Initial Stereotactic Body Radiation Therapy Research Articles

Stereotactic Body Radiation Therapy for Stage IIA to IIIA Inoperable Non-Small Cell Lung Cancer: A Phase 1 Dose-Escalation Trial

IntroductionLarger tumors are underrepresented in most prospective trials on stereotactic body radiation therapy (SBRT) for inoperable non-small cell lung cancer (NSCLC). We performed this phase I trial to specifically study the maximum tolerated dose (MTD) of SBRT for NSCLC >3cm. MethodsA 3+3 dose escalation design (cohort A) with an expansion cohort at the MTD (cohort B) was used. Patients with inoperable NSCLC >3cm (T2-4) were eligible. Select ipsilateral hilar and single station mediastinal nodes were permitted. The initial SBRT dose was 40 Gy in 5 fractions, with planned escalation to 50 and 60 Gy in 5 fractions. Adjuvant chemotherapy was mandatory for cohort A and optional for cohort B, but no patients in cohort B received chemotherapy. The primary endpoint was SBRT-related acute G4+ or persistent G3 toxicities (CTCAE v4.03). Secondary endpoints included local failure (LF), distant-metastases, disease progression and overall survival (OS). ResultsMedian age was 80 years; tumor size was >3cm ≤5cm in 20 (59%) and >5cm in 14 (41%) patients. In cohort A (n=9), 3 patients treated to 50 Gy experienced G3 radiation pneumonitis (RP), thus defining the MTD. In the larger dose expansion cohort B (n=25), no RT-related G4+ toxicities and no G3 RP occurred; only 2 patients experienced G2 RP. The 2-year cumulative incidence of LF was 20.2%, distant failure was 34.7%, and disease progression was 54.4%. Two-year OS was 53%. A biologically effective dose <100 Gy was associated with higher LF (p=0.006); advanced stage and higher neutrophil/lymphocyte ratio (NLR) were associated with greater disease progression (both p=0.004). Conclusions50 Gy in 5 fraSabsctions is the MTD for SBRT to tumors >3cm. A higher BED is associated with less local failures even in larger tumors. Cohort B appears to have had less toxicity, possibly due to the omission of chemotherapy. Trial RegistrationClinicaltrials.gov: xxx

Clinical Outcomes with Stereotactic Body Radiation Therapy for Oligometastatic Prostate Cancer: Results from a Prospective Registry Trial

Metastasis-directed radiation therapy using stereotactic body radiation therapy (SBRT) in oligometastatic prostate cancer (Oligo PCa) has a demonstrated benefit for local control and biochemical recurrence free survival for men with oligorecurrent PCa; however, the impact of SBRT within other oligometastatic states and in the context of systemic therapy remains poorly characterized. In this study, we investigate prognostic factors for clinical outcomes in a prospective cohort of Oligo PCa patients treated with metastasis-directed SBRT. Using a single-institution registry trial, we analyzed a prospective cohort of 86 patients with Oligo PCa (≤5 metastatic lesions) and treated with metastasis-directed SBRT between 2017- 2022. Patients were classified as synchronous, metachronous, or induced oligometastatic disease as per the ESTRO guidelines. We evaluated the time to radiographic progression (TTRP), defined as the time from SBRT start date to radiographic progression, as well as time to initiation of new treatment (TTNT), defined as the time from SBRT end date to initiation of new therapy (systemic or radiation therapy). Time to event (TTE) was defined as the time from SBRT start date to radiographic progression or initiation of new therapy, whichever occurred first. Patients without documented events were censored at the date of last disease assessment. Comparative analyses were performed using Kaplan-Meier and Cox proportional hazards regression methods. Eighty-six men with Oligo PCa treated with SBRT were followed for a median of 16.4 months with M0 (73%), Oligo PCa (21%) or polymetastatic PCa (6%) GS > = 8 (63%) at initial diagnosis. At the time of treatment with initial SBRT, 21% had synchronous oligometastatic disease, 63% had metachronous or repeat oligorecurrence or oligoprogression, and 16% had induced oligometastatic disease. Most patients were treated to 1-3 sites (94%), which predominantly included bone (86%), and the median dose was 35 Gy/5F. Concurrent systemic therapy during SBRT was seen in 85% of patients, including (60.5% with new generation androgen receptor signaling inhibitors). Overall survival at 1-year and 2-years was 96.9% [95% CI, 88.2-99.2%] and 94.4% [95% CI, 83.2-98.2%]. Using univariable analysis, those who did not receive systemic treatment during SBRT had significantly shorter TTRP (HR 3.67, [95% CI, 1.62-8.32], p = 0.002), TTNT (HR 3.24, 95% CI [1.49-7.06], p = 0.003), and TTE (HR 3.05, [95% CI, 1.44-6.45], p = 0.004). Additionally, patients treated with SBRT for metachronous (HR 2.89, [95% CI 0.68-12.30]) and induced metastatic disease (HR 8.96, [95% CI 1.85-43.37]) had significantly shorter TTE compared to synchronous oligometastatic disease (p = 0.006). Using a prospective registry cohort of men with Oligo PCa treated with SBRT, we identify an association of oligometastatic state and the use of concurrent systemic therapy with improved TTRP and TTNT. Further prospective studies are warranted.

