Avoidance Radiation Therapy Research Articles

Endoscopic Bilateral Nipple-sparing Mastectomy via a Single Axillary Incision with Immediate Pre-pectoral Implant-based Breast Reconstruction.

Oncoplastic breast surgery, with its focus on improving cosmetic outcomes while maintaining oncological safety, has fundamentally transformed the landscape of breast cancer surgical treatment, giving rise to an array of techniques for breast reconstruction. Nipple-sparing mastectomy (NSM) with immediate implant-based breast reconstruction (IBBR) has emerged as a cornerstone in managing early breast cancer. Aligned with the principles of minimally invasive surgery, recent years have witnessed the widespread integration of endoscopic approaches in breast surgery, encompassing procedures like endoscopic breast-conserving surgery (E-BCS) and endoscopic nipple-sparing mastectomy (E-NSM), among others. Capitalizing on the advantages of inconspicuous and shorter incisions, improved visibility, and the avoidance of radiation therapy, the popularity of E-NSM with IBBR is on the rise. However, conventional E-NSM with IBBR often requires two or more incisions, which can result in suboptimal cosmetic outcomes and even prosthesis loss.This paper presents a comprehensive account of the intricate surgical procedures involved in endoscopic bilateral nipple-sparing mastectomy with immediate pre-pectoral implant-based breast reconstruction. The insights shared are drawn from the collective experience of our institution. Notable benefits associated with the described surgical approach encompass enhanced cosmetic outcomes, improved postoperative quality of life, and enhanced physiological functions attributable to the application of pre-pectoral implant-based breast reconstruction through a single incision.

Functional Lung Avoidance Planning Using Multicriteria Optimization

Functional lung avoidance (FLA) radiation therapy is an evolving field. The aim of FLA planning is to reduce dose to areas of functioning lung, with comparable target coverage and dose to organs at risk. Multi-criteria optimisation (MCO) is a planning tool that may assist with FLA planning. This study assessed the feasibility of using MCO to adapt radiation therapy plans in order to avoid functional regions of lung that were identified using a 68Ga-4D-V/Q PET/CT.Methods A prospective clinical trial [anonymized for review] was performed in which patients had a 68Ga-4D-V/Q PET/CT prior to radiation treatment. Of the 72 patients enrolled in this trial, 38 patients had stage III non-small cell lung cancer and were eligible for selection into this planning study. Functional lung target volumes HF lung (highly-functioning lung) and F lung (functional lung) were defined using the ventilated and perfused lung. Using knowledge-based planning, a baseline anatomical plan was created, and then a functional adapted plan was generated using multi-criteria optimisation. The primary aim was to spare dose to HF lung. Using the MCO tools, a clinician selected the final FLA plan. Dose to functional lung, target volumes, organs at risk and measures of plan quality were compared using standard statistical methods.Results The HF lung volume was successfully spared in all patients. The F lung volume was successfully spared in 36 of the 38 patients. There were no clinically significant differences in dose to anatomically defined organs at risk. There were differences in the planning target volume (PTV) near maximum and minimum doses. Across the entire population, there was a statistically significant reduction in the functional mean lung dose but not in the functional volume receiving 20 Gy. All trade-off decisions were made by the clinician.Conclusion Using MCO for FLA was achievable, but did result in changes to PTV coverage. A distinct advantage in using MCO was that all decisions regarding the cost and benefits of FLA could be made in real time.

Prospective Trial of Functional Lung Avoidance Radiation Therapy for Lung Cancer: Quality of Life Report

PurposeA novel form of lung function imaging has been developed that uses 4DCT data to generate lung ventilation images (4DCT-ventilation). Functional avoidance uses 4DCT-ventilation to reduce doses to functional lung with the aim of reducing pulmonary side-effects. A 4DCT-ventilation functional avoidance, phase II, multi-center clinical trial was completed. The purpose of this work is to quantify patient reported outcomes (PRO) changes for patients treated with functional avoidance and to determine which metrics are predictive of PRO changes. Materials and MethodsPatients with locally advanced lung cancer receiving curative intent radiotherapy were accrued. Each patient had a 4DCT-ventilation image generated using 4DCT data and image processing. PRO instruments included the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire, administered pre-treatment, 3, 6, and 12 months post-treatment. FACT-TOI (Trial Outcome Index) and the FACT-LCS (Lung Cancer Subscale) percentage of clinically meaningful declines (CMD) were determined. A linear mixed-effects model was used to determine which patient, clinical, dose, and dose-function metrics were predictive of PRO decline. Results59 patients completed baseline PRO surveys. 83% of patients had non-small-cell lung cancer, with 75% having stage III disease. The median dose was 60 Gy in 30 fractions. CMD FACT-TOI decline was 46.3%, 38.5%, and 26.8%, at 3, 6, and 12 months, respectively. CMD FACT-LCS decline was 33.3%, 33.3%, and 29.3%, at 3, 6, and 12 months, respectively. While an increase in most dose and dose-function parameters was associated with a modest decline in PROs, none of the results were significant (all p>0.053). ConclusionThe current work provides an innovative combination of functional avoidance and PROs and is the first report of PROs for patients treated with prospective 4DCT-ventilation functional avoidance. Approximately 30% of patients had clinically significant decline in PROs at 12 months. The study provides additional data on outcomes with 4DCT-ventilation functional avoidance.

