Acute Radiation Pneumonitis Research Articles

Dosimetric predictors of acute radiation pneumonitis and esophagitis in hypofractionated thoracic irradiation of non-small cell lung cancer patients with poor prognostic factors

Dosimetric predictors of acute radiation pneumonitis and esophagitis in hypofractionated thoracic irradiation of non-small cell lung cancer patients with poor prognostic factors

Oxytocin: A Shield against Radiation-Induced Lung Injury in Rats.

Radiation-induced lung injury (RILI), a serious side effect of thoracic radiotherapy, can lead to acute radiation pneumonitis (RP) and chronic pulmonary fibrosis (PF). Despite various interventions, no effective protocol exists to prevent pneumonitis. Oxytocin (OT), known for its anti-inflammatory, antiapoptotic, and antioxidant properties, has not been explored for its potential in mitigating RILI. This study involved 24 female Wistar albino rats, divided into three groups: control group, radiation (RAD) + saline, and RAD + OT. The RAD groups received 18 Gy of whole-thorax irradiation. The RAD + OT group was treated with OT (0.1 mg/kg/day) intraperitoneally for 16 weeks. Computerizing tomography (CT) imaging and histopathological, biochemical, and blood gas analyses were performed to assess lung tissue damage and inflammation. Histopathological examination showed significant reduction in alveolar wall thickening, inflammation, and vascular changes in the RAD + OT group compared to the RAD + saline group. Biochemical analysis revealed decreased levels of TGF-beta, VEGF, and PDGF, and increased BMP-7 and prostacyclin in the RAD + oxytocin group (p < 0.05). Morphometric analysis indicated significant reductions in fibrosis, edema, and immune cell infiltration. CT imaging demonstrated near-normal lung parenchyma density in the RAD + oxytocin group (p < 0.001). Oxytocin administration significantly mitigates radiation-induced pneumonitis in rats, implying that is has potential as a therapeutic agent for preventing and treating RILI.

Long-term outcome of definitive radiotherapy for locally advanced non-small cell lung cancer: A real-world single-center study in the pre-durvalumab era.

There was limited research data on large-scale locally advanced non-small cell lung cancer (LA-NSCLC) radical radiotherapy (RT) reported in China. This study examined overall survival (OS), progression-free survival (PFS), treatment effectiveness, and toxicity in patients with LA-NSCLC treated with definitive RT in the pre-durvalumab era. A retrospective analysis of demographic information, clinical characteristics, treatment patterns, and clinical outcomes of 789 patients with LA-NSCLC who underwent radical RT at our center between January 2005 and December 2015 was performed. The Kaplan-Meier method and log-rank test were used for survival comparisons, and Cox regression was used for multivariate analysis. There were 328 patients with stage IIIA disease and 461 with stage IIIB disease. By the last follow-up, there were 365 overall deaths and 576 cases of recurrence, metastasis, or death. The median survival time was 31 months. The OS rates at 1, 2, 5, and 10 years were 83.7%, 59.5%, 28.8%, and 18.9%, respectively. PFS rates at 1, 2, 5, and 10 years were 48%, 24.5%, 11.9%, and 5.5%, respectively. Rates of ≥grade 3 acute radiation pneumonitis or esophagitis were 7.6% and 1.9%, respectively. Rates of ≥grade 3 chronic radiation pneumonitis and esophagitis were 11% and 0.4%, respectively. Multivariate analysis showed that the Karnofsky Performance Status (KPS) score, smoking status, and combined chemotherapy were prognostic factors for OS (p < 0.05). Multivariate analysis revealed that combined chemotherapy and radiation dose were prognostic factors for PFS (p < 0.05). Our center's data showed that the survival prognosis of locally advanced patients receiving RT and chemotherapy in China was consistent with international levels during the same period. Patients with a KPS score of 80 or higher, who had never smoked or received combined RT, had a more favorable prognosis than those with a KPS of less than 80, who had smoked, or only received RT. The combination of RT and chemotherapy, with a reasonable radiation dose, was the key to improving the therapeutic effect.

