Course Of Stereotactic Body Radiotherapy Research Articles

Phase II Clinical Trial of Second Course of Stereotactic Body Radiotherapy for Spinal Metastases

Purpose: The optimal method for the second course of stereotactic body radiotherapy (SBRT) for spinal metastases remains poorly established. This single-center, single-arm, phase II trial was conducted to propose a safe and effective salvage spine SBRT. Methods: The patients initially treated with SBRT for spine-targeted protocol treatment, or for areas adjacent to the spine, were enrolled. The second SBRT dose was 30 Gy delivered in five fractions; the spinal cord dose constraint was 15.5 Gy at the maximum point dose. The brachial or lumbosacral plexuses were dose-constrained to <30 Gy if the boundary between the nerves and tumors was detected. The primary endpoint was dose-limiting toxicity (DLT) (grade ≥ 3 severe radiation-related toxicity) within a year after the second SBRT. Results: The second SBRT was administered to the same spinal level in 12 patients and to an adjacent spinal level in 8 patients. SBRT2 was performed for 14 painful lesions, 10 MESCC, and 6 oligometastases, with some lesions having multiple indications. The median interval between SBRT sessions was 21 months (range: 6–51 months). The median follow-up duration was 14 months. No radiation myelopathy or local failure was reported during the follow-up period. DLT was confirmed in two patients (10%) within a year, both of whom developed grade 3 lumbosacral plexopathy. These two patients received SBRT twice to the S1–2 and S1–5 vertebrae, respectively, and both experienced paralysis of the tibialis anterior muscle (L5 level). Grade 3 late adverse effects (including lumbosacral plexopathy and vertebral compression fracture) were observed in 25% of the patients throughout the entire follow-up period. Conclusions: The second spine SBRT achieved good local control without causing myelopathy. However, one-quarter of the patients experienced grade 3 late adverse effects, suggesting that the treatment protocol carries a risk of toxicity.

Safety and Efficacy of Stereotactic Body Radiation Therapy for Ultra-central Thoracic Tumors: A Single Center Retrospective Review

Purpose/Objective(s)We sought to evaluate the toxicity and efficacy of stereotactic body radiotherapy (SBRT) for ultra-central thoracic tumours at our institution. Materials/MethodsPatients with ultra-central lung tumours or nodes, defined as having the planning target volume (PTV) overlapping or abutting the central bronchial tree and/or esophagus, treated at our institution with SBRT between 2009 and 2019 were retrospectively reviewed. All SBRT plans were generated with the goal of creating homogenous dose distributions. The primary endpoint was incidence of SBRT-related grade ≥3 toxicity, defined using the Common Terminology Criteria for Adverse Events (V5.0). Secondary endpoints included local failure (LF), progression-free survival (PFS) and overall survival (OS). Competing risk analysis was used to estimate incidence and identify predictors of severe toxicity and LF, while the Kaplan-Meier method was used to estimate PFS and OS. Results154 patients receiving 162 ultra-central courses of SBRT were included. The most common prescription was 50Gy in 5 fractions (42%), with doses ranging from 30-55Gy in 5 fractions (BED10 range 48-115Gy). The incidence of severe toxicity was 9.4% at 3 years. The most common severe toxicity was pneumonitis (n=4). There was 1 possible treatment related death from pneumonitis/pneumonia. Predictors of severe toxicity included increased PTV size, decreased PTV V95%, lung V5Gy, and lung V20Gy. The incidence of LF was 14% at 3 years. Predictors of LF included younger age, and greater volume of overlap between the PTV and esophagus. Median PFS was 8.8 months, while median OS was 44.0 months. ConclusionIn the largest case series of ultra-central thoracic SBRT to date, homogenously prescribed SBRT was associated with relatively low rates of severe toxicity and LF. Predictors of toxicity should be interpreted in the context of the heterogeneity in toxicities observed.

40 Gray in 5 Fractions for Salvage Reirradiation of Spine Lesions Previously Treated With Stereotactic Body Radiotherapy.

A retrospective single-center analysis of the safety and efficacy of reirradiation to 40 Gy in 5 fractions (reSBRT) in patients previously treated with stereotactic body radiotherapy to the spine was performed. We identified 102 consecutive patients treated with reSBRT for 105 lesions between 3/2013 and 8/2021. Sixty-three patients (61.8%) were treated to the same vertebral level, and 39 (38.2%) to overlapping immediately adjacent levels. Local control was defined as the absence of progression within the treated target volume. The probability of local progression was estimated using a cumulative incidence curve. Death without local progression was considered a competing risk. Most patients had extensive metastatic disease (54.9%) and were treated to the thoracic spine (53.8%). The most common regimen in the first course of stereotactic body radiotherapy was 27 Gy in 3 fractions, and the median time to reSBRT was 16.4 months. At the time of simulation, 44% of lesions had advanced epidural disease. Accordingly, 80% had myelogram simulations. Both the vertebral body and posterior elements were treated in 86% of lesions. At a median follow-up time of 13.2 months, local failure occurred in 10 lesions (9.5%). The 6- and 12-month cumulative incidences of local failure were 4.8% and 6%, respectively. Seven patients developed radiation-related neuropathy, and 1 patient developed myelopathy. The vertebral compression fracture rate was 16.7%. In patients with extensive disease involvement, reSBRT of spine metastases with 40 Gy in 5 fractions seems to be safe and effective. Prospective trials are needed to determine the optimal dose and fractionation in this clinical scenario.

Canine primary liver tumors treated with stereotactic body radiation therapy: A case series.