A Phase 2 Randomized Clinical Trial Evaluating 4-Dimensional Computed Tomography Ventilation-Based Functional Lung Avoidance Radiation Therapy for Non-Small Cell Lung Cancer

PurposeTo determine whether 4-dimensional computed tomography (4DCT) ventilation-based functional lung avoidance radiotherapy preserves pulmonary function compared with standard radiotherapy for non-small cell lung cancer (NSCLC). Material and MethodsThis single center, randomized, phase 2 trial enrolled patients with NSCLC receiving curative intent radiotherapy with either stereotactic body radiotherapy or conventionally fractionated radiotherapy between 2016 and 2022. Patients were randomized 1:1 to standard of care radiotherapy or functional lung avoidance radiotherapy. The primary endpoint was the change in Jacobian-based ventilation as measured on 4DCT from baseline to three months post-radiation. Secondary endpoints included changes in volume of high- and low-ventilating lung, pulmonary toxicity, and changes in pulmonary function tests (PFTs). ResultsA total of 122 patients were randomized and 116 were available for analysis. Median follow up was 29.9 months. Functional avoidance plans significantly (P<.05) reduced dose to high-functioning lung without compromising target coverage or organs at risk constraints. When analyzing all patients, there was no difference in the amount of lung showing a reduction in ventilation from baseline to 3 months between the two arms (1.91% vs 1.87%; P=.90). Overall grade ≥2 and grade ≥3 pulmonary toxicities for all patients were 24.1% and 8.6%, respectively. There was no significant difference in pulmonary toxicity or changes in PFTs between the two study arms. In the conventionally fractionated cohort, there was a lower rate of grade ≥2 pneumonitis (8.2% vs 32.3%; P=.049) and less of a decline in change in FEV1 (-3 vs -5; P=.042) and FVC (1.5 vs -6; P=.005) at 3 months, favoring the functional avoidance arm. ConclusionsThere was no difference in post-treatment ventilation as measured by 4DCT between the arms. In the cohort of patients treated with conventionally fractionated radiotherapy with functional lung avoidance, there was reduced pulmonary toxicity, and less decline in PFTs suggesting a clinical benefit in patients with locally advanced NSCLC. Trial RegistrationClinicalTrials.gov Identifier: NCTXXXX Anonymized for Review XXXX

Comprehensive Quality of Life Report from a Prospective Clinical Trial of 4DCT-Ventilation Functional Lung Avoidance Radiation Therapy

Functional imaging has been developed that uses 4DCT images and image processing to generate lung ventilation maps (4DCT-ventilation). 4DCT-ventilation functional avoidance uses 4DCT-images to generate plans that avoid functional regions of the lung with the goal of reducing pulmonary toxicity. A 4DCT-ventilation functional avoidance, phase II, multi-center clinical trial was completed, and patient reported outcomes (PRO) measured. PROs are an essential measure of quality-of-life following radiotherapy. The purpose of this work is to quantify PRO changes for lung cancer patients treated with functional avoidance and to compare PROs against clinical pneumonitis. Patients with locally advanced lung cancer receiving curative intent radiotherapy (prescriptions of 45-75 Gy) and chemotherapy were accrued. Each patient had a 4DCT-ventilation image generated using 4DCT data. Favorable arc geometry and optimization techniques were used to generate functional avoidance plans. PRO instruments included the Functional Assessment of Cancer Therapy Lung (FACT-L) questionnaire and the Visual Analog Scale (VAS) administered pre-treatment and 3-, 6-, and 12-months post-treatment to gather data on physical, social, emotional, functional, and pulmonary well-being. The percentage of patients with clinically significant decline was calculated using the FACT-TOI (Trial Outcome Index), FACT-LCS (Lung Cancer Subscale), and VAS instruments. To evaluate the correlation between PROs and clinical toxicity, the percentage of clinically significant FACT-LCS decline was compared (Chi-square test) for patients who did or did not experience grade 2+ pneumonitis. Fifty-nine patients completed baseline PRO surveys. Median age was 65, 83% of patients had non-small-cell lung cancer, with 75% having stage III disease. Clinically significant FACT-TOI decline at, 3, 6, and 12 months was 46.3%, 38.5%, and 26.8%, respectively. The percentage of patients with clinically significant FACT-LCS decline was 33.3%, 33.3%, and 29.3%, at 3 months, 6 months, and 12 months, respectively. The percentage of patients with clinically significant VAS decline at 3, 6, and 12 months was 18.9%, 20.0%, and 18.6%, respectively. Patients who experienced grade 2+ pneumonitis had a greater percentage of clinically significant decline at all time-points with the results reaching significance (p = 0.045) at 6 months. The study presents the first comprehensive evaluation of PROs for patients treated with 4DCT-ventilation functional avoidance. The data show that 20-40% of patients had clinically significant decline and that PROs had a strong correlation with pneumonitis. The PRO data demonstrate that functional avoidance results in low rates of patient reported outcome clinical decline and provide seminal results to be used in phase III studies.

