Coronary vasomotor dysfunction in cancer survivors treated with thoracic irradiation.

BACKGROUND: We sought to test the hypothesis that thoracic radiation therapy (RT) is associated with impaired myocardial flow reserve (MFR), a measure of coronary vasomotor dysfunction. METHODS: We retrospectively studied thirty-five consecutive patients (71% female, mean ± standard deviation (SD) age: 66 ± 11 years) referred clinically for positron emission tomography/computed tomography (PET/CT) myocardial perfusion imaging at a median (interquartile range, IQR) interval of 4.3 (2.1, 9.7) years following RT for a variety of malignancies. Radiation dose-volume histograms were generated for the heart and coronary arteries for each patient. RESULTS: The median (IQR) of mean cardiac radiation doses was 12.0 (1.2, 24.2) Gray. There were significant inverse correlations between mean radiation dose and global MFR (MFRGlobal) and MFR in the left anterior descending artery territory (MFRLAD): Pearson's correlation coefficient = - .37 (P = .03) and - .38 (P = .03), respectively. For every one Gray increase in mean cardiac radiation dose, there was a mean ± standard error decrease of .02 ± .01 in MFRGlobal (P = .04) and MFRLAD (P = .03) after adjustment. CONCLUSIONS: In patients with a history of RT clinically referred for cardiac stress PET, we found an inverse correlation between mean cardiac radiation dose and coronary vasomotor function.

Prospective Evaluation of the Clinical Benefits of a Novel Tattoo-less Workflow for Nonspine Bone Stereotactic Body Radiation Therapy: Integrating Surface-Guidance With Triggered Imaging Reduces Treatment Time and Eliminates the Need for Tattoos.

PURPOSE: Oligometastatic disease has expanded the indications for nonspine bone stereotactic body radiation therapy (NSB SBRT). We investigated whether optical surface monitoring systems (OSMS) could enable tattoo-less setup and substitute for 2-dimensional/3-dimensional or cone beam computed tomography (CBCT)-based mid-imaging in NSB SBRT. METHODS AND MATERIALS: OSMS was incorporated in parallel with an existing workflow using pretreatment CBCT and 2-dimensional/3-dimensional kV/kV mid-imaging beginning November 2019. The ability of OSMS to detect out-of-tolerance (>2 mm/>2°) and commanded couch shifts was analyzed. A workflow incorporating OSMS reference captures, CBCT for pretreatment verification, and OSMS/triggered imaging (TI) for intrafraction monitoring was developed for rib/sternum SBRT beginning November 2021 and all NSB SBRT beginning February 2022. Treatment time and CBCT-related radiation dose between the OSMS and the non-OSMS intrafraction monitoring group was analyzed pre- and post-OSMS/TI workflow adoption. All fractions were analyzed through statistical process control with use of an XmR chart of treatment time per quarter from February 2019 to February 2023. Special cause rules were based on Institute for Healthcare Improvement criteria. RESULTS: From February 2019 to February 2023, 1993 NSB SBRT fractions were delivered, including 234 rib, 109 sternum, 214 ilium, and 682 multisite. Over 20 commanded shifts, OSMS could detect 2-mm shifts to within 0.4 mm 67% of the time and 0.8 mm 95% of the time. All NSB SBRT sites showed significant reductions in treatment time, including the greatest improvement in rib total treatment (21.6-13.4 minutes; P = 1.16 × 10-17) and beam time (7.9-3.2 minutes; P = 7.32 × 10-27). Significant reductions in CBCT-related radiation were also observed for several NSB sites. These process improvements were associated with OSMS adoption. CONCLUSIONS: Adoption of a novel NSB SBRT workflow incorporating OSMS/TI for bone intrafraction motion monitoring reduced treatment time and CBCT-related radiation exposure while also allowing for more continuous intrafraction motion monitoring for NSB SBRT. OSMS/TI enabled the transition to a tattoo-less workflow.

Clinical Outcomes Among Patients Treated With Stereotactic Body Radiation Therapy to Femur Metastases for Oligometastatic Disease Control or Reirradiation: Results From a Large Single-Institution Experience.