CT-based different regions of interest radiomics analysis for acute radiation pneumonitis in patients with locally advanced NSCLC after chemoradiotherapy

PurposeTo establish a radiomics model using radiomics features from different region of interests (ROI) based on dosimetry-related regions in enhanced computed tomography (CT) simulated images to predict radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC). MethodsOur retrospective study was conducted based on a cohort of 236 NSCLC patients (59 of them with RP≥2) who were treated in 2 institutions and divided into the primary cohort (n = 182,46 of them with RP≥2) and external validation cohort (n = 54,13 of them with RP≥2). Radiomic features extracted from three ROIs were defined as the whole lung (WL), the dose volume histogram (DVH) of the lung V20 (V20_Lung) and the DVH of the V30 of lung minus the planning target volume (PTV) (V30 Lung-PTV). A total of 107 radiomics features were extracted from each ROIs. The U test, correlation coefficient and least absolute shrinkage and selection operator (LASSO) were performed for features selection. Six models based on different classification algorithms were developed to select the best radiomics model (R model).In addition, we built a dosimetry model then combined it with the best R model to create a mixed model (R+D model) The receiver operating characteristic (ROC) curve was delineated to assess the predictive efficacy of the models. Decision curve analysis could benefit from the model proposals through the assessment of clinical utility. ResultsAmong the three ROIs, the best R model constructed from the LightGBM algorithm demonstrated the strongest discriminative ability in the ROI of V30 Lung-PTV. The corresponding area under the curve (AUC) value was 0.930 (95 % confidence interval (CI): 0.829–0.941). The D model, R model and R+D model achieved AUC values of 0.798 (95 %CI: 0.732–0.865), 0.930 (95 %CI: 0.829–0.941) and 0.940 (95 %CI: 0.906–0.974) in primary cohort, and in external validation cohort, the AUC values were 0.793 (95 %CI:0.637–0.949), 0.887 (95 %CI:0.810–0.993), 0.951 (95CI%:0.891–1.000). Decision curve demonstrate that R+D model could benefit for patients through the assessment of clinical utility. ConclusionThe radiomics model was able to predict the acute RP more effectively in comparison with the traditional dosimetry model. Especially the radiomics model based on the V30 Lung-PTV region was able to achieve a higher accuracy when compared to the other regions.

Randomized prospective trial comparing two schedules of hypofractionated adjuvant radiotherapy 3 weeks against 1 week fractionation regimen in females with breast cancer

Purpose Acceleration of radiotherapy in five fractions for breast cancer can improve treatment accessibility, especially in low, middle-income countries and during pandemics. We report on acute toxicity after whole breast irradiation/chest wall irradiation±nodal irradiation, radiotherapy interruption and reported acute pneumonitis with an ultra-hypofractionation schedule compared to modest hypofractionation protocol during the coronavirus disease pandemic. Patients and methods Acute toxicity assessment using the RTOG acute toxicity scoring system. One of two specified doses was administered to the breast: 15 × 2.67 Gy (40.05 Gy) or 5 × 5.2 Gy (26 Gy), tumor boost when indicated prescribed dose 5 × 200 Gy with three-dimensional conformal radiotherapy technique. Inclusion criteria were: T1–T3 invasive breast cancer, N0–N1 and N2 after breast conserving or modified radical surgery. Results A total of 101 patients were included in the study. Median age was 53 ± 10.29 years, with median follow-up time 14 months (12–20 months). A significant difference was observed for acute skin toxicity after radiotherapy in favor of better tolerability for the ultrafractionation schedule (P&lt;0.0001). None of the cases in ultra-hypofractionation had interrupted radiotherapy course for more than 2 days, on the other hand, 45.8% of the cases in modest hypofractionation had interrupted course with chest infection as the second most common cause. Regarding acute radiation pneumonitis none of the cases in both arms reported grades 3–4 acute radiation pneumonitis within the first 90 days postradiotherapy. Conclusion Regarding initial toxicity and patient adherence to the radiation course, this single institute study suggests that hypofractionated breast irradiation in 15 fractions compares favorably to accelerated breast radiotherapy in five fractions over 5 days. However, a longer time for follow-up and larger enrolled numbers are needed to confirm noninferiority of this approach.

Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab for locally advanced esophageal squamous cell carcinoma (ESCC): A phase II clinical trial