Systematic Evaluation of the Impact of Lung Segmentation Methods on 4-Dimensional Computed Tomography Ventilation Imaging Using a Large Patient Database

A novel form of lung functional imaging applied for functional avoidance radiation therapy has been developed that uses 4-dimensional computed tomography (4DCT) data and image processing techniques to calculate lung ventilation (4DCT-ventilation). Lung segmentation is a common step to define a region of interest for 4DCT-ventilation generation. The purpose of this study was to quantitatively evaluate the sensitivity of 4DCT-ventilation imaging using different lung segmentation methods. The 4DCT data of 350 patients from 2 institutions were used. Lung contours were generated using 3 methods: (1) reference segmentations that removed airways and pulmonary vasculature manually (Lung-Manual), (2) standard lung contours used for planning (Lung-RadOnc), and (3) artificial intelligence (AI)-based contours that removed the airways and pulmonary vasculature (Lung-AI). The AI model was based on a residual 3-dimensional U-Net and was trained using the Lung-Manual contours of 279 patients. We compared the Lung-RadOnc or Lung-AI with Lung-Manual contours for the entire 4DCT-ventilation functional avoidance process including lung segmentation (surface Dice similarity coefficient [Surface DSC]), 4DCT-ventilation generation (correlation), and subanalysis of 10 patients on a dosimetric endpoint (percentage of high functional volume of lung receiving ≥20 Gy [fV20{%}]). Surface DSC comparing Lung-Manual/Lung-RadOnc and Lung-Manual/Lung-AI contours was 0.40 ± 0.06 and 0.86 ± 0.04, respectively. The correlation between 4DCT-ventilation images generated with Lung-Manual/Lung-RadOnc and Lung-Manual/Lung-AI were 0.48 ± 0.14 and 0.85 ± 0.14, respectively. The difference in fV20[%] between 4DCT-ventilation generated with Lung-Manual/Lung-RadOnc and Lung-Manual/Lung-AI was 2.5% ± 4.1% and 0.3% ± 0.5%, respectively. Our work showed that using standard planning lung contours can result in significantly variable 4DCT-ventilation images. The study demonstrated that AI-based segmentations generate lung contours and 4DCT-ventilation images that are similar to those generated using manual methods. The significance of the study is that it characterizes the lung segmentation sensitivity of the 4DCT-ventilation process and develops methods that can facilitate the integration of this novel imaging in busy clinics.

Deep learning-based combination of [18F]-FDG PET and CT images for producing pulmonary perfusion image.

