Radiation Pneumonitis Symptoms Research Articles

High-dose thoracic radiation therapy for non-small cell lung cancer: a novel grading scale of radiation-induced lung injury for symptomatic radiation pneumonitis

BackgroundSymptomatic radiation pneumonitis (RP) may be a serious complication after thoracic radiation therapy (RT) for non-small cell lung cancer (NSCLC). This prospective observational study sought to evaluate the utility of a novel radiation-induced lung injury (RILI) grading scale (RGS) for the prediction of RP.Materials and methodsData of 41 patients with NSCLC treated with thoracic RT of 60–66 Gy were analysed. CT scans were scheduled before RT, one month post-RT, and every three months thereafter for one year. Symptomatic RP was defined as Common Terminology Criteria for Adverse Events grade ≥ 2. RGS grading ranged from 0 to 3. The inter-observer variability of the RGS was assessed by four senior radiologists. CT scans performed 28 ± 10 days after RT were used to analyse the predictive value of the RGS. The change in the RGS severity was correlated to dosimetric parameters.ResultsThe CT obtained one month post-RT showed RILI in 36 (88%) of patients (RGS grade 0 [5 patients], 1 [25 patients], 2 [6 patients], and 3 [5 patients]). The inter-observer agreement of the RGS grading was high (Kendall’s W coefficient of concordance = 0.80, p < 0.01). Patients with RGS grades 2–3 had a significantly higher risk for development of RP (relative risk (RR): 2.4, 95% CI 1.6–3.7, p < 0.01) and RP symptoms within 8 weeks after RT (RR: 4.8, 95% CI 1.3–17.6, p < 0.01) compared to RGS grades 0–1. The specificity and sensitivity of the RGS grades 2–3 in predicting symptomatic RP was 100% (95% CI 80.5–100%) and 45.4% (95% CI 24.4–67.8%), respectively. Increase in RGS severity correlated to mean lung dose and the percentage of the total lung volume receiving 5 Gy.ConclusionsThe RGS is a simple radiologic tool associated with symptomatic RP. A validation study is warranted.

Changes in Pulmonary Function and Development of Clinical Radiation Pneumonitis in Breast Cancer Patients following Post Mastectomy Radiation Therapy

Background: Lung is the main organ at risk for radiation induced injury while treating breast cancers with Post Mastectomy Radiotherapy (PMRT). Restrictive lung changes are usually seen in spirometry which tends to normalize by 1 year. Central Lung Distance (CLD) is shown to correlate well with the percentage of ipsilateral lung volume irradiated. Aims and Objectives: Spirometric changes following Radiation Therapy (RT) to chest wall in breast cancer patients using conventional fractionation and its correlation with acute radiation pneumonitis. Materials and Methodology: Thirty Breast cancer patients who received RT to chest wall +/- supraclavicular fossa and axilla, following Modified Radical Mastectomy (MRM) and neoadjuvant or adjuvant chemotherapy using tangential beams with Co60 teletherapy to a dose of 50 Gray in conventional fractionation were included and followed up till 6 months post RT. Baseline chest X-ray and spirometry done pre-RT were compared with those taken at 1, 3 and 6 months after completion of RT. Patients were evaluated at each visit for signs and symptoms of radiation pneumonitis, when present were graded as per Radiation Therapy Oncology Group (RTOG) criteria. Results: There was a significant fall in Forced Vital Capacity (FVC) by the end of 3 months (p value &lt;0.01) which improved by 6 months without any active intervention in 95% of the patients. Mean baseline FVC was 83% which decreased to 70% by the end of 3 months and 79% at 6 months. Forced Expiratory Volume in first second (FEV1) and FEV1/FVC did not show any significant change compared to baseline. Spirometric changes correlated with reversible restrictive lung changes. One out of 30 patients developed symptomatic acute radiation pneumonitis (5%) of grade 3 severity who had moderate restrictive lung disease. Conclusion: Significant decrease in FVC of the lungs is present following PMRT in carcinoma of breast patients in the initial 3 months which tends to normalize by 6 months. 5% of the patients develop symptomatic acute lung toxicity which can be further reduced by minimizing the irradiated lung volume.