Purpose: There are limited data regarding outcomes after stereotactic body radiation therapy (SBRT) for femur metastases, which was an exclusion criteria for the Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers (SABR-COMET) trial. We aimed to characterize clinical outcomes from a large single institution experience. Methods and Materials: Forty-eight patients with 53 lesions were consecutively treated with femur SBRT from May 2017 to June 2022. The Kaplan-Meier method and Cox proportional hazard models were used to characterize time-to-event endpoints and associations between baseline factors and clinical outcomes, respectively. Local control and locoregional control were defined as the absence of tumor progression within the radiation treatment field or within the treated femur, respectively. Results: Most patients had Eastern Cooperative Oncology Group performance status 0 to 1 (90%), prostate (52%) or breast/lung (17%) cancer, and 1 to 3 lesions (100%), including 29 proximal and 5 distal. Fifty-seven percent of the lesions were treated with concurrent systemic therapy. Median planning target volume was 49.1 cc (range, 6.6-387 cc). Planning target volume V100 (%) was 99% (range, 90-100). Fractionation included 18 to 20 Gy/1F, 27 to 30 Gy/3F, and 28.5-40 Gy/5F. Forty-two percent had Mirels score ≥7 and most (94%) did not have extraosseous extension. Acute toxicities included grade 1 fatigue (15%), pain flare (7.5%), nausea (3.8%), and decreased blood counts (1.9%). Late toxicities included fracture (1.9%) at 1.5 years and osteonecrosis (4%) from dose of 40 Gy in 5F and 30 Gy in 5F (after prior 30 Gy/10F). One patient (2%) required fixation postradiation for progressive pain. With median follow-up 19.4 months, 1- and 2-year rates of local control were 94% and 89%, locoregional control was 83% and 67%, progression-free survival were 56% and 25%, and overall survival were 91% and 73%. Fifty percent of local regional recurrence events occurred within 5 cm of gross tumor volume. Conclusions: Femur SBRT for oligometastatic disease control in well-selected patients was associated with good outcomes with minimal rates of acute and late toxicity. Patterns of local regional recurrence warrant consideration of larger elective volume coverage. Additional prospective study is needed.

Association between radiation dose to organs at risk and acute patient reported outcome during radiation treatment for head and neck cancers.

BACKGROUND: Associations between patient-reported outcomes and dose to organs at risk (OARs) may promote management and guide future investigations. METHODS: We retrospectively evaluated PROs and OAR dose in head and neck (H&N) cancer. RESULTS: In 169 patients, we identified weak associations between: "Difficulty swallowing/chewing" and increased mean RT dose to the oral cavity, larynx, pharyngeal constrictor muscles (PCM) and contralateral parotid; "choking/coughing" and larynx mean dose; "problems with mucus in mouth and throat" and oral cavity, contralateral parotid mean dose and parotid V30, contralateral submandibular gland and PCM mean dose; "difficulty with voice/speech" and oral cavity, contralateral parotid, contralateral submandibular gland and larynx mean dose; and "dry mouth" and ipsilateral submandibular gland, oral cavity and PCM mean dose. CONCLUSION: We identified weak associations between PRO and dose to OARs-these data can guide on treatment management, patient counseling, and serve as a baseline for future investigations.

Retrospective Review of Outcomes After Radiation Therapy for Oligoprogressive Disease on Immune Checkpoint Blockade.

PURPOSE: We retrospectively evaluated outcomes after radiation therapy for patients with oligoprogression on immune checkpoint inhibitors (ICI). METHODS AND MATERIALS: We identified patients irradiated to ≤5 progressive lesions while receiving ICI between 2010 and 2020. We excluded patients whose systemic therapy was switched after radiation but before progression. We evaluated predictors of local control (LC), progression-free survival (PFS) and overall survival (OS). RESULTS: We screened 1423 patients and identified 120 who were eligible; the most common histologies were lung cancer (n = 59) and melanoma (n = 36). The median number of oligoprogressive lesions was 1. For the median LC of irradiated oligoprogressive lesions, PFS and OS were not reached at 6.41 (4.67-7.66) and 29.80 (22.54-43.33) months, respectively. Tumor histology, radiated site, or radiation modality were not associated with LC, PFS, or OS. Local response to radiation (P < .0001) and radiation of newly developed lesions (P = .02) were associated with LC. Predictors of PFS on univariate and multivariate analyses were best response to radiation (P = .006) and high programmed death ligand 1 tumor proportion score (P = .02). On multivariate analyses, OS was associated with cumulative oligoprogressive lesion volumes (P = .02) and duration of ICI before oligoprogression (P = .03). CONCLUSIONS: Promising outcomes were observed among patients irradiated for oligoprogression on ICI, especially those with a favorable local response, high tumor programmed death ligand 1 expression, and those receiving ICI for longer periods before oligoprogression. These data can help identify patients well suited for radiation therapy versus those who should switch systemic treatment.