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]

Radiation pneumonitis after repeat stereotactic body radiation therapy for early-stage non-small cell lung cancer: A case series of two patients

Introduction: Stereotactic body radiation therapy (SBRT) is a well-established treatment option for patients with early-stage non-small cell lung cancer (NSCLC). We retrospectively identified 82 patients with early-stage NSCLC treated with SBRT at our institution between November 2009 and September 2019. Among these patients, two developed local recurrence or new primary lung cancer and lung metastasis or new primary lung cancer, respectively, and were treated with repeat SBRT. We herein report a case series of two patients with radiation pneumonitis after repeat SBRT. Case Series: Case A was an 80-year-old woman diagnosed with stage I (T1aN0M0) squamous cell carcinoma. She received initial SBRT at an irradiation dose of 48 Gy in 4 fractions at the isocenter. Two years and three months after initial SBRT, the patient was clinically diagnosed with post-SBRT local recurrence or primary lung cancer and, thus, was treated with repeat SBRT at an irradiation dose of 60 Gy in 10 fractions. Six months later, the patient developed grade 5 radiation pneumonitis. Case B was an 89-year-old man diagnosed with stage I (T1cN0M0) adenocarcinoma. He received initial SBRT at an irradiation dose of 48 Gy in 4 fractions at the isocenter. Three years and six months after initial SBRT, the patient was clinically diagnosed with post-SBRT lung metastasis or primary lung cancer and, thus, was treated with repeat SBRT at an irradiation dose of 50 Gy in 4 fractions. Six months later, the patient developed grade 3 radiation pneumonitis. Conclusion: Caution is needed when performing repeat SBRT.

Prospective Evaluation of Stereotactic Body Radiation Therapy (SBRT) for Patients with Metastatic Epidural Spinal Cord Compression

<h3>Purpose/Objective(s)</h3> Metastatic epidural spinal cord compression (MESCC) can be very painful and disabling. We hypothesized that an initial fraction of SBRT would provide rapid decompression and allow for potential dose escalation via a follow up treatment. Our primary objective was to assess the feasibility of a staged SBRT approach to provide short-interval treatment response. Secondary endpoints included pain control and quality of life (QoL). <h3>Materials/Methods</h3> This single institution, prospective study enrolled non-surgical candidates with MESCC from 07/2015 to 02/2018. Those with spine instability (SINS>12), bony retropulsion, or radiosensitive histologies were excluded. After baseline imaging (MRIpre), patients received SBRT (10-16 Gy) and a short interval MRI within 2-3 weeks (MRI1). Subsequently, patients could receive an additional treatment at the discretion of the treating physician. A second MRI was completed 8-10 weeks post-tx (MRI2). QoL questionnaires and pain scores were obtained at all time points. The primary endpoint was the smallest cord-disease distance (CDD) in the axial plane and the thecal sac patency (TSP), defined as the thecal sac area at the level of maximal compression divided by the average thecal sac area one level above and below. Secondary endpoints included pain scores and QoL using the Functional Assessment of Cancer Therapy – General (FACT-G). Statistical comparisons utilized the Wilcoxson signed-rank test. <h3>Results</h3> 22 patients were enrolled in the study and received SBRT. The most common primary diagnoses were lung (36%) and prostate (32%) cancer. The most common initial SBRT doses were 16 Gy (41%) and 14 Gy (36%). 12 patients completed all 3 scans and 3 other patients completed 2 scans (MRIpre and either MRI1 or MRI2). No patient received a second,adaptive fraction of radiation (due to lost to follow up, systemic progression, or no local progression). TSP significantly increased on MRI1 (median change 9%, IQR 1%-28%, p = 0.034) and on MRI2 (median change 24%, IQR 12-32%, p = 0.002). CDD did not increase significantly on MR1 (median change 0.0 mm, IQR 0-0.3 mm, p = 0.125) but did on MRI2 (median change 1.5 mm, IQR 0-1.8 mm, p = 0.001). On radiology report, 23% had disease improvement on MRI1, all of whom received 16 Gy. 64% had disease improvement on MRI2. No patients progressed neurologically. There was a numerical decrease in best and worst pain score over time (p=0.093). FACT-G scores did not change significantly over time. There were no grade 3 or greater toxicities related to RT. <h3>Conclusion</h3> Single-fraction SBRT can provide rapid decompression of epidural disease safely and quickly. Radiosurgical decompression can be a feasible alternative to surgery in patients with MESCC, especially as a large segment of such patients are non-surgical candidates. A follow up study comparing SBRT to 3D CRT is being planned.

