Postoperative Stereotactic Body Radiotherapy Research Articles

Stereotactic Body Radiotherapy for Treatment of Spinal Metastasis: A Systematic Review of the Literature

Abstract Advances in local and systemic therapies continue to improve overall survival for patients with cancer, resulting in an increase in the incidence of spine metastases. Metastases to the spine are the most common bony metastasis. Up to 15% of patients with solid tumors develop spinal metastases. Spinal metastases can be particularly devastating for quality of life given the potential pain, neurological deficits from spinal cord compression or cauda equina syndrome, spinal instability, and pathological fractures that may result. Stereotactic body radiotherapy (SBRT) with or without the addition of less invasive surgical techniques for stabilization or separation has gained favor. SBRT uses smaller, more precise treatment volumes, allowing for higher doses per fracture, thus increasing ablative abilities. In this systematic review we discuss the literature regarding SBRT’s effectiveness in providing local control and pain control for patients with metastatic disease to the spine. This remains true for patients with spinal cord compression managed with surgical separation followed by postoperative spine SBRT. While not all patients are appropriate candidates for SBRT, careful consideration of appropriate frameworks which take into account the patient’s overall prognosis can guide a multidisciplinary team towards the patients who will benefit the most from this treatment modality.

Dosimetric Implications of Prostate Bed Deformability: An Analysis of the SCIMITAR Clinical Trial.

The post-operative prostate bed is a dynamic target volume due to the deformable nature of the bladder and rectum. These changes can lead to incorrect dosing of the prostate bed and organs at risk (OARs). Our objective was to quantify the dosimetric impact of prostate bed and OAR deformation. SCIMITAR (NCT03541850) is a prospective phase II clinical trial evaluating stereotactic body radiotherapy (SBRT) in the post-prostatectomy setting. This analysis included a subset of patients who received 5 fractions of 6-6.8 Gy to the prostate bed under CT-based image guidance. The clinical target volume (CTV) and OARs were contoured on fractional CBCT images. Changes in volume, shape (via the dice similarity coefficient [DSC]), and dosimetry were quantified. Student's t-test was used to analyze the differences between planning and daily treatment outcomes. A total of 29 patients (145 fractional images) were analyzed. We found the CTV volume remained stable (median change 1.1%; IQR: -15.1% - 16.1%), whereas the CTV shape was deformable (DSC of 0.76 [IQR: 0.71 - 0.79]). The bladder and rectum exhibited changes with median volume change of 5.7% (IQR: -24.3% - 51.0%) and 5.5% (IQR: -8.7% - 21.9%), respectively and median DSC of 0.77 (IQR: 0.68 - 0.84) and 0.74 (IQR: 0.69 - 0.80) respectively. The CTV received less radiation dose than planned (volume receiving 95%: 93.2% actual vs 99.6% planned, p < 0.01). 39% (56/145) of total fractions and 52% (15/29) of patients met criteria for CTV under-coverage (volume receiving 95% of the prescription dose < 93%). The rectum received higher dose than planned on several parameters (e.g., V27.5 Gy increased from 15.4% to 21.0% [p = 0.009] and V32.5 Gy increased from 6.0% to 10.9% [p = 0.006]) (Table 1). We found underdosing of the prostate CTV and overdosing of the rectum in patients receiving CT-guided postoperative SBRT. While future work will correlate these dosimetric consequences with toxicity, these data suggest that approaches such as adaptive radiotherapy may be beneficial.

Dosimetric Impact of Radiolucent Carbon Fiber Hardware for Post-Operative Spine Stereotactic Body Radiation Therapy