Stereotactic body radiation therapy (SBRT) is an increasingly used alternative treatment option for nonresectable hepatocellular carcinoma (HCC) in people. Comparatively, the publication of SBRT of dogs with HCC is limited. The objective of this retrospective, descriptive case series was to evaluate the clinical outcomes and toxicity data of SBRT in dogs with HCC and imaging-documented primary liver tumors using volumetric-modulated arc therapy delivery at two private institutions. Medical records of 14 dogs treated between 2018 and 2023 were reviewed. All dogs had macroscopic tumors, and 9 of 14 dogs had HCC diagnoses confirmed on cytology or histopathology. The median longest tumor diameter was 5.5cm. The median percentage of planning target volume relative to liver volume was 27.1%. Most dogs were treated with three daily fractions of 7-7.5Gy. All dogs completed their radiotherapy protocols. Three of nine HCC dogs experienced partial responses and clinical improvement. Five of nine HCC dogs had stable disease. Overall median survival time was 164 days for nine HCC dogs (range: 93-706 days). One late grade 5 liver and two late grade 3 kidney side effects were reported. One dog received repeated SBRT to the same HCC treatment field, and one dog had two courses of SBRT to bifocal HCC treatment fields, both with no more than grade 2 acute and chronic toxicities.

Clinical and Dosimetric Impact of 2D kV Motion Monitoring and Intervention in Liver Stereotactic Body Radiation Therapy

PurposePositional errors resulting from motion are a principal challenge across all disease sites in radiation therapy. This is particularly pertinent when treating lesions in the liver with stereotactic body radiation therapy (SBRT). To achieve dose escalation and margin reduction for liver SBRT, kV real-time imaging interventions may serve as a potential solution. In this study, we report results of a retrospective cohort of liver patients treated using real-time 2D kV-image guidance SBRT with emphasis on the effect of (1) clinical workflow, (2) treatment accuracy, and (3) tumor dose. Methods and MaterialsData from 33 patients treated with 41 courses of liver SBRT were analyzed. During treatment, planar kV images orthogonal to the treatment beam were acquired to determine treatment interventions, namely treatment pauses (ie, adequacy of gating thresholds) or treatment shifts. Patients were shifted if internal markers were >3 mm, corresponding to the PTV margin used, from the expected reference condition. The frequency, duration, and nature of treatment interventions (ie, pause vs shift) were recorded, and the dosimetric effect associated with treatment shifts was estimated using a machine learning dosimetric model. ResultsOf all fractions delivered, 39% required intervention, which took on average 1.9 ± 1.6 minutes and occurred more frequently in treatments lasting longer than 7 minutes. The median realignment shift was 5.7 mm in size, and the effect of these shifts on minimum tumor dose in simulated clinical scenarios ranged from 0% to 50% of prescription dose per fraction. ConclusionReal-time kV-based imaging interventions for liver SBRT minimally affect clinical workflow and dosimetrically benefit patients. This potential solution for addressing positional errors from motion addresses concerns about target accuracy and may enable safe dose escalation and margin reduction in the context of liver SBRT.

Survival, Treatment Outcome, and Safety of Multiple and Repeated Courses of Stereotactic Body Radiotherapy for Pulmonary Oligometastases of Head and Neck Squamous Cell Carcinoma.

Current literature regarding survival and treatment outcome of SBRT in patients with pulmonary oligometastatic head and neck squamous cell carcinoma (HNSCC) is limited. Additionally, most of the published studies include metastatic lesions deriving also from primaries with histologies other than SCC when investigating the outcome of SBRT. The aim of the present retrospective study is to explore local control (LC) of treated metastases, progression-free survival (PFS), and overall survival (OS) of exclusively pulmonary oligometastatic HNSCC-patients treated with SBRT. Between 2006 and 2021, a total of 46 patients were treated with SBRT for a maximum of four pulmonary oligometastases (PM) concurrently (mean PM per patient = 2.0; range 1 to 6 PM, total of 92). Of these, 17 patients (37.0%) developed new pulmonary metastases after their first SBRT. Repeated courses of SBRT were required once in 15 patients (88.2%) and twice in 2 patients (11.8%). Median follow-up was 17 months (range, 0-109 months). One year after completion of SBRT, LC rate, PFS, and OS were 98.7%, 37.9%, and 79.5%, respectively. After two years, LC rate, PFS, and OS were 98.7%, 28.7%, and 54.9%; as well as 98.7%, 16.7%, and 31.0% after five years. Radiochemotherapy (HR 2.72, p < 0.001) or radiotherapy as primary treatment (HR 8.60; p = 0.003), as well as reduced patient performance status (HR 48.30, p = 0.002), were associated with lower PFS. Inferior OS correlated with poor performance status (HR 198.51, p < 0.001) and surgery followed by radiochemotherapy (HR 4.18, p = 0.032) as primary treatment, as well as radiotherapy alone (HR 7.11, p = 0.020). Treatment of more than one PM is an independent predictor of impaired OS (HR 3.30, p = 0.016). SBRT of HNSCC-derived PMs results in excellent LC rates and encouraging OS rates of 54.9% at two years along with good tolerability (no more than grade 2 toxicities). Favourable outcome and low toxicity also apply to repeated courses of SBRT of newly emerging PMs.