Motion artifacts occurring at the lung/diaphragm interface using 4D CT attenuation correction of 4D PET scans.

For PET/CT, fast CT acquisition time can lead to errors in attenuation correction, particularly at the lung/diaphragm interface. Gated 4D PET can reduce motion artifacts, though residual artifacts may persist depending on the CT dataset used for attenuation correction. We performed phantom studies to evaluate 4D PET images of targets near a density interface using three different methods for attenuation correction: a single 3D CT (3D CTAC), an averaged 4D CT (CINE CTAC), and a fully phase matched 4D CT (4D CTAC). A phantom was designed with two density regions corresponding to diaphragm and lung. An 8 mL sphere phantom loaded with 18F-FDG was used to represent a lung tumor and background FDG included at an 8:1 ratio. Motion patterns of sin(x) and sin4(x) were used for dynamic studies. Image data was acquired using a GE Discovery DVCT-PET/CT scanner. Attenuation correction methods were compared based on normalized recovery coefficient (NRC), as well as a novel quantity "fixed activity volume" (FAV) introduced in our report. Image metrics were compared to those determined from a 3D PET scan with no motion present (3D STATIC). Values of FAV and NRC showed significant variation over the motion cycle when corrected by 3D CTAC images. 4D CTAC- and CINE CTAC-corrected PET images reduced these motion artifacts. The amount of artifact reduction is greater when the target is surrounded by lower density material and when motion was based on sin4(x). 4D CTAC reduced artifacts more than CINE CTAC for most scenarios. For a target surrounded by water equivalent material, there was no advantage to 4D CTAC over CINE CTAC when using the sin(x) motion pattern. Attenuation correction using both 4D CTAC or CINE CTAC can reduce motion artifacts in regions that include a tissue interface such as the lung/diaphragm border. 4D CTAC is more effective than CINE CTAC at reducing artifacts in some, but not all, scenarios.

Patient reported outcomes in patients with head and neck cancer treated with concurrent chemoradiation with weekly versus bolus cisplatin.

BACKGROUND: Patient Reported Outcome (PRO) data comparing bolus (B-CP) with weekly (W-CP) cisplatin concurrent with radiation are lacking. METHODS: We performed a retrospective study comparing PRO among 99 patients with head and neck radiation, 26% who received concurrent B-CP and 73% treated with W-CP. RESULTS: W-CP patients had a higher Charlson comorbidity index (CCI) (P = .004). There were no differences in median cisplatin dose, PROs, percutaneous endoscopic gastrostomy (PEG) dependence or hospitalization between arms. Patients with a greater decline in their self-reported dysphagia score were more often PEG dependent at the end of radiation therapy (P = .03). There was also a trend toward PEG dependence with a higher maximum dysphagia score and greater change in aspiration score (P = .06). The maximum decline in white cell count and absolute neutrophil count were greater in the W-CP group (P = .04, P = .01). CONCLUSION: Both B-CP and W-CP are well tolerated. PROs do not suggest a benefit to W-CP.

Infrared-guided patient setup for lung cancer patients.

