Risk Of Radiation Pneumonitis Research Articles

Decreased Risk of Radiation Pneumonitis With Coincident Concurrent Use of Angiotensin-converting Enzyme Inhibitors in Patients Receiving Lung Stereotactic Body Radiation Therapy.

Angiotensin-converting enzyme inhibitors (ACEi) have demonstrated decreased rates of radiation-induced lung injury in animal models and clinical reports have demonstrated decreased pneumonitis in the setting of conventionally fractionated radiation to the lung. We tested the role of ACEi in diminishing rates of symptomatic (grade ≥2) pneumonitis in the setting of lung stereotactic body radiation therapy (SBRT). We analyzed patients treated with thoracic SBRT to 48 to 60 Gy in 4 to 5 fractions from 2006 to 2014. We reviewed pretreatment and posttreatment medication profiles to document use of ACEi, angiotensin receptor blockers, bronchodilators, aspirin, PDE-5 inhibitors, nitrates, and endothelin receptor antagonists. Pneumonitis was graded posttreatment based on Common Terminology Criteria for Adverse Events Version 4.0. Univariate and multivariate analysis was performed and time to development of pneumonitis was evaluated by the Kaplan-Meier method. A total of 189 patients were evaluated with a median follow-up of 24.8 months. The overall 1-year rate of symptomatic pneumonitis was 13.2%. The 1-year rate of symptomatic pneumonitis was 4.2% for ACEi users versus 16.3% in nonusers (P=0.03). On univariate analysis, the odds of developing grade 2 or greater pneumonitis were significantly lower for patients on ACEi (P=0.03). On multivariate analysis, after controlling for clinicopathologic characteristics and dosimetric endpoints, there was a significant association between ACEi use and decreased risk of clinical pneumonitis (P=0.04). Angiotensin receptor blockers or other bronchoactive medications did not show significant associations with development of pneumonitis. Incidental concurrent use of ACEi demonstrated efficacy in diminishing rates of symptomatic pneumonitis in the setting of lung SBRT.

Influence of respiratory motion management technique on radiation pneumonitis risk with robotic stereotactic body radiation therapy.

Purpose/ObjectivesFor lung stereotactic body radiation therapy (SBRT), real‐time tumor tracking (RTT) allows for less radiation to normal lung compared to the internal target volume (ITV) method of respiratory motion management. To quantify the advantage of RTT, we examined the difference in radiation pneumonitis risk between these two techniques using a normal tissue complication probability (NTCP) model.Materials/Method20 lung SBRT treatment plans using RTT were replanned with the ITV method using respiratory motion information from a 4D‐CT image acquired at the original simulation. Risk of symptomatic radiation pneumonitis was calculated for both plans using a previously derived NTCP model. Features available before treatment planning that identified significant increase in NTCP with ITV versus RTT plans were identified.ResultsPrescription dose to the planning target volume (PTV) ranged from 22 to 60 Gy in 1–5 fractions. The median tumor diameter was 3.5 cm (range 2.1–5.5 cm) with a median volume of 14.5 mL (range 3.6–59.9 mL). The median increase in PTV volume from RTT to ITV plans was 17.1 mL (range 3.5–72.4 mL), and the median increase in PTV/lung volume ratio was 0.46% (range 0.13–1.98%). Mean lung dose and percentage dose–volumes were significantly higher in ITV plans at all levels tested. The median NTCP was 5.1% for RTT plans and 8.9% for ITV plans, with a median difference of 1.9% (range 0.4–25.5%, pairwise P < 0.001). Increases in NTCP between plans were best predicted by increases in PTV volume and PTV/lung volume ratio.ConclusionsThe use of RTT decreased the risk of radiation pneumonitis in all plans. However, for most patients the risk reduction was minimal. Differences in plan PTV volume and PTV/lung volume ratio may identify patients who would benefit from RTT technique before completing treatment planning.

