A real-time contouring feedback tool for consensus-based contour training.

Purpose: Variability in contouring structures of interest for radiotherapy continues to be challenging. Although training can reduce such variability, having radiation oncologists provide feedback can be impractical. We developed a contour training tool to provide real-time feedback to trainees, thereby reducing variability in contouring. Methods: We developed a novel metric termed localized signed square distance (LSSD) to provide feedback to the trainee on how their contour compares with a reference contour, which is generated real-time by combining trainee contour and multiple expert radiation oncologist contours. Nine trainees performed contour training by using six randomly assigned training cases that included one test case of the heart and left ventricle (LV). The test case was repeated 30 days later to assess retention. The distribution of LSSD maps of the initial contour for the training cases was combined and compared with the distribution of LSSD maps of the final contours for all training cases. The difference in standard deviations from the initial to final LSSD maps, ΔLSSD, was computed both on a per-case basis and for the entire group. Results: For every training case, statistically significant ΔLSSD were observed for both the heart and LV. When all initial and final LSSD maps were aggregated for the training cases, before training, the mean LSSD ([range], standard deviation) was -0.8 mm ([-37.9, 34.9], 4.2) and 0.3 mm ([-25.1, 32.7], 4.8) for heart and LV, respectively. These were reduced to -0.1 mm ([-16.2, 7.3], 0.8) and 0.1 mm ([-6.6, 8.3], 0.7) for the final LSSD maps during the contour training sessions. For the retention case, the initial and final LSSD maps of the retention case were aggregated and were -1.5 mm ([-22.9, 19.9], 3.4) and -0.2 mm ([-4.5, 1.5], 0.7) for the heart and 1.8 mm ([-16.7, 34.5], 5.1) and 0.2 mm ([-3.9, 1.6],0.7) for the LV. Conclusions: A tool that uses real-time contouring feedback was developed and successfully used for contour training of nine trainees. In all cases, the utility was able to guide the trainee and ultimately reduce the variability of the trainee's contouring.

Acute and Late Pulmonary Effects After Radiation Therapy in Childhood Cancer Survivors: A PENTEC Comprehensive Review.

OBJECTIVES: The Pediatric Normal Tissue Effects in the Clinic (PENTEC) pulmonary task force reviewed dosimetric and clinical factors associated with radiation therapy (RT)-associated pulmonary toxicity in children. METHODS: Comprehensive search of PubMed (1965-2020) was conducted to assess available evidence and predictive models of RT-induced lung injury in pediatric cancer patients (<21 years old). Lung dose for radiation pneumonitis (RP) was obtained from dose-volume histogram (DVH) data. RP grade was obtained from standard criteria. Clinical pulmonary outcomes were evaluated using pulmonary function tests (PFTs), clinical assessment, and questionnaires. RESULTS: More than 2,400 abstracts were identified; 460 articles had detailed treatment and toxicity data; and 11 articles with both detailed DVH and toxicity data were formally reviewed. Pooled cohorts treated during 1999 to 2016 included 277 and 507 patients age 0.04 to 22.7 years who were evaluable for acute and late RP analysis, respectively. After partial lung RT, there were 0.4% acute and 2.8% late grade 2, 0.4% acute and 0.8% late grade 3, and no grade 4 to 5 RP. RP risk after partial thoracic RT with mean lung dose (MLD) <14 Gy and total lung V20Gy <30% is low. Clinical and self-reported pulmonary outcomes data included 8,628 patients treated during 1970 to 2013, age 0 to 21.9 years. At a median 2.9- to 21.9-year follow-up, patients were often asymptomatic; abnormal PFTs were common and severity correlated with lung dose. At ≥10-year follow-up, multi-institutional studies suggested associations between total or ipsilateral lung doses >10 Gy and pulmonary complications and deaths. After whole lung irradiation (WLI), pulmonary toxicity is higher; no dose response relationship was identified. Bleomycin and other chemotherapeutics at current dose regimens do not contribute substantially to adverse pulmonary outcomes after partial lung irradiation but increase risk with WLI. CONCLUSIONS: After partial lung RT, acute pulmonary toxicity is uncommon; grade 2 to 3 RP incidences are <1%. Late toxicities, including subclinical/asymptomatic impaired pulmonary function, are more common (<4%). Incidence and severity appear to increase over time. Upon review of available literature, there appears to be low risk of pulmonary complications in children with MLD < 14 Gy and V20Gy <30% using standard fractionated RT to partial lung volumes. A lack of robust data limit guidance on lung dose/volume constraints, highlighting the need for additional work to define factors associated with RT-induced lung injury.