The spine is the most common site of osseous metastases. In the non-operative setting, there is growing support for stereotactic body radiation therapy (SBRT) over conventional radiation therapy for improved pain relief and local control. Hybrid therapy consisting of separation surgery and post-operative SBRT is considered in patients with biomechanical instability and epidural cord compression. Surgery traditionally requires titanium (Ti) implants, which introduce artifacts on post-operative imaging in addition to increased uncertainty and beam attenuation. Use of radiolucent carbon fiber reinforced polyetheretherketone (CFR-PEEK) hardware has been shown to provide safe and comparable surgical outcomes as compared to Ti. Our primary objective is to assess the dosimetric impact of Ti versus carbon fiber implants in spine SBRT. Single institution retrospective series of post-operative spine SBRT from 2019-2020. Re-irradiation cases were excluded. The electronic medical record and treatment planning systems (TPS) were queried. Dosimetric analyses compared original Ti plans with reoptimized plans, replacing Ti hardware electronic density with carbon fiber. Maintaining clinical goals, dose calculations were performed in a treatment planning system using a collapsed cone algorithm. All treatments used step and shoot intensity modulated radiation therapy to avoid beam angles with significant metal along the beam path. Metallic artifacts were contoured and assigned the appropriate tissue density. A D'Agostino-Pearson test was used to assess data for normality. We used paired Student's t-tests to compare three dosimetric outcomes in the setting of Ti and carbon fiber implants. Planning target volume (PTV) coverage was represented by the volume receiving at least the prescribed dose (%), the maximum point dose (dmax, cGy) to the spinal cord planning risk volume (PRV, 2 mm margin), and the overall hot spot intensity (plan dmax). A series of 14 consecutive SBRT cases were evaluated (dose 27-30 Gy in 3-5 fractions). All dosimetric outcomes were normally distributed (p>0.05). We found a statistically significant difference in PTV coverage between the original SBRT treatment plans with Ti hardware (mean 85.1 ± 7.9%) and reoptimized carbon fiber hardware (87.3 ± 6.6%; p = 0.002). There was no significant difference in mean spinal cord PRV dmax between Ti and carbon fiber plans (1846 ± 483 cGy vs. 1842 ± 495 cGy; p>0.05). We observed a nonsignificant increase in mean overall dmax from 3932 ± 416 cGy in the Ti cohort to 4111 ± 906 cGy in the carbon fiber cohort (p>0.05). Carbon fiber implants provide a significant increase in SBRT target coverage, without impacting the overall plan and spinal cord PRV dmax in this retrospective series. In addition to improved post-operative imaging and reduced uncertainty, carbon fiber hardware may offer dosimetric advantages as compared to traditional Ti spinal implants, and warrants further investigation in a larger cohort.

Novel Intrafraction Motion Tracking During Postoperative Spine Stereotactic Irradiation for a Patient With Carbon Fiber Fixation Hardware

Carbon-fiber reinforced (CFR) polyetheretherketone hardware is an alternative to traditional metal hardware used for spinal fixation surgeries before postoperative radiation therapy for patients with spinal metastases. CFR hardware's radiolucency decreases metal artifact, improving visualization and accuracy of treatment planning. We present the first clinical use and proof of principle of CFR spinal hardware with tantalum markers used for successful tracking of intrafraction motion (IM) using Varian TrueBeam IMR (Intrafraction Motion Review) software module during postoperative spine stereotactic radiation. A 63-year-old woman with history of endometrial cancer presented with acute back pain. Imaging demonstrated pathologic T12 vertebral fracture with cord compression. She underwent T12 vertebrectomy with circumferential decompression and posterior instrumented T10-L2 fusion at our facility using CFR-polyetheretherketone hardware with tantalum screw markers followed by postoperative stereotactic body radiation therapy to 3000 cGy in 5 fractions delivered to T11-T12. Tantalum screw markers were used for IMR tracking. During irradiation, 260 kV images were acquired, and IMR software was able to identify and track markers. During the entire treatment, the IM motions were less than 3 mm. This is the first presented case of CFR spinal hardware with tantalum markers used for successful IMR tracking of IM during daily spine stereotactic treatment. Future work will be needed to improve workflow and create a spine-specific IMR protocol.

Treatment outcomes of postoperative ultra-hypofractionated stereotactic body radiotherapy in prostate cancer.

This study aimed to evaluate the safety and efficacy of ultra-hypofractionated stereotactic body radiation therapy (SBRT) to prostate bed. Sixty-six prostate cancer patients treated with postoperative ultra-hypofractionated SBRT between 2018 and 2020 were retrospectively reviewed. All patients received a total dose of 35 Gy to prostate bed in 5 fractions. Biochemical complete response (BCR), biochemical failure (BF), acute and late toxicities were assessed. After a median follow-up of 24.2 months (range, 6.4-37.2), seven patients (10.6%) developed BF, and the 2-year freedom from BF (FFBF) rate was 88.4%. BCR was observed in 57 patients (86.4%). The 2-year FFBF in patients with pre-SBRT PSA value of <0.2 ng/mL was higher than those with pre-SBRT PSA of ≥0.2 ng/mL (100% vs. 81.4%; P = 0.04). The 2-year FFBF in patients with BCR was significantly higher than in those without BCR (94.5% vs. 58.3%; P < 0.001). In multivariate analysis, pre-SBRT PSA and post-SBRT PSA values were prognostic factors for FFBF (P = 0.009 and P = 0.01, respectively). Nine patients (13.6 %) developed acute and late grade 2 genitourinary (GU) toxicities. There was no acute or late grade ≥3 GU toxicity. Acute and late grade ≥2 gastrointestinal (GI) toxicity was observed in 9 (13.6%) and 2 (3%) patients, respectively. Postoperative ultra-fractionated SBRT showed no severe acute toxicity and late toxicity rates of about 15%, in addition to excellent biochemical control rates. Pre- and post-SBRT PSA levels may be a predictor of BCR in patients receiving post-operative ultra-fractionated SBRT.