Using benchmarked lung radiation dose constraints to predict pneumonitis risk: Developing a nomogram for patients with mediastinal lymphoma

PurposeWe identified lung dosimetric constraints to assist in predicting the radiation pneumonitis (RP) risk in patients with mediastinal lymphoma and then identified the clinical prognostic factors that were associated with the achievement of key dosimetric constraints. Methods and MaterialsIn 190 patients who received mediastinal intensity modulated radiation therapy, we used univariate χ2 and multivariate logistic models to identify the predictors of RP and achievement of lung dose-volume histogram (DVH) constraints and build a predictive nomogram for RP. ResultsAn increased risk of RP was strongly associated with mean lung dose (MLD) > 13.5 Gy (odds ratio [OR]: 8.13; 95% confidence interval [CI], 3.01-21.93; P < .001) and the percent of lung volume receiving ≥5 Gy (V5) > 55% (OR: 7.01; 95% CI, 2.94-16.72; P < .001). Therefore, patients had low RP risk (8%) if both MLD ≤13.5 and V5 ≤55 constraints were achieved, moderate risk (24%) if only MLD was achieved, and the highest risk (48%) if MLD was not achieved. Deep-inspiration breath-hold (DIBH) technique during treatment strongly prognosticated achieving MLD and V5 DVH constraints (OR,3.88; 95% CI, 1.84-8.19; P < .001). Specifically, 86% of patients who were treated with DIBH versus 63% without DIBH achieved DVH constraints (P < .001). This translated into a “number needed to treat” with DIBH of 4 patients to enable 1 additional patient to achieve both constraints. In comparison, the clinical characteristics were marginal prognosticators: DVH constraints were more likely achieved in nonbulky disease (OR: 3.01; 95% CI, 0.89-4.53; P = .09) and patients who had not previously received salvage chemotherapy (OR, 2.44; 95% CI, 0.98-6.11; P = .06). Nomogram-predicted risks of RP ranged from 4% to 60% on the basis of MLD and V5, total radiation dose, and use of salvage chemotherapy. ConclusionsAchieving mean lung and V5 DVH constraints is critical to reduce RP risk in patients with lymphoma who receive mediastinal intensity modulated radiation therapy. The use of the DIBH technique is a promising risk-modifying treatment approach in patients with mediastinal lymphoma and especially in patients with a history of nonmodifiable risk factors for RP such as bulky disease and salvage chemotherapy.

Is severe emphysema, as defined by quantitative CT measurement, a negative risk factor of radiation fibrosis?

To investigate whether patients with emphysema, as evaluated by quantitative CT image measurement, are at risk of developing radiation pneumonitis (RP) after radiotherapy (RT) for non-small cell lung cancer (NSCLC). Between March 2011 and June 2015, 68 consecutive patients with Stage I NSCLC treated with a RT dose of 75 Gy given in 30 fractions were enrolled. The median age was 79 years and there were 45 males and 23 females. The number of patients with T1 and T2 were 49 and 19, respectively. The severity of emphysema was evaluated by the percentages of the low attenuation area (LAA) of ≤-860 or -950 Hounsfield unit (HU) and average HU in the whole lung. The mean difference percentages of LAA of ≤-860 (p = 0.0004) or -950 HU (p = 0.005) and average HU (p = 0.001) in patients with RP were significantly lower than those in patients without RP. The area under curve (AUC) of average HU was significantly higher than AUC of LAA of ≤-860 (p < 0.0001) or -950 HU (p < 0.0001). The RP rate after RT was significantly lower when the average HU values were ≤-850 HU (p = 0.0003). Patients with emphysema evaluated by average HU (≤-850 HU) in the whole lung were found to be at low risk of RP after RT. Advances in Knowledge: Quantitative measurement of average HU from CT images was predicted of RP after RT.