Need for Caution in the Diagnosis of Radiation Pneumonitis During the COVID-19 Pandemic

PurposePatients with cancer are at high risk for mortality from coronavirus disease 2019 (COVID-19). Radiation pneumonitis (RP) is a common toxicity of thoracic radiation therapy with clinical and imaging features that overlap with those of COVID-19; however, RP is treated with high-dose corticosteroids, which may exacerbate COVID-19–associated lung injury. We reviewed patients who presented with symptoms of RP during the intensification of a regional COVID-19 epidemic to report on their clinical course and COVID-19 testing results. Methods and MaterialsThe clinical course and chest computed tomography (CT) imaging findings of consecutive patients who presented with symptoms of RP in March 2020 were reviewed. The first regional COVID-19 case was diagnosed on March 1, 2020. All patients underwent COVID-19 qualitative RNA testing. ResultsFour patients with clinical suspicion for RP were assessed. Three out of 4 patients tested positive for COVID-19. All patients presented with symptoms of cough and dyspnea. Two patients had a fever, of whom only 1 tested positive for COVID-19. Two patients started on an empirical high-dose corticosteroid taper for presumed RP, but both had clinical deterioration and ultimately tested positive for COVID-19 and required hospitalization. Chest CT findings in patients suspected of RP but ultimately diagnosed with COVID-19 showed ground-glass opacities mostly pronounced outside the radiation field. ConclusionsAs this pandemic continues, patients with symptoms of RP require diagnostic attention. We recommend that patients suspected of RP be tested for COVID-19 before starting empirical corticosteroids and for careful attention to be paid to chest CT imaging to prevent potential exacerbation of COVID-19 in these high-risk patients.

Early variations in lymphocytes and T lymphocyte subsets are associated with radiation pneumonitis in lung cancer patients and experimental mice received thoracic irradiation.

There were no ideal markers to predict the development of radiation pneumonitis (RP). We want to investigate the value of variations of lymphocytes and T lymphocyte subsets in predicting RP after radiotherapy (RT) of lung cancer based on previous clinical findings. A total of 182 lung cancer patients who received RT were retrospectively analyzed. Circulating lymphocytes and T lymphocyte subsets were measured before, during, and after RT. Patients were evaluated from the start of RT to 6 months post‐RT. A mice model with acute radiation‐induced lung injury was established and circulating lymphocytes were measured weekly until 8 weeks after irradiation. Univariate and multivariate analyses were adopted to identify risk factors of RP. Lymphocyte levels significantly decreased (P < .001) in patients before RP symptoms developed that also was able to be seen in the mice model and the values recovered during remission of symptoms. The decrease in lymphocyte count reflected the severity of RP. Meanwhile, CD4+ T lymphocyte count was significantly lower during the occurrence of symptoms in patients with RP than in those without RP (P < .001), and it improved along with RP recovery. Levels of lymphocytes and CD4+ T lymphocyte subsets proved as independent predictors of RP. Here we showed that lower peripheral blood levels of lymphocytes and CD4+ T lymphocyte were associated with an increased risk of RP, which was validated by this mice model, and thus are associated with differences in radiation‐induced lung toxicity among individuals and help identify those who are susceptible to developing RP after RT.

Investigating of relationship between the parameters related to the treatment planning and the biological parameters in radiation induced pneumonitis in breast cancer patients

Introduction: The purpose in this study is to analyze of DVH parameters as predictors of radiation pneumonitis and investigation on the relationship between dosimetric and clinical parameters based on PFTs as response in NTCP model and therefore achieve to lung dose- response relation in breast cancer patients. Prescribed dose to treatment volumes was 50 Gy in 2.0 Gy/fractions Materials and Methods: Clinical and dosimetric data for 51 patients with stages II, III breast cancer who were undergone modified radical mastectomy (MRM) or mastectomy, and they had received prior chemotherapy with a same regimen of 8 steps, were included. Dose delivery technique was SAD and the prescribed dose was 50 Gy in 25 fractions. All of these pulmonary function tests were done before and after completion of radiotherapy, 3 and 6 months afterwards. Relationship between dosimetrical and clinical parameters patients are analyzed according to the univariate logistic regression and by Lyman NTCP model for investigation probability SRP. Results: All of these pulmonary function tests (PFTs) were decreased after completion of radiotherapy, and 6 months afterwards. According to our results, in this research pulmonary complications has appeared from six months after treatment. 17 patients (33.3%) were with radiation pneumonitis without symptoms and 5 (9.8%) patients suffering radiation pneumonitis symptoms with grade 2. Lyman NTCP model parameters were obtained for prediction radiation pneumonitis. Conclusion: Lung dose- response relation was obtained and analyzed according to Lyman NTCP model and DMH as input data in Lyman NTCP model comparison of DVH. IV20, irradiated volume and mass and mean lung dose parameters are related with radiation pneumonitis in patients. Our results indicated that pulmonary function changes occurs at 6 months after RT. we present that in the structure as lung, DMH concept has important effect in the Lyman model

