Intrafraction Imaging Can Replace the Midtreatment Cone Beam Tomography for Lung Stereotactic Ablative Radiation Therapy Patients for Increased Treatment Efficiency.

Purpose: To determine the feasibility of replacing the mid treatment cone beam computed tomography (MT CBCT) image with Intrafraction Imaging (IFI) acquired concurrently during dose delivery in lung Stereotactic Ablative Body Radiation therapy (SABR) patients, and thus improve treatment efficiency. Methods and Materials: A review of departmental imaging data was performed on ten lung SABR patients treated with dual arc volumetric modulated arc therapy (VMAT) on an Elekta Versa HD linear accelerator with XVI imaging software.IFI data was extracted and a database of the translational (TX, TY, TZ) and the rotational (RX, RY, RZ) position errors was created for retrospective comparison, with the values of the MT CBCT for the same patients, treated between March 2021 and March 2022 at our center. The data was evaluated for correlation between the values in all 6° of freedom. Results: The inter-class correlation (ICC) coefficient for Tx was 0.89 (95% CI, 0.80-0.94), Ty was 0.69 (95% CI, 0.49-0.82), Tz was 0.89 (95% CI, 0.82-0.95) in the translational planes, and Rx was 0.79 (95% CI, 0.65-0.88), Ry was 0.79 (95% CI, 0.65-0.88), and Rz was 0.91 (95% CI, 0.84-0.95) in rotational planes.The Bland-Altman (BA) statistics for Tx had a bias of -1.22 × 10-3, with an upper limit of agreement (UOA) of 0.07, and a lower limit of agreement (LOA) of -0.07, for Ty the bias was 0.01 (UOA: 0.18; LOA: -0.16), Tz bias was 2.6 × 10-3(UOA: 0.10; LOA: -0.09), Rx bias was 0.09 (UOA: 0.82; LOA: -0.64), Ry bias was -0.04 (UOA: 1.08; LOA: -1.16) and Rz was -0.03 (UOA: 0.44; LOA: -0.51). Conclusions: The ICC was excellent for Tx, Tz, Rx, y, z, and good for Ty. The data demonstrated promising correlation between IFI and MT CBCT values, and therefore supports the use of IFI for clinical decision making and improving treatment efficiency.

Treatment patterns and long-term survival outcomes for patients with stage III non-small cell lung cancer: A retrospective study.

AIM: Lung cancer is the leading cause of cancer-related deaths in Australia with poor long-term survival outcomes. Stage III non-small cell lung cancer (NSCLC) is a highly heterogenous group with diverse tumor characteristics and multiple, possible treatment options. We present retrospective data on patient characteristics, treatment patterns, and long-term outcomes in stage III NSCLC patients treated at a single cancer center in New South Wales, Australia. METHODS: Stage III NSCLC patients were identified from the 'Nepean Cancer Research Biobank'. Patient demographics, cancer-related information, and long-term follow-up data were collected and analyzed. RESULTS: A total of 88 patients were eligible for analysis with 61% of them diagnosed as stage IIIA, 35% IIIB, and 4% IIIC. Induction chemotherapy was administered in 20% of the patients. Overall, 48% of the study population underwent surgery, and 38% underwent concurrent chemoradiotherapy (CCRT). Both median progression-free survival and overall survival (OS) were superior in stage IIIA patients in comparison to stage IIIB (and IIIC) patients (22 vs. 11 months, p = .018; and 58 vs. 19 months, p = .048, respectively). Patients who were younger (<65 years old), good Eastern Cooperative Oncology Group performance status (ECOG PS <2), and females had better prognosis on univariate analysis. There was a nonstatistically significant trend toward better median OS with CCRT in comparison to surgery (58 vs. 37 months, p = .87). CONCLUSIONS: Long-term outcomes remain poor, and hence better treatment strategies are urgently needed in stage III NSCLC. Equally, more robust, prospective studies would help delineate the optimal treatment modality in these patients.

SABR for Early Non-Small Cell Lung Cancer: Changes in Pulmonary Function, Dyspnea, and Quality of Life.