Clinical implementation of automated treatment planning for whole-brain radiotherapy.

The purpose of the study was to develop and clinically deploy an automated, deep learning-based approach to treatment planning for whole-brain radiotherapy (WBRT). We collected CT images and radiotherapy treatment plans to automate a beam aperture definition from 520 patients who received WBRT. These patients were split into training (n = 312), cross-validation (n = 104), and test (n = 104) sets which were used to train and evaluate a deep learning model. The DeepLabV3+ architecture was trained to automatically define the beam apertures on lateral-opposed fields using digitally reconstructed radiographs (DRRs). For the beam aperture evaluation, 1st quantitative analysis was completed using a test set before clinical deployment and 2nd quantitative analysis was conducted 90 days after clinical deployment. The mean surface distance and the Hausdorff distances were compared in the anterior-inferior edge between the clinically used and the predicted fields. Clinically used plans and deep-learning generated plans were evaluated by various dose-volume histogram metrics of brain, cribriform plate, and lens. The 1st quantitative analysis showed that the average mean surface distance and Hausdorff distance were 7.1 mm (±3.8 mm) and 11.2 mm (±5.2 mm), respectively, in the anterior-inferior edge of the field. The retrospective dosimetric comparison showed that brain dose coverage (D99%, D95%, D1%) of the automatically generated plans was 29.7, 30.3, and 32.5 Gy, respectively, and the average dose of both lenses was up to 19.0% lower when compared to the clinically used plans. Following the clinical deployment, the 2nd quantitative analysis showed that the average mean surface distance and Hausdorff distance between the predicted and clinically used fields were 2.6 mm (±3.2 mm) and 4.5 mm (±5.6 mm), respectively. In conclusion, the automated patient-specific treatment planning solution for WBRT was implemented in our clinic. The predicted fields appeared consistent with clinically used fields and the predicted plans were dosimetrically comparable.

Our Experience Leading a Large Medical Physics Practice During the COVID-19 Pandemic.

PURPOSE: To provide a series of suggestions for other Medical Physics practices to follow in order to provide effective radiation therapy treatments during the COVID-19 pandemic. METHODS AND MATERIALS: We reviewed our entire Radiation Oncology infrastructure to identify a series of workflows and policy changes that we implemented during the pandemic that yielded more effective practices during this time. RESULTS: We identified a structured list of several suggestions that can help other Medical Physics practices overcome the challenges involved in delivering high quality radiotherapy services during this pandemic. CONCLUSIONS: Our facility encompasses 4 smaller Houston Area Locations (HALs), a main campus with 8 distinct services based on treatment site (ie. Thoracic, Head and Neck, Breast, Gastrointestinal, Gynecology, Genitourinary, Hematologic Malignancies, Melanoma and Sarcoma and Central Nervous System/Pediatrics), a Proton Center facility, an MR-Linac, a Gamma Knife clinic and an array of brachytherapy services. Due to the scope of our services, we have gained experience in dealing with the rapidly changing pandemic effects on our clinical practice. Our paper provides a resource to other Medical Physics practices in search of workflows that have been resilient during these challenging times.

The utility of quantitative CT radiomics features for improved prediction of radiation pneumonitis.