Inhalative steroids as an individual treatment in symptomatic lung cancer patients with radiation pneumonitis grade II after radiotherapy - a single-centre experience.

PurposeTo assess efficacy of our single-centre experience with inhalative steroids (IS) in lung cancer patients with symptomatic radiation pneumonitis (RP) grade II.Material and methodsBetween 05/09 and 07/10, 24 patients (female, n = 8; male, n = 16) with lung cancer (non-small cell lung carcinoma [NSCLC]: n = 19; small cell lung cancer [SCLC]: n = 3; unknown histology: n = 2) and good performance status (ECOG ≤1) received definitive radiotherapy to the primary tumour site and involved lymph nodes with concurrent chemotherapy (n = 18), sequential chemotherapy (n = 2) or radiation only (n = 4) and developed symptomatic RP grade II during follow-up. No patient presented with oxygen requiring RP grade III. The mean age at diagnosis was 66 years (range: 50–82 years). Nine patients suffered from chronic obstructive pulmonary disease (COPD) before treatment, and 18 patients had a smoking history (median pack years: 48). The mean lung dose was 15.5 Gy (range: 3.0–23.1 Gy). All patients were treated with IS. If a patient’s clinical symptoms did not significantly improve within two weeks of IS therapy initiation, their treatment was switched to oral prednisolone.ResultsAll 24 patients were initially treated with a high dose IS (budesonide 800 μg 1-0-1) for 14 days. Of the patients, 18 showed a significant improvement of clinical symptoms and 6 patients did not show significant improvement of clinical symptoms and were classified as non-responders to IS. Their treatment was switched to oral steroids after two weeks (starting with oral prednisolone, 0.5 mg/kg bodyweight; at least 50 mg per day). All of these patients responded to the prednisolone. None of non-responders presented with increased symptoms of RP and required oxygen and / or hospitalization (RP grade III). The median follow-up after IS treatment initiation was 18 months (range: 4–66 months). The median duration of IS treatment and prednisolone treatment was 8.2 months (range: 3.0–48.3 months) and 11.4 months (range: 5.0–44.0 months), respectively. Of the 18 IS treatment responders, 2 (11.1 %) patients with pre-existing grade 2 COPD still required IS (400 μg twice a day) 45.0 and 48.3 months after radiotherapy, respectively. For the remaining 16 responders (88.9 %), IS therapy was stopped after 7.7 months (range: 3.0–18.2 months). None of the patients treated with IS developed any specific IS-related side effects such as oral candidiasis.ConclusionThis single-centre experience shows that high-dose IS is an individual treatment option for radiation-induced pneumonitis grade II in patients with a good performance status.

Pre-Radiation Therapy Fluorine 18 Fluorodeoxyglucose PET Helps Identify Patients with Esophageal Cancer at High Risk for Radiation Pneumonitis.

To examine the association between pre-radiation therapy (RT) fluorine 18 fluorodeoxyglucose (FDG) uptake and post-RT symptomatic radiation pneumonitis (RP). In accordance with the retrospective study protocol approved by the institutional review board, 228 esophageal cancer patients who underwent FDG PET/CT before chemotherapy and RT were examined. RP symptoms were evaluated by using the Common Terminology Criteria for Adverse Events, version 4.0, from the consensus of five clinicians. By using the cumulative distribution of standardized uptake values (SUVs) within the lungs, those values greater than 80%-95% of the total lung voxels were determined for each patient. The effect of pre-chemotherapy and RT FDG uptake, dose, and patient or treatment characteristics on RP toxicity was studied by using logistic regression. The study subjects were treated with three-dimensional conformal RT (n = 36), intensity-modulated RT (n = 135), or proton therapy (n = 57). Logistic regression analysis demonstrated elevated FDG uptake at pre-chemotherapy and RT was related to expression of RP symptoms. Study subjects with elevated 95% percentile of the SUV (SUV95) were more likely to develop symptomatic RP (P < .000012); each 0.1 unit increase in SUV95 was associated with a 1.36-fold increase in the odds of symptomatic RP. Receiver operating characteristic (ROC) curve analysis resulted in area under the ROC curve of 0.676 (95% confidence interval: 0.58, 0.77), sensitivity of 60%, and specificity of 71% at the 1.17 SUV95 threshold. CT imaging and dosimetric parameters were found to be poor predictors of RP symptoms. The SUV95, a biomarker of pretreatment pulmonary metabolic activity, was shown to be prognostic of symptomatic RP. Elevation in this pretreatment biomarker identifies patients at high risk for posttreatment symptomatic RP.

