Rate Of Radiation Pneumonitis Research Articles

Analysis of the risk factors of radiation pneumonitis in patients after radiotherapy for esophageal squamous cell carcinoma.

To predict the risk factors of radiation pneumonitis (RP) in patients with esophageal squamous cell carcinoma (ESCC) who received radiotherapy. From January 2015 to October 2021, 477 ESCC patients were enrolled and were assessed retrospectively. All these patients received radiotherapy for primary lesions or mediastinal metastatic lymph nodes. Clinical efficacy and adverse events (AEs) were observed. Univariate analysis identified clinical and dosimetric factors associated with the development of RP, and multivariate logistic regression analysis identified independent potential risk factors associated with the development of RP. Nomograms were constructed to predict RP based on the results of multivariate logistic regression analysis. Among the 477 ESCC patients, the incidence of RP was 22.2%, and the incidence of grade 4 or higher RP was 1.5%. Univariate analysis indicated that chronic obstructive pulmonary disease (COPD), pulmonary infection, leucopenia, PTV volume, V5, V20, V30 and MLD affected the occurrence of RP. The multivariate logistic regression analysis indicated that COPD (OR:1.821, 95%CI:1.111-2.985; P=0.017), pulmonary infection (OR:2.528, 95%CI:1.530-4.177; P<0.001), higher V20 (OR: 1.129, 95% CI:1.006-1.266; P=0.029) were significant independent predictors of RP in ESCC patients. COPD, pulmonary infection, V20 have been integrated for the RP nomogram. The rate of RP was significantly reduced in the V20<21.45% group. Further analysis indicated that the old age, diabetes, higher V20, and higher MLD were risk factors for grade 4 or higher RP. The area under the curve (AUC) value for V20 was 0.73 (95% CI, 0.567-0.893, P < 0.05). We have determined the risk factors of RP and grade 4 or higher RP in ESCC patients after radiotherapy. MLD, V20, COPD were independent factors for RP. It was necessary to take measures to reduce or avoid the occurrence of RP for patients with these risk factors at the early stage.

Risk factor analysis of the development of severe radiation pneumonitis in patients with non-small cell lung cancer treated with curative radiotherapy, with focus on underlying pulmonary disease

BackgroundWe aim to identify the multifaceted risk factors that can affect the development of severe radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with curative high-dose radiotherapy with or without concurrent chemotherapy.MethodsWe retrospectively reviewed the medical records of 175 patients with stage-I-III NSCLC treated with curative thoracic X-ray radiotherapy at the Korea University Guro Hospital between June 2019 and June 2022. Treatment-related complications were evaluated using the Common Terminology Criteria for Adverse Events (version 4.03).ResultsThe median follow-up duration was 15 months (range: 3–47 months). Idiopathic pulmonary fibrosis (IPF) as an underlying lung disease (P < 0.001) and clinical stage, regarded as the concurrent use of chemotherapy (P = 0.009), were associated with a high rate of severe RP. In multivariate analyses adjusting confounding variables, the presence of IPF as an underlying disease was significantly associated with severe RP (odds ratio [95% confidence interval] = 48.4 [9.09–347]; P < 0.001). In a subgroup analysis of stage-I-II NSCLC, the incidence of severe RP in the control, chronic obstructive pulmonary disease (COPD), and IPF groups was 3.2%, 4.3%, and 42.9%, respectively (P < 0.001). The incidence of severe RP was 15.2%, 10.7%, and 75.0% in the control, COPD, and IPF groups, respectively (P < 0.001) in the stage-III NSCLC group.ConclusionsThis study revealed that IPF as an underlying lung disease and the concurrent use of chemotherapy are associated with a high rate of severe RP. In contrast, COPD did not increase the risk of pulmonary toxicity after receiving curative high-dose radiotherapy.

Effect of Segmental Abutting Esophagus-Sparing Technique to Reduce Severe Esophagitis in Limited-Stage Small-Cell Lung Cancer Patients Treated with Concurrent Hypofractionated Thoracic Radiation and Chemotherapy