ObjectiveTo evaluate the feasibility, safety and efficacy of concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab in the treatment of locally advanced esophageal squamous cell cancer (ESCC).MethodsEligible patients were histologically proven to have locally advanced ESCC, and were unable to tolerate or refuse concurrent chemoradiotherapy (CCRT). Enrolled patients underwent concurrent SIB-IMRT in combination with nimotuzumab. SIB-IMRT: For the planning target volume of clinical target volume (PTV-C), the prescription dose was 50.4 Gy/28fractions, 1.8 Gy/fraction, 5fractions/week, concurrently, the planning target volume of gross tumor (PTV-G) undergone an integrated boost therapy, with a prescription dose of 63 Gy/28fractions, 2.25 Gy/fraction, 5 fractions/week. Nimotuzumab was administered concurrently with radiotherapy, 200 mg/time, on D1, 8, 15, 22, 29, and 36, with a total accumulation of 1200 mg through intravenous infusion. The primary endpoint of the study was the safety and efficacy of the combined treatment regimen, and the secondary endpoints were 1-year, 2-year, and 3-year local control and survival outcomes.Results(1) From December 2018 to August 2021, 35 patients with stage II-IVA ESCC were enrolled and 34 patients completed the full course of radiotherapy and the intravenous infusion of full-dose nimotuzumab. The overall completion rate of the protocol was 97.1%. (2) No grade 4–5 adverse events occurred in the entire group. The most common treatment-related toxicity was acute radiation esophagitis, with a total incidence of 68.6% (24/35). The incidence of grade 2 and 3 acute esophagitis was 25.7% (9/35) and 17.1% (6/35), respectively. The incidence of acute radiation pneumonitis was 8.6% (3/35), including one case each of Grades 1, 2, and 3 pneumonitis. Adverse events in other systems included decreased blood cells, hypoalbuminemia, electrolyte disturbances, and skin rash. Among these patients, five experienced grade 3 electrolyte disturbances during the treatment period (three with grade 3 hyponatremia and two with grade 3 hypokalemia). (3) Efficacy: The overall CR rate was 22.8%, PR rate was 71.4%, ORR rate was 94.2%, and DCR rate was 97.1%.(4) Local control and survival: The 1-, 2-, and 3-year local control (LC) rate, progression-free survival(PFS) rate, and overall survival(OS) rate for the entire group were 85.5%, 75.4%, and 64.9%; 65.7%, 54.1%, and 49.6%; and 77.1%, 62.9%, and 54.5%, respectively.ConclusionsThe combination of SIB-IMRT and nimotuzumab for locally advanced esophageal cancer demonstrated good feasibility, safety and efficacy. It offered potential benefits in local control and survival. Acute radiation esophagitis was the primary treatment-related toxicity, which is clinically manageable. This comprehensive treatment approach is worthy of further clinical exploration (ChiCTR1900027936).

Hydrogen-rich solution alleviates acute radiation pneumonitis by regulating oxidative stress and macrophages polarization.

This study was aimed to investigate the effect of hydrogen-rich solution (HRS) on acute radiation pneumonitis (ARP) in rats. The ARP model was induced by X-ray irradiation. Histopathological changes were assessed using HE and Masson stains. Inflammatory cytokines were detected by ELISA. Immunohistochemistry and flow cytometry were performed to quantify macrophage (CD68) levels and the M2/M1 ratio. Western blot analysis, RT-qPCR, ELISA and flow cytometry were used to evaluate mitochondrial oxidative stress injury indicators. Immunofluorescence double staining was performed to colocalize CD68/LC3B and p-AMPK-α/CD68. The relative expression of proteins associated with autophagy activation and the adenosine 5'-monophosphate-activated protein kinase/mammalian target of rapamycin/Unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway were detected by western blotting. ARP decreased body weight, increased the lung coefficient, collagen deposition and macrophage infiltration and promoted M1 polarization in rats. After HRS treatment, pathological damage was alleviated, and M1 polarization was inhibited. Furthermore, HRS treatment reversed the ARP-induced high levels of mitochondrial oxidative stress injury and autophagy inhibition. Importantly, the phosphorylation of AMPK-α was inhibited, the phosphorylation of mTOR and ULK1 was activated in ARP rats and this effect was reversed by HRS treatment. HRS inhibited M1 polarization and alleviated oxidative stress to activate autophagy in ARP rats by regulating the AMPK/mTOR/ULK1 signaling pathway.

Properties of [18F]FAPI monitoring of acute radiation pneumonia versus [18F]FDG in mouse models

ObjectiveIn this study, the uptake characteristics of [18F]fibroblast activation protein inhibitor (FAPI) molecular imaging probe were investigated in acute radiation pneumonia and lung cancer xenografted mice before and after radiation to assess the future applicability of [18F]FAPI positron emission tomography/computed tomography (PET/CT) imaging in early radiotherapy response.MethodsInitially, the biodistribution of [18F]FAPI tracer in vivo were studied in healthy mice at each time-point. A comparison of [18F]FAPI and [18F]fluorodeoxyglucose (FDG) PET/CT imaging efficacy in normal ICR, LLC tumor-bearing mice was evaluated. A radiation pneumonia model was then investigated using a gamma counter, small animal PET/CT, and autoradiography. The uptake properties of [18F]FAPI in lung cancer and acute radiation pneumonia were investigated using autoradiography and PET/CT imaging in mice.ResultsThe tumor area was visible in [18F]FAPI imaging and the tracer was swiftly eliminated from normal tissues and organs. There was a significant increase of [18F]FDG absorption in lung tissue after radiotherapy compared to before radiotherapy, but no significant difference of [18F]FAPI uptake under the same condition. Furthermore, both the LLC tumor volume and the expression of FAP-ɑ decreased after thorax irradiation. Correspondingly, there was no notable [18F]FAPI uptake after irradiation, but there was an increase of [18F]FDG uptake in malignancies and lungs.ConclusionsThe background uptake of [18F]FAPI is negligible. Moreover, the uptake of [18F]FAPI may not be affected by acute radiation pneumonitis compared to [18F]FDG, which may be used to more accurately evaluate early radiotherapy response of lung cancer with acute radiation pneumonia.