Should All Limited-Stage Small Cell Lung Cancer Be Treated Alike? Impact of AJCC Stage on Brain Metastasis, Survival, and Patterns of Failure

Purpose/Objective(s): To determine if higher irradiated lung dose rather than irradiated lung volume or mean lung dose (MLD) is more critical for induction of radiation pneumonitis (RP) symptoms. Materials/Methods: We retrospectively analyzed the clinical and dosimetric data from 275 esophageal cancer cases treated with thoracic radiation therapy using IMRT, proton, or 3D-CRT. RP symptoms were evaluated using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv4). For each patient, the percentage lung volume irradiated, mean irradiated lung dose (MILD), mean lung dose (MLD), lung dose regions (low dose volume, 10 Gy or CGE, Vlow; moderatedose volume, > 10-40 Gy or CGE, Vmod; and high dose volume > 40 Gy or CGE, Vhigh), as well as V5 to V50 were determined. The effects of MILV, MILD, MLD, lung dose regions, percentage lung volume irradiated, dosimetric parameters, patient and treatment characteristics, or metabolic radiation dose response (PMRR) with pulmonary toxicity were studied using logistic regression. Results: Proton therapy irradiated less lung volume (> 0.1 Gy or CGE) than IMRT (3.711 L in IMRT, 1.261 L in proton and 3.058 L in 3D-CRT) but the mean irradiated lung dose is higher in the proton versus IMRT group (12.04 Gy in IMRT, 17.21 CGE in proton and 11.70 Gy in 3D-CRT), despite the lower MLD received by the proton group (11.26 Gy in IMRT, 6.09 CGE in proton, and 10.62 Gy in 3D-CRT). We found the rate of symptomatic radiation pneumonitis is 2 times higher for proton than IMRT (25% in proton, 13.6% in IMRT, and 27.8% in 3DCRT). The PMRR was significantly different between the three modalities (0.15 in proton, 0.10 in IMRT, and 0.10 in 3DCRT, p Z 0.044 Kruskal-Wallis test). Conclusions: Despite smaller irradiated lung volumes, subjects treated with proton therapy (vs IMRT) were two times more likely to develop symptomatic RP. The higher mean irradiated lung dose resulting in a more intense local response is the likely culprit. Author Disclosure: N. Pham: None. R. Castillo: None. R. Castillo: None. B. Hobbs: None. T. Guerrero: None.

Pre-radiotherapy FDG PET predicts radiation pneumonitis in lung cancer

BackgroundA retrospective analysis is performed to determine if pre-treatment [18 F]-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) image derived parameters can predict radiation pneumonitis (RP) clinical symptoms in lung cancer patients.Methods and MaterialsWe retrospectively studied 100 non-small cell lung cancer (NSCLC) patients who underwent FDG PET/CT imaging before initiation of radiotherapy (RT). Pneumonitis symptoms were evaluated using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv4) from the consensus of 5 clinicians. Using the cumulative distribution of pre-treatment standard uptake values (SUV) within the lungs, the 80th to 95th percentile SUV values (SUV80 to SUV95) were determined. The effect of pre-RT FDG uptake, dose, patient and treatment characteristics on pulmonary toxicity was studied using multiple logistic regression.ResultsThe study subjects were treated with 3D conformal RT (n = 23), intensity modulated RT (n = 64), and proton therapy (n = 13). Multiple logistic regression analysis demonstrated that elevated pre-RT lung FDG uptake on staging FDG PET was related to development of RP symptoms after RT. A patient of average age and V30 with SUV95 = 1.5 was an estimated 6.9 times more likely to develop grade ≥ 2 radiation pneumonitis when compared to a patient with SUV95 = 0.5 of the same age and identical V30. Receiver operating characteristic curve analysis showed the area under the curve was 0.78 (95% CI = 0.69 – 0.87). The CT imaging and dosimetry parameters were found to be poor predictors of RP symptoms.ConclusionsThe pretreatment pulmonary FDG uptake, as quantified by the SUV95, predicted symptoms of RP in this study. Elevation in this pre-treatment biomarker identifies a patient group at high risk for post-treatment symptomatic RP.

