score (SINS) ≤ 12 points. All radiation target volumes were defined and planned with the support of the dedicated software Elements® (Brainlab™ Germany). Different dose prescription have been used: 12 Gy in single fraction, 12 Gy, 18 Gy, 21 Gy and 24 Gy in 3 fractions. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. SPSS version 20 was used for statistical analysis.ResultsFrom April 2018 to April 2019, 54 spinal metastases in 32 recruited patients were treated with Linac-based SBRT. With a median follow-up of 6 months (range 3–12), local control rates at 6 months and 9 months were 86 and 86%, respectively. No adverse events ≥3 grade were observed.ConclusionsThis preliminary experience shows that with respect to acute toxicity and early clinical response, linac-based using Elements® Spine SRS is a feasible and effective approach.

Linac-based stereotactic body radiation therapy vs moderate hypofractionated radiotherapy in prostate cancer: propensity-score based comparison of outcome and toxicity.

Prostate cancer represents the second most common malignancy in the world and majority of patients have diagnosis of localized disease. The aim of the present study was to compare two cohorts of patients treated with moderate hypofractionation (MHRT) or stereotactic body radiation therapy (SBRT). We included patients treated between 2010 and 2015. Inclusion criteria were: adenocarcinoma of the prostate; class risks low or intermediate; WHO performance status 0-2. We evaluated rectal, gastrointestinal toxicity and genitourinary. Measures of outcome were biochemical disease-free survival and overall survival. Propensity score was used to approximate the balance in covariates. 209 patients were included, treated with MHRT (n = 109) or SBRT (n = 100). Median follow-up time was 37.4 months. Rates of biochemical disease-free survival at 1- and 3 years were 100 and 95%, respectively. There was no significant difference between the two groups (p = 0.868). Rates of overall survival at 1- and 3 years were 100 and 97.1%, respectively with no differences between the two groups (p = 0.312). After propensity scoring matching, no differences were observed in terms of acute and late rectal and gastrointestinal toxicity. While mild genitourinary side-effects were more common in SBRT group (45.5% vs 19.5 %), Grade 2 and 3 toxicity was increased after MHRT (11.7% vs 2.6 %; p = 0.029). Moderate hypofractionation and SBRT are two effective and safe options for the treatment of low- and intermediate-risk prostate cancer. The analysis showed no difference in terms of disease's control and survival but increased moderate and severe toxicity after MHRT. Moderate hypofractionation and SBRT are comparable in terms of efficacy while moderate and severe toxicity is more common in the first one.

Pattern of recurrence after CyberKnife stereotactic body radiotherapy for peripheral early non-small cell lung cancer.

The treatment efficacy after CyberKnife stereotactic body radiotherapy (SBRT) have not been adequately addressed. The purpose of this study was to investigate pattern of recurrence according to irradiation field after CyberKnife SBRT for early-stage non-small cell lung cancer (NSCLC). This retrospective study included patients with peripheral cT1/2N0M0 NSCLC that was treated with SBRT using a CyberKnife between May 2013 and March 2016 at single institute and followed up by more than two imaging examinations. Both operable and inoperable patients were included. Overall survival (OS) and progression-free survival (PFS) curves were estimated using the Kaplan-Meier method with 95% confidence intervals (CI). Cumulative incidence curves of recurrence were calculated and compared using the Gray's test. Total 71 patients were included and analyzed in this study. The median follow-up period for surviving patients was 34 months (range, 7-64 months). The 2-year OS and PFS rate were 93% (95% CI: 83-97%) and 77% (95% CI: 65-86%), respectively. The 2-year cumulative incidence rate of infield recurrence and out-of-field recurrence were 6% (95% CI: 2-14%) and 17% (95% CI: 9-27%), respectively. Gross tumor volume (GTV) ≥9 mL and diagnosis-to-treatment interval (DTI) ≥90 days were significantly associated with infield recurrence (P<0.001 and P=0.007), and epidermal growth factor receptor (EGFR) mutation was significantly associated with out-of-field recurrence (P=0.014). Treatment efficacy after CyberKnife SBRT for peripheral early-stage NSCLC was identical to previous conventional linac-based SBRT reports. With short follow-up period, it was found that GTV and DTI were the significant predictive factor of infield recurrence, and EGFR mutation was the significant predictive factor of out-of-field recurrence.