PURPOSE: The purpose of this study was to explore gains in predictive model performance for radiation pneumonitis (RP) using pretreatment CT radiomics features extracted from the normal lung volume. METHODS: A total of 192 patients treated for nonsmall cell lung cancer with definitive radiotherapy were considered in the current study. In addition to clinical and dosimetric data, CT radiomics features were extracted from the total lung volume defined using the treatment planning scan. A total of 6851 features (15 clinical, 298 total lung and heart dosimetric, and 6538 image features) were gathered and considered candidate predictors for modeling of RP grade ≥3. Models were built with the least absolute shrinkage and selection operator (LASSO) logistic regression and applied to the set of candidate predictors with 50 iterations of tenfold nested cross-validation. RESULTS: In the current cohort, 30 of 192 patients (15.6%) presented with RP grade ≥3. Average cross-validated AUC (CV-AUC) using only the clinical and dosimetric parameters was 0.51. CV-AUC was 0.68 when total lung CT radiomics features were added. Analysis with the entire set of available predictors revealed seven different image features selected in at least 40% of the model fits. CONCLUSIONS: We have successfully incorporated CT radiomics features into a framework for building predictive RP models via LASSO logistic regression. Addition of normal lung image features produced superior model performance relative to traditional dosimetric and clinical predictors of RP, suggesting that pretreatment CT radiomics features should be considered in the context of RP prediction.

Differences in Normal Tissue Response in the Esophagus Between Proton and Photon Radiation Therapy for Non-Small Cell Lung Cancer Using In Vivo Imaging Biomarkers.

PURPOSE: To determine whether there exists any significant difference in normal tissue toxicity between intensity modulated radiation therapy (IMRT) or proton therapy for the treatment of non-small cell lung cancer. METHODS AND MATERIALS: A total of 134 study patients (n=49 treated with proton therapy, n=85 with IMRT) treated in a randomized trial had a previously validated esophageal toxicity imaging biomarker, esophageal expansion, quantified during radiation therapy, as well as esophagitis grade (Common Terminology Criteria for Adverse Events version 3.0), on a weekly basis during treatment. Differences between the 2 modalities were statically analyzed using the imaging biomarker metric value (Kruskal-Wallis analysis of variance), as well as the incidence and severity of esophagitis grade (χ2 and Fisher exact tests, respectively). The dose-response of the imaging biomarker was also compared between modalities using esophageal equivalent uniform dose, as well as delivered dose to an isotropic esophageal subvolume. RESULTS: No statistically significant difference in the distribution of esophagitis grade, the incidence of grade ≥3 esophagitis (15 and 11 patients treated with IMRT and proton therapy, respectively), or the esophageal expansion imaging biomarker between cohorts (P>.05) was found. The distribution of imaging biomarker metric values had similar distributions between treatment arms, despite a slightly higher dose volume in the proton arm (P>.05). Imaging biomarker dose-response was similar between modalities for dose quantified as esophageal equivalent uniform dose and delivered esophageal subvolume dose. Regardless of treatment modality, there was high variability in imaging biomarker response, as well as esophagitis grade, for similar esophageal doses between patients. CONCLUSIONS: There was no significant difference in esophageal toxicity from either proton- or photon-based radiation therapy as quantified by esophagitis grade or the esophageal expansion imaging biomarker.

(18)F-Fluorodeoxyglucose Positron Emission Tomography Can Quantify and Predict Esophageal Injury During Radiation Therapy.

PURPOSE: We sought to investigate the ability of mid-treatment (18)F-fluorodeoxyglucose positron emission tomography (PET) studies to objectively and spatially quantify esophageal injury in vivo from radiation therapy for non-small cell lung cancer. METHODS AND MATERIALS: This retrospective study was approved by the local institutional review board, with written informed consent obtained before enrollment. We normalized (18)F-fluorodeoxyglucose PET uptake to each patient's low-irradiated region (<5 Gy) of the esophagus, as a radiation response measure. Spatially localized metrics of normalized uptake (normalized standard uptake value [nSUV]) were derived for 79 patients undergoing concurrent chemoradiation therapy for non-small cell lung cancer. We used nSUV metrics to classify esophagitis grade at the time of the PET study, as well as maximum severity by treatment completion, according to National Cancer Institute Common Terminology Criteria for Adverse Events, using multivariate least absolute shrinkage and selection operator (LASSO) logistic regression and repeated 3-fold cross validation (training, validation, and test folds). This 3-fold cross-validation LASSO model procedure was used to predict toxicity progression from 43 asymptomatic patients during the PET study. Dose-volume metrics were also tested in both the multivariate classification and the symptom progression prediction analyses. Classification performance was quantified with the area under the curve (AUC) from receiver operating characteristic analysis on the test set from the 3-fold analyses. RESULTS: Statistical analysis showed increasing nSUV is related to esophagitis severity. Axial-averaged maximum nSUV for 1 esophageal slice and esophageal length with at least 40% of axial-averaged nSUV both had AUCs of 0.85 for classifying grade 2 or higher esophagitis at the time of the PET study and AUCs of 0.91 and 0.92, respectively, for maximum grade 2 or higher by treatment completion. Symptom progression was predicted with an AUC of 0.75. Dose metrics performed poorly at classifying esophagitis (AUC of 0.52, grade 2 or higher mid treatment) or predicting symptom progression (AUC of 0.67). CONCLUSIONS: Normalized uptake can objectively, locally, and noninvasively quantify esophagitis during radiation therapy and predict eventual symptoms from asymptomatic patients. Normalized uptake may provide patient-specific dose-response information not discernible from dose.