Frequent Friers: Outcomes in Patients Who Receive Multiple Courses of Lung SBRT

Stereotactic body radiation therapy (SBRT) is a definitive therapy for early-stage non-small cell lung cancer and solitary pulmonary metastases with high tolerability and excellent survival rates. With longer survival and patients developing subsequent primaries or oligometastatic disease, patients are receiving multiple repeat lung SBRT courses. This study aims to assess safety and efficacy of high-frequency SBRT (HF-SBRT) to the lung, defined as >3 courses. A retrospective review was performed of patients who received >3 courses of lung SBRT. Logistic regression was performed to identify predictors of radiation pneumonitis (RP) and worsening pulmonary function (WPF). Local control (LC) and overall survival (OS) were evaluated using the Kaplan-Meier method. Ninety-four courses of HF-SBRT to the lung were identified among 28 patients. 78% of patients received 3 SBRT courses, 12% received 4 courses, and 7.1% received >5 courses. Median follow-up was 4.4 years. Median age at time of treatment was 73 years-old; 58% males; 42% had an underlying pulmonary comorbidity; 39% prior lung surgery; 52% history of cardiac disease; 52% prior tobacco use; median ECOG 0. Median SBRT dose was 48 Gy. Median interval between courses was 5.6 months. Zero patients experienced greater than grade 2 acute CTCAE v5 toxicity. 7.2% (7) of patients developed RP at median time of 2.6 months [IQR: 1.4,7.4]; grade 1: 3 patients, grade 2: 1 patient, grade 3: 2 patients. Of patients who developed RP, 42% (3) went on to receive further SBRT without experiencing significant adverse events (AEs). History of pulmonary disease, prior lung surgery, and history of tobacco use strongly correlated with WPF but not RP (WPF p-values: <0.001, 0.003, <0.001, respectively). History of cardiac disease did not correlate with WPF or RP. Receiving bilateral lung SBRT treatment (vs unilateral) trended towards correlation with WPF (p = 0.06) and RP (p = 0.08). Time between SBRT courses did not significantly differ for those who developed RP (p = 0.62) or WPF (p = 0.42). No individual or plan sum dosimetric constraint (GTV, PTV, unilateral lung V5, lung V10, lung V20, unilateral mean lung dose, or total lung V20) significantly differed in those who experienced RP. WPF correlated with the plan sum unilateral lung V10 (p = 0.05). LC at 1-year was 100%, 1 local failure occurred at 13 months; 2-year OS was 91.7%, median OS 5.4 years. Overall, HF-SBRT was well tolerated. Development of RP did not correlate with a specific individual or plan sum dosimetric parameter, with patients receiving subsequent courses of SBRT without increased AEs. WPF increasingly occurred with subsequent SBRT courses and correlated with unilateral plan sum V10. This study suggests that in appropriately selected patients, SBRT after RP can still be provided as definitive care, while further studies should validate this and focus attention on mitigating long-term WPF in patients who receive HF-SBRT.

Safety and Efficacy of Stereotactic Body Radiotherapy for Ultra-Central Thoracic Tumors

Stereotactic body radiotherapy (SBRT) is increasingly utilized in the management of ultra-central thoracic tumors, although concerns regarding significant toxicity remain. We sought to evaluate the toxicity and efficacy of SBRT to these tumors at our institution. Patients with ultra-central lung tumors or nodes treated at our institution with SBRT between 2009 and 2019 were retrospectively reviewed. Ultra-central was defined as having the planning target volume (PTV) overlapping or abutting the central bronchial tree and/or esophagus. All SBRT plans were generated with homogenous dose distributions using target coverage objectives of ITV V100% >99%, PTV V95% >99%, and an ideal PTV Dmax <105% (strict <120%). All plans were reviewed in quality assurance rounds by a team of dosimetrists, physicists, and radiation oncologists. The primary endpoint was incidence of severe toxicity (ST), defined as SBRT-related grade ≥3 toxicities, graded using the Common Terminology Criteria for Adverse Events V5.0. Secondary endpoints included local failure (LF), progression-free survival (PFS) and overall survival (OS). Competing risk analysis was used to estimate incidence and predictors of ST and LF, with death as a competing risk. Kaplan-Meier method was used to estimate PFS and OS. A total of 154 patients who received 162 ultra-central courses of SBRT were included, with a median follow-up of 21.5 months. Treatment intent was most commonly for oligoprogression (46%), oligometastasis (30%), followed by curative (20%). The most frequent tumor histologies were NSCLC (41%) and RCC (26%). SBRT prescription doses ranged from 30-55 Gy in 5 fractions (BED10 range 48-115 Gy). The most common prescription was 50 Gy in 5 fractions (42%). The cumulative incidence of ST was 8.9% at 3-years. The most common ST was pneumonitis (n = 4). Notable toxicities included bronchopleural fistula (n = 2, grade 3 and 4), bronchial stricture (n = 1, grade 3), and esophagitis leading to bleeding (n = 1, grade 4). There were no esophageal strictures or perforations, and no bronchial bleeds. There was 1 possible treatment related death from pneumonitis/pneumonia. Predictors of any ST included increased lung V5 Gy, decreased PTV V95%, and not having prior radiation therapy to the chest. The cumulative incidence of LF was 4.8%, 11% and 14% at 1-, 2-, and 3-years respectively. Predictors of LF included younger age, and greater volume of overlap between the PTV and esophagus. Median PFS was 8.4 months, while median OS was 3.7 years. In one of the largest case series of ultra-central thoracic SBRT reported to date, homogenously prescribed SBRT plans were associated with relatively low rates of ST and LF across a variety of treatment indications. Predictors of ST should be interpreted recognizing the heterogeneity in toxicities observed. Identified predictors of both ST and LF can contribute to future work to optimize the therapeutic ratio in treatment of ultra-central thoracic tumors.