Handcrafted Radiomics, Deep Learning Radiomics in the Prediction of Radiation Pneumonitis for NSCLC Patients Treated with Immunotherapy Followed with Thoracic Radiotherapy

Our previous study has shown that NSCLC patients previously received immune checkpoint inhibitors (ICIs) underwent thoracic intensity modulated radiotherapy have a higher risk of acute radiation pneumonitis (RP). This study aimed to establish machine learning models using handcrafted radiomics (HCR), deep learning-based radiomics (DLR) and clinical characteristics to improve the prediction of symptomatic radiation pneumonitis (RP) (grade ≥ 2) status for NSCLC patients treated with immunotherapy followed with thoracic radiotherapy. This study retrospectively collected data of 61 NSCLC patients meeting the requirements of study enrollment. Of these 61 patients, 35 developed symptomatic graded ≥ 2 RP. We defined 3 regions of interest (ROIs) in planning CT images including gross tumor volume (GTV), planning tumor volume (PTV), PTV-GTV. We calculated the mean dose, V5, V10, V20, and V30 within TL-GTV, and the volume of GTV, PTV and total lung. A total of 516 handcrafted radiomics features and 512 deep features were extracted from each 3 ROIs. Person Correlation Analysis and Least Absolute Shrinkage and Selection Operator (LASSO) were used to reduce the dimension of features. The HCR models, DLR models and the fusion models across different ROIs with machine learning classifiers were built and compared. In multi-classifier modeling, models with PTV under logistic regression (LR) classifiers showed better prediction than other ROIs under different machine learning algorithms. Based on PTV with LR, HCR+ DLR model had better performance, with an area under the curve (AUC) of 0.95 (95% confidence interval (CI): 0.893-1) in the training cohort and 0.87 (95% CI: 0.698-1) in the test cohort, which was higher than that of HCR model, with an AUC of 0.86 (95% CI: 0.755-0.9) in the training cohort and 0.82 (95% CI: 0.624-1) in the test cohort, the results of fusion model with HCR, DLR and 7 clinical characteristics including T, N, clinical stage, age, smoking, radiotherapy alone/combined and V30, demonstrated the best distinguishing performance, with an AUC of 0.99 (95% CI: 0.970-1) in the training cohort and 0.91 (95% CI: 0.784-1) in the test cohort. The combination of HCR, DLR and clinical characteristic underwent machine learning algorithms can improve the prediction of symptomatic RP in NSCLC patients treated with ICIs followed with thoracic radiotherapy.

Analysis of clinical and physical dosimetric factors that determine the outcome of severe acute radiation pneumonitis in lung cancer patients

ObjectiveWe conducted a retrospective statistical analysis of clinical and physical dosimetric factors of lung cancer patients who had previously undergone lung and/or mediastinal radiotherapy and died of or survived severe acute radiation pneumonitis (SARP). Our study was the first to reveal the heterogeneity in clinical factors, physical dosimetric factors, and SARP onset time that determined the clinical outcomes of lung cancer patients who developed SARP.Materials and methodsThe clinical characteristics, physical dosimetry factors, and SARP onset time of deceased and surviving patients were retrospectively analyzed. SPSS 20.0 was used for data analysis. Student’s t-test was used for intergroup comparison, and a Mann–Whitney U test was used for data with skewed distribution. Qualitative data were represented using frequencies (%), and Fisher’s exact test or χ2 test was used for intergroup comparison of nonparametric data. Binary logistic analysis was used for univariate and multivariate analyses. Differences with a P < 0.05 were considered statistically significant.ResultsUnivariate analysis revealed that the potential predictors of SARP death were as follows: ipsilateral lung V5 and V30, contralateral lung V5, V10, and V30, total lung V5, V10, and V30, mean lung dose, mean heart dose, and maximum spinal cord dose. Multivariate analysis showed that ipsilateral lung V5 and total lung V5 were predictors that determined the final outcome of SARP patients. In addition, we analyzed the time from the completion of radiotherapy to SARP onset, and found significant difference between the two groups.ConclusionsThere was no decisive correlation between clinical characteristics and SARP outcome (i.e., death or survival) in lung radiotherapy patients. Ipsilateral lung V5 and total lung V5 were independent predictors of death in SARP patients.