PURPOSE: The aim of this study was to report pulmonary function tests (PFTs) and clinician-reported and patient-reported quality-of-life (QoL) outcomes on a cohort of patients with non-small cell lung cancer (NSCLC) treated with SABR. METHODS AND MATERIALS: A total of 119 patients with NSCLC were treated with SABR in the prospective cohort SSBROC study of patients with T1-T2N0M0 NSCLC. PFTs and QoL measures were obtained at baseline pretreatment and at 6-month intervals. Here we report on the 6- to 18-month time points. Analysis of covariance (ANCOVA) methods adjusting for baseline analyzed potential predictors on outcomes of PFTs and patient-reported dyspnea at 18 months. RESULTS: The only statistically significant decline in PFTs was seen in forced expiratory volume in 1 second (FEV1) at 18 months post-SABR, with a decline of -0.11 L (P = .0087; 95% CI, -0.18 to -0.02). Of potential predictors of decline, only a 1-unit increase in smoking pack-years resulted in a -0.12 change in diffusing capacity for carbon monoxide (P = .026; 95% CI, -0.02 to -0.23) and a 0.003 decrease in FEV1 (P = .026; 95% CI, -0.006 to -0.0004). For patient-reported outcomes, statistically significant worsening in both the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (QLQ-C30 Version 3) and the lung module (QLQ-LC13) dyspnea scores occurred at the 18-month time point, but not earlier. No potential predictors of worsening dyspnea were statistically significant. There was no statistically significant decline in clinician-reported outcomes or global QoL scores. CONCLUSIONS: We found a statistically significant decline in FEV1 at 18 months posttreatment. Smoking pack-years was a predictor for decline in diffusing capacity for carbon monoxide and FEV1 at 18 months. Worsening of patient-reported dyspnea scores was observed, consistent with the expected progression of lung comorbid disease.

A Systematic Review Into the Radiologic Features Predicting Local Recurrence After Stereotactic Ablative Body Radiotherapy (SABR) in Patients With Non-Small Cell Lung Cancer (NSCLC).

PURPOSE: Posttreatment surveillance for local recurrence (LR) after stereotactic ablative body radiotherapy (SABR) can include both fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT). Radiation-induced lung injury shares a similar appearance to LR after treatment, making the detection of LR on imaging difficult for clinicians. We aimed to summarize radiologic features of CT and FDG-PET predicting LR and to evaluate radiomics as another tool for detecting LR. METHODS AND MATERIALS: We searched MEDLINE, EMBASE, and PubMed databases for published studies and Web of Science, Wiley Online, and Science Direct databases for conference abstracts that had patient populations with non-small cell lung cancer and reported post-SABR radiologic features of FDG-PET or CT and radiomics from either FDG-PET or CT. Studies for inclusion were independently reviewed by 2 authors. RESULTS: Across 32 relevant studies, the incidence of LR was 13% (222/1726). On CT, certain gross radiologic appearances and kinetic features of changes in size, diameter, volume, or 3 consecutive rises in volume of masslike consolidation are suggestive of LR. **Particular regard should be made for the presence of any ≥3 high-risk features on CT or the individual high-risk features of enlarging opacity at ≥12 month's post-SABR as being highly suspicious of LR. On FDG-PET a relative reduction of <5% of maximum standardised uptake value (SUVmax) from baseline in the first 12 months or cut-offs of SUVmax >5 and SUVmean >3.44 after 12 months can indicate LR. There is limited evidence available to corroborate radiomic features suggestive of LR. CONCLUSIONS: This research has identified common features of LR compared with radiation-induced lung injury, which may aid in early and accurate detection of LR post-SABR; further research is required to validate these findings.

Collaborative implementation of stereotactic ablative body radiotherapy: A model for the safe implementation of complex radiotherapy techniques in Australia.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) for lung cancer is a modality of treatment that has improved outcomes for lung cancer patients. However, radiotherapy for lung cancer is underutilized and fewer than half of elderly patients with non-small cell lung cancer (NSCLC) receive active treatment. The purpose of this study is to report on a collaboration in implementing an NSCLC SABR (stereotactic ablative body radiation) program safely, efficiently, and uniformly across several centers, including regional sites. The first aim of this paper is to detail the collaboration and implementation that started in 2013 and is ongoing. The second aim of this paper is to document early toxicities and quality of life outcomes. METHOD: A tripartite approach was used to develop the protocol and networks required for the implementation of SABR across multiple sites in NSW. Departments starting the programmes were supported and physics credentialing with central site submission was required before commencing the treatment. Additional ongoing support was available via an email discussion group involving all members of the collaboration. RESULTS: Between July 22, 2013 and February 22, 2016, 41 patients were enrolled with 34 patients in active follow up. The toxicity profile so far is similar to those of published studies with no appreciable effect on quality of life outcomes. CONCLUSION: The collaboration formed an effective framework in facilitating the implementation of SABR across several sites in NSW and could be used as a model for the safe and uniform implementation of new technologies in Australia.