PURPOSE: To evaluate the utility of an infrared-guided patient setup (iGPS) system to reduce the uncertainties in the setup of lung cancer patients. METHODS AND MATERIALS: A total of 15 patients were setup for lung irradiation using skin tattoos and lateral leveling marks. Daily electronic portal device images and iGPS marker locations were acquired and retrospectively reviewed. The iGPS-based shifts were compared with the daily electronic portal device image shifts using both the central axis iGPS marker and all five iGPS markers. For shift calculation using the five markers, rotational misalignment was included. The level of agreement between the iGPS and portal imaging to evaluate the setup was evaluated as the frequency of the shift difference in the range of 0-5 mm, 5-10 mm, and >10 mm. RESULTS: Data were obtained for 450 treatment sessions for 15 patients. The difference in the isocenter shifts between the weekly vs. daily images was 0-5 mm in 42%, 5-10 mm in 30%, and >10 mm in 10% of the images. The shifts seen using the iGPS data were 0-5 mm in 81%, 5-10 mm in 14%, and >10 mm in 5%. Using only the central axis iGPS marker, the difference between the iGPS and portal images was <5 mm in 77%, 5-10 mm in 16%, and >10 mm in 7% in the left-right direction and 73%, 18%, and 9% in the superoinferior direction, respectively. When all five iGPS markers were used, the disagreements between the iGPS and portal image shifts >10 mm were reduced from 7% to 2% in the left-right direction and 9% to 3% in the superoinferior direction. Larger reductions were also seen (e.g., a reduction from 50% to 0% in 1 patient). CONCLUSION: The daily iGPS-based shifts correlated well with the daily electronic portal device-based shifts. When patient movement has nonlinear rotational components, a combination of surface markers and portal images might be particularly beneficial to improve the setup for lung cancer patients.

Inter fractional variability of breathing phase definition as determined by fiducial location.

Reconstruction of four-dimensional (4D) imaging typically requires an externally measurable surrogate to represent the real-time relative phase of respiration. A common method is to use a reflective marker on the external surface of the patient which moves with respiration and can be tracked in real time. The location of the marker is often chosen to maximize the observable motion, though this location may not be at the region of interest. We evaluate the importance of infrared (IR) marker placement location on breathing phase definition for the purpose of respiratory gating and 4D computed tomography (CT) image reconstruction. Data were collected for ten patients enrolled on an approved IRB protocol. Real-time position data were collected during CT imaging and daily treatments for two external IR reflective markers: one placed near the xyphoid and another at the approximate location of the treatment isocenter. Motion traces from the markers were compared using cross-correlation coefficient and by estimating the relative respiratory phase, based on either marker, as would be used for 4D-CT reconstruction. Cross-correlation analysis revealed differences in the motion waveform, as well as phase differences, both of which were variable between patients as well as day to day for the same patient. Estimated relative phases from each marker were compared by the percentage amount of time the estimated phase for each marker was different, binned based on increments of 10% of a full cycle. For all collected data combined, the frequency with which breathing phase mismatch led to different bin allocation in steps of 10% was as follows: T0%-10% = 65.1%, T10%-20% = 25.3%, T20%-30% = 7.8%, T30%-40% = 1.5% and T40%-50% = 0.4%. Based on ten images per cycle, this indicates that 4D reconstructions would be influenced, depending on which marker was used, by at least 1 bin 34.9% of the time. This number was noticeably higher for some patients; the maximum was 71% of the time for one patient of ten. In conclusion, the respiratory amplitude and relative phase depend significantly on the location of the IR marker used to monitor respiration. For some patients the xyphoid and isocentric markers may be completely out of phase. More importantly, this relationship varies day to day, suggesting that a single marker may be inadequate for the purposes of respiratory gating.

Pilot study on the impact of F18-labeled thymidine PET/CT on gross tumor volume identification and definition for pancreatic cancer.

PURPOSE: Accurate target definition for radiation therapy planning in localized pancreatic cancer is critical, particularly when using strategies that omit elective coverage. Standard imaging modalities such as computed tomography (CT), magnetic resonance imaging, and endoscopic ultrasound have limited concordance with pathologic evaluation. Biologic imaging with [F18]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) can also be difficult to interpret because increased activity is indicative of increased glucose metabolism, rather than cellular proliferation. [F18]-3'-deoxy-3'-fluorothymidine labeled thymidine (FLT) is a proliferative marker which exploits the expression of pyrimidine-metabolizing enzymes. We evaluate the impact of FLT-PET on pancreatic target definition for radiation planning. METHODS AND MATERIALS: Patients with biopsy-proven, newly diagnosed, untreated pancreatic adenocarcinoma were enrolled on an institutional review board-approved prospective study. Patients were injected with FLT and scanned 20 to 30 minutes later. Two physicians (referred to as observer 1 and observer 2) independently contoured the gross tumor volume (GTV) and involved nodes on CT scan only and then again with the assistance of coregistered FLT-PET. Conformality index (CI), the ratio of the volumes of intersection and union, was used as the metric for volume comparison (where CI = 0 represents no overlap and CI = 1 represents perfect overlap). RESULTS: Nine patients were enrolled in this study. FLT-avidity was discerned in 8 of 9 patients. Average CT-GTV volume for observers 1 and 2 was 38.1 and 26.5 mL, respectively. Average FLT-GTV volume for observers 1 and 2 was 39.1 and 25.0 mL, respectively. For the 8 patients with FLT-avid tumors, addition of FLT data improved concordance of GTV definition between physicians in 6 of 8 tumors. Average CI for interobserver CT-GTV was 0.325. Addition of FLT-PET information improved the average CI to 0.400. CONCLUSIONS: FLT-PET improves interobserver concordance in GTV definition. Further studies will focus on verification of these findings, pathologic verification of the FLT-PET signal, and optimization of the FLT-PET signal threshold for autosegmentation.