To evaluate the effect of segmental abutting esophagus-sparing (SAES) radiotherapy to reduce severe (G3+) acute esophagitis from 20% to 5% in patients with limited-stage small cell lung cancer (LS-SCLC) treated with concurrent chemoradiotherapy. Patients with a clinical target volume (CTV) ≤1 cm close to the esophagus were enrolled in the experimental arm (45 Gy in 3 Gy daily fractions in 3 weeks) of an ongoing phase III randomized clinical trial (NCT02675088), which enrolled patients with histologically confirmed SCLC and clinically staged as LS or I-IIIB (AJCC 7th). This trial was designed to determine whether HYPO TRT (45 Gy in 3 Gy QD, experimental arm) has the same efficacy as CF TRT (60 Gy in 2 Gy QD, controlled arm) in patients with LS-SCLC. The whole esophagus was divided into the involved esophagus and abutting esophagus (AE) to receive different dose limitations according to the distance from the edge of the CTV. The primary endpoint was grade ≥ 3 acute esophagitis. From 1 May 2021 to 30 April 2022, 30 patients were enrolled and completed four cycles of planned chemotherapy and radiotherapy. Our patient population was predominantly male (66.7% men vs. 33.3% women), with a median age of 62 years. A majority of patients presented with Stage N2-3 (90.0%) and T2-4 (76.7%), in which 4 patients had ultracentral-located primary tumors. With the SAES technique, all dosimetric parameters were significantly reduced for the whole esophagus and AE. The maximal and mean dose of the esophagus (47.4±1.9 Gy and 13.5 ± 5.8 Gy, respectively) and AE (42.9±2.3 Gy and 8.6 ± 3.6 Gy, respectively) in the SAES plan were significantly lower than those (esophagus 48.0±1.9 Gy and 14.7± 6.1 Gy, AE 45.1±2.4 Gy and 9.8± 4.2 Gy, respectively) in the non-SAES plan. After the follow-up of more than 7 months (range, 7.0-18.1 months) for all patients, only one patient (3.3%, 95% CI 0.1%-17.2%) experienced grade 3 acute esophagitis and no grade 4-5 acute esophagitis happened (Table 3). For late toxicities, one patient suffered sustained grade 1 late esophagitis and all others had no symptoms of esophagitis. The rate of radiation pneumonitis was very low, with one grade 3 event and no grade 4-5 event. Twelve (40.0%) patients had G3+ hematologic toxic events, including 2 patients with febrile neutropenia. The 1-year OS, LRFS, DMFS and PFS was 96.4%, 88.7%, 78.4% and 64.3%, respectively. No patient developed local recurrence in the abutting esophagus-sparing region. SAES radiotherapy has significant dosimetric advantages compared with standard radiotherapy, which are successfully translated into clinical benefits for patients with LS-SCLC treated with 45 Gy in 3 Gy daily fractions. This may facilitate dose escalation for TRT in LS-SCLC patients.

Clinicoradiological outcomes after radical radiotherapy for lung cancer in patients with interstitial lung disease.

Interstitial lung disease (ILD) is relatively common in patients with lung cancer with an incidence of 7.5%. Historically pre-existing ILD was a contraindication to radical radiotherapy owing to increased radiation pneumonitis rates, worsened fibrosis and poorer survival compared with non-ILD cohorts. Herein, the clinical and radiological toxicity outcomes of a contemporaneous cohort are described. Patients with ILD treated with radical radiotherapy for lung cancer at a regional cancer centre were collected prospectively. Radiotherapy planning, tumour characteristics, and pre- and post-treatment functional and radiological parameters were recorded. Cross-sectional images were independently assessed by two Consultant Thoracic Radiologists. Twenty-seven patients with co-existing ILD received radical radiotherapy from February 2009 to April 2019, with predominance of usual interstitial pneumonia subtype (52%). According to ILD-GAP scores, most patients were Stage I. After radiotherapy, localised (41%) or extensive (41%) progressive interstitial changes were noted for most patients yet dyspnoea scores (n = 15 available) and spirometry (n = 10 available) were stable. One-third of patients with ILD went on to receive long-term oxygen therapy, which was significantly more than the non-ILD cohort. Median survival trended towards being worse compared with non-ILD cases (17.8 vs 24.0 months, p = 0.834). Radiological progression of ILD and reduced survival were observed post-radiotherapy in this small cohort receiving lung cancer radiotherapy, although a matched functional decline was frequently absent. Although there is an excess of early deaths, long-term disease control is achievable. For selected patients with ILD, long-term lung cancer control without severely impacting respiratory function may be possible with radical radiotherapy, albeit with a slightly higher risk of death.

Subpleural fibrotic interstitial lung abnormalities are implicated in non-small cell lung cancer radiotherapy outcomes.