Functional perfusion image guided radiation treatment planning for locally advanced lung cancer.

BACKGROUND AND PURPOSE: Functional avoidance radiation therapy (RT) aims at sparing functional lung regions. The purpose of this simulation study was to evaluate the feasibility of functional lung avoidance methodology in RT of lung cancer and to characterize the achievable dosimetry of single photon emission computed tomography (SPECT) guided treatment planning. MATERIALS AND METHODS: Fifteen consecutive lung cancer patients were included and planned for definitive RT of 60-66 Gy in 2-Gy fractions. Two plans were optimized: a standard CT-plan, and functional SPECT-plan. The objective was to reduce dose to the highly functional lung subvolumes without compromising tumour coverage, and respecting dose to other organs at risk. For each patient a 3D-conformal, intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy plans were created for standard and functional avoidance. Standard versus functional dose-volume parameters for functional lung (FL) subvolumes, organs at risk and tumour coverage were compared. RESULTS: The largest dose reduction was achieved with IMRT plans. Functional plans resulted in dose reduction from 9.0 Gy to 6.7 Gy (mean reduction of 2.3 Gy or 26%) to the highest functional subvolume FL80% (95%CI 1.1; 3.5). Dose to FL40% was reduced from 13.3 Gy to 11.6 Gy with functional planning. Dose reduction to FL40% was 1.7 Gy (95%CI 0.9; 2.6). Functional volume of lung receiving over 20 Gy improved by 5% (standard 22%, functional 17%). Dose to organs at risk and tumour coverage were not significantly different between plans. CONCLUSIONS: SPECT/CT-guided planning resulted in improved dose-volumetric outcomes for functional lung. This methodology may lead to potential reduction in radiation-induced lung toxicity.

Audiovisual biofeedback breathing guidance for lung cancer patients receiving radiotherapy: a multi-institutional phase II randomised clinical trial.

BACKGROUND: There is a clear link between irregular breathing and errors in medical imaging and radiation treatment. The audiovisual biofeedback system is an advanced form of respiratory guidance that has previously demonstrated to facilitate regular patient breathing. The clinical benefits of audiovisual biofeedback will be investigated in an upcoming multi-institutional, randomised, and stratified clinical trial recruiting a total of 75 lung cancer patients undergoing radiation therapy. METHODS/DESIGN: To comprehensively perform a clinical evaluation of the audiovisual biofeedback system, a multi-institutional study will be performed. Our methodological framework will be based on the widely used Technology Acceptance Model, which gives qualitative scales for two specific variables, perceived usefulness and perceived ease of use, which are fundamental determinants for user acceptance. A total of 75 lung cancer patients will be recruited across seven radiation oncology departments across Australia. Patients will be randomised in a 2:1 ratio, with 2/3 of the patients being recruited into the intervention arm and 1/3 in the control arm. 2:1 randomisation is appropriate as within the interventional arm there is a screening procedure where only patients whose breathing is more regular with audiovisual biofeedback will continue to use this system for their imaging and treatment procedures. Patients within the intervention arm whose free breathing is more regular than audiovisual biofeedback in the screen procedure will remain in the intervention arm of the study but their imaging and treatment procedures will be performed without audiovisual biofeedback. Patients will also be stratified by treating institution and for treatment intent (palliative vs. radical) to ensure similar balance in the arms across the sites. Patients and hospital staff operating the audiovisual biofeedback system will complete questionnaires to assess their experience with audiovisual biofeedback. The objectives of this clinical trial is to assess the impact of audiovisual biofeedback on breathing motion, the patient experience and clinical confidence in the system, clinical workflow, treatment margins, and toxicity outcomes. DISCUSSION: This clinical trial marks an important milestone in breathing guidance studies as it will be the first randomised, controlled trial providing the most comprehensive evaluation of the clinical impact of breathing guidance on cancer radiation therapy to date. This study is powered to determine the impact of AV biofeedback on breathing regularity and medical image quality. Objectives such as determining the indications and contra-indications for the use of AV biofeedback, evaluation of patient experience, radiation toxicity occurrence and severity, and clinician confidence will shed light on the design of future phase III clinical trials. TRIAL REGISTRATION: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), its trial ID is ACTRN12613001177741 .

