Darby Erler

Predictors of Chest Wall Toxicity after Lung Stereotactic Ablative Radiotherapy

AIMS To determine the incidence and predictive factors of rib fracture and chest wall pain after lung stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS Patients were treated with lung SABR of 48-60 Gy in four to five fractions. The treatment plan and follow-up computed tomography scans of 289 tumours in 239 patients were reviewed. Dose-volume histogram (DVH) metrics and clinical factors were evaluated as potential predictors of chest wall toxicity. RESULTS The median follow-up was 21.0 months (range 6.2-52.1). Seventeen per cent (50/289) developed a rib fracture, 44% (22/50) were symptomatic; the median time to fracture was 16.4 months. On univariate analysis, female gender, osteoporosis, tumours adjacent (within 5 mm) to the chest wall and all of the chest wall DVH metrics predicted for rib fracture, but only tumour location adjacent to the chest wall remained significant on the multivariate model (P < 0.01). The 2 year fracture-free probability for those adjacent to the chest wall was 65.6%. Among those tumours adjacent to the chest wall, only osteoporosis (P = 0.02) predicted for fracture, whereas none of the chest wall DVH metrics were predictive. Eight per cent (24/289) experienced chest wall pain without fracture. CONCLUSIONS None of the chest wall DVH metrics independently predicted for SABR-induced rib fracture when tumour location is taken into account. Patients with tumours adjacent (within 5 mm) to the chest wall are at greater risk of rib fracture after lung SABR, and among these, an additional risk was observed in osteoporotic patients.

Stereotactic body radiation therapy for non-spine bone metastases—a review of the literature

BACKGROUND Stereotactic body radiation therapy (SBRT) has the ability to deliver significantly higher biologically equivalent doses (BED) compared to conventional radiation treatment. The main goal of SBRT is to improve local tumor control while reducing pain. The side effects however may be greater than those of conventional treatment. METHODS A review of the literature was conducted and articles pertaining to studies of SBRT in non-spine bone metastases were included. Data on outcomes and toxicities were collected in addition to inclusion and exclusion criteria for each study. RESULTS A total of 14 studies were included in this review. Very rarely were grade 3 and 4 toxicities reported. Endpoints for the studies varied significantly, which made conclusions of overall local control and progression free survival near impossible. In studies that reported local control rates, these rates were all greater than 85%. Progression free survival varied significantly between studies. CONCLUSIONS Due to the lack of consistency in endpoint definitions, it is difficult to compare outcomes across trials. There is a need for consensus in endpoint definitions.

Radiological changes on CT after stereotactic body radiation therapy to non-spine bone metastases: a descriptive series

BACKGROUND In recent years, stereotactic body radiation therapy (SBRT) has become increasingly used for the management of non-spine bone metastases. Few studies have examined the radiological changes in bone metastases after treatment with SBRT and there is no consensus about what constitutes radiologic response to therapy. This article describes various changes on CT after SBRT to non-spine bone metastases in eight selected cases. METHODS A retrospective review was conducted for patients treated with SBRT to non-spine bone metastases between November 2011 and April 2014 at Sunnybrook Health Sciences Centre. A musculoskeletal radiologist identified eight illustrative cases of interest and provided a description of the findings. RESULTS Different radiological changes following SBRT were described, including: remineralization of lytic bone metastases, demineralization of sclerotic bone metastases, pathologic fracture, size progression and response in different lesions, as well as lung fibrosis after SBRT to a rib metastasis. CONCLUSIONS We reviewed the radiological images of eight selected cases after SBRT to nonspine bone metastases and a number of characteristic findings were highlighted. We recommend future studies to correlate radiologic changes with clinical outcomes including pain relief, toxicity and long-term local control.