When Failure is Final: Subsequent Outcomes of Patients with Stage I NSCLC who Fail Initial Stereotactic Body Radiation Therapy Monitored with Circulating Tumor Cells

Stage I non-small cell lung cancer (NSCLC) is increasingly treated with stereotactic body radiation therapy (SBRT), but regional and distant disease progression frequently occur. In a pilot trial of stage I NSCLC patients treated with SBRT accompanied by sequential circulating tumor cell (CTC) assays, we previously found that pretreatment CTCs > 5 /ml and persistent CTCs after SBRT were associated with a significantly higher risk of regional or distant disease progression. To better understand the disease history and impact of salvage treatment on this cohort, we extended analysis of patients with disease progression. Among 92 consecutive patients with clinical stage I NSCLC treated with definitive SBRT prospectively enrolled on an IRB-approved protocol with serial telomerase-based CTC assays, 19 subjects (21%) developed disease progression while on study. Medical records were assessed for new clinical events, treatment details, and status at last follow-up. Initial SBRT was delivered to a median dose of 50 Gy (range, 40-60 Gy) in 4-5 fractions. No patient received chemo- or immunotherapy prior to first disease progression. Median follow-up was 29 months (range, 14-69 mo.) from time of initial SBRT. Additional follow-up was obtained in all but 2 patients (1 withdrew and 1 was lost to follow-up). Four, 5, and 8 patients had local, regional, or distant recurrences, respectively, as the first site of progression. Five (29%) patients who progressed after initial definitive SBRT are alive, of which 4 (24%) were successfully treated with a 2nd course of SBRT without systemic therapy (2 for local recurrences and 2 for oligometastatic distant) at a median of 32.8 months after initial SBRT (range: 32.7 to 35.3 mo.). The remaining 12 patients were deceased, with mean and median time to death following initial SBRT of 26.6 (14-52 mo.) and 24 months, respectively. Of the deceased, the mean and median time to disease progression following initial SBRT were 14.5 (3.2-44.2) and 11.4 months, and all but four received chemo-, immuno-, and/or targeted therapy before succumbing (only one received SBRT). Pre-SBRT or 3 months post-SBRT CTCs were elevated in 9 (or 75%) of the 12 deceased patients, versus only 5 (or 8.3%) of the 62 patients confirmed to be still alive, a significant difference (p < 0.001). Less than a third of patients who fail initial SBRT for stage I NSCLC in this study received a 2nd course of SBRT and remain alive. In contrast, the majority of patients who progressed rapidly succumbed to disease progression, most within 2 years after initial SBRT. The window for intervention with salvage treatment is, therefore, surprisingly narrow. These results support the usefulness of CTC assays for rapidly denoting the subset of patients who may benefit from adjuvant systemic therapy, added to SBRT, for maximizing survival.