Stereotactic body radiotherapy for spine metastases: a review of 24 Gy in 2 daily fractions.

Stereotactic body radiotherapy (SBRT) has proven to be a highly effective treatment for selected patients with spinal metastases. Randomized evidence shows improvements in complete pain response rates and local control with lower retreatment rates favoring SBRT, compared to conventional external beam radiotherapy (cEBRT). While there are several reported dose-fractionation schemes for spine SBRT, 24 Gy in 2 fractions has emerged with Level 1 evidence providing an excellent balance between minimizing treatment toxicity while respecting patient convenience and financial strain. We provide an overview of the 24 Gy in 2 SBRT fraction regimen for spine metastases, which was developed at the University of Toronto and tested in an international Phase 2/3 randomized controlled trial. The literature summarizing global experience with 24 Gy in 2 SBRT fractions suggests 1-year local control rates ranging from 83-93.9%, and 1-year rates of vertebral compression fracture ranging from 5.4-22%. Reirradiation of spine metastases that failed prior cEBRT is also feasible with 24 Gy in 2 fractions, and 1-year local control rates range from 72-86%. Post-operative spine SBRT data are limited but do support the use of 24 Gy in 2 fractions with reported 1-year local control rates ranging from 70-84%. Typically, the rates of plexopathy, radiculopathy and myositis are under 5% in those series reporting mature follow up, with no cases of radiation myelopathy (RM) reported in the de novo setting when the spinal cord avoidance structure is limited to 17 Gy in 2 fractions. However, re-irradiation RM has been observed following 2 fraction SBRT. More recently, 2-fraction dose escalation with 28 Gy, with a higher dose constraint to the critical neural tissues, has been reported suggesting improved rates of local control. This regimen may be important in those patients with radioresistant histologies, high grade epidural disease, and/or paraspinal disease. The dose-fractionation of 24 Gy in 2 fractions is well-supported by published literature and is an ideal starting point for centers looking to establish a spine SBRT program.

Impact of Postoperative Stereotactic Body Radiation Therapy on Survival of Patients with Spinal Metastases in the Context of Additional Systemic Adjuvant Therapy

Stereotactic body radiotherapy (SBRT) has been established as a safe and effective treatment modality for control of long-term pain and tumor growth. However, few studies have investigated the efficacy of postoperative SBRT versus conventional external beam radiation therapy (EBRT) in extending survival within the context of systemic therapy. A retrospective chart review of patients who underwent surgery for spinal metastasis at our institution was conducted. Demographic, treatment and outcome data were collected. SBRT was compared with EBRT and non-SBRT, and analyses were stratified by whether or not patients received systemic therapy. Survival analysis was conducted using propensity score matching. Bivariate analysis in the non-systemic therapy group revealed longer survival with SBRT compared to EBRT and non-SBRT. Further analysis also showed that primary cancer type and preoperative mRS significantly affected survival. Within patients who received systemic therapy, overall median survival for SBRT patients was 22.7 months (95% CI: 12.1 - 52.3) versus 16.1 months (95% CI: 12.7 - 44.0; p = 0.28) for EBRT patients and 16.1 months (95% CI: 12.2 - 21.9; p = 0.07) for non-SBRT patients. Within patients who did not receive systemic therapy, overall median survival for SBRT patients was 62.1 months (95% CI: 18.1 - unknown) versus 5.3 months (95% CI: 2.8 - unknown; p = 0.08) for EBRT patients and 6.9 months (95% CI: 5.0 - 45.6; p = 0.02) for non-SBRT patients. In patients who do not receive systemic therapy, treatment with postoperative SBRT may increase survival time compared to patients not receiving SBRT.

The Impact of Targetable Mutations on Clinical Outcomes of Metastatic Epidural Spinal Cord Compression in Patients With Non-Small-Cell Lung Cancer Treated With Hybrid Therapy (Surgery Followed by Stereotactic Body Radiation Therapy).