Radiation pneumonitis and pulmonary function with lung dose-volume constraints in breast cancer irradiation.

We studied symptomatic radiation pneumonitis (RP) and changes in pulmonary function tests (PFTs) after loco-regional radiotherapy (LRRT) with V20 lung constraints in breast cancer (BC). Sixty-four women underwent PFTs before and 5 months after 3D planned LRRT for BC. The incidentally irradiated ipsilateral lung V20 was minimised to <30%. Patients were monitored for symptoms of RP 1, 4 and 7 months after radiotherapy (RT) and data on covariates were collected prospectively. The outcome was compared with previous treatment series. Pneumonitis was less frequent with the applied constraint, that is, four mild and one moderate case, than in our previous report (p < 0·001). In multivariate analyses, neither dosimetric data nor covariates appeared to influence mean changes in vital capacity [-0·11L, standard error of the mean (SEM) 0·03] or diffusing capacity of the lung for carbon monoxide (DLCO) (-0·20 mmol/kPa/min, SEM 0·01), except for pre-RT chemotherapy, which diminished the change in DLCO 5 months post-RT. The used constraint and 3D planning lowered the rate of RP and short-term changes in PFTs compared with our previous treatment series. Pre-RT chemotherapy affects DLCO baseline levels. Rates of side effects should be continuously studied when new target definitions or therapies are introduced in LRRT of BC.

WE‐G‐BRA‐05: Post‐Radiation Normalized FDG‐PET versus Radiation Dose Correlates with Radiation Pneumonitis Symptoms and the Nitric Oxide Ratio

Purpose: To quantify the relationship between the post‐treatment [18F]‐2‐fluoro‐2‐deoxyglucose (18F‐FDG) positron emission tomography (PET) uptake and radiation dose received and correlate this relationship with prospectively scored pulmonary radiation toxicity. Methods: 34 patients treated for esophageal cancer with thoracic radiotherapy were evaluated prospectively at the MD Anderson Cancer Center. The treatment planning computed tomography (CT) imaging was registered with the restaging PET/CT. Using histogram analysis, the voxel average FDG‐PET uptake vs. radiation dose was obtained for each case and linear regression was performed. The slope of the linear regression was termed the pulmonary metabolic response rate (PMRR). Common Toxicity Criteria version 4 was used to score pneumonitis. Exhaled nitric oxide (eNO) was measured on the first and last days of radiation treatment. Receiver operating characteristic curves were used to determine the threshold PMRR, mean lung dose, volume of lung receiving 5, 10, 20 and 30 Gy and eNO ratio (End/beginning) that can best predict symptomatic patients. Results: 29 patients were evaluable. The median of the mean standard uptake value from lung that received 0–5 Gy was 0.51 (range, 0.34–1.24), 5–10 Gy was 0.71 (range, 0.39–1.32), 10–20 Gy was 0.78 (0.40–1.56), and &gt; 20 Gy was 1.10 (range, 0.43–3.01). 25 patients had grade 0 or 1 pulmonary symptom score and 4 patients had grade 2 or higher (symptomatic) score. Both PMRR and the eNO ratio gave a significant area under the curve of 0.86 (p = 0.02) and 1 (p&lt;0.001) respectively. Using a PMRR threshold of 0.0184 yielded a true positive rate of 0.75 and false positive rate of 0.125. Conclusions: In this prospective study, the PMRR predicted for development of radiation pneumonitis. This unique quantitative assessment of radiation pnuemonitis can be used for quality control to deliver higher doses of radiation safely.