The relationship between interstitial lung abnormalities (ILAs) and the outcomes of lung cancer radiotherapy is unclear. This study investigated whether specific ILA subtypes are risk factors for radiation pneumonitis (RP). This retrospective study analysed patients with non-small cell lung cancer treated with radical-intent or salvage radiotherapy. Patients were categorised into normal (no abnormalities), ILA, and interstitial lung disease (ILD) groups. The ILA group was further subclassified into non-subpleural (NS), subpleural non-fibrotic (SNF), and subpleural fibrotic (SF) types. The Kaplan-Meier and Cox regression methods were used to determine RP and survival rates and compare these outcomes between groups, respectively. Overall, 175 patients (normal, n = 105; ILA-NS, n = 5; ILA-SNF, n = 28; ILA-SF, n = 31; ILD, n = 6) were enrolled. Grade ≥2 RP was observed in 71 (41%) patients. ILAs (hazard ratio [HR]: 2.33, p = 0.008), intensity-modulated radiotherapy (HR: 0.38, p = 0.03), and lung volume receiving 20 Gy (HR: 54.8, p = 0.03) contributed to the cumulative incidence of RP. Eight patients with grade 5 RP were in the ILA group, seven of whom had ILA-SF. Among radically treated patients, the ILA group had worse 2-year overall survival (OS) than the normal group (35.3% vs 54.6%, p = 0.005). Multivariate analysis revealed that the ILA-SF group contributed to poor OS (HR: 3.07, p =0.02). ILAs, particularly ILA-SF, may be important risk factors for RP, which can worsen prognosis. These findings may aid in making decisions regarding radiotherapy.

Comparison of the Incidence Rate of Radiation Pneumonitis Observed in Patients with Advanced Lung Adenocarcinoma Treated with Simultaneous Thoracic Radiotherapy and 1G/2G/3G EGFR-TKIs.

The present study aimed to evaluate the incidence rate of radiation pneumonitis (RP) in patients with advanced lung adenocarcinoma treated with first-generation (1G), second-generation (2G), or third-generation (3G) epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with thoracic radiotherapy (TRT). Patients with advanced lung adenocarcinoma simultaneously treated with 1G/2G/3G EGFR-TKIs and TRT between 2015-2021 at Shandong Cancer Hospital and Institute were screened. The incidence rate of clinical and imaging RP was compared between the three groups. A total of 200 patients treated with EGFR-TKIs were enrolled in this study, including 100 patients who were treated with 1G EGFR-TKIs, 50 patients who were treated with 2G EGFR-TKIs, and 50 patients who were treated with 3G EGFR-TKIs (patients matched in a 2:1:1 ratio for tumor characteristics). The overall incidence of clinical RP in the 1G, 2G, and 3G EGFR-TKI groups were 29%, 48%, and 28% (p=0.043), respectively, and that of imaging RP were 33%, 58%, and 36% (p=0.010), respectively. The incidence of RP with a clinical grade ≥3 in the three groups were 14%, 28%, and 12% (p=0.055), respectively, and that with an imaging grade ≥3 in the three groups were 11%, 32%, and 10% (p=0.002), respectively. The incidence of clinical RP was higher in the CFRT group than in the SBRT group, with an overall clinical grade of 38% vs 10% (p<0.001) and imaging grade of 46% vs 10% (p<0.001), respectively. In the multivariate analysis, only GTV volume was an independent predictive factor for all risks of clinical and imaging RP. V20 and grouping of 1G/2G/3G EGFR-TKIs were other independent predictive factors for the risk factors of RP for imaging grades. Compared with 2G EGFR-TKIs combined with TRT, 1G or 3G EGFR-TKIs combined with TRT achieved a lower incidence of RP.

Risk of Radiation Pneumonitis in Patients Receiving Osimertinib and Thoracic Radiotherapy

Risk of Radiation Pneumonitis in Patients Receiving Osimertinib and Thoracic Radiotherapy

The Incidence Rate of Radiation Pneumonitis Observed in Patients Treated with Thoracic Radiotherapy and Concurrent First-Generation EGFR-TKIs, Second-Generation EGFR-TKIs or Third-Generation EGFR-TKIs in Advanced Lung Adenocarcinoma

<h3>Purpose/Objective(s)</h3> The main aim of this study was to evaluate the incidence rate of radiation pneumonitis (RP) in advanced lung adenocarcinoma treated with first-generation, second-generation, or third-generation EGFR-TKIs combined with thoracic radiotherapy. <h3>Materials/Methods</h3> We retrospectively evaluated advanced lung adenocarcinoma patients simultaneously treated with first-generation EGFR-TKIs, second-generation, or third-generation EGFR-TKIs and thoracic radiotherapy between January 2015 to December 2021 at Shandong Cancer Hospital and Institute. The clinical grades of RP were evaluated according to the pneumonitis of Common Toxicity Criteria (CTC) 5.0 Grading System, and the imaging grading of RP was evaluated using the pulmonary fibrosis of CTC 5.0 Grading System. <h3>Results</h3> Consecutive 100 patients who were treated with first-generation EGFR-TKIs were enrolled, 20 patients were treated with second-generation EGFR-TKIs and 50 patients who received third-generation EGFR-TKIs (10:2:5 matched with patients and tumor characteristics), and all three groups were concurrent with thoracic radiotherapy. In terms of overall incidence of RP, first-generation group versus second-generation group versus third-generation group of clinical grades were 2.083 vs 2.389 vs 1.935, and their imaging grades were 1.753 vs 1.895 vs 1.524. The incidence of the imaging grading of grade greater than or equal to 3 RP in three groups were 22% vs 15% vs 4%, and the clinical grades of grade greater than or equal to 3 RP in three groups were 28% vs 55% vs 20%. Other details can be referred to in the Table. <h3>Conclusion</h3> Patients treated with third-generation EGFR-TKIs combined with thoracic radiotherapy achieved minimum probability of RP. In contrast, the second-generation EGFR-TKIs concomitant thoracic radiotherapy are the most likely to happen RP. The clinical grades and imaging grades were not completely same in RP.