In treatment of metastatic epidural spinal cord compression (MESCC), hybrid therapy, consisting of separation surgery, followed by stereotactic body radiation therapy, has become the mainstay of treatment for radioresistant pathologies, such as non-small-cell lung cancer (NSCLC). To evaluate clinical outcomes of MESCC secondary to NSCLC treated with hybrid therapy and to identify clinical and molecular prognostic predictors. This is a single-center, retrospective study. Adult patients (≥18 years old) with pathologically confirmed NSCLC and spinal metastasis who were treated with hybrid therapy for high-grade MESCC or nerve root compression from 2012 to 2019 are included. Outcome variables evaluated included overall survival (OS) and progression-free survival, local tumor control in the competing risks setting, surgical and radiation complications, and clinical-genomic correlations. One hundred and three patients met inclusion criteria. The median OS for this cohort was 6.5 months, with progression of disease noted in 5 (5%) patients at the index tumor level requiring reoperation and/or reirradiation at a mean of 802 days after postoperative stereotactic body radiation therapy. The 2-year local control rate was 94.6% (95% CI: 89.8-99.3). Epidermal growth factor receptor (EGFR) treatment-naïve patients who initiated EGFR-targeted therapy after hybrid therapy had significantly longer OS (hazard ratio 0.47, 95% CI 0.23-0.95, P = .04) even after adjusting for smoking status. The presence of EGFR exon 21 mutation was predictive of improved progression-free survival. Hybrid therapy in NSCLC resulted in 95% local control at 2 years after surgery. EGFR treatment-naïve patients initiating therapy after hybrid therapy had significantly improved survival advantage. EGFR-targeted therapy initiated before hybrid therapy did not confer survival benefit.

Postoperative SBRT in the treatment of early-stage oropharyngeal and oral cavity cancers with high-risk margins: A dosimetric comparison of volumetric modulated arc therapy with or without non-coplanar arcs and acute toxicity outcomes from the STEREOPOSTOP GORTEC 2017–03 phase 2 trial

Background and purposeThe STEREO POSTOP GORTEC 2017–03 phase 2 trial (NCT03401840) evaluates postoperative stereotactic body radiotherapy (SBRT) in case of high-risk margins for pT1-T2/N0 oropharyngeal and oral cavity tumors. The present ancillary study aimed to compare the dosimetric impact of adding non-coplanar arcs to the volumetric modulated arc therapy (VMAT) technique and to evaluate acute toxicities on the first patients included in this trial. Materials and methodsTen patients were included. Patients were treated with Novalis TX®. The total dose was 36 Gy (100 % isodose line) in 6 fractions, treated every other day. Two treatment plans were created for each patient: one plan using 2 coplanar arcs only (VMATc) and one plan using coplanar and 3 non-coplanar arcs (VMATc + nc). Acute toxicity was evaluated according to NCI CTCAE criteria V4.03. ResultsMedian age was 62 years. Localization of tumor was the mobile tongue for 6 patients, floor of mouth for 2, cheek for 1, and gingiva for 1. Six patients had pT2N0 tumors (AJCC 7th edition) and 4 had pT1N0. Mean CTV and PTV volumes were 36.4 and 56.1 cc respectively. Mean PTV coverage by the 36 Gy isodose was 98.2 % for both techniques (p = ns), with comparable conformity indexes (1.1 for VMATc vs 1.07 for VMATc + nc; p = 0.23). VMATc + nc had a significantly better gradient index (3.45 vs 2.97; p = 0.01), resulting in a significantly better sparing of most organs at risk. For example, mean Dmean to the oral cavity, lips, and homolateral parotid were respectively of 16.8 Gy, 11.1 Gy, and 10.4 Gy for VMATc vs 14.8 Gy (p = 0.005), 8.1 Gy (p = 0.001), 6.5 Gy (p = 0.04) for VMATc + nc. No grade ≥ 4 or higher acute toxicity was reported. The most common acute toxicity was grade ≥ 2 mucositis. ConclusionVMATc + nc had better dosimetric outcomes than VMATc and has become the standard technique for patients treated in the STEREO POSTOP GORTEC 2017–03 trial (NCT03401840) in our institution. Acute toxicity appears acceptable.