The main application of [18F] FDG-PET (18 FDG-PET) and CT images in oncology is tumor identification and quantification. Combining PET and CT images to mine pulmonary perfusion information for functional lung avoidance radiation therapy (FLART) is desirable but remains challenging. To develop a deep-learning-based (DL) method to combine 18 FDG-PET and CT images for producing pulmonary perfusion images (PPI). Pulmonary technetium-99m-labeled macroaggregated albumin SPECT (PPISPECT ), 18 FDG-PET, and CT images obtained from 53 patients were enrolled. CT and PPISPECT images were rigidly registered, and registration displacement was subsequently used to align 18 FDG-PET and PPISPECT images. The left/right lung was separated and rigidly registered again to improve the registration accuracy. A DL model based on 3D Unet architecture was constructed to directly combine multi-modality 18 FDG-PET and CT images for producing PPI (PPIDLM ). 3D Unet architecture was used as the basic architecture, and the input was expanded from a single-channel to a dual-channel to combine multi-modality images. For comparative evaluation, 18 FDG-PET images were also used alone to generate PPIDLPET . Sixty-seven samples were randomly selected for training and cross-validation, and 36 were used for testing. The Spearman correlation coefficient (rs ) and multi-scale structural similarity index measure (MS-SSIM) between PPIDLM /PPIDLPET and PPISPECT were computed to assess the statistical and perceptual image similarities. The Dice similarity coefficient (DSC) was calculated to determine the similarity between high-/low- functional lung (HFL/LFL) volumes. The voxel-wise rs and MS-SSIM of PPIDLM /PPIDLPET were 0.78 ± 0.04/0.57 ± 0.03, 0.93 ± 0.01/0.89 ± 0.01 for cross-validation and 0.78 ± 0.11/0.55 ± 0.18, 0.93 ± 0.03/0.90 ± 0.04 for testing. PPIDLM /PPIDLPET achieved averaged DSC values of 0.78 ± 0.03/0.64 ± 0.02 for HFL and 0.83 ± 0.01/0.72 ± 0.03 for LFL in the training dataset and 0.77 ± 0.11/0.64 ± 0.12, 0.82 ± 0.05/0.72 ± 0.06 in the testing dataset. PPIDLM yielded a stronger correlation and higher MS-SSIM with PPISPECT than PPIDLPET (p < 0.001). The DL-based method integrates lung metabolic and anatomy information for producing PPI and significantly improved the accuracy over methods based on metabolic information alone. The generated PPIDLM can be applied for pulmonary perfusion volume segmentation, which is potentially beneficial for FLART treatment plan optimization.

EPEN-09. UTILITY OF RADIATION THERAPY IN SPINAL CORD MYXOPAPILLARY EPENDYMOMAS: A REVIEW OF THE LITERATURE

Abstract INTRODUCTION Myxopapillary ependymomas (MPEs) are slow-growing tumors that comprise about 25% of spinal ependymomas. Although historically designated as grade 1, the recent WHO classification has upgraded MPEs to grade 2 given their potential for recurrence and dissemination. While the National Comprehensive Cancer Network guidelines recommend avoiding radiation therapy (RT) unless a gross-total resection (GTR) is not achieved, several reports have suggested a potential benefit of adjuvant RT in improving relapse-free survival in children after GTR. This literature review was conducted to compare available data to determine the utility of upfront irradiation in these patients. METHODS A comprehensive literature review from 1984-2021 was performed on PubMed using keywords: “pediatric myxopapillary ependymoma” and “radiation.” One case was censored for unknown radiation status. RESULTS 17 analyses from 1984-2021 were reviewed, yielding 140 pediatric cases of MPE, of whom 59% (n=83) received a GTR. Of those that received a GTR, average age was 13.7 yrs (range, 6-21), and 66% were male. The most common location was lumbosacral (25%), followed by thoracolumbar (19%). 22.8% (n=19) of patients received upfront focal RT. Relapse occurred in eight (42%) patients who received upfront RT, and 30 (47%) of those who did not, with no clear age or gender discrimination in those that relapsed. Distant recurrence occurred in 75% of those who received RT, and 68% of those that did not. The duration of event-free survival will be included in the final presentation. CONCLUSIONS While some individual studies have suggested a survival advantage in pediatric MPE after focal RT, in this meta-analysis, both relapse rate and location seemed similar regardless of receipt of RT. From this available evidence, the efficacy of upfront RT has not been demonstrated.

Validation of CT-based ventilation and perfusion biomarkers with histopathology confirms radiation-induced pulmonary changes in a porcine model

Imaging biomarkers can assess disease progression or prognoses and are valuable tools to help guide interventions. Particularly in lung imaging, biomarkers present an opportunity to extract regional information that is more robust to the patient’s condition prior to intervention than current gold standard pulmonary function tests (PFTs). This regional aspect has particular use in functional avoidance radiation therapy (RT) in which treatment planning is optimized to avoid regions of high function with the goal of sparing functional lung and improving patient quality of life post-RT. To execute functional avoidance, detailed dose–response models need to be developed to identify regions which should be protected. Previous studies have begun to do this, but for these models to be clinically translated, they need to be validated. This work validates two metrics that encompass the main components of lung function (ventilation and perfusion) through post-mortem histopathology performed in a novel porcine model. With these methods validated, we can use them to study the nuanced radiation-induced changes in lung function and develop more advanced models.