The risk and predictors for severe radiation pneumonitis in lung cancer patients treated with thoracic reirradiation

BackgroundThoracic reirradiation (re-RT) is increasingly administered. However, radiation pneumonitis (RP) remains to be the most common side effect from retreatment. This study aimed to determine the risk and predictors for severe RP in patients receiving thoracic re-RT.MethodsSixty seven patients with lung cancer received thoracic re-RT for recurrent or metastatic disease. Three-dimensional conformal radiotherapy (3D-CRT)/intensity modulated radiotherapy (IMRT) was used for 60 patients, and stereotactic body radiation therapy (SBRT) was used in 7 patients. Deformable image registration (DIR) was performed to create a composite plan. Severe (grade ≥ 3) RP was graded according to Common Terminology Criteria for Adverse Events version 4.0.ResultsEighteen patients (26.9%) developed grade ≥ 3 RP (17 of grade 3, and 1 of grade 4). In univariate analyses, V5 and mean lung dose (MLD) of initial RT or re-RT plans, V5 and V20 of composite plans, and the overlap between V5 of initial RT and V5 of re-RT plans/V5 of re-RT plans (overlap-V5/re-V5) were significantly associated with grade ≥ 3 RP (P < 0.05 for each comparison). Multivariate analysis revealed that MLD of the initial RT plans (HR = 14.515, 95%CI:1.778–118.494, P = 0.013), V5 of the composite plans (HR = 7.398, 95%CI:1.319–41.495, P = 0.023), and overlap-V5/re-V5 (P = 0.041) were independent predictors for grade ≥ 3 RP. Out-of-field failures with medium overlap-V5/re-V5 of 0.4–0.8 was associated with higher risk of grade ≥ 3 RP compared with in-field failures (18.3% vs. 50%, P = 0.014).ConclusionsThe risk of grade ≥ 3 RP could be predicted not only by dose-volume variables from re-RT plan, but also by some from initial-RT and composite plans. Out-of-field failures was associated with higher risk of severe RP compared with in-field failures in some cases.

Clinical and Dosimetric Factors Predicting Grade ≥2 Radiation Pneumonitis After Postoperative Radiotherapy for Patients With Non-Small Cell Lung Carcinoma

Toidentify clinical and dosimetric factors that would predict grade ≥2 radiation pneumonitis (RP) for patients undergoing postoperative radiation therapy (PORT) for non-small cell lung cancer (NSCLC); and to use the factors identified to generate a predictive model to quantify risk of RP in such patients. We retrospectively reviewed radiation therapy, radiographic, and clinical data from 199 patients who had received PORT, with or without chemotherapy, for NSCLC. Potential associations between dosimetric and clinical factors and RP were evaluated in univariate and multivariate Cox regression hazard models and competing risk analysis. Kaplan-Meier analysis was used to estimate overall survival and the cumulative incidence of RP, and receiver operating characteristic curve analysis to identify cutpoints for variables found to influence RP risk. The endpoint was grade ≥2 RP (symptomatic, requiring steroids or limiting instrumental activities of daily living). Thirty-seven patients (19%) developed grade ≥2 RP. Patient-related factors, type of surgery or chemotherapy, and radiation therapy-related factors were not associated with grade ≥2 RP; only lung V10>30% and lung V20>20% predicted grade ≥2 RP. Risk groupings were as follows: high risk, V10>30% and V20>20% (24 of 72 patients, 33%); intermediate risk, V10>30% and V20≤20% or V10≤30% and V20>20% (6 of 26 patients, 23%); and low risk, V10≤30% and V20≤20% (6 of 101 patients, 6%) (P<.0001). In a subgroup analysis of patients who had had lobectomy, corresponding incidences of RP were as follows: high risk, 20 of 59 (34%); intermediate risk, 5 of 22 (23%); and low risk, 6 of 70 (9%) (P=.001). The lung dose-volume variables V10 and V20 predicted risk of grade ≥2 RP among patients who underwent PORT for NSCLC.

Which is the optimal threshold for defining functional lung in single-photon emission computed tomography lung perfusion imaging of lung cancer patients?