Stereotactic Body Radiotherapy for Spine Oligometastases: A Multicentre Retrospective Study From the Italian Association of Radiotherapy and Clinical Oncology (AIRO)

AimTo evaluate the efficacy of stereotactic body radiotherapy (SBRT) for spine oligometastases. Materials and methodsThis was a multicentre retrospective study of a series of patients who received SBRT for spine oligometastases. The efficacy of SBRT was evaluated in terms of local control as the primary endpoint. Survival outcomes were also analysed to identify predictive factors for clinical outcomes. Toxicity was assessed according to CTCAE v4.0. ResultsBetween March 2018 and July 2022, 183 lesions in 177 patients were analysed. In most patients, SBRT was delivered to a single spine metastasis (82%) for a median total dose of 21 Gy (14–35 Gy) in three fractions (one to five fractions) and a median BED10 = 119 Gy (57.7–152 Gy). Local control rates were 90.3% at 1 year, 84.3% at 2 years and 84.3% at 3 years. Distant progression-free survival rates were 33.1%, 18.5% and 12.4% at 1, 2 and 3 years, with prostate histology (P = 0.023), oligorecurrent disease (P = 0.04) and BED10 > 100 Gy (P = 0.04) found to be predictive on univariate analysis. A further oligometastatic progression was observed in 33 patients (18.6%) treated with a second course of SBRT, reporting at univariate analysis improved overall survival rates (P = 0.01). Polymetastases-free survival rates were 57.8%, 43.4% and 32.4%; concurrent therapy was related to improved outcomes at multivariate analysis (P = 0.009). Overall survival rates were 91.8%, 79.6% and 65.9%, with prostate histology and non-cervical metastases related to better overall survival at multivariate analysis. Pain-flare after SBRT was recorded in 3.3%; five patients underwent surgical decompression after SBRT; there were no grade ≥3 adverse events. ConclusionsIn our experience of only oligometastatic patients, spine SBRT gave excellent results in terms of safety and efficacy. Prostate histology and oligorecurrent disease were predictive factors for improved clinical outcomes; also, patients who experienced a further oligoprogression after SBRT maintained a survival advantage compared with polymetastatic progression. No severe adverse events were reported.

Clinical and Dosimetric Risk Factors Associated With Radiation-Induced Lung Toxicities After Multiple Courses of Lung Stereotactic Body Radiation Therapy

Data are limited on radiation-induced lung toxicities (RILT) after multiple courses of lung stereotactic body radiation therapy (SBRT). We herein analyze a large cohort of patients to explore the clinical and dosimetric risk factors associated with RILT in such settings. A single institutional database of patients treated with multiple courses of lung SBRT between January 2014 and December 2019 was analyzed. Grade 2 or higher (G2+) RILT after the last course of SBRT was the primary endpoint. Composite plans were generated with advanced algorithms including deformable registration and equivalent dose adjustment. Logistic regression analyses were performed to examine correlations between patient or treatment factors including dosimetry and G2+ RILT. Risk stratification of patients and lung constraints based on acceptable normal tissue complication probability were calculated based on risk factors identified. Among 110 eligible patients (56 female and 54 male), there were 64 synchronous (58.2%; defined as 2 courses of SBRT delivered within 30 days) and 46 metachronous (41.8%) courses of SBRT. The composite median lung V20, lung V5, and mean lung dose were 9.9% (interquartile range [IQR], 7.3%-12.4%), 32.2% (IQR, 25.5%-40.1%), and 7.0 Gy (IQR, 5.5 Gy-8.6 Gy), respectively. With a median follow-up of 21.1 months, 30 patients (27.3%) experienced G2+ RILT. Five patients (4.5%) developed G3 RILT, and 1 patient (0.9%) developed G4 RILT, and no patients developed G5 RILT. On multivariable regression analysis, female sex (odds ratio [OR], 4.35; 95% CI, 1.49%-14.3%; P=.01), synchronous SBRT (OR, 8.78; 95% CI, 2.27%-47.8%; P=.004), prior G2+ RILT (OR, 29.8; 95% CI, 2.93%-437%; P=.007) and higher composite lung V20 (OR, 1.18; 95% CI, 1.02%-1.38%; P=.030) were associated with significantly higher likelihood of G2+ RILT. Our data suggest an acceptable incidence of G2+ RILT after multiple courses of lung SBRT. Female sex, synchronous SBRT, prior G2+ RILT, and higher composite lung V20 may be risk factors for G2+ RILT.

Sequential metastasis-directed therapy (MDT) for oligometastatic prostate cancer (Oligo PCa) assessed by PET-based imaging.