Salvage Treatment Outcomes of Non-small Cell Lung Cancer Patients with Non-distant Recurrence after Initial Stereotactic Body Radiation Therapy

Salvage Treatment Outcomes of Non-small Cell Lung Cancer Patients with Non-distant Recurrence after Initial Stereotactic Body Radiation Therapy

Management of local recurrences and regional failure in early stage non-small cell lung cancer after stereotactic body radiation therapy.

Stereotactic body radiation therapy (SBRT) is a very effective way to treat early stage non-small cell lung cancer (NSCLC) and small oligometastatic lung lesions with consistently high rates of local control, but both local and regional/distant recurrences still occur. The management of recurrences remains unsettled and may entail repeat SBRT, conventionally fractionated external beam RT (EF-EBRT), chemotherapy or surgery. Most patients with local recurrences [within the initial planning target volume (PTV)] can be salvaged successfully with good cancer specific survival. Nonetheless, proximity of the initial SBRT delivery to organs at risk (ribs, blood vessels, airways) may make retreatment more difficult. With attention to detail and careful patient selection, both surgery and reirradiation can be performed safely and effectively. Strategies for management of regional (nodal) recurrences may require conventional therapies tailored to the patterns of failure. The role of immunotherapy in salvage has not been elucidated as yet. We review here data on the available literature concerning salvage of SBRT lung patients.

Repeat stereotactic body radiation therapy (SBRT) for salvage of isolated local recurrence after definitive lung SBRT

PurposeOptimal management of isolated local recurrences after stereotactic body radiation therapy (SBRT) for early non-small cell lung cancer (NSCLC) is unknown and literature describing repeat SBRT for in-field recurrences after initial SBRT are sparse. We investigate the safety and efficacy of salvage SBRT for isolated local failures after initial SBRT for NSCLC. Methods/MaterialsPatients receiving SBRT for isolated local recurrence after initial SBRT for early NSCLC were identified using a prospective registry. Both courses were 3–5 fractions with a biologically effective dose (BED10) of ≥100 Gy. Local failure was defined as within 1 cm of the initial planning target volume (PTV) or an overlap of the ≥25% isodose lines of the first and second treatments. Failures >1 cm beyond the PTV and without ≥25% overlap, or with additional recurrence sites were excluded. Kaplan-Meier analysis was used to estimate survival. ResultsA total 21 patients receiving salvage SBRT from 2008 to 2017 were identified. Median interval from initial SBRT to salvage SBRT was 23 months (7–52). Six patients (29%) had central tumors. Median follow-up time from salvage SBRT was 24 months (3–60). Median overall survival after salvage was 39 months. After reirradiation, two-year primary tumor control was 81%, regional nodal control was 89%, distant control was 75% and overall survival was 68%. Grade 2 pneumonitis occurred in 2 patients (10%) and grade 2 chest wall toxicity in 4 patients (19%). No grade 3+ toxicity was observed. ConclusionsSalvage SBRT for isolated local failures after initial SBRT appears safe, with low treatment-related toxicity and encouraging rates of tumor control.

Efficacy and tolerability of stereotactic body radiotherapy for lung metastases in three patients with pediatric malignancies.

Purpose: To report a case series of 3 pediatric patients treated with Stereotactic Body Radiation Therapy (SBRT) for lung metastases.Patients and methods: Three patients (ages 9, 11, and 21) received SBRT for rhabdoid tumor, Ewing sarcoma, and Wilms tumor histologies, respectively. SBRT doses were 37.5–50 Gy in 3–5 fractions treating twelve lesions.Results: Three patients (ages 9, 11, and 21) received photon SBRT for pulmonary metastases. The patients were as follows: 1) 21-year-old male with favorable histology Wilms tumor and 1 lesion treated, 2) 11-year-old female with Ewing sarcoma and 1 lesion treated for relapse after previous whole lung radiation (15 Gy), and 3) 9-year-old female with rhabdoid tumor of the left thigh with 10 lesions treated over a two-year period. Median dose delivered was 40 Gy (range, 37.5–50 Gy), delivered in a median of 4 fractions (range, 4–5) of a median of 10 Gy per fraction (range, 9.4–10 Gy). Within a minimum follow-up of 1.9 years (range 1.9–4 years), local control for all 13 treated metastases is 100% without any observed acute toxicities. One possible late toxicity (grade 2 rib fracture) developed 1.3 years following SBRT for treatment of a peripheral lesion (rhabdoid tumor) in an area of disease progression and was managed conservatively. Two patients are surviving 2.9 years (Wilms tumor) and 1.9 years (Ewing sarcoma) after SBRT, and one (rhabdoid tumor) expired 2 years after her final course (4 years after initial SBRT). Two patients (rhabdoid tumor and Ewing sarcoma) suffered disease progression outside of the treated lesions and one patient (Wilms tumor) is without evidence of disease and has not required whole lung irradiation or further systemic therapy.Conclusion: SBRT appears effective and well tolerated for pediatric lung metastases, however further studies are warranted.