Stereotactic Body Radiation Therapy (SBRT) for Hepatocellular Carcinoma: High Rates of Local Control With Low Toxicity.

Stereotactic body radiotherapy (SBRT) is potentially curative treatment for small hepatocellular carcinomas (HCC), but data are limited on its efficacy and toxicity. We hypothesized that SBRT can achieve excellent local control (LC) with acceptable toxicity treating HCC lesions, even in advanced cirrhosis. Thirty-seven nonmetastatic HCC patients received SBRT to 43 lesions between October 2012 and April 2016. Median dose was 50 Gy/5 fractions. All Child-Pugh (CP) ≥B patients underwent a planned 1-month break after the first 3 fractions to assess hepatic toxicity. Patients were treated without separately placed fiducial markers using Linac-based SBRT with breath-hold (67%) or 4D-computed tomography with compression belt (33%) to reduce motion. Patients underwent magnetic resonance imaging q3 months post-SBRT. Median age was 65 (range, 44 to 88). Pre-SBRT mean CP was 6.4 (range, A5 to C11). Nine (24%) had CP≥B8. Thirty-one of 33 patients (93%) had prior liver-directed therapy (median 2). Seventeen (40%) had solitary lesions. Median lesion diameter was 2.7 cm (range, 1.1 to 5.6). Median follow-up was 14 months (range, 2 to 45). There was 1 local failure (multifocal HCC with 3 prior transarterial chemoembolization). LC, freedom from liver progression, and overall survival at 12 months was 95%, 66%, 87% in the full cohort, and 100%, 76%, 93% for patients with solitary lesions. Four had grade 3 toxicity (ascites [n=2]/gastrointestinal bleed [n=1]/capsular pain [n=1]). Eight of 9 CP≥B8 patients had no grade ≥3 hepatic toxicity. SBRT for HCC is well-tolerated even in patients with advanced cirrhosis and prior liver-directed treatment and provides excellent LC even for larger lesions that cannot be controlled with radiofrequency ablation. LC with SBRT compares favorably to other liver-directed therapies. Prospective studies comparing SBRT with other liver-directed therapies are warranted.

Clinical Outcomes Using Magnetic Resonance-Guided Stereotactic Body Radiation Therapy in Patients with Locally Advanced Cholangiocarcinoma

Previous studies demonstrate that stereotactic body radiation therapy (SBRT) increases local control for cholangiocarcinoma, but gastrointestinal toxicity resulting from treatment remains a concern. Our previous published experience of 31 cholangiocarcinoma patients definitively treated with SBRT using Linac reported a median overall survival (OS) of 15.7 months, 1-year OS of 59%, and 1-year local control of 78% (Sandler, https://doi.org/10.1016/j.adro.2016.10.008). Six patients (19%) in this series suffered severe toxicities. SBRT using magnetic resonance-guided radiation therapy (MRgRT) may improve the therapeutic index of treatment for cholangiocarcinoma patients. Seventeen consecutive patients with cholangiocarcinoma were treated with SBRT using MRgRT between May 2015 and August 2017 with a median follow-up time of 8.8 months. Twelve patients presented with extrahepatic cholangiocarcinoma and five patients with intrahepatic tumors, with two patients treated for locally recurrent cholangiocarcinoma. SBRT was administered at a median dose of 40 Gy in 5 fractions. Notably, one patient received concurrent hyperthermia, and one patient received an SBRT boost after IMRT. Clinical efficacy was retrospectively analyzed, with survival curve analysis performed by the Kaplan-Meier method; treatment toxicities were graded according to the designations outlined in the CTCAE V4.0. Acute and late toxicities were defined using a cutoff of 90 days from completion of radiation therapy. The median OS was 18.2 months, with a 1-year OS of 86.7%. The median progression-free survival (PFS) was 6.6 months, with a 1-year PFS of 41.6%. Three of the 17 patients progressed locally, yielding a median local control time of 16.2 months and 1-year local control of 80.8%. 12 of 17 patients experienced an acute grade 1 toxicity, with mild nausea and fatigue accounting for 80% of toxicities. No grade 2 acute toxicities were experienced; however, one patient suffered a grade 3 duodenal ulcer with perforation (6%). Only one patient had a latent radiation-related toxicity – grade 2 gastritis/colitis; no other latent toxicities occurred. Our findings using MRgRT for cholangiocarcinoma patients demonstrate excellent overall survival while maintaining rates of local control comparable with the outcomes of our previous retrospective study of 31 cholangiocarcinoma patients using Linac-based SBRT. Treatment delivered through MRgRT resulted in one grade 3 toxicity (6%), while the Linac study determined that six patients (19%) suffered severe toxicities with the same median radiation dose and fractionation. Our clinical outcomes, coupled with a diminished toxicity profile, suggest SBRT using MRgRT is a promising new treatment approach.