Hypofractionated stereotactic body radiation therapy (SBRT) in pediatric patients: results of a national prospective multicenter study

<h3>Objectives</h3> Efficiency and toxicity of hypofractionated Stereotactic Body Radiation Therapy (SBRT) in pediatric situations need to be assessed. We conducted a prospective multicentric National study on SBRT in young patients (1.5-20 y.) <h3>Methods</h3> Indications of SBRT had to be approved by a multi-disciplinary tumor board. SBRT indications were either locally relapsed ependymoma after complete surgery (randomization between 24 Gy/3 fr or 25 Gy/5 fr, isodose 80%), or brain, lung or spinal metastases of any origin after incomplete or no resection in first-line, or in re-irradiation (re-RT) situations The main objective was to evaluate the 6-month local control (LC) rate (RECIST 1.1). Secondary objectives were to evaluate 1 and 2-year LC rates, acute (< 3 months) and medium-term toxicities (3-24 months) using NCI-CTC-v-4.0. <h3>Results</h3> Sixty-one patients, median age 13y., (range 3-20) were included in 10 institutions (12/2013-12/2019). Four patients did finally not receive SBRT and were excluded from the analysis. Eighteen patients (32%) were irradiated in first intention (5 brain, 5 lung, 8 spinal lesions, median dose 35 Gy/5fr, isodose 80%. Thirty-nine patients (68 %) were included for re-RT: 14 patients (7 patients/randomization arm) for post-operative SBRT for locally relapsed ependymoma, 25 patients for re-RT in other situations (brain, spine, lung…) (median dose 25 Gy/5 fr, isodose 80%). No pt required general anesthesia. Median follow-up was 24 months (22-28 months). Six-month, 1- and 2-year local control rates will be reported during the congress (undergoing analysis). Gr.2 and 3 acute RT toxicities were observed in 7 and 1 (epilepsy) patients respectively. Medium-term RT toxicity was identified in 4 patients (gr.2) and 1 patients (gr.3, brain radio-necrosis). No grade 4/5 was reported. <h3>Conclusion</h3> SBRT is feasible and safe in childhood in selected brain, lung and spine treatment or in selected cases of re-RT. More details (especially efficiency) will be available for the congress.

In Situ Real-Time Dosimetric Studies for Spine Stereotactic Body Radiation Therapy in a Cadaver Implanted with Carbon-Fiber and Titanium Instrumentation

We sought to compare the dosimetric accuracy of postoperative stereotactic body radiation therapy in a carbon-fiber (CF) versus titanium instrumented spine using a cadaveric model. In situ cadaveric implantation of titanium and CF instrumentation and dosimeter chips in a thoracic spine. The cadaver underwent stereotactic body radiation therapy, and a dose of radiation therapy was calculated, measured, and compared. The sensors were placed in positions to provide data on dosimetry near the screws (within 1 cm) and between the screws. The differences between calculated and measured doses were reported as percentages. There was a significant difference in the dosimetry from calculated versus measured values near the screws of CF compared with titanium (P= 0.0057) with a mean percentage difference of only 2.93 for CF and a much higher value of 19.32 for titanium near the screws. There was also greater variability in the percent difference for the 2 screw types, with differences ranging from-16.54% to 35.20% near titanium screws and-3.37% to 1.66% near CF screws. More accurate dosimetry and radiation therapy delivery with CF screws compared with traditional titanium screws may have implications on optimal radiation delivery, as well as complication avoidance. This may be due to reduced scatter and thus lower variability in radiation delivery with the volumetric modulated arc therapy technique.

Feasibility of postoperative spine stereotactic body radiation therapy in proximity of carbon and titanium hybrid implants using a robotic radiotherapy device

Background and purposeTo assess the feasibility of postoperative stereotactic body radiation therapy (SBRT) for patients with hybrid implants consisting of carbon fiber reinforced polyetheretherketone and titanium (CFP-T) using CyberKnife.Materials and methodsAll essential steps within a radiation therapy (RT) workflow were evaluated. First, the contouring process of target volumes and organs at risk (OAR) was done for patients with CFP-T implants. Second, after RT-planning, the accuracy of the calculated dose distributions was tested in a slab phantom and an anthropomorphic phantom using film dosimetry. As a third step, the accuracy of the mandatory image guided radiation therapy (IGRT) including automatic matching was assessed using the anthropomorphic phantom. For this goal, a standard quality assurance (QA) test was modified to carry out its IGRT part in presence of CFP-T implants.ResultsUsing CFP-T implants, target volumes could precisely delineated. There was no need for compromising the contours to overcome artifact obstacles. Differences between measured and calculated dose values were below 11% for the slab phantom, and at least 95% of the voxels were within 5% dose difference. The comparisons for the anthropomorphic phantom showed a gamma-passing rate (5%, 1 mm) of at least 97%. Additionally the test results with and without CFP-T implants were comparable. No issues concerning the IGRT were detected. The modified machine QA test resulted in a targeting error of 0.71 mm, which corresponds to the results of the unmodified standard tests.ConclusionDose calculation and delivery of postoperative spine SBRT is feasible in proximity of CFP-T implants using a CyberKnife system.