Computed Tomography Appearance of Early Radiation Injury to the Lung: Correlation With Clinical and Dosimetric Factors

To systematically assess the spectrum of radiologic changes in the lung after radiation therapy for non-small-cell lung cancer. We reviewed the cases of 146 patients treated with radical radiotherapy at our institution. All patients had computed tomography (CT) scans performed 3 months after completion of therapy. Radiographic appearances were categorized using a standard grading system. The association of these abnormalities with pretreatment factors and clinical radiation pneumonitis (RP) was investigated. New intrapulmonary abnormalities were seen in 92 patients (63%). These were ground-glass opacity in 16 (11%), patchy consolidation in 19 (13%), and diffuse consolidation in 57 (39%). Twenty-five patients (17%) developed clinical symptoms of RP. Although 80% of the patients with RP had areas of consolidation seen on the posttreatment CT scan, the majority (74%) of patients with such radiographic changes were asymptomatic. For patients with lung infiltrates, the minimum isodose encompassing the volume of radiologic abnormality was usually ≥27 Gy. Traditional dose-volume metrics, pulmonary function tests, and the coadministration of angiotensin converting enzyme inhibitors (ACE-I) were all strongly correlated with the presence of radiologic injury on univariate analysis (p≤0.002). There was also an inverse correlation between prior smoking history and CT scan changes (p=0.02). On multivariate analysis, dosimetric parameters and the use of ACE-I retained significance (p=0.005). Our findings suggest that there is substantial interindividual variation in lung radiosensitivity. ACE-I prevented the radiologic changes seen after high-dose radiation therapy, and their role as radioprotectants warrants further investigation.

Chemotherapy Significantly Increases the Risk of Radiation Pneumonitis in Radiation Therapy of Advanced Lung Cancer

The reported rate of developing radiation pneumonitis (RP) in patients receiving definitive radiation therapy (RT) for lung cancer is 5% to 36%. However, this incidence is probably underreported because of the nonspecific symptoms of RP that may be erroneously attributed to another cardiovascular or respiratory disorder. The objective of this study was to evaluate the incidence of RP in lung cancer patients receiving RT or chemoradiation therapy. Of the 110 patients that were reviewed, 86 were chosen for a retrospective analysis. A diagnosis of RP was made based on clinical assessment in the first 6 to 12 months after RT. Radiation pneumonitis was graded as per Radiation Therapy Oncology Group grading criteria. The incidence of developing grade 2 or higher RP was significantly associated with addition of chemotherapy. The incidence of RP in patients receiving chemotherapy was 62.7% (42/67) versus 15.8% (3/19) in patients receiving no chemotherapy (P < 0.001). However, there was no significant effect of the type or sequence of chemotherapy on the incidence of RP. The risk of developing RP is 5 times greater in patients receiving chemotherapy when compared with those not receiving this treatment (hazard ratio: 5.0; 95% confidence interval 1.5, 16.1). In addition, patients in age group 61 to 70 years had a significantly increased risk of developing RP compared with patients of age 60 or younger (hazard ratio: 3.0; 95% confidence interval: 1.4, 6.5). Histology and radiation dose were not significant factors in development of RP. The incidence of RP in patients receiving external-beam RT is significantly increased with addition of chemotherapy and 61 to 70 year age group.

Imaging Sunitinib-induced Vascular Changes by DCE-MRI to Schedule Radiotherapy for Murine Renal Cell Carcinoma

Results: Twenty-eight patients were evaluable, all received 50.4 Gy with concurrent chemotherapy. Pneumonitis CTCAEv4 toxicity scores were: 1 grade 3, 3 grade 2, 7 grade 1, and 17 grade 0. Dosimetric factors were not predictive of symptoms. Exhaled NO measured before, at completion, and at restaging were 17.3 (SD 8.5; range 5.5 - 36.7), 16.0 (14.2; 5.8 - 67.7), 14.7 (6.2; 5.5 - 28.0) parts perbillion(ppb)respectively.Eachmeasurementwasmadeintriplicatewithanaveragestandarderrorof0.8ppb.Theratioof exhaledNOattheendofradiotherapyversuspre-treatmentwas3.4(1.7-6.7)forthesymptomaticand0.8(0.3-1.3)fortheasymptomatic (p value = 0.0017). Elevation in exhaled NO preceded peak symptoms by 33 (21 - 50) days. The time to peak symptoms wasfoundtobeinverselyrelatedtotheexhaled NOelevation.TheexhaledNOratio (endversusbefore)wastestedas apredictorof symptomsusingthedatafromthistrialandthek-nearestneighborclassifierschemedescribed.TheNOratiopredictedsymptomatic patients with an average error rate of 8%. Conclusions: Elevation in the exhaled NO at the end of radiotherapy was found to predict for radiation pneumonitis symptoms. Time to peak symptoms was inversely related to the elevation in exhaled NO, higher elevation was associated with a shorter time. Author Disclosure: T. Guerrero, None; J. Martinez, None; M.R. McCurdy, None; M.J. Wolski, None; M.F. McAleer, None.