Local control and fracture risk following stereotactic body radiation therapy for non-spine bone metastases

AIMS To report local control and toxicity rates for patients treated with stereotactic body radiotherapy (SBRT) for non-spine bone metastases. METHODS AND MATERIALS Eighty-one patients with 106 non-spine bone metastases were treated between 2011 and 2014 and retrospectively reviewed. Indications included: oligometastases (63%), oligoprogression (17.3%), retreatment (2.4%) or other (17.3%). Cumulative incidence function was used to assess local recurrence and fracture probability. Bivariate relationships were investigated based on selected patient, tumour and dose-volume factors. RESULTS Mean follow-up was 13 months (range, 0.25-45.6) and the median patient age was 66.4 years (range, 36-86). Most patients were male (60.5%) and the predominant histology prostate cancer (32%). Bone metastases were most commonly located in the pelvis (41.5%) and almost half sclerotic. The most common prescriptions were 30 Gy/5 (30.2%) and 35 Gy/5 (42.5%). The cumulative incidence of local recurrence at 6,18 and 24 months respectively was 4.7%, 8.3% and 13.3% with a mean time to local recurrence of 11.8 months (range, 3.9-23.4). A significant association was found between local recurrence and volume of the PTV (p = 0.02), with larger PTVs having a greater risk of local failure. Fracture was observed radiographically in the treatment volume in 9/106 (8.5%) of treated lesions and the mean time to fracture was 8.4 months (range, 0.7-32.5 months). With respect to predictors, a trend was observed for lytic lesions (p = 0.11) and female gender (p = 0.09). CONCLUSIONS The results of this study confirm that SBRT yields high rates of long-term local control for non-spine bone metastases with a low fracture risk.

Evaluation of kidney motion and target localization in abdominal SBRT patients

The purpose of this study was to evaluate bilateral kidney and target translational/rotational intrafraction motion during stereotactic body radiation therapy treatment delivery of primary renal cell carcinoma and oligometastatic adrenal lesions for patients immobilized in the Elekta BodyFIX system. Bilateral kidney motion was assessed at midplane for 30 patients immobilized in a full-body dual-vacuum-cushion system with two patients immobilized via abdominal compression. Intrafraction motion was assessed for 15 patients using kilovoltage cone-beam computed tomography (kV-CBCT) datasets (n=151) correlated to the planning CT. Patient positioning was corrected for translational and rotational misalignments using a robotic couch in six degrees of freedom if setup errors exceeded 1 mm and 1°. Absolute bilateral kidney motion between inhale and exhale 4D CT imaging phases for left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions was 1.51±1.00mm,8.10±4.33mm, and 3.08±2.11mm, respectively. Residual setup error determined across CBCT type (pretreatment, intrafraction, and post-treatment) for x (LR), y (SI), and z (AP) translations was 0.63±0.74mm,1.08±1.38mm, and 0.70±1.00mm; while for x (pitch), y (roll), and z (yaw) rotations was 0.24±0.39°,0.19±0.34°, and 0.26±0.43°, respectively. Targets were localized to within 2.1 mm and 0.8° 95% of the time. The frequency of misalignments in the y direction was significant (p<0.05) when compared to the x and z directions with no significant difference in translations between IMRT and VMAT. This technique is robust using BodyFIX for patient immobilization and reproducible localization of kidney and adrenal targets and daily CBCT image guidance for correction of positional errors to maintain treatment accuracy. PACS number(s): 87.55.-x, 87.56.-v, 87.56.Da.The purpose of this study was to evaluate bilateral kidney and target translational/rotational intrafraction motion during stereotactic body radiation therapy treatment delivery of primary renal cell carcinoma and oligometastatic adrenal lesions for patients immobilized in the Elekta BodyFIX system. Bilateral kidney motion was assessed at midplane for 30 patients immobilized in a full‐body dual‐vacuum‐cushion system with two patients immobilized via abdominal compression. Intrafraction motion was assessed for 15 patients using kilovoltage cone‐beam computed tomography (kV‐CBCT) datasets (n=151) correlated to the planning CT. Patient positioning was corrected for translational and rotational misalignments using a robotic couch in six degrees of freedom if setup errors exceeded 1 mm and 1°. Absolute bilateral kidney motion between inhale and exhale 4D CT imaging phases for left–right (LR), superior–inferior (SI), and anterior–posterior (AP) directions was 1.51±1.00mm,8.10±4.33mm, and 3.08±2.11mm, respectively. Residual setup error determined across CBCT type (pretreatment, intrafraction, and post‐treatment) for x (LR), y (SI), and z (AP) translations was 0.63±0.74mm,1.08±1.38mm, and 0.70±1.00mm; while for x (pitch), y (roll), and z (yaw) rotations was 0.24±0.39°,0.19±0.34°, and 0.26±0.43°, respectively. Targets were localized to within 2.1 mm and 0.8° 95% of the time. The frequency of misalignments in the y direction was significant (p<0.05) when compared to the x and z directions with no significant difference in translations between IMRT and VMAT. This technique is robust using BodyFIX for patient immobilization and reproducible localization of kidney and adrenal targets and daily CBCT image guidance for correction of positional errors to maintain treatment accuracy. PACS number(s): 87.55.‐x, 87.56.‐v, 87.56.Da