The aim of this study was to investigate the optimal threshold for the functional lung (FL) definition of single-photon emission computed tomography (SPECT) lung perfusion imaging. Forty consecutive stage III non-small-cell lung cancer patients underwent SPECT lung perfusion scans and PET/CT scans for treatment planning, and the images were coregistered. Total lung and perfusion lung volumes corresponding to 10, 20, …, 60% of the maximum SPECT count were segmented automatically. The SPECT-weighted mean lung dose (SWMDx%) and the percentage of FL volume receiving more than 20 Gy (Fx%V20) of different thresholds were investigated using SPECT-weighted dose-volume histograms. Receiver-operator characteristic curves were used to identify SWMD and FV20 of different thresholds in predicting the incidence of radiation pneumonitis (RP). Eleven (27.5%) patients developed RP (grades 1, 2, 3, and 4 were 10.0, 7.5, 7.5, and 2.5%, respectively) after treatment. The largest area under the receiver-operator characteristic curve was 0.881 for the ability of SWMD to predict RP with 20% as the threshold and 0.928 for the ability of FV20 with 20% as the threshold. The SWMD20% and FV20 of FL using 20% of the maximum SPECT count as the threshold may be better predictors for the risk of RP.

GSTP1 Ile105Val polymorphism might be associated with the risk of radiation pneumonitis among lung cancer patients in Chinese population: A prospective study.

Background: Growing data suggest that DNA damage repair and detoxification pathways play crucial roles in radiation-induced toxicities. To determine whether common functional single-nucleotide polymorphisms (SNPs) in candidate genes from these pathways can be used as predictors of radiation pneumonitis (RP), we conducted a prospective study to evaluate the associations between functional SNPs and risk of RP.Methods: We recruited a total of 149 lung cancer patients who had received intensity modulated radiation therapy (IMRT). GSTP1 and XRCC1 were genotyped using the SurPlexTM-xTAG method in all patients. RP events were prospectively scored using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Kaplan-Meier analysis was used to determine the cumulative probability of RP of grade ≥ 2. Cox proportional hazard regression was performed to identify clinical variables and SNPs associated with risk of RP grade ≥ 2, using univariate and multivariate analysis, respectively.Results: With a median follow-up of 9 months, the incidence of RP of grade ≥ 2 was 38.3%. A predicting role in RP was observed for the GSTP1 SNP (adjusted hazard ratio 3.543; 95% CI 1.770-7.092; adjusted P< 0.001 for the Ile/Val and Val/Val genotypes versus Ile/Ile genotype). Whereas, we found that patients with XRCC1 399Arg/Gln and Gln/Gln genotypes had a lower risk of RP compares with those carrying Arg/Arg genotype (adjusted HR 0.653; 95% CI 0.342-1.245), but with no statistical significance observed (adjusted P = 0.195).Conclusions: Our results suggested a novel association between GSTP1 SNP 105Ile/Val and risk of RP development, which suggests the potential use of this genetic polymorphism as a predictor of RP. In addition, genetic polymorphisms of XRCC1 399Arg/Gln may also be associated with RP.

The Association Between the Serum KL-6 Level and the Risk of Radiation Pneumonitis

The Association Between the Serum KL-6 Level and the Risk of Radiation Pneumonitis

Association of DNA repair gene polymorphisms with the risk of radiation pneumonitis in lung cancer patients.

A total of 149 lung cancer patients were recruited to receive intensity modulated radiation therapy (IMRT). The association of developing radiation pneumonitis (RP) with genetic polymorphism was evaluated. The risks of four polymorphic sites in three DNA repair related genes (ERCC1, rs116615:T354C and rs3212986:C1516A; ERCC2, rs13181:A2251C; XRCC1, rs25487:A1196G) for developing grade ≥ 2 RP were assessed respectively. It was observed that ERCC1 T354C SNP had a significant effect on the development of grade ≥ 2 RP (CT/TT vs. CC, adjusted HR = 0.517, 95% CI, 0.285–0.939; adjusted P = 0.030). It is the first time demonstrating that CT/TT genotype of ERCC1 354 was significantly associated with lower RP risk after radio therapy.