The HI-FIVE Trial: A Prospective Trial Using 4-Dimensional 68Ga Ventilation-Perfusion Positron Emission Tomography-Computed Tomography for Functional Lung Avoidance in Locally Advanced Non-small Cell Lung Cancer

Functional lung avoidance (FLA) radiation therapy aims to spare regions of functional lung to reduce toxicity. We report the results of the first prospective trial of FLA using 4-dimensional gallium 68 ventilation-perfusion positron emission tomography-computed tomography (68Ga-4D-V/Q PET/CT). Inclusion criteria required a diagnosis of stage III non-small cell lung cancer and the ability to undergo radical-intent chemoradiation therapy. Functional volumes were generated using planning 68Ga-4D-V/Q PET/CT. These volumes were used to generate a clinical FLA plan to 60 Gy in 30 fractions. The primary tumor was boosted to 69 Gy. A comparison anatomic plan was generated for each patient. Feasibility was met if FLA plans (compared with anatomic plans) allowed (1) a reduction in functional mean lung dose of ≥2% and a reduction in the functional lung volume receiving 20 Gy (fV20Gy) of ≥4%, and (2) a mean heart dose ≤30 Gy and relative heart volume receiving 50 Gy of <25%. In total, 19 patients were recruited; 1 withdrew consent. Eighteen patients underwent chemoradiation with FLA. Of the 18 patients, 15 met criteria for feasibility. All patients completed the entire course of chemoradiation therapy. Using FLA resulted in an average reduction of the functional mean lung dose of 12.4% (SD, ±12.8%) and a mean relative reduction of the fV20Gy of 22.9% (SD, ±11.9%). At 12 months, Kaplan-Meier estimates for overall survival were 83% (95% CI, 56%-94%) and estimates for progression-free survival were 50% (95% CI, 26%-70%). Quality-of-life scores were stable across all time points. Using 68Ga-4D-V/Q PET/CT to image and avoid functional lung is feasible.

Robust quantification of CT-ventilation biomarker techniques and repeatability in a porcine model.

Biomarkers estimating local lung ventilation have been derived from computed tomography (CT) imaging using various image acquisition and post-processing techniques. CT-ventilation biomarkers have potential clinical use in functional avoidance radiation therapy (RT), in which RT treatment plans are optimized to reduce dose delivered to highly ventilated lung. Widespread clinical implementation of CT-ventilation biomarkers necessitates understanding of biomarker repeatability. Performing imaging within a highly controlled experimental design enables quantification of error associated with remainingvariables. To characterize CT-ventilation biomarker repeatability and dependence on image acquisition and post-processing methodology in anesthetized and mechanically ventilatedpigs. Five mechanically ventilated Wisconsin Miniature Swine (WMS) received multiple consecutive four-dimensional CT (4DCT) and maximum inhale and exhale breath-hold CT (BH-CT) scans on five dates to generate CT-ventilation biomarkers. Breathing maneuvers were controlled with an average tidal volume difference <200 cc. As surrogates for ventilation, multiple local expansion ratios (LERs) were calculated from the acquired CT scans using Jacobian-based post-processing techniques. measured local expansion between an image pair using either inhale and exhale BH-CT images or two 4DCT breathing phase images. measured the maximum local expansion across the 4DCT breathing phase images. Breathing maneuver consistency, intra- and interday biomarker repeatability, image acquisition and post-processing technique dependence were quantitatively analyzed. Biomarkers showed strong agreement with voxel-wise Spearman correlation for intraday repeatability and for all other comparisons, including between image acquisition techniques. Intra- and interday repeatability were significantly different (p < 0.01). LER2 and LERN post-processing did not significantly affect intraday repeatability. 4DCT and BH-CT ventilation biomarkers derived from consecutive scans show strong agreement in controlled experiments with nonhumansubjects.

Characterizing Pulmonary Function Test Changes for Patients With Lung Cancer Treated on a 2-Institution, 4-Dimensional Computed Tomography-Ventilation Functional Avoidance Prospective Clinical Trial

PurposeFour-dimensional computed tomography (4DCT)–ventilation-based functional avoidance uses 4DCT images to generate plans that avoid functional regions of the lung with the goal of reducing pulmonary toxic effects. A phase 2, multicenter, prospective study was completed to evaluate 4DCT-ventilation functional avoidance radiation therapy. The purpose of this study was to report the results for pretreatment to posttreatment pulmonary function test (PFT) changes for patients treated with functional avoidance radiation therapy. Methods and MaterialsPatients with locally advanced lung cancer receiving chemoradiation were accrued. Functional avoidance plans based on 4DCT-ventilation images were generated. PFTs were obtained at baseline and 3 months after chemoradiation. Differences for PFT metrics are reported, including diffusing capacity for carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC). PFT metrics were compared for patients who did and did not experience grade 2 or higher pneumonitis. ResultsFifty-six patients enrolled on the study had baseline and posttreatment PFTs evaluable for analysis. The mean change in DLCO, FEV1, and FVC was –11.6% ± 14.2%, –5.6% ± 16.9%, and –9.0% ± 20.1%, respectively. The mean change in DLCO was –15.4% ± 14.4% for patients with grade 2 or higher radiation pneumonitis and –10.8% ± 14.1% for patients with grade <2 radiation pneumonitis (P = .37). The mean change in FEV1 was –14.3% ± 22.1% for patients with grade 2 or higher radiation pneumonitis and –3.9% ± 15.4% for patients with grade <2 radiation pneumonitis (P = .09). ConclusionsThe current work is the first to quantitatively characterize PFT changes for patients with lung cancer treated on a prospective functional avoidance radiation therapy study. In comparison with patients treated with standard thoracic radiation planning, the data qualitatively show that functional avoidance resulted in less of a decline in DLCO and FEV1. The presented data can help elucidate the potential pulmonary function improvement with functional avoidance radiation therapy.