Safety of hypofractionated volumetric modulated arc therapy for early breast cancer: A preliminary report.

The present study attempts to evaluate the acute and subacute toxicities of hypofractionated volumetric modulated arc therapy (HFX-VMAT) in patients with early breast cancer (EBC). It is a retrospective analysis of 23 patients treated with HFX-VMAT after breast-conserving surgery between September 2021 and February 2022. A total dose of 50.05 to 52.55 Gy was delivered, consisting of 40.05 Gy to the ipsilateral whole breast in 15 fractions of 2.67 Gy and a tumor bed boost dose of 10-12.5 Gy in 4-5 fractions. The primary endpoint was acute/subacute radiation pneumonitis (RP). The secondary endpoint was poor cosmesis, indicating acute/subacute radiation dermatitis. Chest computed tomography (CT) and the Common Terminology Criteria for Adverse Events v.5.0 were used to assess acute and subacute RP and dermatitis, respectively, during radiotherapy (RT) and at 3- and 6-months post-RT. The median follow-up duration was 3.8 months (range, 2.3-4.2). A total of seven patients developed RP. None of these patients presented RP-related symptoms; the diagnosis was based on radiologic findings observed on follow-up chest CT. Among the seven patients with RP, five had right-sided, and two had left-sided breast tumors (71.4 vs. 28.6%; P=0.026). Grade 1 erythema was observed in 19 patients (82.6%) and grade 2 erythema in four (17.4%). The mean target dose, D105% (the dose received by 105% of the target volume), homogeneity index, mean lung dose, ipsilateral lung V20 (the percentage volume receiving 20 Gy), and V30 (the percentage volume receiving 30 Gy) for ipsilateral whole breast RT were significantly associated with RP (P=0.039, 0.047, 0.018, 0.015, 0.018 and 0.003, respectively.). HFX-VMAT showed tolerable acute/subacute toxicities. Therefore, HFX-VMAT is an effective and safe treatment option for EBC.

Phase 2 small cell lung cancer (SCLC) cohort of a phase 1b/2 trial of a liposomal formulation of eribulin in combination with nivolumab.

8593 Background: E7389-LF is a liposomal formulation of the microtubule dynamics inhibitor eribulin. Combining E7389-LF with an immune checkpoint inhibitor (ICI; eg, nivolumab) may improve antitumor response via vascular remodeling. The phase 1b part of the open-label Study 120 evaluated the dosing and safety of E7389-LF in combination with nivolumab in patients (pts) with solid tumors. The phase 2 part assessed efficacy and safety in disease cohorts; herein, we report results from the SCLC cohort. Methods: Pts with unresectable and measurable SCLC who had progression during or after 1st-line (1L) platinum-based chemotherapy with/without an ICI were enrolled to the SCLC cohort of the phase 2 part of Study 120. Pts received E7389-LF 2.1 mg/m2 in combination with nivolumab 360 mg IV Q3W. The primary objective of the phase 2 part was to assess the objective response rate (ORR). Secondary objectives included assessments of safety and progression-free survival (PFS); exploratory objectives included the disease control rate (DCR), overall survival (OS), and biomarker analysis. Tumor response was assessed by investigators per RECIST v1.1 Q6W. All adverse events (AEs) were monitored and recorded. Results: In the SCLC cohort, 34 pts were enrolled; the median age was 66.0 years (range 46–81). At data cutoff (May 31, 2022), 5 pts (14.7%) were undergoing treatment. Discontinuations occurred in 29 pts (85.3%)—26 (76.5%) primarily due to disease progression, 3 (8.8%) due to an AE. Efficacy analyses included 33 pts, as 1 pt had their diagnosis of SCLC changed to a different cancer type after being enrolled. Of the 33 evaluable pts, 27 (81.8%) had an ICI as part of their prior 1L therapy. The ORR of E7389-LF in combination with nivolumab was 24.2% (95% CI 11.1–42.3) in the evaluable population; the DCR was 75.8% (95% CI 57.7–88.9). Median PFS was 3.98 mos (95% CI 2.63–4.40); the 6-mo PFS rate was 27.7% (95% CI 13.0–44.6). At a median follow-up period of 10.6 mos, median OS was not reached (95% CI not estimable); the 6-mo OS rate was 90.9% (95% CI 74.4–97.0). Treatment-related, treatment-emergent (TE)AEs of any grade and of grade ≥3 severity occurred in 97.1% (n = 33) and 82.4% (n = 28) of the 34 enrolled pts, respectively; the most common treatment-related TEAE was neutropenia (any grade: 58.8% [n = 20]; grade ≥3: 52.9% [n = 18]). The neutrophil count nadir occurred around cycle 1 day 8. TEAEs led to dose reduction of E7389-LF in 19 pts (55.9%). Withdrawal of E7389-LF or nivolumab occurred in 5 pts (14.7%): acute kidney injury, cough, myocarditis, pneumonitis, and radiation pneumonitis (n = 1 each). Changes in vascular and immune-related plasma markers were observed. Conclusions: E7389-LF in combination with nivolumab showed notable antitumor activity as 2L therapy in pts with SCLC, as evidenced by the notable ORR of 24.2%. No new safety signals were observed for this combination. Clinical trial information: NCT04078295 .