Incidence of Radiation Pneumonitis Among Patients Treated with Concurrent Thoracic Radiotherapy and Osimertinib for Metastatic Non-Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> A case series from China published in 2020 reported a high rate of radiation pneumonitis (RP) among 11 patients treated with concurrent thoracic radiotherapy (TRT) and osimertinib, including 9% who developed a fatal complication. We analyzed the RP rates for patients at our institution who were also treated with a similar combination for metastatic non-small cell lung cancer (NSCLC). <h3>Materials/Methods</h3> This retrospective study was performed at a single academic medical center in the US. We identified all patients who were treated with concurrent TRT and osimertinib between June 2016 and December 2021. Baseline patient characteristics, tumor size and location, and dosimetric parameters were evaluated. The highest grade of RP that developed within 6 months of treatment was scored in accordance with CTCAE v5.0. Fisher's exact test and logistic regression were performed to investigate the association of pre-treatment factors with development of grade ≥2 and grade ≥3 RP. <h3>Results</h3> Sixteen patients with metastatic NSCLC were treated with concurrent TRT and osimertinib over the study time period. The treatment site of each patient's pulmonary metastases was as follows: peripheral in 4 (25%), central in 4 (25%) (within 1-2 cm of the proximal bronchial tree [PBT]), ultra-central in 7 (44%) (within 1 cm of the PBT), and mediastinal in 1 (6%). Two of 16 patients withheld osimertinib 24-48 hours before and after TRT, both of which had tumors in an ultra-central location. Patients were treated with a median dose of 50 Gy (11-65 Gy) in a median of 7.5 fractions (1-15 fractions); the median duration of TRT was 10 days (1-22 days). The median follow-up time was 13 months (1 – 61 months). Nine patients developed grade ≥2 RP (56%) with a median time to onset of 29 days (1-84 days). The severity of RP was grade ≥3 in 6 (37.5%) and grade 4 in 1 (6.3%); no patients had grade 5 RP. Of the 6 patients who developed grade ≥3 RP, 2 (33.3%) were treated with stereotactic body radiotherapy (SBRT) while 4 (66.6%) were treated with hypofractionated TRT. All patients who developed grade ≥3 RP were female. Tumor location for patients who developed grade ≥3 RP was central in 3 (50%), ultra-central in 2 (33%) and mediastinal in 1 (17%); no patients with peripheral tumors developed grade ≥3 RP. Both patients who withheld osimertinib before and after TRT did not develop RP. The association of female sex and non-peripheral tumor location with grade ≥3 RP was not statistically significant in the context of a small case series (p=0.23). RP was not associated with the use of SBRT vs hypofractionated TRT or mean lung dose. <h3>Conclusion</h3> TRT with concurrent osimertinib was associated with a high rate of RP, particularly when the site of pulmonary metastases was in a central, ultra-central, or mediastinal location. Withholding osimertinib 24-48 hours before and after TRT may mitigate this risk. These data raise safety concerns that are not currently listed in treatment guidelines. Further research is indicated to validate these findings in larger cohorts.

The safety and efficacy of durvalumab consolidation therapy in the management of patients with stage III non-small-cell lung cancer and preexisting interstitial lung disease

Some lung cancer patients have preexisting interstitial lung disease (ILD), which is considered a risk factor for lung cancer treatment. This study investigated the safety and efficacy of durvalumab consolidation therapy for patients with stage III non-small-cell lung cancer (NSCLC) and preexisting ILD. Fifty consecutive patients who were judged to be tolerable to concurrent chemoradiotherapy (CCRT) for stage III NSCLC were enrolled. Differences in the incidence rate of radiation pneumonitis (RP) and progression-free survival (PFS) were assessed in patients with or without ILD of which CT showed non-usual interstitial pneumonia pattern between the durvalumab consolidation group and chemotherapy (combination of carboplatin and paclitaxel [CP]) consolidation group. The incidence of RP was higher in patients with preexisting ILD (40% and 20% in the durvalumab and CP groups, respectively) than in those without ILD (26% and 8% in the durvalumab and CP groups, respectively). Univariate analysis showed that durvalumab therapy tended to increase the incidence of RP; however, preexisting ILD did not significantly increase the incidence of RP. The condition of all patients who developed RP improved with the administration of oral prednisolone. Among patients without ILD, the median PFS was 17 and 16 months in the durvalumab and CP groups, respectively. Among patients with preexisting ILD, median PFS was not achieved in the durvalumab group and was 8 months in the CP group. Although durvalumab consolidation therapy tended to increase the incidence of RP, it might be tolerable in stage III NSCLC patients with preexisting ILD.