Four-Dimensional Computed Tomography Ventilation Image-Guided Lung Functional Avoidance Radiation Therapy: A Single-Arm Prospective Pilot Clinical Trial

The primary objective of this prospective pilot trial was to assess the safety and feasibility of lung functional avoidance radiation therapy (RT) with 4-dimensional (4D) computed tomography (CT) ventilation imaging. Patients with primary lung cancer or metastatic disease to the lungs to receive conventionally fractionated RT (CFRT) or stereotactic body RT (SBRT) were eligible. Standard-of-care 4D-CT scans were used to generate ventilation images through image processing/analysis. Each patient required a standard intensity modulated RT plan and ventilation image guided functional avoidance plan. The primary endpoint was the safety of functional avoidance RT, defined as the rate of grade ≥3 adverse events (AEs) that occurred ≤12 months after treatment. Protocol treatment was considered safe if the rates of grade ≥3 pneumonitis and esophagitis were <13% and <21%, respectively for CFRT, and if the rate of any grade ≥3 AEs was <28% for SBRT. Feasibility of functional avoidance RT was assessed by comparison of dose metrics between the 2 plans using the Wilcoxon signed-rank test. Between May 2015 and November 2019, 34 patients with non-small cell lung cancer were enrolled, and 33 patients were evaluable (n=24 for CFRT; n=9 for SBRT). Median follow-up was 14.7 months. For CFRT, the rates of grade ≥3 pneumonitis and esophagitis were 4.2% (95% confidence interval, 0.1%-21.1%) and 12.5% (2.7%-32.4%). For SBRT, no patients developed grade ≥3 AEs. Compared with the standard plans, the functional avoidance plans significantly (P < .01) reduced the lung dose-function metrics without compromising target coverage or adherence to standard organs at risk constraints. This study, representing one of the first prospective investigations on lung functional avoidance RT, demonstrated that the 4D-CT ventilation image guided functional avoidance RT that significantly reduced dose to ventilated lung regions could be safely administered, adding to the growing body of evidence for its clinical utility.

EP05.01-023 Feasibility of Functional Lung Avoidance using Ga-68 4D Ventilation Perfusion PET/CT: The HI-FIVE Trial

Functional lung avoidance (FLA) radiation therapy spares regions of functional lung with an aim of reducing toxicity. We present results of a prospective trial of FLA using Ga-68 PET/CT to image both ventilation (V) and perfusion (Q). The primary objective of this single arm interventional trial (NCT03569072, protocol doi:10.1136/bmjopen-2020-042465) was to test the feasibility of achieving FLA whilst increasing dose to the primary tumour.

Xenon-Enhanced Ventilation Computed Tomography for Functional Lung Avoidance Radiation Therapy in Patients With Lung Cancer

This phase 2 trial aimed to determine whether xenon-enhanced ventilation computed tomography (XeCT)-guided functional-lung-avoidance radiation therapy could reduce the radiation pneumonitis (RP) rate in patients with lung cancer undergoing definitive chemoradiation therapy. Functional lung ventilation was measured via pulmonary function testing (PFT) and XeCT. A standard plan (SP) without reference to XeCT and a functional-lung-avoidance plan (fAP) optimized for lowering the radiation dose to the functional lung at the guidance of XeCT were designed. Dosimetric parameters and predicted RP risks modeled by biological evaluation were compared between the 2 plans in a treatment planning system (TPS). All patients received the approved fAP. The primary endpoint was the rate of grade ≥2 RP, and the secondary endpoints were the survival outcomes. The study hypothesis was that fAP could reduce the rate of grade ≥2 RP to 12% compared with a 30% historical rate. Thirty-six patients were evaluated. Xenon-enhanced total functional lung volumes positively correlated with PFT ventilation parameters (forced vital capacity, P=.012; forced expiratory volume in 1 second, P=.035), whereas they were not correlated with the diffusion capacity parameter. We observed a 17% rate of grade ≥2 RP (6 of 36 patients), which was significantly different (P=.040) compared with the historical control. Compared with the SP, the fAP significantly spared the total ventilated lung, leading to a reduction in predicted grade ≥2 RP (P=.001) by TPS biological evaluation. The median follow-up was 15.2 months. The 1-year local control (LC), disseminated failure-free survival (DFFS), and overall survival (OS) rates were 88%, 66%, and 91%, respectively. The median LC and OS were not reached, and the median DFFS was 24.0 months (95% confidence interval, 15.7-32.3 months). This report of XeCT-guided functional-lung-avoidance radiation therapy provided evidence showing its feasibility in clinical practice. Its benefit should be assessed in a broader multicenter trial setting.