Pilot study of serial FLT and FDG-PET/CT imaging to monitor response to neoadjuvant chemoradiotherapy of esophageal adenocarcinoma: correlation with histopathologic response.

OBJECTIVE: The aim of this prospective pilot study was to investigate the potential of serial FLT-PET/CT compared to FDG-PET/CT to provide an early indication of esophageal cancer response to concurrent neoadjuvant chemoradiation therapy. METHODS: Five patients with biopsy-proven esophageal adenocarcinomas underwent neoadjuvant chemoradiation (Tx) prior to minimally invasive esophagectomy. The presence of residual tumor was classified histologically using the Mandard et al. criteria, categorizing patients as pathologic responders and non-responders. Participants underwent PET/CT imaging 1 h after intravenous administration of FDG and of FLT on two separate days within 48 h of each other. Each patient underwent a total of 3 scan "pairs": (1) pre-treatment, (2) during treatment, and (3) post-treatment. Image-based response to therapy was measured in terms of changes in SUVmax (ΔSUV) between pre- and post-therapeutic FLT- and FDG-PET scans. The PET imaging findings were correlated with the pathology results after surgery. RESULTS: All tumors were FDG and FLT avid at baseline. Lesion FLT uptake was lower than with FDG. Neoadjuvant chemoradiation resulted in a reduction of tumor uptake of both radiotracers in pathological responders (n = 3) and non-responders (n = 2). While the difference in the reduction in mean tumor FLT uptake during Tx between responders (ΔSUV = - 55%) and non-responders (ΔSUV = - 29%) was significant (P = 0.007), for FDG it was not, [responders had a mean ΔSUV = - 39 vs. - 31% for non-responders (P = 0.74)]. The difference in the reduction in tumor FLT uptake at the end of treatment between responders (ΔSUV = - 62%) and non-responders (ΔSUV = - 57%) was not significant (P = 0.54), while for FDG there was a trend toward significance [ΔSUV of responders = - 74 vs. - 52% in non-responders (P = 0.06)]. CONCLUSION: The results of this prospective pilot study suggest that early changes in tumor FLT uptake may be better than FDG in predicting response of esophageal adenocarcinomas to neoadjuvant chemoradiation. These preliminary results support the need to corroborate the value of FLT-PET/CT in a larger cohort.

Clinical Outcomes After Lung Stereotactic Body Radiation Therapy in Patients With or Without a Prior Lung Resection.

OBJECTIVES: Tumor control (TC), toxicity and survival, following stereotactic body radiation therapy (SBRT) were compared between patients with and without a prior lung resection (PLR). MATERIALS AND METHODS: The study is comprised of 130 patients with 141 peripheral tumors treated with SBRT at our institution from 2009 to 2013. Primary TC and lobar control (LC) were defined per RTOG 0236. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Survival/TC and toxicity were compared between patients with and without PLR using the Kaplan-Meier method and cumulative incidence, respectively. Fine and Gray regression was used for univariable/multivariable analysis for radiation pneumonitis (RP). RESULTS: Of the 130 patients with median age 70 years (range, 42 to 93 y), 50 had undergone PLR (median time between PLR and SBRT: 33 mo; range, 1 to 206), including pneumonectomy (12%), lobectomy (46%), wedge resection (42%). With a median follow-up of 21 months in survivors, the PLR group had better TC (1-y 100% vs. 93%; P<0.01) and increased grade ≥2 (RP; 1-y 12% vs. 1%; P<0.01). OS was not significantly different between the 2 groups (1-y 91% vs. 85%; P=0.24). On univariable/multivariable analyses, biologically effective dose was associated with TC (hazard ratios, 0.97; 95% confidence interval, 0.94-0.999; P=0.04). Chemotherapy use was associated with grade ≥2 RP for all patients (hazard ratios, 14.92; 95% confidence interval, 5.68-39.21; P<0.0001) in multivariable analysis. PLR was not associated with increased RP in multivariable analysis. CONCLUSIONS: Patients with PLR who receive lung SBRT for lung tumors have high local control and relatively low toxicity. SBRT is an excellent option to treat second lung tumors or pulmonary metastases in patients with PLR.