The safety and effectiveness of stereotactic body radiotherapy for central versus ultracentral lung tumors

BACKGROUND AND PURPOSE Recent studies have postulated that patients undergoing lung stereotactic body radiotherapy (SBRT) for ultracentral tumors have higher toxicity and mortality rates than those with central tumors. Our aim was to compare the outcomes after lung SBRT for central versus ultracentral tumors in our own series. MATERIAL AND METHODS This was a retrospective review of patients with primary and metastatic lung tumors treated with SBRT from 1 September 2009 to 30 June 2015. Patients were included if they were treated with five-fraction SBRT to central or ultracentral tumors. Central tumors were defined as tumors where the closest point was within 2 cm of (but not abutting) the proximal bronchial tree, or within 2 cm of (whether abutting or not) mediastinal structures. Ultracentral tumors were defined as tumors abutting the proximal bronchial tree. The 2-year overall survival (OS), 2-year local failure (LF), and 2-year grade ≥3 toxicity rates were compared between patients with central and ultracentral tumors. RESULTS A total of 107 patients were included in this study. There were no significant differences in 2-year OS between the two groups, with 2-year OS 57.7% for central tumors, and 50.4% for ultracentral tumors (p = 0.10). There were no significant differences in 2-year LF between the two groups, with 2-year LF 3.4% for central tumors and 4.3% for ultracentral tumors (p = 0.92). There were no significant differences in 2-year grade ≥3 toxicity rate for the two groups, with 3.5% with central tumors and 8.7% with ultracentral tumors (p = 0.23). CONCLUSIONS There were no significant differences in OS, LF, or grade ≥3 toxicity between patients with central and ultracentral lung tumors. Although these results indicate that SBRT for ultracentral tumors may be safe, caution should be applied in selecting and treating these patients until the completion of large prospective trials.

Multisite stereotactic body radiotherapy for metastatic non-small-cell lung cancer: Delaying the need to start or change systemic therapy?

OBJECTIVES The purpose of this study was to review the clinical outcomes following the use of stereotactic body radiotherapy (SBRT) in patients with metastatic non-small-cell lung cancer (NSCLC) from a large academic institution. MATERIALS AND METHODS Metastatic NSCLC patients treated with extracranial SBRT were identified from an institutional database. Treatment indications were: (1) oligometastases, (2) oligoprogression, and (3) local control of dominant tumors. Endpoints included overall survival (OS), progression-free survival (PFS), time to starting/changing systemic therapy (SCST), and local failure (LF). Univariate and multivariable analyses were performed to look for predictive factors. RESULTS 108 patients with 165 tumors were treated. SBRT was delivered for oligometastases in 66 patents, for oligoprogression in 20 patients, and for local control in 22 patients. Median OS and PFS for all patients were 27.3 months and 4.4 months, respectively, with treatment indication being the only predictive factor on multivariable analysis (patients with oligometastases having the highest median OS and PFS of 39.3 months and 7.6 months respectively). Cumulative incidence of SCST was only 21.5% at 1 year after SBRT, with larger tumor size and positivity for EGFR/ALK mutation being predictive of higher rates of SCST on multivariable analysis. LF was 15.6% at 1 year, with larger tumor size and exposure to previous systemic therapy being predictive of higher rates of LF on multivariable analysis. CONCLUSION Patients treated with SBRT for oligometastases have better OS and PFS than those treated for oligoprogression or for local control of dominant tumors. Use of SBRT may delay the need for SCST. Larger tumors and previous exposure to systemic therapy were predictive of higher rates of LF.