Minimum Lung Volume Spared for Lung Stereotactic Ablative Therapy: A Useful Metric or Outdated Endpoint?

Stereotactic body radiation therapy (SBRT) is the preferred treatment for malignant lesions of the lung in patients unable to tolerate an anatomic resection. While this modality is typically well-tolerated, there is potential for morbidity or even mortality in this population. Radiation pneumonitis (RP) is one such toxicity, and ongoing NRG protocols recommend Lung V20 < 10-15% and minimum volume of lung spared (MVLS) from 12.4 or 13.5 Gy for four and five fraction SBRT as the only two lung parameters for planning. There is some controversy on whether to include additional lung factors besides V20 in the treatment planning process. We sought to assess the performance of MVLS compared with cutoffs associated with RP from our team's previous study [1] using data from another institution.Inclusion criteria from our previous study [1] were applied to a new dataset. Patients receiving SBRT to the lung between 2010 and 2018 with tumoricidal (BED10 > 100 Gy) fractionation schemes (e.g., 50-55/5, 48-50/4, 60/8) were included. A minimum clinical follow-up of 6 months or documentation of RP was required. Symptomatic RP was defined as imaging consistent with RP and indication for corticosteroids (CTCAE Grade 2-3). Various dosimetric parameters and patient factors were recorded. The univariate logistic regression and dosimetric constraints from Institution #1 to predict probabilities of symptomatic RP have been published [1]. The accuracy of these predictive probabilities was assessed by applying derived dosimetric values predicting a 20%, 33% and 50% probability of developing symptomatic RP to Institution #2.For the sample from Institution #2, 25.7% (n = 17/66) developed symptomatic RP, which is higher than the published rate of 8.6% (n = 8/93) observed in the Institution #1. Minimum volume of lung spared (MVLS) from 12.4 or 13.5 Gy > 1000 ccs was achieved by all but one patient (a pediatric patient with small lung volumes). Multiple DVH thresholds predicting a 20% rate of symptomatic RP from Institution #1 correlated well with Institution #2 (Table 1). However, the model was not reliable for the 33% and 50% predicted probability cutoffs.This study of symptomatic RP identified several dosimetric parameters that accurately captured RP between two cohorts. MVLS appears to have limited utility in the clinical setting. In addition to Lung V20, future SBRT consortium trials may benefit from more correlative dose constraints.

Chemoradiotherapy for limited-stage small-cell lung cancer and interstitial lung abnormalities

BackgroundPatients with lung cancer and interstitial lung disease treated with radiotherapy are at risk of developing radiation pneumonitis. However, the association between interstitial lung abnormalities (ILAs) and radiation pneumonitis in patients with limited-stage small-cell lung cancer (LS-SCLC) remains unclear. Furthermore, the prognosis is uncertain for patients with SCLC and ILAs treated with chemoradiotherapy. We investigated the impact of ILAs on radiation pneumonitis and assessed the prognosis of patients with LS-SCLC and ILAs treated with chemoradiotherapy.MethodsWe retrospectively reviewed the medical records of 149 patients with LS-SCLC who received first-line treatment between January 2009 and December 2016.ResultsIn the univariate analysis, the patients with ILAs showed a higher incidence rate of radiation pneumonitis compared with those without ILAs (64% vs. 10%, P < 0.001). Multivariate analysis confirmed that ILAs were significantly associated with the incidence of radiation pneumonitis. In the univariate analysis, patients with ILAs showed poorer overall survival than those without ILAs (median, 18.9 vs. 67.9 months, P = 0.0338). Multivariate analysis showed that ILAs were a significant independent negative prognostic factor. However, the 2-year and 5-year survival rates for the patients with ILAs treated with chemoradiotherapy were 36% and 26%, respectively, and 8% and 0%, respectively, for those treated with chemotherapy alone.ConclusionsILAs were found to be a predictive factor for radiation pneumonitis in patients with LS-SCLC treated with chemoradiotherapy. Patients with LS-SCLC and ILAs who were treated with chemoradiotherapy had both the possibility of long-term survival and risk of radiation pneumonitis.