Variability among breast radiation oncologists in delineation of the postsurgical lumpectomy cavity.

PURPOSE: Partial breast irradiation (PBI) is becoming more widely used. Accurate determination of the surgical lumpectomy cavity volume is more critical with PBI than with whole breast radiation therapy. We examined the interobserver variability in delineation of the lumpectomy cavity among four academic radiation oncologists who specialize in the treatment of breast cancer. METHODS AND MATERIALS: Thirty-four lumpectomy cavities in 33 consecutive patients were evaluated. Each physician contoured the cavity and a 1.5-cm margin was added to define the planning target volume (PTV). A cavity visualization score (CVS) was assigned (1-5). To eliminate bias, the physician of record was eliminated from the analysis in all cases. Three measures of variability of the PTV were developed: average shift of the center of mass (COM), average percent overlap between the PTV of two physicians (PVO), and standard deviation of the PTV. RESULTS: Of variables examined, pathologic resection volume was significantly correlated with CVS, with larger volumes more easily visualized. Shift of the COM decreased and PVO increased significantly as CVS increased. For CVS 4 and 5 cases, the average COM shift was 3 mm and 2 mm, respectively, and PVO was 77% and 87%, respectively. In multiple linear regression, pathologic diameter >4 cm and CVS > or =3 were significantly associated with smaller COM shift. When CVS was omitted from analysis, PVO was significantly larger with pathologic diameter > or =5 cm, days to planning <36, and older age. CONCLUSIONS: Even among radiation oncologists who specialize in breast radiotherapy, there can be substantial differences in delineation of the postsurgical radiotherapy target volume. Large treatment margins may be prudent if the cavity is not clearly defined.

An independent dose calculation algorithm for MLC-based stereotactic radiotherapy.

We have developed an algorithm to calculate dose in a homogeneous phantom for radiotherapy fields defined by multi-leaf collimator (MLC) for both static and dynamic MLC delivery. The algorithm was developed to supplement the dose algorithms of the commercial treatment planning systems (TPS). The motivation for this work is to provide an independent dose calculation primarily for quality assurance (QA) and secondarily for the development of static MLC field based inverse planning. The dose calculation utilizes a pencil-beam kernel. However, an explicit analytical integration results in a closed form for rectangular-shaped beamlets, defined by single leaf pairs. This approach reduces spatial integration to summation, and leads to a simple method of determination of model parameters. The total dose for any static or dynamic MLC field is obtained by summing over all individual rectangles from each segment which offers faster speed to calculate two-dimensional dose distributions at any depth in the phantom. Standard beam data used in the commissioning of the TPS was used as input data for the algorithm. The calculated results were compared with the TPS and measurements for static and dynamic MLC. The agreement was very good (<2.5%) for all tested cases except for very small static MLC sizes of 0.6 cm x 0.6 cm (<6%) and some ion chamber measurements in a high gradient region (<4.4%). This finding enables us to use the algorithm for routine QA as well as for research developments.

Computerized System for Safety Verification of External Beam Radiation Therapy Planning.