Adjuvant stereotactic body radiotherapy after marginal resection for hepatocellular carcinoma with microvascular invasion: A randomised controlled trial

BackgroundMarginal resection frequently occurred in hepatectomy for hepatocellular carcinoma (HCC), leading to increased local recurrence, especially among patients with microvascular invasion (MVI). Stereotactic body radiotherapy (SBRT) showed effectiveness in controlling tumour and tumour thrombosis. This study aimed to investigate the efficacy of SBRT, targeting on suboptimal resection margin, as adjuvant setting in MVI-positive HCC. MethodsThis was a single-centre randomised controlled trial conducted in Eastern Hepatobiliary Surgery Hospital, Shanghai, China. Participants with MVI-positive HCC receiving marginal resection were randomly assigned to the postoperative adjuvant SBRT or surgery alone (SA) group. SBRT was delivered by the CyberKnife® system with marker tracking devices, targeting on resection margin one month after surgery. The disease-free survival (DFS) and overall survival (OS) were compared between the groups, and the adverse events (AEs) were monitored. This trial was registered on ClinicalTrials.gov, NCT04891874. FindingsA total of 76 participants were enrolled, with 38 in each group. The one-, three-, and five-year DFS rates were 92.1%, 65.8%, and 56.1% in SBRT group versus 76.3%, 36.8%, and 26.3% in SA group, respectively (p = 0.005). The one-, three-, and five-year OS rates were 100%, 89.5%, and 75.0% in SBRT group versus 100.0%, 68.4%, and 53.7% in SA group, respectively (p = 0.053). The total dose of SBRT for single participant was 35 Gy, and the biological effective dose (BED) was 59.5 Gy. The overall incidence of radiotherapy-related AE was 31.6% (12/38), and no grade 3 or higher grade AE was developed. InterpretationSBRT on the resection margin provides a safe therapeutic modality of adjuvant setting in MVI-positive HCC with suboptimal resection margin. It prevents local recurrence and improves DFS. Trial registration numberNCT04891874.

Postoperative Stereotactic Body Radiotherapy for Spinal Metastasis and Predictors of Local Control

Postoperative Stereotactic Body Radiotherapy for Spinal Metastasis and Predictors of Local Control

Patterns of Failure After SBRT Reirradiation for Recurrent Head and Neck Cancer

Stereotactic body radiotherapy (SBRT) is an emerging modality for the reirradiation of head and neck cancers (HNC). The need to use smaller reirradiation volumes to limit severe toxicity concerns represents a challenge in determining optimal target coverage. Herein, we investigate the associated patterns of failure after SBRT using previously defined spatial and dosimetric analysis (Mohamed et al, Radiat Oncol. 2017).SBRT reirradiation HNC cases treated between 2014-2019 and surveilled by CT, PET/CT, and/or MRI were reviewed retrospectively in this IRB approved study. Patients with radiographic evidence of recurrence within the head and neck region after SBRT were identified. Multifocal disease was defined as any non-contiguous FDG-avid or biopsy positive disease seen on imaging. Diagnostic scans were co-registered with planning CT scans (pCT) for manual segmentation of recurrent gross volumes (rGTV). rGTVs were then deformed to co-registered pCTs for failure classification. The classification followed a granular typology of 5 failure categories: central high-dose (type A or "in-field"), peripheral high-dose (type B), central low-dose (type C), peripheral low-dose (type D or "marginal"), and extraneous-dose (type E or "out of field"). Each type was determined based on the centroid location of rGTV relative to the planning target volumes plus the dose received by 95% of rGTV volume.A total of 106 SBRT cases were reviewed out of which 34 patients (32%) recurred after SBRT; 27 (79%) patients had squamous cell carcinomas, 7 (21%) received postoperative SBRT, and 24 (71%) received concurrent systemic therapy. Twenty-three (68%) patients received 42.5-45 Gy in 5 fractions (Fx) and 7 (21%) patients received 36 Gy in 6 Fx. Median time to failure was 5.5 months (range, 1-22 months). Twenty-two recurrences (65%) were out-of-field type E failures, 6 (18%) type A, 3 (9%) type C, and 3 (9%) type D. Fourteen of 16 (88%) multifocal SBRT reirradiation cases had Type E failures compared to 8 of 18 (44%) unifocal SBRT cases. Among the 6 in-field failures, 3 received 36 Gy in 6 Fx and 3 received 42.5-45 Gy in 5 Fx.Post SBRT reirradiation recurrences were seen in one-third of cases with the majority of failures being Type E (outside the treatment field), particularly in patients who were treated for multifocal disease. The use of 42.5-45 Gy in 5 Fx appears to be an effective biological dose for local tumor control. Marginal (Type C and D) failures may be reduced with larger margins, but limit feasibility of SBRT. Therefore, future reirradiation strategies should aim to improve patient selection, multimodal therapy, and margin definition in the HNC SBRT reirradiation setting.