Potential benefits and pitfalls of respiratory-gated radiotherapy in the treatment of thoracic malignancy.

AIM: Despite advances in radiotherapy delivery, the prognosis of lung cancer remains poor. Higher doses of radiation have been associated with improved outcomes but may result in higher toxicities. Respiratory gated radiotherapy (RGRT) has the potential to reduce pulmonary toxicity but there are significant limitations and pitfalls to its use. The aim of this article is to (i) describe the RGRT technique currently employed at Nepean and Westmead Hospitals; (ii) discuss the practical issues of implementing such a program; (iii) present the results of our RGRT program and (iv) review the potential uncertainties in using this technique and the methods we have used to overcome these. METHODS: A retrospective review of all patients who had a 4D-computed tomography (4D-CT) scan was undertaken. Records from treatment planning systems were used to assess the prospective gating program. RESULTS: Between September 2007 and June 2011, 53 patients at Nepean and 26 patients at Westmead Hospital underwent a 4D-CT. Between April and August 2011, 26 patients at Westmead Hospital underwent a prospective 4D-CT scan as treatment verification. Two of the 26 patients (7.7%) were found to have incomplete coverage of the planning target volume. Both patients underwent respiratory re-coaching, alleviating the need for replanning. CONCLUSION: RGRT may reduce doses to organs at risk with the potential for dose escalation. However its implementation requires significant staff training, treatment time and resources. Treatment verification with image guided radiation therapy are essential for safe delivery.

Minimal benefit of respiratory-gated radiation therapy in the management of thoracic malignancy.

BACKGROUND: Respiratory-gated radiotherapy (RGRT) is used in several centres around the world. However, there is continuing controversy regarding the benefit of this technique. The aims of this study are to quantify the dosimetric benefits and the potential predictive factors. METHODS: Thirty-four consecutive patients were planned using the RGRT and the Free Breathing (FB) approach and compared with regard to target volume coverage and normal tissue parameters. Potential predictive factors were also evaluated. RESULTS: Tumour coverage was similar 94.4% versus 95.5%. Use of RGRT was not associated with a significant reduction in spinal cord, oesophagus or cardiac dosimetric parameters. However, it did reduce the lung mean dose by 1.33 Gy (P < 0.001) and V20 by 2.2% (P < 0.001). Only superior/inferior displacement of >1 cm was predictive of a >5% reduction in lung V20 parameter, and these patients all had a gross tumour volume (GTV) of <100 cm(3). CONCLUSIONS: The dosimetric benefit of applying RGRT is small when applied in an unselected population of patients. Superior/inferior displacement of >1 cm for tumours with GTV less than 100 cm(3) may be used to select patients who may derive a >5% reduction in lung V20 parameters.

Estimating risks of radiotherapy complications as part of informed consent: the high degree of variability between radiation oncologists may be related to experience.

PURPOSE: Estimating the risks of radiotherapy (RT) toxicity is important for informed consent; however, the consistency in estimates has not been studied. This study aimed to explore the variability and factors affecting risk estimates (REs). METHODS AND MATERIALS: A survey was mailed to Australian radiation oncologists, who were asked to estimate risks of RT complications given 49 clinical scenarios. The REs were assessed for association with oncologist experience, subspecialization, and private practice. RESULTS: The REs were extremely variable, with a 50-fold median variability. The least variability (sevenfold) was for estimates of late, small intestinal perforation/obstruction after a one-third volume received 50 Gy with concurrent 5-fluorouracil (RE range 5-35%). The variation between the smallest and largest REs in 17 scenarios was >or=100-fold. The years of experience was significantly associated with REs of soft/connective-tissue toxicity (p = 0.01) but inversely associated with estimates of neurologic/central nervous system toxicity (p = 0.08). Ninety-six percent of respondents believed REs were important to RT practice; only 24% rated evidence to support their estimates as good. Sixty-seven percent believed national/international groups should pursue the issue further. CONCLUSION: Enormous variability exists in REs for normal tissue complications due to RT that is influenced by the years of experience. Risk estimation is perceived as an important issue without a good evidence base. Additional studies are strongly recommended.