MS 06.05 The Use of Adjuvant IMRT after Pleurectomy/Decortication

MS 06.05 The Use of Adjuvant IMRT after Pleurectomy/Decortication

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

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

Evaluating Which Dose-Function Metrics Are Most Critical for Functional Guided Radiation Therapy with CT Ventilation Imaging

4DCT-ventilation imaging is increasingly being used to calculate lung ventilation and implement functional guided radiotherapy in clinical trials. There has been little exhaustive work evaluating which dose-function metrics should be used for treatment planning and plan evaluation for functional guided radiotherapy. Our study evaluated which dose-function metrics are most critical in assessing the risk of radiation pneumonitis (RP). Seventy lung cancer patients with 4DCT imaging and RP grading were used. Pre-treatment 4DCTs of each patient were used to calculate ventilation images. We evaluated 3 different types of dose function metrics that combined that patient’s 4DCT-ventilation image and treatment planning dose distribution: 1) structure-based approaches 2) image-based approaches using the dose-function histogram (DFH) and 3) non-linear weighting schemes. Structure-based approaches used a binary approximation in which the lung was binned to either functional or non-functional status. A full range of cutoff values to delineate between functional and non-functional and the volume of functional lung receiving ≥ 5Gy, 10Gy, 20Gy, and 30Gy was investigated. Imaging-based and non-linear approaches investigated the fraction of lung function receiving ≥ 5Gy, 10Gy, 20Gy, and 30Gy. Maximum likelihood methods were used to generate normal tissue complication probability (NTCP) models predicting grade 3+ RP for the dose-function schemes and all tested dose-function metrics. The area under the curve (AUC) for each model was used to quantify the ability to predict for toxicity. All techniques were compared to NTCP models based on traditional, total lung dose metrics. The most predictive models for grade 3+ RP were structure-based approaches that focused on the volume of functional lung receiving ≥20Gy (AUC=0.70) where functional lung was treated as regions with ventilation values ≥84th percentile. Imaging-based analysis with the DFH and non-linear weighted ventilation values yielded AUCs of 0.66 and 0.67, respectively, when evaluating the fraction of functionality receiving ≥20Gy. All dose-function metrics outperformed the traditional lung dose metrics (mean lung dose, AUC = 0.55). A full range of dose-function metrics and functional thresholds were examined. The AUC values for the most predictive functional models occupied a narrow range (0.66-0.70) and all demonstrated improvements over AUC from traditional lung dose metrics (0.55). Identifying the dose-function parameters most predictive of grade 3+ RP provides valuable data for treatment planning and plan evaluation parameters. With prospective clinical trials of functional guided radiotherapy using 4DCT-ventilation imaging underway, this work provides seminal data to help establish guidelines for the implementation of functional guided radiotherapy.

Dosimetric comparison between volumetric-modulated arc therapy and intensity-modulated radiotherapy for esophageal cancer: a meta-analysis

Objective To investigate the dosimetric comparison of target volumes and organs at risk (OAR) between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) for esophageal cancer by a meta-analysis. Methods A literature search was performed to collect the clinical studies on dosimetric comparison between VMAT and IMRT. The primary endpoints of interest were dosimetric parameters of target volumes and OAR, number of monitor units (MUs), and treatment time (TT). Results A total of 17 studies involving 323 patients were included in this meta-analysis. When the total dose was>50.4 Gy, VMAT showed significantly lower mean dose (Dmean) of gross tumor volume (GTV) and maximum dose (Dmax) of planning target volume (PTV) than IMRT (P=0.009; P=0.039). There were no significant differences in Dmean, V30, and V40 of the heart, Dmax of the spinal cord, and V5, V10, and Dmean of the lung between VMAT and IMRT (P>0.05). VMAT showed significantly lower V15, V20, and V30 of the lung than IMRT (P=0.001; P=0.000; P=0.023). When the single dose was 1.8 Gy and 2.0 Gy, VMAT showed significantly lower TT (reduced by 323.5 s and 193.7 s) and number of MUs (reduced by 275.4 MU and 134.2 MU) than IMRT (P=0.000 and 0.009; P=0.000 and 0.022). Conclusions VMAT can significantly reduce TT, MUs, irradiation dose to the lung, and the risk of radiation pneumonitis, and improve the utilization rate of equipment. Compared with IMRT, VMAT has no significant advantages in protection of the spinal cord and the heart and dosimetric parameters of target volumes except Dmean of PTV and Dmean and Dmax of GTV when the total dose was ≤50.4 Gy. Key words: Esophageal neoplasms/volumetric-modulated arc therapy; Esophageal neoplasms/intensity-modulated radiotherapy; Meta-analysis