Initial clinical experience with ArcCHECK for IMRT/VMAT QA.

Many devices designed for the purpose of performing patient-specific IMRT/VMAT QA are commercially available. In this work we report our experience and initial clinical results with the ArcCHECK. The ArcCHECK consists of a cylindrical array of diode detectors measuring entry and exit doses. The measured result is a cumulative dose displayed as a 2D matrix. The detector array requires both an absolute dose calibration, and a calibration of the detector response, relative to each other. In addition to the calibrations suggested by the manufacturer, various tests were performed in order to assess its stability and performance prior to clinical introduction. Tests of uniformity, linearity, and repetition rate dependence of the detector response were conducted and described in this work. Following initial test-ing, the ArcCHECK device was introduced in the clinic for routine patient-specific IMRT QA. The clinical results from one year of use were collected and analyzed. The gamma pass rates at the 3%/3 mm criterion were reported for 3,116 cases that included both IMRT and VMAT treatment plans delivered on 18 linear accelera-tors. The gamma pass rates were categorized based on the treatment site, treatment technique, type of MLCs, operator, ArcCHECK device, and LINAC model. We recorded the percent of failures at the clinically acceptable threshold of 90%. In addition, we calculated the threshold that encompasses two standard deviations (2 SD) (95%) of QAs (T95) for each category investigated. The commissioning measurements demonstrated that the device performed as expected. The uniformity of the detector response to a constant field arc delivery showed a 1% standard deviation from the mean. The variation in dose with changing repetition rate was within 1 cGy of the mean, while the measured dose showed a linear relation with delivered MUs. Our initial patient QA results showed that, at the clinically selected passing criterion, 4.5% of cases failed. On average T95 was 91%, rang-ing from 73% for gynecological sites to 96.5% for central nervous system sites. There are statistically significant differences in passing rates between IMRT and VMAT, high-definition (HD) and non-HD MLCs, and different LINAC models (p-values << 0.001). An additional investigation into the failing QAs and a com-parison with ion-chamber measurements reveals that the differences observed in the passing rates between the different studied factors can be largely explained by the field size dependence of the device. Based on our initial experience with the ArcCHECK, our passing rates are, on average, consistent with values reported in the AAPM TG-119. However, the significant variations between QAs that were observed based on the size of the treatment fields may need to be corrected to improve the specificity and sensitivity of the device.

NSCLC tumor shrinkage prediction using quantitative image features.

The objective of this study was to develop a quantitative image feature model to predict non-small cell lung cancer (NSCLC) volume shrinkage from pre-treatment CT images. 64 stage II-IIIB NSCLC patients with similar treatments were all imaged using the same CT scanner and protocol. For each patient, the planning gross tumor volume (GTV) was deformed onto the week 6 treatment image, and tumor shrinkage was quantified as the deformed GTV volume divided by the planning GTV volume. Geometric, intensity histogram, absolute gradient image, co-occurrence matrix, and run-length matrix image features were extracted from each planning GTV. Prediction models were generated using principal component regression with simulated annealing subset selection. Performance was quantified using the mean squared error (MSE) between the predicted and observed tumor shrinkages. Permutation tests were used to validate the results. The optimal prediction model gave a strong correlation between the observed and predicted tumor shrinkages with r=0.81 and MSE=8.60×10(-3). Compared to predictions based on the mean population shrinkage this resulted in a 2.92 fold reduction in MSE. In conclusion, this study indicated that quantitative image features extracted from existing pre-treatment CT images can successfully predict tumor shrinkage and provide additional information for clinical decisions regarding patient risk stratification, treatment, and prognosis.