A multinational report of technical factors on stereotactic body radiotherapy for oligometastases

AIM Oligometastatic cancer is being increasingly managed with aggressive local therapy using stereotactic body radiation therapy (SBRT). However, few guidelines exist. We summarize the results of an international survey reviewing technical factors for extracranial SBRT for oligometastatic disease to guide safe management. MATERIALS & METHODS Seven high-volume centers contributed. Levels of agreement were categorized as strong (6-7 common responses), moderate (4-5), low (2-3) or no agreement. RESULTS & CONCLUSION We present the results of a multi-national and multi-institutional survey of technical factors of SBRT for extracranial oligometastases. Key methods including target delineation, prescription doses, normal tissue constraints, imaging and set-up for safe implementation and practice of SBRT for oligometastasis have been identified. This manuscript will serve as a foundation for future clinical evaluations.

Quantifying Health Utilities in Patients Undergoing Stereotactic Body Radiation Treatment for Liver Metastases for Use in Future Economic Evaluations

AIM Stereotactic body radiation therapy (SBRT) is increasingly used as an option for those with liver metastases. In order to facilitate future economic impact of health technologies, health utility scores may be used. The EuroQOL-5D-3L (EQ-5D) preference-based healthy utility instrument was used to evaluate the impact of treatment with SBRT on health utility scores. MATERIALS AND METHODS Between August 2013 and October 2014, 31 patients treated with 3-5 fractions of SBRT for liver metastases were enrolled in this study. The EQ-5D instrument was administered at baseline, during and up to 6 months post-SBRT. RESULTS Mean EQ-5D score at baseline was 0.857, which remained stable across the entire study time period. Transient increases in difficulties with mobility (9.7% reported at baseline to 16.1% on the last day of treatment) and usual activities (3.2% reported at baseline to 34.5% on day two) were found during the course of treatment; these returned to baseline levels subsequently. The mean visual analogue score at baseline was 65.8 and remained unchanged throughout treatment and follow-up. CONCLUSIONS The stability of health utility scores and problems reported by patients undergoing treatment indicate that SBRT for liver metastases does not impart a significant adverse effect on quality of life. These results may be used for future economic evaluation of SBRT.

58: Acute Quality of Life Changes after Stereotactic Ablative Radiotherapy for Liver Metastasis: A Prospective Cohort Analysis

Abstract Purpose To report the changes in quality of life (QoL) after stereotactic ablative radiotherapy (SABR) in patients with liver metastases (LM). Materials and methods A prospective cohort study was undertaken to measure the acute changes in QoL after SABR. Patients with 1–3 treated LM were eligible. Doses of 30–60 Gy in 3–5 fractions were delivered. Prospective QoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires, Core 15 for Palliative Care (EORTC QLQ-C15-PAL) and liver metastases (LM21), at baseline, 1st week and last day of treatment, then 1, 6 and 12 weeks after SABR. The functional living index-emesis (FLIE) was collected at baseline, 1st week, last day and 1 week after treatment. Univariable and multivariable linear mixed modeling were performed as appropriate to assess changes in QoL over time. Results Sixty patients were included. The most common primary cancer was colorectal (42%). The global health score measured by QLQ-C15-PAL was significantly worse at treatment completion (p = 0.001), 1 week (p = 0.003) and 6 weeks (p = 0.002) after SABR but recovered by 12 weeks (p = 0.124). Nausea and constipation were worse at treatment completion (p  Conclusion SABR offers a non-invasive mean of ablating LM with minimal impact on acute QoL.