Overlap time is an independent risk factor of radiation pneumonitis for patients treated with simultaneous EGFR-TKI and thoracic radiotherapy

BackgroundThe exact rate and relevant risk factors of radiation pneumonitis (RP) for non-small-cell cancer (NSCLC) patients treated with the combination of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and thoracic radiotherapy have not been reported. Thus, this study aimed to investigate the rate and risk factors of RP for EGFR-positive NSCLC patients simultaneously treated with first-generation EGFR-TKI and TRT.Patients and methodsWe retrospectively evaluated NSCLC patients simultaneously treated with first-generation EGFR-TKI and thoracic radiotherapy between January 2012 and December 2019 at Shandong Cancer Hospital and Institute, Shandong, China. RP was diagnosed via computed tomography and was classified according to the Common Terminology Criteria for Adverse Events v5.0. The risk factors of RP were identified using uni- and multivariate analyses.ResultsOf the 67 patients included, 44.78% (30/67) developed grade ≥ 2 RP. Grade ≥ 2 RP occurred within a median of 3.48 (range 1.07–13.6) months. The EGFR-TKI icotinib, ipsilateral lung V30 > 34%, and overlap time of > 20 days between EGFR-TKI and thoracic radiotherapy were identified to be independent predictive factors of grade ≥ 2 RP.ConclusionsGrade ≥ 2 RP is highly frequent in NSCLC patients simultaneous treated with first-generation EGFR-TKI and thoracic radiotherapy. Icotinib, ipsilateral lung V30 ≤ 34%, and overlap time of ≤ 20 days for EGFR-TKI and thoracic radiotherapy will be helpful to lower the risk of RP in these patients. The addition of thoracic radiotherapy should be cautious, and the treatment strategies can be optimized to reduce the rate of RP for patients treat with simultaneous EGFR-TKI and thoracic radiotherapy.

The Plasma Levels and Polymorphisms of Vitronectin Predict Radiation Pneumonitis in Patients With Lung Cancer Receiving Thoracic Radiation Therapy

Our previous findings have identified vitronectin (VTN) as a potential biomarker for radiation pneumonitis (RP) through proteomics and molecular mechanism studies. In a recent study, we further explored associations of plasma level and single nucleotide polymorphisms of VTN with the risk of RP in patients with lung cancer receiving radiation therapy. A total of 165 patients with lung cancer were prospectively enrolled with detection of VTN concentration before radiation therapy. VTN reference single nucleotide polymorphisms, rs704 and rs2227721, were genotyped by Taqman probe method. Cox proportional hazard models were performed to identify clinical variables and genotypes associated with the risk of RP on univariate and multivariate analyses, and t tests and analysis of variance were conducted to evaluate the expression level of VTN. The baseline secretion level of VTN in patients with grade ≥3 RP was significantly higher than that in grade <3 RP patients (P < .0001), and elevated levels were observed in patients having the AA genotype compared with GA/GG genotypes of rs704. The VTN rs704 GA/GG and rs2227721 AA/AC genotypes had a significantly lower risk of RP (hazard ratio [HR], 0.448, P = .005; HR, 0.419, P = .008, respectively). In addition, combining cut-off values of mean lung dose (MLD) and VTN plasma level, grade ≥3 RP risk groupings were as follows: high risk: MLD ≥12 Gy and VTN level ≥132 μg/mL (RP rate, 10 of 16 patients, 62.5%); intermediate risk: MLD ≥12 Gy and VTN level <132 μg/mL or MLD <12 Gy and VTN level ≥132 μg/mL (8 of 70 patients, 11.4%); and low risk: MLD <12 Gy and VTN level <132 μg/mL (1 of 79 patients, 1.3%) (P < .0001). Among patients receiving radiation therapy, relatively high plasma levels of VTN before radiation therapy were associated with the higher incidence of RP, and VTN rs704 and rs2227721 each had a significant effect on predicting RP risk. Combining VTN concentration with MLD appeared to facilitate stratification of patients with lung cancer who received radiation therapy into low-, intermediate-, and high-risk RP groups. This study indicated that VTN may serve as a blood biomarker for susceptibility to RP in patients with lung cancer.