Marginal Failures with Stereotactic Body Radiation Therapy(SBRT) for Early Stage Lung Cancer: Room for Improvement?

SBRT is an effective treatment for early stage non-small cell lung cancer (NSCLC). Prior series distinguish local from regional/distant recurrences, but detailed patterns of local failure are not well-described. We evaluate the location of local failures to provide further insight for treatment planning. Patients treated with SBRT for T1-2N0 NSCLC from 2007-2016 at a single institution were included. Prescribed dose was 48-54Gy in 3 to 5 fractions and planning target volume (PTV) margins were generally 5mm radially and 8mm superior/inferior. Site of first failure was classified as local, regional (hilar/mediastinal lymph nodes) or metastatic. For patients with a component of local failure, post-treatment diagnostic scans at time of recurrence were fused to the initial planning scan using rigid registration to lung features proximal to recurrence. The recurrence volume was delineated and compared to the treatment PTV. For each local failure, percent overlap of the PTV and recurrence volume was calculated. Distance from centroid (geometric center) of recurrence to PTV edge was measured in 3 planes and average distance was calculated. Local failures were categorized as: in-field failure (≥80% overlap or centroid >1cm inside PTV), marginal failure (20-80% overlap and centroid <1 cm inside/outside PTV), or involved lobe failure (overlap <20% or centroid >1cm outside PTV). Parametric statistics compared characteristics of recurrences. A total of 217 patients were treated with robotic radiosurgery (94%) or linac-based (6%) SBRT. 83% were T1 tumors, 69% upper lobe tumors, and 74% biopsy-proven malignancy. With a median follow-up of 20 months (range 0-98), 38% had progression of disease. 16% (N=34) had a component of local progression at time of first failure: 18 local only, 8 locoregional, 8 metastatic. 60% were pathologically confirmed. Of the local failures, 9 were classified as in-field, 15 marginal and 10 involved lobe. For in-field, marginal, and involved lobe failures there were differences in mean PTV/recurrence overlap (93% vs 43% vs 2%) and distance from centroid to PTV margin (1.39cm vs 0.56cm vs 1.78cm). For all local failures, PTV D95 was at least prescription dose. Marginal failures developed earlier than other local failures (mean 15 vs 25 months, p<0.05). Upper and lower lobe tumors had similar rates of local failure (16% vs 18%); however, 8 of the 11 local failures seen in lower lobe tumors were marginal failures compared to only 7 of 23 local failures in upper lobe tumors. Local progression is seen in roughly 16% of patients following SBRT. Marginal failures represent nearly half of these events, and appear to be of particular concern for lower lobe tumors. These findings highlight an opportunity to further evaluate margin size, motion management, and accuracy of dose calculations at the PTV margin to further improve local control in lung SBRT.

Safety and efficacy of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein

Background: To report the safety, efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Materials and methods: Seventy patients treated with Linac-based SBRT for HCC with PVTT between Dec 2015 and June 2017 were analyzed. SBRT was designed to target the tumor thrombosis and adjacent primary tumor (if it is feasible). Deliver a median total dose of 40Gy (range, 25-50Gy) in five fractions during one week. Fourty patients received TACE(1-5 cycles) followed SBRT. Three patients received operation followed SBRT. Results: The median follow-up was 10 months. After six months of SBRT, assessments of PVTT response showed complete response(CR) in 2 of 26 (7.6%) patients, partial response(PR) in 15 (57.6%), progression disease(PD) in 6(23.0%),stable disease（SD）in 3 (11.5%), with an objective response rate of 65.2%. No treatment-related Grade 4/5 toxicity was seen within three months after SBRT. The one-year overall survival rate was 36.6%. The predictive factor associated with better survival was response to radiotherapy and SBRT followed by TACE. Conclusions: Linac-based SBRT is a safe and effective treatment option for PVTT in HCC. Prospective randomized controlled trials are warranted to validate the role of SBRT in these patients.