Avoiding Radiation Therapy for Low-Grade Luminal A-Type Breast Cancer

Avoiding Radiation Therapy for Low-Grade Luminal A-Type Breast Cancer

A Transfer Learning Framework for Deep Learning-Based CT-to-Perfusion Mapping on Lung Cancer Patients.

PurposeDeep learning model has shown the feasibility of providing spatial lung perfusion information based on CT images. However, the performance of this method on lung cancer patients is yet to be investigated. This study aims to develop a transfer learning framework to evaluate the deep learning based CT-to-perfusion mapping method specifically on lung cancer patients.MethodsSPECT/CT perfusion scans of 33 lung cancer patients and 137 non-cancer patients were retrospectively collected from two hospitals. To adapt the deep learning model on lung cancer patients, a transfer learning framework was developed to utilize the features learned from the non-cancer patients. These images were processed to extract features from three-dimensional CT images and synthesize the corresponding CT-based perfusion images. A pre-trained model was first developed using a dataset of patients with lung diseases other than lung cancer, and subsequently fine-tuned specifically on lung cancer patients under three-fold cross-validation. A multi-level evaluation was performed between the CT-based perfusion images and ground-truth SPECT perfusion images in aspects of voxel-wise correlation using Spearman’s correlation coefficient (R), function-wise similarity using Dice Similarity Coefficient (DSC), and lobe-wise agreement using mean perfusion value for each lobe of the lungs.ResultsThe fine-tuned model yielded a high voxel-wise correlation (0.8142 ± 0.0669) and outperformed the pre-trained model by approximately 8%. Evaluation of function-wise similarity indicated an average DSC value of 0.8112 ± 0.0484 (range: 0.6460-0.8984) for high-functional lungs and 0.8137 ± 0.0414 (range: 0.6743-0.8902) for low-functional lungs. Among the 33 lung cancer patients, high DSC values of greater than 0.7 were achieved for high functional volumes in 32 patients and low functional volumes in all patients. The correlations of the mean perfusion value on the left upper lobe, left lower lobe, right upper lobe, right middle lobe, and right lower lobe were 0.7314, 0.7134, 0.5108, 0.4765, and 0.7618, respectively.ConclusionFor lung cancer patients, the CT-based perfusion images synthesized by the transfer learning framework indicated a strong voxel-wise correlation and function-wise similarity with the SPECT perfusion images. This suggests the great potential of the deep learning method in providing regional-based functional information for functional lung avoidance radiation therapy.

Combining Serial and Parallel Functionality in Functional Lung Avoidance Radiation Therapy

Functional lung avoidance (FLA) radiation therapy (RT) aims to minimize post-RT pulmonary toxicity by preferentially avoiding dose to high-functioning lung (HFL) regions. A common limitation is that FLA approaches do not consider the conducting architecture for gas exchange. We previously proposed the functionally weighted airway sparing (FWAS) method to spare airways connected to HFL regions, showing that it is possible to substantially reduce risk of radiation-induced airway injury. Here, we compare the performance of FLA and FWAS and propose a novel method combining both approaches. We used breath-hold computed tomography (BHCT) and simulation 4-dimensional computed tomography (4DCT) from 12 lung stereotactic ablative radiation therapy patients. Four planning strategies were examined: (1) Conventional: no sparing other than clinical dose-volume constraints; (2) FLA: using a 4DCT-based ventilation map to delineate the HFL, plans were optimized to reduce mean dose and V13.50 in HFL; (3) FWAS: we autosegemented 11 to 13 generations of individual airways from each patient's BHCT and assigned priorities based on the relative contribution of each airway to total ventilation. We used these priorities in the optimization along with airway dose constraints, estimated as a function of airway diameter and 5% probability of collapse; and (4) FLA+FWAS: we combined information from the 2 strategies. We prioritized clinical dose constraints for organs at risk and planning target volume in all plans. We performed the evaluation in terms of ventilation preservation accounting for radiation-induced damage to both lung parenchyma and airways. We observed average ventilation preservation for FLA, FWAS, and FLA+FWAS as 3%, 8.5%, and 14.5% higher, respectively, than for Conventional plans for patients with ventilation preservation in Conventional plans <90%. Generalized estimated equations showed that all improvements were statistically significant (P ≤ .036). We observed no clinically relevant improvements in outcomes of the sparing techniques in patients with ventilation preservation in Conventional plans ≥90%. These initial results suggest that it is crucial to consider the parallel and the serial nature of the lung to improve post-radiation therapy lung function and, consequently, quality of life for patients.