Lung Size and the Risk of Radiation Pneumonitis.

PURPOSE: The purpose of this study was to identify patient populations treated for non-small cell lung cancer (NSCLC) who may be more at risk of radiation pneumonitis. METHODS AND MATERIALS: A total of 579 patients receiving fractionated 3D conformal or intensity modulated radiation therapy (IMRT) for NSCLC were included in the study. Statistical analysis was performed to search for cohorts of patients with higher incidences of radiation pneumonitis. In addition to conventional risk factors, total and spared lung volumes were analyzed. The Lyman-Kutcher-Burman (LKB) and cure models were then used to fit the incidence of radiation pneumonitis as a function of lung dose and other factors. RESULTS: Total lung volumes with a sparing of less than 1854 cc at 40 Gy were associated with a significantly higher incidence of radiation pneumonitis at 6 months (38% vs 12% for patients with larger volumes, P<.001). This patient cohort was overwhelmingly female and represented 22% of the total female population of patients and nearly 30% of the cases of radiation pneumonitis. An LKB fit to normal tissue complication probability (NTCP) including volume as a dose modifying factor resulted in a dose that results in a 50% probability of complication for the smaller spared volume cohort that was 9 Gy lower than the fit to all mean lung dose data and improved the ability to predict radiation pneumonitis (P<.001). Using an effective dose parameter of n=0.42 instead of mean lung dose further improved the LKB fit. Fits to the data using the cure model produced similar results. CONCLUSIONS: Spared lung volume should be considered when treating NSCLC patients. Separate dose constraints based on smaller spared lung volume should be considered. Smaller spared lung volume patients should be followed closely for signs of radiation pneumonitis.

Objectively Quantifying Radiation Esophagitis With Novel Computed Tomography-Based Metrics.

PURPOSE: To study radiation-induced esophageal expansion as an objective measure of radiation esophagitis in patients with non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy. METHODS AND MATERIALS: Eighty-five patients had weekly intra-treatment CT imaging and esophagitis scoring according to Common Terminlogy Criteria for Adverse Events 4.0, (24 Grade 0, 45 Grade 2, and 16 Grade 3). Nineteen esophageal expansion metrics based on mean, maximum, spatial length, and volume of expansion were calculated as voxel-based relative volume change, using the Jacobian determinant from deformable image registration between the planning and weekly CTs. An anatomic variability correction method was validated and applied to these metrics to reduce uncertainty. An analysis of expansion metrics and radiation esophagitis grade was conducted using normal tissue complication probability from univariate logistic regression and Spearman rank for grade 2 and grade 3 esophagitis endpoints, as well as the timing of expansion and esophagitis grade. Metrics' performance in classifying esophagitis was tested with receiver operating characteristic analysis. RESULTS: Expansion increased with esophagitis grade. Thirteen of 19 expansion metrics had receiver operating characteristic area under the curve values >0.80 for both grade 2 and grade 3 esophagitis endpoints, with the highest performance from maximum axial expansion (MaxExp1) and esophageal length with axial expansion ≥30% (LenExp30%) with area under the curve values of 0.93 and 0.91 for grade 2, 0.90 and 0.90 for grade 3 esophagitis, respectively. CONCLUSIONS: Esophageal expansion may be a suitable objective measure of esophagitis, particularly maximum axial esophageal expansion and esophageal length with axial expansion ≥30%, with 2.1 Jacobian value and 98.6 mm as the metric value for 50% probability of grade 3 esophagitis. The uncertainty in esophageal Jacobian calculations can be reduced with anatomic correction methods.

Reirradiation of Recurrent Pediatric Brain Tumors after Initial Proton Therapy.