Doses aux organes à risque en radiothérapie conformationnelle et en radiothérapie stéréotaxique : les poumons

Radiation-induced lung disease (RILD) is common after radiation therapy and represents cornerstone toxicities after treatment of thoracic malignancies. From a review of literature, the objective of this article was to summarize clinical and non-clinical parameters associated with the risk of RILD in the settings of normo-fractionated radiotherapy and stereotactic body radiation therapy (SBRT). For the treatment of lung cancers with a normo-fractionated treatment, the mean lung dose (MLD) should be below 15–20Gy. For a thoracic SBRT, V20Gy<10% and MLD<6Gy are recommended. One should pay attention to central tumors and respect specific dose constraints to the bronchial tree. The recent technological improvements may represent an encouraging way to decrease lung toxicities. Finally, our team developed a calculator in order to predict the risk of radiation pneumonitis.

Survival Impact of Cardiac Dose Following Lung Stereotactic Body Radiotherapy

IntroductionThe purpose of this study was to determine the impact of radiation dose to substructures of the heart in lung stereotactic body radiotherapy (SBRT) patients on non–cancer-related deaths. MethodsPatients treated with lung SBRT at a single institution from 2005 to 2013 were included. The heart and its substructures were contoured, and dose was calculated including mean, max, and max 10 cc dose. Clinical variables including stage, histology, age, gender, Charlson comorbidity index (CCI), preexisting cardiac disease, pulmonary function (forced expiratory volume in 1 second, diffusion capacity), and smoking status were explored for association with non–cancer-related deaths in univariable (UVA) and multivariable (MVA) analyses. Heart dosimetric parameters were correlated with the risk of radiation pneumonitis (RP) using UVA and MVA. ResultsA total of 189 patients were included with median age of 76 years (range, 48-93 years). Of these patients, 45.5% were female, 27.5% were T2, 16.9% were current smokers, 64% had preexisting cardiac risk factors, and 34.5% had CCI score of ≥ 3. Mean lung dose ± SD was 456 ± 231 cGy. Heart max, mean, and 10 cc doses were 1867 ± 1712 cGy, 265 ± 269 cGy, and 1150 ± 1075 cGy, respectively. There were 14 (7.4%) ≥ Grade 2 RP and 3 (1.6%) were ≥ Grade 3. The median overall survival was 37.3 months (95% confidence interval, 29.8-45.3 months). On UVA, female gender (P < .01), higher Eastern Cooperative Oncology Group (P = .01), cardiac risk (P < .01), CCI (P < .01), and bilateral ventricles max dose (P = .02) were associated with non–cancer-related deaths; on MVA, bilateral ventricles max dose was significant (P = .05). No heart parameters were associated with RP. ConclusionsHigher bilateral ventricles max dose is associated with poorer survival. Heart dose parameters should be considered when planning patients for SBRT.