Osimertinib Greatly Increase the Risk of Radiotherapy Pneumonitis when Concurrent with Thoracic Radiotherapy

Osimertinib have prolonged the survival for NSCLC patients who harboring EGFR-TKI sensitizing or T790M resistance mutations. Osimetinib concurrent with thoracic radiotherapy is also a pattern for some people who experienced progression during the treatment of osimertinib or the transformation from first generation EGFR-TKI to osimertinib owe to the progression of primary lesion. But the risk of radiation pneumonitis (RP) for the concurrent osimertinib with thoracic radiotherapy have not been reported. We report a high rate of RP when concurrent osimertinib with thoracic radiotherapy. All patients from January 2017 to December 2019 at one institution were treated with concurrent osimertinib with thoracic radiotherapy were identified and all clinical records were reviewed. All people were treated with concurrent osimertinib with thoracic radiotherapy were included; the people who have a history of interstitial pneumonitis (ILD), immune checkpoint inhibitor therapy, thoracic radiotherapy was excluded. All patients were included treated with intensity-modulated radiotherapy, and osimertinib was administered orally at 80mg/d along with radiotherapy until the progression disease or intolerable toxicity. The diagnostic of RP was based on imaging manifestation of computed tomography, RP was graded from 1 to 5 according to CTCAE v5.0. Nine females and two males of lung adenocarcinoma patients harboring EGFR T790M treated with concurrent osimertinib and thoracic radiotherapy were included, nine of them experience progression disease of primary lesion during the treatment of first generation TKI and converted to osimertinib concurrent thoracic radiotherapy, two patients receive thoracic radiotherapy during the treatment of osimertinib because of the progression of primary lesion. The median age of 11 patients is 59 years old. The median follow time is 7.83 months, all 11 patients experience RP from grade 1 to grade 5. Seven patients (63.63%) developed to grade 2 or higher RP, 1 patient for grade 2, 5 patients for grade 3, 1 patient developed to fetal RP. The median dose for PTV is 60Gy (range 30-64Gy), the median fractioned dose is 2Gy (range 2-5Gy). The median volume for GTV is 11.70ml (range 2.50-247.71ml), PTV is 76.60ml (range 18.70-448.80ml). The median total-lung V5 is 29.92% (range 17.94-47.05%), V20 is 10.93% (range 6.26-28.06%), the median mean lung dose (MLD) is 6.40Gy (range 4.22-14.82Gy). We report up to 63.63% patients who receive concurrent osimertinib and thoracic radiotherapy developed to grade 2 or higher RP, and a patient developed to fetal RP, but they only have lower MLD and lesser V5, V20 compared to some patients who receive Concurrent Chemoradiation developed to RP. Compared with the 37.5% rate of RP for concurrent erlotinib and thoracic radiotherapy, our study pointed out a higher rate for osimertinib and come up with a warning for RP when concurrent osimertinib with thoracic radiotherapy.

An especially high rate of radiation pneumonitis observed in patients treated with thoracic radiotherapy and simultaneous osimertinib

Our study is the first to report an especially high rate of grade 2 or worse radiation pneumonitis in patients treated with thoracic radiotherapy and simultaneous Osimertinib, despite total lung V5, V20 and MLD seeming unlikely to induce radiation pneumonitis.

Risk of radiation pneumonitis in patients with emphysema after stereotactic body radiotherapy for non-small cell lung cancer assessed by quantitative CT.

Quantitative CT assessment of patients with pulmonary emphysema is used to measure pulmonary function. The present study evaluated whether the quantitative CT value can accurately estimate the risk of radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) in patients with and without emphysema. A total of 80 patients with stage I NSCLC receiving SBRT at a dose of 50 or 60 Gy in five fractions at our hospital between November 2003 and October 2015 were included in the analysis. A total of 33 (41%) patients were diagnosed with emphysema on CT examination. Dosimetric parameters, quantitative CT percentage value of low attenuation area (LAA%) in the whole lung, and average whole lung CT density values were used to examine the risk of RP. Among the 80 patients, 26 (33%) and 3 (4%) experienced Grade 1 and Grade 2 RP, respectively, during the median observation period of 18.8 (1.8-106.8) months. The RP rate for patients with a LAA% (<-910 HU) of ≤25% was significantly higher than that of subjects with LAA% (<-910 HU) >25% (P=0.037). The RP rate in subjects with an average HU value of >-790 HU was significantly higher compared with that of patients with ≤-790 HU (P=0.036). Age (hazard ratio [HR]=2.46; P=0.03) and average HU (HR=3.39; P=0.02) were significantly associated with RP, whereas mean lung dose was not identified to be significant in multivariate analysis. The quantitative CT value was associated with RP after SBRT.