Commentary: Postoperative Stereotactic Body Radiotherapy for Spinal Metastasis and Predictors of Local Control.

Commentary: Postoperative Stereotactic Body Radiotherapy for Spinal Metastasis and Predictors of Local Control.

Postoperative Stereotactic Body Radiotherapy for Spinal Metastasis and Predictors of Local Control.

Spine surgery is indicated for select patients with mechanical instability, pain, and/or malignant epidural spinal cord compression, with or without neurological compromise. Stereotactic body radiotherapy (SBRT) is an option for durable local control (LC) for metastatic spine disease. To determine factors associated with LC and progression-free survival (PFS) for patients receiving postoperative stereotactic spine radiosurgery. We analyzed consecutive patients from 2013 to 2019 treated with surgical intervention followed by SBRT. Surgical interventions included laminectomy and vertebrectomy. SBRT included patients treated with 1 to 5 fractions of radiosurgery. We analyzed LC, PFS, overall survival (OS), and toxicity. Univariate and multivariate analyses were performed. A total of 63 patients were treated with a median follow-up of 12.5 mo. Approximately 75% of patients underwent vertebrectomy and 25% underwent laminectomy. One-year cumulative incidence of local failure was 19%. LC was significantly improved for patients receiving radiosurgery ≤40 d from surgery compared to that for patients receiving radiosurgery ≥40 d from surgery, 94%vs 75%, respectively, at 1 yr (P=.03). Patients who received preoperative embolization had improved LC with 1-yr LC of 88%vs 76% for those who did not receive preoperative embolization (P=.037). Significant predictors for LC on multivariate analysis were time from surgery to radiosurgery, higher radiotherapy dose, and preoperative embolization. The 1-yr PFS and OS was 56% and 60%, respectively. Postoperative radiosurgery has excellent and durable LC for spine metastasis. An important consideration when planning postoperative radiosurgery is minimizing delay from surgery to radiosurgery. Preoperative embolization and higher radiotherapy dose were associated with improved LC warranting further study.

Narrow-Margin Hepatectomy Resulted in Higher Recurrence and Lower Overall Survival for R0 Resection Hepatocellular Carcinoma.

PurposeTo evaluate the impact of resection margin on recurrence pattern and survival for hepatocellular carcinoma (HCC) with narrow margin resection, with the aim to guide postoperative treatment.Materials and MethodsTwo hundred forty HCC patients after curative hepatectomy between 2014 and 2016 were reviewed retrospectively. The cases were divided into narrow-margin (width of resection margin <1cm, n=106) and wide-margin (width of resection margin ≥1cm, n=134) groups based on the width of resection margin. Recurrence pattern, recurrence-free survival (RFS), and overall survival (OS) were compared between the above two groups. An additional cohort of nine cases with positive margin plus post-operative stereotactic body radiotherapy (SBRT) was also analyzed for the recurrence pattern.ResultsPostoperative recurrence was found in 128 (53.3%) patients. The recurrence rate was significantly higher in narrow-margin group than that in wide-margin group (P=0.001), especially for the pattern of marginal recurrence (20.8 vs. 4.5%, P=0.003). The 1-, 2-, 3-year RFS rates for the narrow-margin and wide-margin groups were 55.8, 43.9, 36.9, and 78.7, 67.9, 60.2%, respectively, with significant difference between the two groups (P<0.001). Patients with narrow margin showed a tendency of decreased OS than those with wide margin (P<0.001). As comparison, the nine cases with positive margin treated with postoperative SBRT showed low recurrence rate and no marginal recurrence was found.ConclusionPatients with narrow resection margin were associated with higher recurrence rate and worse survival than those with wide resection margin. These patients may benefit from adjuvant local treatment, such as radiotherapy.