Radiotherapy of Lung Tumours in Idiopathic Pulmonary Fibrosis

This article is a joint statement of the Czech Pneumological and Physiological Society and the Czech Society for Radiation Oncology, Biology and Physics, and reviews current opinions on radiotherapy in patients with idiopathic pulmonary fibrosis (IPF). In general, radiotherapy of lung tumours is associated with risk of radiation pneumonitis (RP); moreover, IPF may be complicated by acute exacerbations (AE-IPF). Both complications may immediately threaten patients lives. Assessment of individual radiotherapy modalities has shown that conventional radiotherapy is not appropriate, especially in large tumours. Up to 30% of patients are at risk of developing AE-IPF. As a result, as many as 83% of patients die within 3 months of initiation of lung cancer treatment. Fatal RP is most commonly observed within 2 months of radiotherapy. In IPF accompanied by early-stage non-small cell lung cancer (NSCLC), stereotactic body radiation therapy (SBRT) may be considered. NSCLC should be treated with chemotherapy. Several cases report severe exacerbations of subclinical IPF after SBRT even with minimal signs of previous interstitial involvement. Grade 2 RP has been reported in up to 50% of cases with any level of interstitial change detected by lung CT prior to radiotherapy. In palliative radiotherapy, external radiation may be considered as an exception if the main bronchi are involved. Similarly, brachytherapy may be indicated for certain cases of bronchial stenosis. The presence of any level of interstitial change suggests a risk for fatal RP and AE-IPF. This is also supported by the fact that, at the present time, there are no dose limitations for radiation therapy of lung cancer in IPF, irrespective of whether conventional fractionated radiotherapy or SBRT is used. Moreover, there are no reliable predictive factors for lung involvement. In some studies, RP was more frequently associated with high CRP and LDH levels, PS 2 and interstitial changes of 10% or more. Treatment depends on the severity of the involvement. In more severe forms, corticosteroids, antibiotics and oxygen therapy should be administered. Ventilation support is often needed. Radiotherapy for patients with IPF and lung cancer or other chest tumours requires an individual approach depending on the local findings, the patients lung function and general condition, and the prognosis of the primary disease. Decision-making should take into consideration potential benefits and risks, and be carried out by a multidisciplinary team comprising a pulmonologist and clinical and radiation oncologists. Treatment should always be thoroughly discussed with the patient signing an informed consent form.Key words: idiopathic pulmonary fibrosis - chest radiotherapy - indications - radiation pneumonitis - acute exacerbation of idiopathic pulmonary fibrosis - treatment This work was supported by grant AZV 16-32-318 A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 4. 5. 2017Accepted: 18. 5. 2017.

Measurement of exhaled nitric oxide and serum surfactant protein D levels for monitoring radiation pneumonitis following thoracic radiotherapy

The present study aimed to examine the role of exhaled nitric oxide (eNO) and serum surfactant protein D (SP-D) level in the determination of radiation pneumonitis (RP) after thoracic radiotherapy (RT). The study included 34 treatments for 33 patients, including 16 three-dimensional conformal and 18 stereotactic body RT treatments. eNO levels were measured prior to RT, immediately subsequent to RT, every week during the RT course and at 1, 3, 6, 9 and 12 months following the treatment. The therapy reduced the eNO from 24.3±12.8 ppb prior to RT to 19.0±10.4 ppb immediately subsequent to RT (P=0.04). A total of 5 patients (14%) developed symptomatic RP of grade 2 or higher 3–5 months later, and exhibited an eNO elevation of 2.1±0.68-fold the minimum value, whereas the RP- group exhibited 1.4±0.6-fold elevation (P=0.02). The sensitivity of a cut-off of a 1.4-fold increase in the eNO ratio at the onset of RP was 100%; however, the specificity was 52%, and no predictive alterations to eNO levels were observed prior to the onset of RP. RT was associated with an elevated serum SP-D level at 3–6 months after RT. There was a statistically significant difference in the initial serum SP-D level between RP+ and RP- patients. In conclusion, obtaining the eNO ratio was a useful RP monitoring tool but did not predict RP occurrence in the present setting, whereas serum SP-D level may be a potential predictor for the detection of RP risk.