Biological sex differences in renin angiotensin system enzymes ACE and ACE2 regulate normal tissue response to radiation injury.

Introduction: In experimental animal models, biological sex-differences in the manifestation and severity of normal tissue radiation injury have been well-documented. Previously we demonstrated male and female rats have differential and highly reproducible responses to high-dose partial body irradiation (PBI) with male rats having greater susceptibility to both gastrointestinal acute radiation syndrome (GI-ARS) and radiation pneumonitis than female rats. Methods: In the current study, we have investigated whether differential expression of the renin-angiotensin system (RAS) enzymes angiotensin converting enzyme (ACE) and ACE2 contribute to the observed sex-related differences in radiation response. Results: During the period of symptomatic pneumonitis, the relative ratio of ACE to ACE2 (ACE/ACE2) protein in the whole lung was significantly increased by radiation in male rats alone. Systemic treatment with small molecule ACE2 agonist diminazene aceturate (DIZE) increased lung ACE2 activity and reduced morbidity during radiation pneumonitis in both sexes. Notably DIZE treatment also abrogated morbidity in male rats during GI-ARS. We then evaluated the contribution of the irradiated bone marrow (BM) compartment on lung immune cell infiltration and ACE imbalance during pneumonitis. Transplantation of bone marrow from irradiated donors increased both ACE-expressing myeloid cell infiltration and immune ACE activity in the lung during pneumonitis compared to non-irradiated donors. Discussion: Together, these data demonstrate radiation induces a sex-dependent imbalance in the renin-angiotensin system enzymes ACE and ACE2. Additionally, these data suggest a role for ACE-expressing myeloid cells in the pathogenesis of radiation pneumonitis. Finally, the observed sex-differences underscore the need for consideration of sex as a biological variable in the development of medical countermeasures for radiation exposure.

Acute Post-Radiation Pneumonitis: A Case Report

Acute radiation pneumonitis is a rare cause of pneumonitis. The diagnosis is considered in the presence of respiratory symptoms that appear with recent thoracic exposure. We report the case of a 67-year-old patient followed for mediastinal lymphoma who presented an acute pneumonitis when she started her radiotherapy sessions. Two diagnostics were suspected: radiotherapy toxicity or metastatic origin. Acute post-radiation pneumonitis can be very serious if the diagnostic is delayed. The diagnosis of acute post-radiation pneumonitis constitutes a diagnosis of elimination of any pneumonitis with an unfavorable evolution under antibiotic therapy, in the context of semi-recent thoracic radiotherapy.

Survival of Patients With Inoperable Non-Small Cell Lung Cancer With Baseline Severe Pulmonary Dysfunction: Impacts of Thoracic Radiotherapy and Predictive Analysis for Acute Radiation Pneumonitis.

Currently, there is no standard treatment for patients with lung cancer with deteriorated pulmonary function. In this study, we aimed to assess the efficacy of thoracic radiotherapy for unresectable non-small cell lung cancer (NSCLC) with baseline severe pulmonary dysfunction and severe acute radiation pneumonitis (SARP). Patients were categorized into a radiotherapy group and a nonradiotherapy group, followed by analysis of clinical variables. A Cox regression was used to evaluate the impact of various factors on overall survival (OS). Each SARP factor's predictive value was assessed using logistic regression, receiver operating characteristic curve, and Kaplan-Meier analyses. The median OS in the radiotherapy group was 21.6 months vs 8.9 months in the nonradiotherapy group. Cox analysis revealed that chemotherapy (HR, 0.221; 95% CI, 0.149-0.329; P < .001) and radiotherapy (HR, 0.589; 95% CI, 0.399-0.869; P = .008) are independent prognostic factors for the current cohort. The data suggested that the ipsilateral lung V10 (ilV10, the percentage of the lung volume that received more than 10 Gy) was an independent predictor of SARP. Our findings suggested that thoracic radiotherapy might be associated with clinical benefits to inoperable NSCLC in patients with severe pulmonary dysfunction and that ilV10 may be involved in the prediction of risk for SARP in these patients.