Adjuvant Stereotactic Body Radiotherapy After Marginal Resection for Hepatocellular Carcinoma With Micro-Vascular Invasion: A Randomized Controlled Trial

Background: Marginal resection frequently occurred in hepatectomy for hepatocellular carcinoma (HCC), which led to increased local recurrence, especially among patients with microvascular invasion (MVI). Stereotactic body radiotherapy (SBRT) shows effective in tumor controlling, while limited research reported the efficacy of SBRT as adjuvant setting for HCC after surgery. We hypothesized existence of residual tumor cells or foci in unsafe margin parenchyma caused local recurrence in HCC patients with MVI, and SBRT might be a solution to resolve the problem. This study aimed to investigate the efficacy of SBRT targeting on the susceptible area with residue MVI as adjuvant setting for HCC patients. Methods: This was a single center, randomized controlled trial conducted in Eastern Hepatobiliary Surgery Hospital, Shanghai, China. Participants with HCC and MVI receiving marginal resection were randomly assigned to postoperative adjuvant SBRT group or surgery alone (SA) group. SBRT was delivered by the CyberKnife® system (Accuracy Inc., Sunnyvale) with marker tracking devices. Patients in SBRT group received SBRT targeting on the resection marginal parenchyma where MVI most likely occurred one month after surgery. The disease-free survival (DFS) and overall survival (OS) were compared between the groups and the adverse events (AE) in the SBRT group were monitored. This trial was registered with ClinicalTrials.gov, NCT04891874. Findings: A total of 76 participants were enrolled from August 1, 2015 to December 31, 2016, with 38 in each group. The 1-, 3-, and 5-year DFS rates were 92.1%, 65.8%, and 56.1% in the SBRT group, versus 76.3%, 36.8%, and 26.3% in the SA group, respectively (p=0.005). The 1-, 3-, and 5-year OS rates were 100%, 89.5%, and 75.0% in the SBRT group, versus 100.0%, 68.4%, and 53.7% in the SA group, respectively (p=0.053). The total dose of SBRT for each participant was 35Gy and the biological effective dose (BED) is 59.5 Gy. The overall incidence of radiotherapy related AE was 31.6% (12/38), and no grade 3 or higher grade AE developed. Fatigue was the most frequent AE. Interpretation: SBRT on resection marginal parenchyma provides a safe therapeutic modality of adjuvant setting in MVI-positive HCC participants without satisfying resection margin. It prevents local recurrence and improves disease-free survival. Further evidence is necessary to evaluate its long-term survival outcome. Clinical Trial Registration Details: This trial was registered with ClinicalTrials.gov, NCT04891874. Funding Information: This research has received funding from the ‘Clinical science and technology innovation project of Shenkang Hospital Development Center’ (SHDC12020104). Declaration of Interests: The authors disclose no conflicts. Ethics Approval Statement: Detailed information of the clinical protocol was explained to every participants and written informed consent were collected before randomization. This trial was approved by the Institutional Ethics Committee of Shanghai Eastern Hepatobiliary Surgery Hospital. The study protocol conformed to the principles of Declaration of Helsinki (1983).

RADT-08. ADJUVANT SBRT FOR RESECTED BRAIN METASTASES: THE EFFECT OF TIMING ON LONG-TERM INTENDED-FIELD CONTROL

Abstract INTRODUCTION Adjuvant stereotactic body radiation therapy (SBRT) improves the local control of resected brain metastases (BrM). However, the dependency of long-term outcomes on SBRT timing relative to surgery remains unclear. METHODS Retrospective analysis of metastasectomy-plus-adjuvant-SBRT patients at Memorial Sloan Kettering (MSK) between 2013-2016 was conducted. Kaplan-Meier methodology was used to describe overall survival (OS) and cumulative incidence in a competing-risks setting recurrence at the surgical site, other SBRT-treated sites, and elsewhere in the brain as defined by RANO-BM criteria. Recursive partitioning analysis (RPA) and competing-risks regression modeling assessed prognostic variables and associated events of interest. RESULTS Two hundred eighty-two patients with BrM including non-small cell lung (34%), breast (16%), melanoma (13%), and other cancers were included. Median time-to-adjuvant-SBRT (TT-SBRT) was 34 days (IQR: 27-39). Median overall survival (OS) from SBRT was 1.5 years (95% CI: 1.2-2.1) with median follow-up of 49.8 months for survivors. Local surgical recurrence, other irradiated-site, and distant progression rates were 14.3% (95%CI: 10.1-18.5), 4.9% (95%CI: 2.3-7.5), and 47.5% (95%CI: 41.4-53.6) at 5 years, respectively. TT-SBRT as a continuous variable significantly associated with surgical-site recurrence (HR 1.05 [1.02-1.07], p=0.0003), but not with distant or other irradiated-site recurrence nor OS. RPA analysis demonstrated the greatest control rate advantage with TT-SBRT &amp;lt; 39 days (HR for 39+ days: 2.81 [1.50-5.27], p=0.001). No association of TT-SBRT with radiation necrosis, wound complication, or development of leptomeningeal dissemination was identified. CONCLUSIONS Delays in initiation of post-operative SBRT can decrease its efficacy. Efforts must be made to minimize logistical, procedural, and socioeconomic factors responsible for these delays.