PURPOSE: To report an assessment of in-house software, Verifier, developed to improve efficacy and efficiency of the radiation therapy (RT) treatment planning process and quality control review (QCR). METHODS AND MATERIALS: Radiation therapy plan parameters retrieved from our treatment planning database are used by automated tests to give 75 types of warnings, such as prescription and plan discrepancies. The software is continuously updated on the basis of new issues, ideas, and planning policies. Verifier was retrospectively assessed (2007-2015) by examining impact on treatment plan revisions, frequency of quality improvement incident reports of avoidable RT plan-related safety events, unaddressed issues, and staff efficiency. RESULTS: Plan revisions for specific issues declined dramatically in response to implementation of corresponding Verifier tests. Between 2012 and 2015 our institution's total rate of plan revisions dropped from 18.0% to 11.2%. Between 2008 and 2015 specific tests were added to Verifier while the rate of corresponding avoidable safety events was reduced from 0.34% to 0.00% over the same period. Simulations suggest Verifier saves approximately 2 to 5 minutes per QCR. CONCLUSIONS: The decrease in quantifiable metrics of plan revisions and incident reports suggests automatic RT plan-checking software enhances patient safety and clinical efficiency. Although only modest time savings may be gained using Verifier for the QCR itself, the greater impact on efficiency is through avoiding late-stage plan modifications and improving documentation via automation. We encourage other institutions to consider working toward adding similar technologies to enhance their RT quality assurance programs.

Radiation toxicity in patients with collagen vascular disease and intrathoracic malignancy treated with modern radiation techniques.

BACKGROUND AND PURPOSE: There is concern that patients with collagen vascular disease (CVD) are at higher risk of developing radiation toxicity. We analyzed radiation toxicities in patients with intrathoracic malignancy and CVD treated using modern radiotherapy. MATERIALS AND METHODS: This single-institution retrospective study included 31 patients with CVD and 825 patients without CVD treated from 1998 to 2014. Radiation esophagitis (RE) and radiation pneumonitis (RP) were scored by RTOG scales. RE was analyzed with logistic regression and RP with Cox regression. RESULTS: CVD patients experienced similar grade ≥3 RE compared to control patients (23% vs. 19%, p = 0.64) but more grade ≥3 RP (26% vs. 10%, p = 0.01). There was no significant association between CVD subtype and toxicities. In multivariate analysis, CVD and lung V20 >30% were associated with grade ≥3 RP. We identified V20 ≤30%, V5 ≤50%, and MLD ≤18 Gy as dose thresholds in patients with CVD. CVD patients with mild severity disease and only 1 organ system involved were at low risk for RP. CONCLUSIONS: Patients with CVD may be at higher risk of RP. However, CVD patients may be offered curative thoracic RT with particular attention to risk-reduction strategies and maintaining recommended dose constraints as described in this study.

Inter-scan and inter-observer tumour volume delineation variability on cone beam computed tomography in patients treated with stereotactic body radiation therapy for early-stage non-small cell lung cancer.

INTRODUCTION: Quantification of volume changes on cone beam computed tomography (CBCT) during lung stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC) may provide a useful radiological marker for radiation response and for adaptive treatment planning. This study quantifies inter-scan and inter-observer variability in tumour volume delineation on CBCT. METHODS: Three clinicians independently contoured the primary gross tumour volume (GTV) manually on CBCTs taken immediately before SBRT treatment (pre) and after the same SBRT treatment (post) for 19 NSCLC patients. Relative volume differences (RVD) were calculated between the pre- and post-CBCTs for a given treatment and between any two of three observers for a given CBCT. Coefficient of variation (CV) was used to quantitatively measure and compare the extent of variability. RESULTS: Inter-observer variability had a significantly higher CV of 0.15 ± 0.13 compared to inter-scan CV of 0.03 ± 0.04 with P < 0.0001. The greatest variability was observed with tumours (<2 cm in diameter) versus larger tumours with 95% limit of agreement (LOA) (Mean ± Standard Deviation) of 1.90% ± 19.55% vs. -0.97% ± 12.26% for inter-scan RVD and 29.99% ± 73.84% vs. 9.37% ± 29.95% for inter-observer RVD respectively. CONCLUSIONS: Inter-observer variability was greater than inter-scan variability for tumour volume delineation on CBCT with greatest variability for small tumours (<2 cm in diameter). LOA for inter-scan variability (~12%) helps defines a threshold for clinically meaningful tumour volume change during SBRT treatment for tumours with diameter greater than 2 cm, with larger thresholds needed for smaller tumours.

Low incidence of chest wall pain with a risk-adapted lung stereotactic body radiation therapy approach using three or five fractions based on chest wall dosimetry.