Dosimetric Risk Factors for Radiation Pneumonitis in Patients with Prior Receipt of Immune Checkpoint Inhibitors: A Retrospective Study

<h3>Purpose/Objective(s)</h3> Dosimetric parameters (e.g., mean lung dose (MLD), V20, and V5) can predict radiation pneumonitis (RP). Constraints thereof were formulated before the era of combined immune checkpoint inhibitors (ICIs) and radiotherapy, which could amplify the RP risk. Dosimetric predictors of acute RP (aRP) in the context of ICIs are urgently needed because no data exist thus far. <h3>Materials/Methods</h3> All included patients underwent thoracic irradiation, previously received ICIs, and followed-up at least once. Logistic regression models examined predictors of aRP (including a priori evaluation of MLD, V20, and V5), and their discriminative capacity was assessed by receiver operating characteristic analysis. <h3>Results</h3> Median follow-up of the 40 patients was 5.3 months. Cancers were lung (80%) or esophageal (20%). ICIs were PD-1 (85%) or PD-L1 (15%) inhibitors (median 4 cycles). Patients underwent definitive (n=19), consolidative (n=14), or palliative (n=7) radiotherapy; the median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy (IQR, 51.8-64 Gy). Grades 1-5 aRP occurred in 25%, 17.5%, 15%, 2.5%, and 5%, respectively. The only variables associated with any-grade aRP were V20 (p=0.014) and MLD (p=0.026), and only V20 with grade ≥2 aRP (p=0.035). Graphs were constructed showing the incrementally increasing risk of aRP based on V20 and MLD, V20=5.2% and MDL=4.0Gy would predict for a 50% risk of ≥ grade 1 pneumonia, and V20=19.3% would predict for a 50% risk for grade 2 pneumonia. <h3>Conclusion</h3> This is the first study illustrating that V20 and MLD may impact aRP in the setting of prior ICIs. If these results are validated by larger studies with more homogeneous populations, the commonly accepted V20/MLD dose constraints could require revision if utilized in the setting of ICIs.

The clinical outcome of postoperative radiotherapy using hybrid planning technique in left breast cancer after breast-conserving surgery.

The purpose of this study is to observe the preliminary clinical outcome and acute toxicity of hybrid intensity modulated radiotherapy and volumetric modulated arc therapy planning technique with simultaneous integrated boost (SIB). From November 2015 to December 2018, 149 female patients with left-side breast cancer who underwent adjuvant radiotherapy with hybrid IMRT and VMAT planning technique with SIB were reviewed retrospectively. The primary endpoint was acute toxicities and the secondary endpoints were local recurrence-free survival (LRFS), distant metastasis-freesurvival (DMFS), disease-free survival (DFS), and overall survival (OS). The median age was 52 years old and median follow-up was 43.4months. Eighty-six percent of patients had acute grade 0 to grade1 dermatitis and 14% had grade 2 dermatitis. No acute radiation pneumonitis, esophagitis, or cardiovascular events were recorded during follow-up. The 3-year LRFS, DMFS, DFS, and OS rates were 95.1%, 95.1%, 90.3%, and 97.9%, respectively. The subgroup analysis revealed that patients with lymphovascular invasion had more local recurrence rate and worse DFS rate. Patients with advanced N stage had the trend of worse DMFS. In conclusion, the hybrid IMRT and VMAT technique is feasible, safe and has less acute radiation related toxicities in SIB postoperative radiotherapy for left-sided breast cancer.

Lung Subregion Partitioning by Incremental Dose Intervals Improves Omics-Based Prediction for Acute Radiation Pneumonitis in Non-Small-Cell Lung Cancer Patients.