5032 Background: Prostate specific membrane antigen (PSMA) and F-18-Fluciclovine PET imaging have high sensitivity for the detection of prostate cancer (PCa) metastases. MDT with stereotactic body radiation therapy (SBRT) to PET-detected Oligo PCa has been shown to improve progression free survival (PFS) and delay androgen deprivation therapy (ADT). However, in those patients (pts) who ultimately develop oligoprogressive disease following MDT, the utility of subsequent courses of MDT has not been well defined. Methods: A single institution retrospective review was undertaken to describe outcomes following ≥2 courses of PET-guided SBRT in pts with Oligo PCa. Pts included in this analysis had undergone initial SBRT for ≤5 PCa lesions detected on PSMA or Fluciclovine PET, and subsequently underwent ≥1 additional course of SBRT at progression. Baseline data collected included stage, PSA level, Gleason Score, tracer type, and concurrent systemic therapy. Endpoints collected for each SBRT course included PSA decline ≥50% (PSA50), PFS, and systemic therapy change free survival (RxFS) (initiation of ADT, or for pts already on ADT, addition of an androgen signaling inhibitor). Association of factors with PFS after SBRT2 were analyzed using multivariable Cox proportional-hazards models. Results: 34 pts underwent ≥2 courses of MDT (SBRT1, SBRT2). At SBRT2, progression was identified by PSMA-PET in 26 (77%) pts, and by Fluciclovine-PET in 8 (23%). With SBRT2, 18 (53%) had a concurrent systemic therapy change; 10 (29%) did not receive any systemic therapy. 12 pts subsequently underwent SBRT3. Progression was detected by PSMA PET in 9 (75%) and Fluciclovine PET in 3 (25%). Clinical outcomes are summarized in the table. In the multivariable analysis, predictors associated with PFS following SBRT2 were 1) PSA decline at SBRT1 (HR 1.10, 95% CI 1.05-1.16, P&lt;0.001) and 2) PSA doubling time (PSADT) &lt; 12 months at the time of SBRT2 (HR 11.52, 95% CI 1.36-97.38, P 0.025). Overall, from SBRT1 to last follow-up (median 25.2 months), 23 (68%) pts remained ADT-free (14 after SBRT2; 9 after SBRT3). Conclusions: Serial MDT for Oligo PCa detected on PSMA or Fluciclovine PET is feasible and results in PSA declines, independent of change in systemic therapy. There is a persistent but diminishing benefit of MDT over successive courses. Overall, 2/3 of pts were able to postpone the use of ADT. PSA decline at SBRT1 and PSADT at SBRT2 may be biomarkers for SBRT2 benefit. Despite the retrospective nature of this study and cohort heterogeneity, these data provide a rationale for serial SBRT in Oligo PCA, and the need for larger, prospective studies of this strategy. [Table: see text]

Identifying predictors of on-table adaptation for pancreas stereotactic body radiotherapy (SBRT)

PurposeTo identify any clinical or dosimetric parameters that predict which individuals may benefit from on-table adaptation during pancreas stereotactic body radiotherapy (SBRT) with MRI-guided radiotherapy. Methods and materialsThis was a retrospective study of patients undergoing MRI-guided SBRTfrom 2016 to 2022.Pre-treatment clinical variables and dosimetric parameters on the patient’s simulation scan were recorded for each SBRT course, and their ability to predict for on-table adaptation was analyzed using ordinal logistic regression. The outcome measure was number of fractions adapted. ResultsSixty-three SBRT courses consisting of 315 fractions were analyzed. Median prescription dose was 40 Gy in five fractions (range, 33–50 Gy); 52% and 48% of courses were prescribed ≤40 Gy and >40 Gy, respectively. The median minimum dose delivered to 95% (D95) of the gross tumor volume (GTV) and planning target volume (PTV) was 40.1 Gy and 37.0 Gy, respectively. Median number of fractions adapted per course was three, with 58% (183 out of 315) total fractions adapted. On univariable analysis, the prescription dose (>40 Gy vs ≤40 Gy), GTV volume, stomach V20 and V25, duodenum V20 and dose maximum, large bowel V33 and V35, GTV dose minimum, PTV dose minimum, and gradient index were significant determinants foradaptation (all p < 0.05). On multivariable analysis, only the prescription dose was significant (adjusted odds ratio 19.7, p = 0.005), but did not remain significant after multiple test correction (p = 0.08). ConclusionsThe likelihood of needing on-table adaptation could not be reliably predicted a priori using pre-treatment clinical characteristics, dosimetry to nearby organs at risk, or other dosimetric parameters based on the patient’s anatomy at the time of simulation, suggesting the critical importance of day-to-day variations in anatomy and increasing access to adaptive technology for pancreas SBRT. A higher (ablative) prescription dose was associated with increased use of adaptation.

Linac-based stereotactic salvage reirradiation for intraprostatic prostate cancer recurrence: toxicity and outcomes

BackgroundThe rates of local failure after curative radiotherapy for prostate cancer (PC) remain high despite more accurate locoregional treatments available, with one third of patients experiencing biochemical failure and clinical relapse occurring in 30–47% of cases. Today, androgen deprivation therapy (ADT) is the treatment of choice in this setting, but with not negligible toxicity and low effects on local disease. Therefore, the treatment of intraprostatic PC recurrence represents a challenge for radiation oncologists. Prostate reirradiation (Re-I) might be a therapeutic possibility. We present our series of patients treated with salvage stereotactic Re‑I for intraprostatic recurrence of PC after radical radiotherapy, with the aim of evaluating feasibility and safety of linac-based prostate Re‑I.Materials and methodsWe retrospectively evaluated toxicities and outcomes of patients who underwent salvage reirradiation using volumetric modulated arc therapy (VMAT) for intraprostatic PC recurrence. Inclusion criteria were age ≥ 18 years, histologically proven diagnosis of PC, salvage Re‑I for intraprostatic recurrence after primary radiotherapy for PC with curative intent, concurrent/adjuvant ADT with stereotactic body radiation therapy (SBRT) allowed, performance status ECOG 0–2, restaging choline/PSMA-PET/TC and prostate MRI after biochemical recurrence, and signed informed consent.ResultsFrom January 2019 to April 2022, 20 patients were recruited. Median follow-up was 26.7 months (range 7–50). After SBRT, no patients were lost at follow-up and all are still alive. One- and 2‑year progression free survival (PFS) was 100% and 81.5%, respectively, while 2‑year biochemical progression-free survival (bFFS) was 88.9%. Four patients (20%) experienced locoregional lymph node progression and were treated with a further course of SBRT. Prostate reirradiation allowed the ADT start to be postponed for 12–39 months. Re‑I was well tolerated by all patients and none discontinued the treatment. No cases of ≥ G3 genitourinary (GU) or gastrointestinal (GI) toxicity were reported. Seven (35%) and 2 (10%) patients experienced acute G1 and G2 GU toxicity, respectively. Late GU toxicity was recorded in 10 (50%) patients, including 8 (40%) G1 and 2 (10%) G2. ADT-related side effects were found in 7 patients (hot flashes and asthenia).ConclusionLinac-based SBRT is a safe technique for performing Re‑I for intraprostatic recurrence after primary curative radiotherapy for PC. Future prospective, randomized studies are desirable to better understand the effectiveness of reirradiation and the still open questions in this field.