Intensity-modulated radiation therapy versus volumetric-modulated arc therapy in non-small cell lung cancer: assessing the risk of radiation pneumonitis

AbstractPurposeThis study aimed to compare intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) regarding plan quality and healthy lung sparing, in stage III non-small cell lung cancer (NSCLC) patients.Materials and methodsThe plans of 60 patients were allocated either to the IMRT (n=30) or the VMAT (n=30) group. The dose prescribed to the planning target volume (PTV) was evaluated at the 95% level and the mean lung dose (MLD) and the healthy lung receiving 5, 10 and 20 Gy (V5, V10and V20, respectively) were analysed. The normal tissue complication probability (NTCP) for radiation pneumonitis was calculated with the Lyman–Kutcher–Burman model.ResultsBoth techniques achieved comparable results for target coverage (V95%=97·87 versus 97·18%,p&gt;0·05) and homogeneity. The MLD (15·57 versus 16·98 Gy,p&gt;0·05), V5(60·35 versus 67·25%,p&gt;0·05) and V10(45·22 versus 53·14%,p=0·011) were lower for IMRT, whereas VMAT reduced V20(26·44 versus 25·90%,p&gt;0·05). The NTCP for radiation pneumonitis was higher for VMAT, but no statistical significance was observed (11·07 versus 12·75,p&gt;0·05).ConclusionBoth techniques seemed suitable for NSCLC treatment, but IMRT presented better results regarding lung sparing thus being beneficial in reducing the risk of radiation-induced pneumonitis.

Safety and feasibility of consolidation pembrolizumab following concurrent chemoradiation for unresectable stage III non-small cell lung cancer: Hoosier Cancer Research Network LUN14-179.

8523 Background: The standard of care for unresectable stage III NSCLC is concurrent chemorad. Following treatment, the risk of radiation pneumonitis is greatest at 1-3 mo. Pneumonitis risk increases with consolidation chemotherapy. A previous trial by our group (Hanna et al, JCO 2008) of consolidation docetaxel showed 80.8% completed 3 planned cycles of chemo with a grade 3-5 pneumonitis rate of 9.6% and 1 death. PD-1 inhibitors are also associated with an increased risk of pneumonitis in the metastatic setting. We conducted a phase II trial of consolidation pembro initiated 1-2 mo after concurrent chemorad, a period during which pts are at high risk of developing pneumonitis. Methods: Pts with stage III NSCLC who completed chemorad with either carbo/paclitaxel, cis/etop, or cis/pemetrexed plus 59-66.6 Gy of radiation and had no PD received pembro 200mg IV q3wk for up to 1 yr. Primary endpoint is time to metastatic disease. The objective of the study is to evaluate both safety and efficacy, and here we report preliminary safety and feasibility results. Evaluable pts for this analysis had ≥3 mo of f/u or went off study due to PD, toxicity, or death &lt; 3 mos after initiation of pembro. Results: 93 pts enrolled. Median age 67 (range 46-84), 59 (63.4%) were male. 87 (93.5%) were former or current smokers. 68 (73.1%) received carbo/pac, 24 (25.8%) received cis/etop, and 1 received cis/pemetrexed. SqCC (n = 41), non-SqCC (n = 43), NSCLC NOS (n = 8), mixed (n = 1). IIIA (n = 56), IIIB (n = 37). At the time of analysis, 83 of 93 pts were evaluable. 66 of 83 (79.5%) received ≥ 3 mo of pembro. 17 (20.5%) pts developed any grade pneumonitis with 14 of 17 occurring in the first 12 wks (median 9 wks). Only 3 (3.6%) pts developed grade 3-5 pneumonitis related to pembro. There was 1 pneumonitis-related death and a second death from respiratory failure possibly related to pembro. Conclusions: This early report indicates that most patients can safely receive consolidation pembro within 1-2 mo of completing chemorad. The incidence of serious pneumonitis during the first 3 mo of treatment appears low. Updated safety data on all 93 pts will be presented at the ASCO meeting. Clinical trial information: NCT02343952.