Clinical and economic impact of molecular testing for BRAF fusion in pediatric low-grade Glioma

BackgroundTreatment personalization via tumor molecular testing holds promise for improving outcomes for patients with pediatric low-grade glioma (PLGG). We evaluate the health economic impact of employing tumor molecular testing to guide treatment for patients diagnosed with PLGG, particularly the avoidance of radiation therapy (RT) for patients with BRAF-fusion.MethodsWe performed a model-based cost-utility analysis comparing two strategies: molecular testing to determine BRAF fusion status at diagnosis against no molecular testing. We developed a microsimulation to model the lifetime health and cost outcomes (in quality-adjusted life years (QALYs) and 2018 CAD, respectively) for a simulated cohort of 100,000 patients newly diagnosed with PLGG after their initial surgery.ResultsThe life expectancy after diagnosis for individuals who did not receive molecular testing was 39.01 (95% Confidence Intervals (CI): 32.94;44.38) years and 40.08 (95% CI: 33.19;45.76) years for those who received testing. Our findings indicate that patients who received molecular testing at diagnosis experienced a 0.38 (95% CI: 0.08;0.77) gain in QALYs and $1384 (95% CI: $-3486; $1204) reduction in costs over their lifetime. Cost and QALY benefits were driven primarily by the avoidance of long-term adverse events (stroke, secondary neoplasms) associated with unnecessary use of radiation.ConclusionsWe demonstrate the clinical benefit and cost-effectiveness of molecular testing in guiding the decision to provide RT in PLGG. While our results do not consider the impact of targeted therapies, this work is an example of the value of simulation modeling in assessing the long-term costs and benefits of precision oncology interventions for childhood cancer, which can aid decision-making about health system reimbursement.

Results of a Multi-Institutional Phase 2 Clinical Trial for 4DCT-Ventilation Functional Avoidance Thoracic Radiation Therapy

Radiation pneumonitis remains a major limitation in the radiation therapy treatment of patients with lung cancer. Functional avoidance radiation therapy uses functional imaging to reduce pulmonary toxic effects by designing radiation therapy plans that reduce doses to functional regions of the lung. Lung functional imaging has been developed that uses 4-dimensional computed tomography (4DCT) imaging to calculate 4DCT-based lung ventilation (4DCT-ventilation). A phase 2 multicenter study was initiated to evaluate 4DCT-ventilation functional avoidance radiation therapy. The study hypothesis was that functional avoidance radiation therapy could reduce the rate of grade ≥2 radiation pneumonitis to 12% compared with a 25% historical rate, with the trial being positive if ≤16.4% of patients experienced grade ≥2 pneumonitis. Lung cancer patients receiving curative-intent radiation therapy (prescription doses of 45-75 Gy) and chemotherapy were accrued. Patient 4DCT scans were used to generate 4DCT-ventilation images. The 4DCT-ventilation images were used to generate functional avoidance plans that reduced doses to functional portions of the lung while delivering the prescribed tumor dose. Pneumonitis was evaluated by a clinician at 3, 6, and 12 months after radiation therapy. Sixty-seven evaluable patients were accrued between April 2015 and December 2019. The median prescription dose was 60 Gy (range, 45-66 Gy) delivered in 30 fractions (range, 15-33 fractions). The average reduction in the functional volume of lung receiving ≥20 Gy with functional avoidance was 3.5% (range, 0%-12.8%). The median follow-up was 312 days. The rate of grade ≥2 radiation pneumonitis was 10 of 67 patients (14.9%; 95% upper CI, 24.0%), meeting the phase 2 criteria. 4DCT-ventilation offers an imaging modality that is convenient and provides functional imaging without an extra procedure necessary. This first report of a multicenter study of 4DCT-ventilation functional avoidance radiation therapy provided data showing that the trial met phase 2 criteria and that evaluation in a phase 3 study is warranted.