Stereotactic body radiotherapy for early-stage non-small cell lung cancer in patients with subclinical interstitial lung disease.

e21050 Background: Stereotactic body radiotherapy (SBRT) is a highly focused radiation treatment, which is now recommended to treat non-small cell lung cancer (NSCLC) patients with early stage disease. The purpose of this study is to evaluate the efficacy and toxicity of SBRT for early stage NSCLC patients with subclinical interstitial lung disease (ILD). Methods: One hundred and nine patients with early stage NSCLC were treated with SBRT between December 2011 and August 2016 in our institution; patients with subclinical (untreated and oxygen-free) ILD were treated with SBRT, while those with clinical ILD (post- or under treatment) were not. The median SBRT dose was 50 Gy in 5 fractions and the median biologically effective dose (BED; α/β = 10) was 100 Gy (range:72-119 Gy). The presence of subclinical ILD in the pre-SBRT CT findings was reviewed by two chest radiologists. The relationships among the efficacy, radiation pneumonitis (RP) and clinical factors were investigated. Results: Subclinical ILD was recognized in 38 (35%) of 109 patients. Grade 2–4 RP was recognized in 48 (44%) of 109 patients, no Grade 5 RP was happened. Grade 2–4 RP was observed in 17 (45%) of 38 patients with subclinical ILD. Subclinical ILD was not found to be a significant factor influencing Grade 2–4 RP; however, extensive RP beyond the irradiated field, including the contralateral lung, was recognized in only two patients who were both suffering from subclinical ILD, and the rate of extensive RP was significantly high in the patients with subclinical ILD. Dosimetric factors of the lungs (V5, V10, V20, MLD, V12.5, V13.5) were significantly associated with Grade 2–4 RP. The three-year overall survival and progression-free survival rates of all patients were 82.8% and 62.5%, respectively. No significant differences were seen in either overall survival or progression-free survival rates among the patients with ILD and those without ILD, or with RP and those without RP. Conclusions: Subclinical ILD was not found to be a significant factor for Grade 2–5 RP or clinical outcomes in early stage NSCLC treated with SBRT; however, uncommon extensive RP can occur in patients with subclinical ILD.

Radiation pneumonitis in lung cancer patients treated with chemoradiation plus durvalumab.

IntroductionDurvalumab after concurrent chemoradiation (cCRT) is now standard of care for unresected stage III non–small cell lung cancer (NSCLC). However, there is limited data on radiation pneumonitis (RP) with this regimen. Therefore, we assessed RP and evaluated previously validated toxicity models in predicting for RP in patients treated with cCRT and durvalumab.MethodsPatients treated with cCRT and ≥ 1 dose of durvalumab were evaluated to identify cases of ≥ grade 2 RP. The validity of previously published RP models was assessed in this cohort as well a reference cohort treated with cCRT alone. The timing and incidence of RP was compared between cohorts.ResultsIn total, 11 (18%) of the 62 patients who received cCRT and durvalumab developed ≥ grade 2 RP a median of 3.4 months after cCRT. The onset of RP among patients treated with cCRT and durvalumab was significantly longer vs the reference cohort (3.4 vs 2.1 months; P = .01). Numerically more patients treated with cCRT and durvalumab developed RP than patients in the reference cohort (18% vs 9%, P = .09). Among patients treated with cCRT and durvalumab, 82% (n = 9) were responsive to treatment with high‐dose glucocorticoids. Previously published RP models widely underestimated the rate of RP in patients treated with cCRT and durvalumab [AUC ~ 0.50; p(Hosmer‐Lemeshow): 0.98‐1.00].ConclusionsOur data suggest a delayed onset of RP in patients treated with cCRT and durvalumab vs cCRT alone, and for RP to develop in a greater number of patients treated with cCRT and durvalumab. Previously published RP models significantly underestimate the rate of symptomatic RP among patients treated with cCRT and durvalumab.

Pretreatment Factors Influencing Radiation Pneumonitis after Stereotactic Body Radiation Therapy in the Treatment of Lung Cancer

ObjectiveRadiation pneumonitis (RP) is a dose-limiting toxicity that affects the treatment of lung cancer. Data on factors predictive of developing symptomatic RP after stereotactic body radiation therapy (SBRT) are limited. We reviewed data to identify pretreatment factors predictive of the development of symptomatic RP in patients’ lung cancer treated with SBRT.MethodsData were collected on 296 patients treated with SBRT for lung cancer. Factors available at time of consultation were analyzed for the development of symptomatic RP, defined as CTCAE v. 4.0 ≥ Grade 2. The factors analyzed included patient demographic, tumor-specific, and pretreatment pulmonary function data. Univariate and multivariate analyses were performed to assess for predictive factors.ResultsMedian follow-up was 22 months. The rate of symptomatic RP was 16%. Univariate analysis showed an increased rate of symptomatic RP with treatments to the right lung (22% vs. 9%, p = 0.007), driven primarily by an increased rate of symptomatic RP when treating the right lower lobe (RLL) vs. other lobes (31 vs. 13%, p = 0.03). Patients with a history of prior lung directed therapy were also more likely to develop symptomatic RP (12% vs. 24%, p = 0.008). These statistical differences were retained on multivariate analysis.ConclusionSBRT to the right lung, especially the RLL, and to patients with a history of prior lung-directed therapy increases the risk of developing symptomatic RP after SBRT. Further studies on ways to predict and prevent symptomatic RP are needed.