PURPOSE: To examine the frequency and potential of dose-volume predictors for chest wall (CW) toxicity (pain and/or rib fracture) for patients receiving lung stereotactic body radiotherapy (SBRT) using treatment planning methods to minimize CW dose and a risk-adapted fractionation scheme. METHODS: We reviewed data from 72 treatment plans, from 69 lung SBRT patients with at least one year of follow-up or CW toxicity, who were treated at our center between 2010 and 2013. Treatment plans were optimized to reduce CW dose and patients received a risk-adapted fractionation of 18 Gy×3 fractions (54 Gy total) if the CW V30 was less than 30 mL or 10-12 Gy×5 fractions (50-60 Gy total) otherwise. The association between CW toxicity and patient characteristics, treatment parameters and dose metrics, including biologically equivalent dose, were analyzed using logistic regression. RESULTS: With a median follow-up of 20 months, 6 (8.3%) patients developed CW pain including three (4.2%) grade 1, two (2.8%) grade 2 and one (1.4%) grade 3. Five (6.9%) patients developed rib fractures, one of which was symptomatic. No significant associations between CW toxicity and patient and dosimetric variables were identified on univariate nor multivariate analysis. CONCLUSIONS: Optimization of treatment plans to reduce CW dose and a risk-adapted fractionation strategy of three or five fractions based on the CW V30 resulted in a low incidence of CW toxicity. Under these conditions, none of the patient characteristics or dose metrics we examined appeared to be predictive of CW pain.

Independent brachytherapy plan verification software: improving efficacy and efficiency.

BACKGROUND AND PURPOSE: To compare the pre-treatment brachytherapy plan verification by a physicist assisted by custom plan verification software (SAV) with those performed manually (MV). MATERIALS AND METHODS: All HDR brachytherapy plans used for treatment in 2013, verified using either SAV or MV, were retrospectively reviewed. Error rate (number of errors/number of plans) was measured and verification time calculated. All HDR brachytherapy safety events recorded between 2010 and 2013 were identified. The rate of patient-related safety events (number of events/number of fractions treated) and the impact of SAV on the underlying errors were assessed. RESULTS: Three/106 errors (2.8%) were found in the SAV group and 24/273 (8.8%) in the MV group (p=0.046). The mean ±1 standard deviation plan verification time was 8.4±4.0min for SAV and 11.6±5.3 for MV (p=0.006). Seven safety events out of 4729 fractions delivered (0.15%) were identified. Four events (57%) were associated with plan verification and could have been detected by SAV. CONCLUSIONS: We found a safety event rate in HDR brachytherapy of 0.15%. SAV significantly reduced the number of undetected errors in HDR treatment plans compared to MV, and reduced the time required for plan verification.

Clinical utility of 4D FDG-PET/CT scans in radiation treatment planning.

PURPOSE: The potential role of four-dimensional (4D) positron emission tomography (PET)/computed tomography (CT) in radiation treatment planning, relative to standard three-dimensional (3D) PET/CT, was examined. METHODS AND MATERIALS: Ten patients with non-small-cell lung cancer had sequential 3D and 4D [(18)F]fluorodeoxyglucose PET/CT scans in the treatment position prior to radiation therapy. The gross tumor volume and involved lymph nodes were contoured on the PET scan by use of three different techniques: manual contouring by an experienced radiation oncologist using a predetermined protocol; a technique with a constant threshold of standardized uptake value (SUV) greater than 2.5; and an automatic segmentation technique. For each technique, the tumor volume was defined on the 3D scan (VOL3D) and on the 4D scan (VOL4D) by combining the volume defined on each of the five breathing phases individually. The range of tumor motion and the location of each lesion were also recorded, and their influence on the differences observed between VOL3D and VOL4D was investigated. RESULTS: We identified and analyzed 22 distinct lesions, including 9 primary tumors and 13 mediastinal lymph nodes. Mean VOL4D was larger than mean VOL3D with all three techniques, and the difference was statistically significant (p < 0.01). The range of tumor motion and the location of the tumor affected the magnitude of the difference. For one case, all three tumor definition techniques identified volume of moderate uptake of approximately 1 mL in the hilar region on the 4D scan (SUV maximum, 3.3) but not on the 3D scan (SUV maximum, 2.3). CONCLUSIONS: In comparison to 3D PET, 4D PET may better define the full physiologic extent of moving tumors and improve radiation treatment planning for lung tumors. In addition, reduction of blurring from free-breathing images may reveal additional information regarding regional disease.