Comprehensive Analysis of Toxicity and Pulmonary Function Tests in Patients Undergoing Repeat Lung Stereotactic Body Radiation Therapy (SBRT) After Initial Lung SBRT

There is a paucity of data on the role of repeat lung SBRT in patients who have undergone a prior course of SBRT. We performed a comprehensive analysis of toxicity and pulmonary function tests in patients who underwent repeat lung SBRT. Using an institutional lung SBRT database (2003-2016), we identified patients who underwent two separate courses of SBRT for early stage lung cancer or oligometastatic disease. We included patients treated with repeat SBRT for local failure, for new primaries or new sites of oligometastasis. Toxicities were graded according to CTCAE v4. Pulmonary function tests (PFTs) were obtained prior to SBRT and at follow-up. Changes in PFTs were evaluated using Repeated Measures Analysis of Variance. Local failure was assessed using Kaplan-Meier estimates and association with clinical and treatment variables was assessed using competing risk regression with death as the competing risk. We identified 111 patients who underwent repeat SBRT, of whom 32 (28.8%) were for local failure, 60 (54.1%) for a new primary and 19 (17.1%) for a new site of oligometastases. Median time between initial and repeat SBRT was 17.9 mo (range, 3.7-86.3) and the median follow-up after repeat SBRT was 16.6 mo (range, 0-64). Median overall survival after repeat lung SBRT was 28.3 mo. At time of initial SBRT, 11 (9.9%) patients underwent other synchronous SBRT treatments and 4 (3.6%) patients had received prior thoracic radiotherapy. Majority (64%) of patients received 50 Gy/5 fx or 48 Gy/4 fx at repeat lung SBRT. Chest wall (CW) toxicity occurred in 10 (9%) patients of whom 3 developed Grade 1, 5 developed Grade 2, and 3 developed Grade 3; one patient developed a rib fracture. All patients with CW toxicity had peripheral tumors. Older age (p=0.03) and peripheral location (p<0.01) were associated with increased risk for CW toxicity. Pneumonitis occurred in 7 (6.3%) patients of whom 3 developed Grade 1, 2 developed Grade 2 and 2 developed Grade 3. No variables predicted for pneumonitis (all p>0.05). Pre-treatment and post-treatment PFTs were available in 51 patients. Median FEV1(L)/FEV1%/DLCO at baseline, prior to repeat SBRT and post-repeat SBRT were 1.3/67%/57, 1.3/59%/51, 1.3/62%/51, respectively. Changes in FEV1 and FEV1% were not statistically significant. DLCO decline after the first course of SBRT was statistically significant (p<0.01), however, there was no statistically significant decline noted after repeat SBRT (p>0.05). At last follow-up, 13 (11.8%) patients developed local failure, 3 (2.7%) developed lobar failure, 13 (11.8%) developed nodal failure and 32 (28.8%) developed distant failure after repeat SBRT. Repeat lung SBRT was well tolerated and associated with a low risk for toxicity. There were no clinically significant PFT changes after repeat lung SBRT and the primary pattern of failure in cases of repeat SBRT was distant failure.

Detection and Treatment of Second Primary Lung Cancers Following Initial Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

Detection and Treatment of Second Primary Lung Cancers Following Initial Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

Early Pulmonary Toxicity of Lung Stereotactic Body Radiation Therapy (SBRT) Delivered as Consecutive Daily Fractions

Early Pulmonary Toxicity of Lung Stereotactic Body Radiation Therapy (SBRT) Delivered as Consecutive Daily Fractions