PURPOSE: The use of reirradiation for recurrent pediatric brain tumors has been increasing, but the effect of repeat radiation on critical cranial structures is unknown. METHODS AND MATERIALS: Between July 2009 and May 2013, the records of 12 pediatric patients initially treated with proton therapy and then with reirradiation for recurrent brain tumors were retrospectively reviewed for toxicity and outcomes. Initial and repeat radiation dose distributions were deformed and merged to determine the maximum dose to 0.03 cm3 of the optic chiasm, optic nerves, spinal cord, brainstem, cochleae, pituitary, and uninvolved brain, and to 1 cm3 of the brainstem and brain on individual and composite plans. These dosimetric results were compared with auditory, neurocognitive, ophthalmologic, and endocrine outcomes to identify radiation-associated toxicities. RESULTS: Median follow-up was 3.5 years from diagnosis. Median ages at initial and repeat radiation were 4.6 and 6.7 years, respectively. All patients initially received proton radiotherapy to a median tumor dose of 55.8 Gy relative biological effectiveness (RBE) (range, 45 to 60 Gy [RBE]). At progression, patients completed a second course of radiation to local fields (n = 7) or the craniospinal axis (n = 5) with a median tumor dose of 40 Gy (RBE) (range, 20 to 54 Gy [RBE]). Median progression-free survival was 22.7 months from the last day of the second radiation course. No patient developed central nervous system necrosis requiring treatment. Of evaluable patients, none developed radiation-related high-grade hearing loss (n = 11), visual pathway deficit (n = 10), or significant change in pre- and post-reirradiation full-scale intelligence quotient (n = 4). Of 11 evaluable patients, 4 (36.4%) developed secondary hypothyroidism and 1 (9.1%) developed growth hormone deficiency. CONCLUSION: Repeat radiation for recurrent brain tumors after proton therapy may be performed in the pediatric population with acceptable short- and long-term toxicity.

Technology for Innovation in Radiation Oncology.

Radiation therapy is an effective, personalized cancer treatment that has benefited from technological advances associated with the growing ability to identify and target tumors with accuracy and precision. Given that these advances have played a central role in the success of radiation therapy as a major component of comprehensive cancer care, the American Society for Radiation Oncology (ASTRO), the American Association of Physicists in Medicine (AAPM), and the National Cancer Institute (NCI) sponsored a workshop entitled "Technology for Innovation in Radiation Oncology," which took place at the National Institutes of Health (NIH) in Bethesda, Maryland, on June 13 and 14, 2013. The purpose of this workshop was to discuss emerging technology for the field and to recognize areas for greater research investment. Expert clinicians and scientists discussed innovative technology in radiation oncology, in particular as to how these technologies are being developed and translated to clinical practice in the face of current and future challenges and opportunities. Technologies encompassed topics in functional imaging, treatment devices, nanotechnology, and information technology. The technical, quality, and safety performance of these technologies were also considered. A major theme of the workshop was the growing importance of innovation in the domain of process automation and oncology informatics. The technologically advanced nature of radiation therapy treatments predisposes radiation oncology research teams to take on informatics research initiatives. In addition, the discussion on technology development was balanced with a parallel conversation regarding the need for evidence of efficacy and effectiveness. The linkage between the need for evidence and the efforts in informatics research was clearly identified as synergistic.

Clinical validation of 4-dimensional computed tomography ventilation with pulmonary function test data.

PURPOSE: A new form of functional imaging has been proposed in the form of 4-dimensional computed tomography (4DCT) ventilation. Because 4DCTs are acquired as part of routine care for lung cancer patients, calculating ventilation maps from 4DCTs provides spatial lung function information without added dosimetric or monetary cost to the patient. Before 4DCT-ventilation is implemented it needs to be clinically validated. Pulmonary function tests (PFTs) provide a clinically established way of evaluating lung function. The purpose of our work was to perform a clinical validation by comparing 4DCT-ventilation metrics with PFT data. METHODS AND MATERIALS: Ninety-eight lung cancer patients with pretreatment 4DCT and PFT data were included in the study. Pulmonary function test metrics used to diagnose obstructive lung disease were recorded: forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity. Four-dimensional CT data sets and spatial registration were used to compute 4DCT-ventilation images using a density change-based and a Jacobian-based model. The ventilation maps were reduced to single metrics intended to reflect the degree of ventilation obstruction. Specifically, we computed the coefficient of variation (SD/mean), ventilation V20 (volume of lung ≤20% ventilation), and correlated the ventilation metrics with PFT data. Regression analysis was used to determine whether 4DCT ventilation data could predict for normal versus abnormal lung function using PFT thresholds. RESULTS: Correlation coefficients comparing 4DCT-ventilation with PFT data ranged from 0.63 to 0.72, with the best agreement between FEV1 and coefficient of variation. Four-dimensional CT ventilation metrics were able to significantly delineate between clinically normal versus abnormal PFT results. CONCLUSIONS: Validation of 4DCT ventilation with clinically relevant metrics is essential. We demonstrate good global agreement between PFTs and 4DCT-ventilation, indicating that 4DCT-ventilation provides a reliable assessment of lung function. Four-dimensional CT ventilation enables exciting opportunities to assess lung function and create functional avoidance radiation therapy plans. The present work provides supporting evidence for the integration of 4DCT-ventilation into clinical trials.