Identifying predictors of on-table adaptation for pancreas stereotactic body radiotherapy (SBRT).

702 Background: There is growing interest in the use of stereotactic body radiotherapy (SBRT) to treat pancreatic cancer. The purpose of this study was to identify any clinical or dosimetric parameters that predict which individuals may benefit from on-table adaptation during pancreas SBRT with MRI-guided radiotherapy. Methods: This was a single center retrospective study of patients undergoing MRI-guided SBRT to the pancreas from 2016 to 2022. An online daily adaptive workflow was in place for all fractions according to pre-specified criteria. Pre-treatment clinical variables and dosimetric parameters on the patient’s simulation scan were recorded for each SBRT course, and their ability to predict for on-table adaptation was analyzed using ordinal logistic regression. The outcome measure was number of fractions adapted. Results: Seventy-three SBRT courses consisting of 365 fractions were included in this study. Median prescription dose was 40 Gy in five fractions (range, 33-50 Gy); 56% and 44% of courses were prescribed ≤ 40 Gy and &gt; 40 Gy, respectively. Median gross and planning target volume (GTV and PTV) coverage were 94.7% and 84.3%, respectively. Median number of fractions adapted per course was three, with overall 58% (211 out of 365) total fractions adapted. On univariable analysis, the prescription dose ( &gt; 40 Gy vs ≤ 40 Gy), GTV size, stomach V20 and V25, duodenum V20 and Dmax, large bowel V33 and V35, heterogeneity index, and gradient index were significant determinants of the use of on-table adaptation (all p &lt; 0.05). On multivariable analysis, only prescription dose remained significant (adjusted odds ratio 7.66, p = 0.003). Conclusions: Prescription dose in MRI-guided pancreas SBRT is the only reliable predictor of on-table adaptation. Providers should strongly consider utilization of adaptive technology when delivering ablative doses to the pancreas.[Table: see text]

Selection of motion management in liver stereotactic body radiotherapy and its impact on treatment time.

Reduction of respiratory tumour motion is important in liver stereotactic body radiation therapy (SBRT) to reduce side effects and improve tumour control probability. We have assessed the distribution of use of voluntary exhale breath hold (EBH), abdominal compression (AC), free breathing gating (gating) and free breathing (FB), and the impact of these on treatment time. We assessed all patients treated in a single institution with liver SBRT between September 2017 and September 2021. Data from pre-simulation motion management assessment using fluoroscopic assessment of liver dome position in repeat breath holds, and motion with and without AC, was reviewed to determine liver dome position consistency in EBH and the impact of AC on motion. Treatment time was assessed for all fractions as time from first image acquisition to last treatment beam off. Of 136 patients treated with 145 courses of liver SBRT, 68% were treated in EBH, 20% with AC, 7% in gating and 5% in FB. AC resulted in motion reduction<1mm in 9/26 patients assessed. Median treatment time was higher using EBH (39min) or gating (42min) compared with AC (30min) or FB (24min) treatments. Motion management in liver SBRT needs to be assessed per-patient to ensure appropriate techniques are applied. Motion management significantly impacts treatment time therefore patient comfort must also be taken into account when selecting the technique for each patient.

Feasibility, safety, and efficacy of circumferential spine stereotactic body radiotherapy.

With advances in systemic therapy translating to improved survival in metastatic malignancies, spine metastases have become an increasingly common source of morbidity. Achieving durable local control (LC) for patients with circumferential epidural disease can be particularly challenging. Circumferential stereotactic body radiotherapy (SBRT) may offer improved LC for circumferential vertebral and/or epidural metastatic spinal disease, but prospective (and retrospective) data are extremely limited. We sought to evaluate the feasibility, toxicity, and cancer control outcomes with this novel approach to circumferential spinal disease. We retrospectively identified all circumferential SBRT courses delivered between 2013 and 2019 at a tertiary care institution for post-operative or intact spine metastases. Radiotherapy was delivered to 14-27.5 Gy in one to five fractions. Feasibility was assessed by determining the proportion of plans for which ≥95% planning target volume (PTV) was coverable by ≥95% prescription dose. The primary endpoint was 1-year LC. Factors associated with increased likelihood of local failure (LF) were explored. Acute and chronic toxicity were assessed. Detailed dosimetric data were collected. Fifty-eight patients receiving 64 circumferential SBRT courses were identified (median age 61, KPS ≥70, 57% men). With a median follow-up of 15 months, the 12-month local control was 85% (eight events). Five and three recurrences were in the epidural space and bone, respectively. On multivariate analysis, increased PTV and uncontrolled systemic disease were significantly associated with an increased likelihood of LF; ≥95% PTV was covered by ≥95% prescription dose in 94% of the cases. The rate of new or progressive vertebral compression fracture was 8%. There were no myelitis events or any grade 3+ acute or late toxicities. For patients with circumferential disease, circumferential spine SBRT is feasible and may offer excellent LC without significant toxicity. A prospective evaluation of this approach is warranted.