Simple SummaryAcute radiation pneumonitis (ARP) is one of the common radiation toxicities in patients with non-small-cell lung cancer (NSCLC) treated by radiotherapy. The prediction for ARP can benefit clinical management and thereby improve the quality of life of patients. Markers derived from radiomics and dosiomics features can be adopted to predict ARP. Moreover, the features from lung subregions can improve the prediction for ARP compared to the whole lung region. The previous studies using lung subregion features for predicting ARP ignored the low-dose covered lung region. In this manuscript, we proposed an incremental-dose-interval-based lung subregion segmentation method by covering the low-dose lung region for ARP modeling and evaluated its effectiveness in improving ARP predictions using pre-treatment CT radiomics features and planning dose features for patients with NSCLC treated by radiotherapy. The performance among ARP models using features from our proposed lung subregion and the whole lung were compared for both multi-omics and single-omics. The results could provide insight into the subregion’s ability to predict the ARP and could be useful in predicting the risk of radiation-induced toxicity. This manuscript and its results were neither published in any conferences nor journals.Purpose: To evaluate the effectiveness of features obtained from our proposed incremental-dose-interval-based lung subregion segmentation (IDLSS) for predicting grade ≥ 2 acute radiation pneumonitis (ARP) in lung cancer patients upon intensity-modulated radiotherapy (IMRT). (1) Materials and Methods: A total of 126 non-small-cell lung cancer patients treated with IMRT were retrospectively analyzed. Five lung subregions (SRs) were generated by the intersection of the whole lung (WL) and five sub-regions receiving incremental dose intervals. A total of 4610 radiomics features (RF) from pre-treatment planning computed tomographic (CT) and 213 dosiomics features (DF) were extracted. Six feature groups, including WL-RF, WL-DF, SR-RF, SR-DF, and the combined feature sets of WL-RDF and SR-RDF, were generated. Features were selected by using a variance threshold, followed by a Student t-test. Pearson’s correlation test was applied to remove redundant features. Subsequently, Ridge regression was adopted to develop six models for ARP using the six feature groups. Thirty iterations of resampling were implemented to assess overall model performance by using the area under the Receiver-Operating-Characteristic curve (AUC), accuracy, precision, recall, and F1-score. (2) Results: The SR-RDF model achieved the best classification performance and provided significantly better predictability than the WL-RDF model in training cohort (Average AUC: 0.98 ± 0.01 vs. 0.90 ± 0.02, p < 0.001) and testing cohort (Average AUC: 0.88 ± 0.05 vs. 0.80 ± 0.04, p < 0.001). Similarly, predictability of the SR-DF model was significantly stronger than that of the WL-DF model in training cohort (Average AUC: 0.88 ± 0.03 vs. 0.70 ± 0.030, p < 0.001) and in testing cohort (Average AUC: 0.74 ± 0.08 vs. 0.65 ± 0.06, p < 0.001). By contrast, the SR-RF model significantly outperformed the WL-RF model only in the training set (Average AUC: 0.93 ± 0.02 vs. 0.85 ± 0.03, p < 0.001), but not in the testing set (Average AUC: 0.79 ± 0.05 vs. 0.77 ± 0.07, p = 0.13). (3) Conclusions: Our results demonstrated that the IDLSS method improved model performance for classifying ARP with grade ≥ 2 when using dosiomics or combined radiomics-dosiomics features.

Pirfenidone for the prevention of radiation-induced lung injury in patients with locally advanced oesophageal squamous cell carcinoma: a protocol for a randomised controlled trial

IntroductionRadiation-induced lung injury (RILI) is one of the most clinically-challenging toxicities and dose-limiting factors during and/or after thoracic radiation therapy for oesophageal squamous cell carcinoma (ESCC). With limited effective protective...

Evaluation of lung adverse events with trastuzumab using the Japanese pharmacovigilance database.

The present study aimed to determine the risk of trastuzumab-induced lung toxicity, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. We analyzed data for the period between April 2004 and March 2021. Data on lung toxicities were extracted, and relative risk of adverse events (AEs) was estimated using the reporting odds ratio. We analyzed 1,772,494 reports and identified 4362 reports of AEs caused by trastuzumab. Of these, 693 lung toxicities were reportedly associated with trastuzumab. Signals were detected for seven lung toxicities: interstitial lung disease, pulmonary edema, pleural effusion, lung disorder, acute pulmonary edema, pulmonary fibrosis, and radiation pneumonitis. Among these, interstitial lung disease was the most frequently reported (61.8%). A histogram of times to onset showed occurrence from 1 to 105days, but some cases of interstitial lung disease occurred even more than one year after the start of administration. The AEs showing the highest fatality rates were interstitial lung disease, pulmonary fibrosis, and radiation pneumonitis. This study focused on lung toxicities caused by trastuzumab as post-marketing AEs. Some cases could potentially involve serious outcomes; therefore, patients should be monitored for signs of the onset of these AEs not only at the start of administration, but also over an extended period, especially for interstitial lung disease.