Acute phase response before treatment predicts radiation esophagitis in non-small cell lung cancer.

BACKGROUND AND PURPOSE: Radiation esophagitis (RE) represents an inflammatory reaction to radiation therapy (RT). We hypothesized that aspects of the physiologic acute phase response (APR) predicts RE. MATERIAL AND METHODS: We retrospectively analyzed 285 patients with non-small cell lung cancer (NSCLC) treated with definitive radiation. The primary analysis was the association of pretreatment lab values reflective of the APR with symptomatic (grade ⩾ 2) RE. Univariate and multivariate odds ratios (ORs) were calculated to test associations of clinical and pretreatment lab values with RE. Optimal cutpoints and multivariable risk stratification groupings were determined via recursive partitioning analysis. RESULTS: Pretreatment platelet counts were higher and hemoglobin levels lower in patients who developed RE (P<0.05). Based on these two pre-treatment risk factors, an APR score was defined as 0 (no risk factors), 1 (either risk factor), or 2 (both risk factors). APR score was significantly associated with RE in both univariate (OR = 2.3 for each point, 95% confidence interval [CI] 1.5-3.4, P = 0.001) and multivariate (OR = 2.1, 95% CI 1.3-3.4, P = 0.002) analyses. CONCLUSIONS: The APR score may represent a novel metric to predict RE. However, pending validation in an independent dataset, caution is advised when interpreting these results given their retrospective and thus exploratory nature.

Is there an impact of heart exposure on the incidence of radiation pneumonitis? Analysis of data from a large clinical cohort.

BACKGROUND: The goal of the present study was to determine, in a large clinical cohort, whether incidental radiation exposure to the heart during definitive radiotherapy of inoperable non-small cell lung cancer (NSCLC) detectably increased the risk of radiation pneumonitis (RP) beyond that resulting from radiation exposure to lung. MATERIAL AND METHODS: Data were analyzed from all patients who received definitive three-dimensional (3D) concurrent radiotherapy or intensity-modulated radiotherapy for the treatment of NSCLC over a 10-year period at our institution, except those who had previous lung cancer or for whom radiation treatment plans were unavailable for calculation of heart and lung dose-volume histograms (DVHs). Parameters computed from heart and lung DVHs included mean lung dose (MLD), effective lung dose computed using volume parameter n = 0.5 (Deff), mean heart dose (MHD), percentage of heart receiving > 65 Gy (V65), and minimum dose to the hottest 10% of heart (D10). Univariate and multivariate normal-tissue complication probability (NTCP) models were used to analyze incidence of Grade ≥ 2 or Grade ≥ 3 RP as a function of these and other parameters. RESULTS: The study cohort included 629 patients, with crude rates of Grade ≥ 2 RP and Grade ≥ 3 RP of N = 263 (42%) and N = 124 (20%), respectively. Univariate NTCP models based on dosimetric lung parameters (MLD and Deff) fit the data better than models based on univariate heart parameters (heart D10, heart V65 or MHD). In multivariate modeling, incorporation of heart parameters did not significantly improve the fit of RP risk models based on lung parameters alone (p > 0.38 in each case). CONCLUSIONS: In this large clinical cohort, there was no evidence that incidental heart exposure during radiotherapy of NSCLC had a detectable impact on the occurrence of moderate or severe RP.