Stereotactic body radiotherapy in oligoprogressive metastatic castration-resistant prostate cancer during abiraterone or enzalutamide.

This monocentric, single-arm, retrospective study investigated the role of stereotactic body radiotherapy in patients with metastatic castration resistant prostate cancer who experienced oligoprogression during androgen receptor targeted agents. We retrospectively enrolled metastatic castration resistant prostate cancer patients treated with androgen receptor targeted agents between December 2016 and January 2022. All patients experienced an oligoprogression (defined as the appearance and/or the progression of ⩽5 bone or nodal or soft tissue metastases) during treatment with androgen receptor targeted agents and received stereotactic body radiotherapy upon oligoprogressive sites, preserving the androgen receptor targeted agents. Further stereotactic body radiotherapy upon new metastatic sites was permitted. Patients showing visceral metastases or receiving palliative radiotherapy were excluded. Progressive disease at >5 metastatic sites or the appearance of visceral metastases led to a change of the systemic treatment. Primary endpoints were 36-month survival rate and 36-month rate of patients receiving treatment with androgen receptor targeted agents. Secondary endpoints were local disease control, biochemical response and safety. We analyzed data from 30 patients. The 36-month survival rate was 90% (27 patients); 36-month rate of patients who were still on treatment with androgen receptor targeted agents was 50%. 20 of 30 patients had performed imaging control after a single course of stereotactic body radiotherapy: overall response rate was 50%, while clinical benefit was 93%. No ⩾G2 adverse events related to stereotactic body radiotherapy were recorded. Stereotactic body radiotherapy in oligoprogressive metastatic sites during androgen receptor targeted agent treatment resulted in a feasible and effective treatment to delay the start of next-line systemic treatment and prolong overall survival in metastatic castration resistant prostate cancer. Longer follow-up and further prospective studies are necessary to confirm our preliminary results.

40 Gray in 5 Fractions for Salvage Re-Irradiation of Spine Lesions Previously Treated with Stereotactic Body Radiotherapy

<h3>Purpose/Objective(s)</h3> This is a retrospective single-center analysis of the safety and efficacy of re-irradiation to 40 Gray (Gy) in 5 fractions in patients previously treated with stereotactic body radiotherapy (SBRT) to the spine. <h3>Materials/Methods</h3> We identified 62 consecutive patients with various solid malignancies treated between January 2016 and December 2021 to 40 Gy in 5 fractions regardless of dose and fractionation at the first course of SBRT. Patients were followed clinically and with routine imaging. Acute (≤3 months) and late (>3 months) toxicities were assessed according to CTCAE v5.0. Local control was defined as absence of progression within the treated target volume. Time to progression was calculated from date of completion of SBRT to the date of an imaging study indicating progression. The probability of local progression before death was estimated using a cumulative incidence curve, and death without local progression was considered a competing risk. <h3>Results</h3> Most patients had oligometastatic disease (53.2%) and treated to the thoracic spine (51.6%). The most common fractionation regimen in the first course of SBRT was 27 Gy in 3 fractions, and the median time to re-irradiation was 13.1 months (range, 2.4-86.9 months). Twenty-four patients (38.7%) had surgery before re-irradiation. At time of simulation, 49 patients (79%) had epidural disease, including 19, 13, 12 and 5 patients with epidural spinal cord compression (ESCC) scale 1a, 1b, 1c and 2, respectively. Accordingly, myelogram simulations were performed in 82.2% of patients. Both the vertebral body and posterior elements were treated in 93.5% of patients. All early toxicities were low grade, apart from one case of grade 3 fatigue, one case of grade 3 diarrhea and one case of grade 3 pneumonitis. Five patients experienced a pain flare (8.1%). Two thirds of patients who reported pain at baseline, achieved improvement (33%) or complete resolution of pain (33%). About 40% of patients had at least a partial response in magnetic resonance imaging (MRI). At a median follow up time of 11.9 months (range, 1.8- 39.6 months), six patients (9.7%) suffered local progression. The median time to progression was 4.1 months (range, 1.93-13.8 months). The estimated incidence rate of local progression before death at 6-months and 12-months was 7%. Five patients (8.1%) developed radiation-related neuropathy (grade 1, 2 and 3 in two, one and two cases, respectively). No patient suffered grade 4 or higher late toxicity. The vertebral compression fracture rate was 16%. Three patients (4.8%) eventually underwent kyphoplasty and two patients underwent surgery (3.2%) for vertebral fractures. <h3>Conclusion</h3> Re-irradiation with 40 Gy in 5 fractions seems safe and effective for the salvage of lesions progressing after a previous course of SBRT in a cohort of patients with extensive disease involvement. Prospective randomized trials are needed to determine the optimal dose and fractionation in this clinical scenario.