SU‐FF‐J‐20: A Multimodality Imaging Approach for Predicting Radiation Induced Lung Injury

Purpose: Radiation pneumonitis (RP), is a major dose limiting toxicity in thoracic irradiation for patients with lung or breast cancer. Multimodality imaging and particularly integrated PET/CT imaging is increasing used in radiotherapy treatment staging, planning, and monitoring. In this work, we are investigating the potential of a new hybrid feature‐based approach utilizing post‐radiotherapy PET/CT images to predict the risk of later RP. Method and Materials: As a demonstrative example for analyzing normal tissue toxicities using the proposed multimodality approach, we analyzed post‐treatment PET/CT scans (typically, 3 mos. post‐RT) of 20 lung cancer radiotherapy patients for the endpoint of pneumonitis. The rate of RP in this group was 20%. The lung region minus the Gross Tumor Volume (GTV) was designated as the region of interest (ROI). We extracted features based on descriptive statistics of intensity (in units of SUV in PET and Hounsfield in CT), image intensity volume histogram (IVH) metrics, and texture‐based features. Statistical association was performed using Spearman's rank correlation (Rs). Results: Thirty candidate features were extracted from each image modality. Preliminary results indicate that texture features in both PET and CT seems to predict RP. For instance, the PET ROI standard deviation had Rs=0.14 in PET and Rs=−0.035 in CT while the texture (related to roughness) local heterogeneity had Rs=0.33 (p=0.08) in PET and Rs=0.63 (p=0.002) in CT. Conclusion: We have proposed a new approach for predicting RP risk pneumonitis from hybrid PET/CT image features. Texture related features on the post‐RT CT scan provide the best prediction. Estimating of these features could provide the physician with an early warning enabling a more proactive management of RP symptoms. Further analysis of these multimodality features, their complementary effect, and the optimal time of imaging, is needed to fully understand this finding.Partially supported by K25 CA128809 and R01 CA85181.

Radiation Pneumonitis: Correlation of Toxicity With Pulmonary Metabolic Radiation Response

To characterize the relationship between radiation pneumonitis (RP) clinical symptoms and pulmonary metabolic activity on post-treatment [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET). We retrospectively studied 101 esophageal cancer patients who underwent restaging FDG-PET/computed tomography imaging 3-12 weeks after completing thoracic radiotherapy. The National Institutes of Health Common Toxicity Criteria, version 3, was used to score the RP clinical symptoms. Linear regression was applied to the FDG-PET/computed tomography images to determine the normalized FDG uptake vs. radiation dose. The pulmonary metabolic radiation response (PMRR) was quantified as this slope. Modeling was performed to determine the interaction of PMRR, mean lung dose (MLD), and the percentage of lung receiving >20 Gy with RP outcomes. Of the 101 patients, 25 had Grade 0, 10 had Grade 1, 60 had Grade 2, 5 had Grade 3, and 1 had Grade 5 RP symptoms. Logistic regression analysis demonstrated that increased values of both MLD and PMRR were associated with a greater probability of RP clinical symptoms (p = 0.032 and p = 0.033, respectively). Spearman's rank correlation found no association between the PMRR and the dosimetric parameters (planning target volume, MLD, percentage of lung receiving >5-30 Gy). Twofold cross-validation demonstrated that the combination of MLD and PMRR was superior to either alone for assessing the development of clinical RP symptoms. The combined MLD (or percentage of lung receiving >20 Gy) and PMRR had a greater sensitivity and accuracy (53.3% and 62.5%, respectively) than either alone. The results of this study have demonstrated a significant correlation between RP clinical symptoms and the PMRR measured by FDG-PET/computed tomography after thoracic radiotherapy.