Recurrence Risk and Survival Following SBRT for Lung Cancer: Impact of Prognostic Factors Used for Patient Selection in a Randomized Trial

<h3>Purpose/Objective(s)</h3> Stereotactic body radiation therapy (SBRT) is the standard treatment for early stage, medically inoperable non-small cell lung cancer (NSCLC), attaining excellent local control. However, rates of regional and distant recurrence are relatively high. Current randomized phase 3 trials are investigating the addition of immunotherapy to SBRT in this setting to improve disease control and survival, with varying patient selection criteria. We investigate the influence of the high-risk factors used for patient selection on the ongoing randomized phase 3 SWOG/NRG trial (tumor size ≥2 cm, SUV ≥6.2, and grade 2-3) on disease control and survival in a single institution cohort and hypothesize that patients with high-risk features will have increased rates of recurrence and death. <h3>Materials/Methods</h3> Following IRB approval, we retrospectively analyzed patients treated with SBRT for early stage (T1-3N0M0) NSCLC between 2007 and 2019 at a single institution. Patient and disease specific characteristics and oncologic outcomes were documented. Risk factors including size ≥2 cm, SUV ≥6.2, and grade 2-3 histology were documented for each patient, and total number of high-risk features for each patient was calculated. In-field control (IFC), distant control (DC) and overall survival (OS) were calculated using the Kaplan Meier method, and the influence of high-risk factors was assessed with the log-rank method. <h3>Results</h3> We identified 217 courses of SBRT performed for early-stage NSCLC. All cases had tumor diameter available, 196 had SUV_max prior to SBRT available, and 68 had histologic grade available. Median patient age was 76.2 years (range 48.9-93.1) and median follow up was 35.1 months (range: 1.6-145-3). Tumors were treated to a median of 50 Gy (range: 40 - 60 Gy) in a median of 4 (range: 3-8) fractions. OS decreased with increasing number of risk factors, with 3-year OS of 73.7%, 72.2%, 50.7%, and 44.4% for patients with 0, 1, 2, and 3 high risk factors, respectively (p<0.001). Patients with 0-1 risk factors had 3-year OS of 73.2% as compared to 48.3% for those with 2-3 risk factors (p<0.001). This appeared to be driven by distant, rather than local recurrence: patients with 0-1 high risk factors had 3-year DC of 85.3% as compared to 73.3% P=0.006), but the assessed risk factors were not predictive of IFC. Individually, size ≥2 cm was the most robust risk factor, with 3-year DC of 72.7% versus 89.2% and OS of 61% versus 70.2% for tumors ≥2 cm and <2 cm, respectively. <h3>Conclusion</h3> High-risk features used for patient selection for an ongoing phase 3 trial testing the addition of immunotherapy to SBRT in early-stage NSCLC were highly predictive in aggregate for DC and OS but not LC in a single institution cohort of patients. Several ongoing randomized trials will determine whether immunotherapy reduces recurrence and improves OS in medically inoperable NSCLC treated with SBRT.

Proton SBRT for Isolated Nodal Recurrence in Gynecological Cancers

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) for isolated lymph node recurrence has been shown to have good rates of local control (LC) in gynecological cancers. However there exists the risk of toxicities to nearby organs. This single institution, retrospective outcome and dosimetric analysis assesses treatment response, associated GI and GU toxicities and associated characteristics for improved or worsened outcomes with proton based SBRT, hypothesizing that there will be low rates of toxicities while maintaining beneficial outcomes. <h3>Materials/Methods</h3> Adult patients diagnosed with primary gynecologic malignancy with isolated nodal recurrence treated with proton SBRT from 2006-2021 at a single institution were included. Toxicities were evaluated using RTOG/EORTC and CTCAE grading. Descriptive statistics were used to describe characteristics associated with local recurrence, toxicity, and survival. <h3>Results</h3> Fourteen patients with 21 nodal lesions were treated with 19 courses of proton SBRT. Median age was 64.5 (range: 47-78) years at time of initial cancer diagnosis and median of 66.0 (range: 51- 80) years at initial lymph node recurrence. Patients recurred within an average of 13.00 (range: 0.66- 31.41) months from end of initial treatment. Primary cancer sites included endometrium (n= 9), cervix (n= 2), ovary (n= 2), and vagina (n= 2). SBRT doses ranged from 30- 50 Gy (median 40 Gy) in 5-15 fractions with mean BED (alpha beta 10) of 69.93 (range: 48.00- 100.00) and mean BED (alpha beta 3) of 139.95 (range: 72.00- 216.67). Nodal locations treated included para-aortic (n= 7), pelvis (n= 5), iliacs (n= 4), and distant nodes (n= 3, supraclavicular, perirectal, periadrenal). Three pelvic and iliac lesions recurred locally at a median of 2.9 months (range 1.25-29.23) and 50% of patients developed local or distant recurrence. Local control at 3 months, 6 months, 1 year, and 2 years was 84.6%, 83.3%, 81.8%, and 70.0% respectively. Local recurrence free survival (LRFS) at 1 year and 2 years was 80.0%, 75.0% and overall survival (OS) was 54.5%, 44.4% respectively. Six patients developed grade 1 or 2 GI treatment related toxicity (Grade 1: 3, Grade 2: 3). 2 patients developed grade 1 GU toxicity. There were no GI grade 3-5 toxicities or GU grade 2-5 toxicities. Average Dmax to bladder was 14.42 Gy (median 18.62 Gy), range (0.6- 30.6). Average rectum Dmax was 15.75 Gy (range: 0.1- 34.2), median: 15.8 Gy. Median small bowel D2cc was 27 Gy (range: 10- 50.5) <h3>Conclusion</h3> Patients treated with proton SBRT had excellent rates of LC and LRFS and low rates of GI and GU toxicity. Dosimetric analysis also demonstrates low dose to nearby OARs. Based on these findings, Phase I/II trials evaluating dose escalation using proton techniques to further improve local control of isolated nodal recurrences should be considered.