Assessment of Radiation Induced Pneumonitis and Pericarditis in Patients Undergoing Breast Conservative Treatment Using Hypofractionated Simultaneous Integrated Boost Technique.

INTRODUCTION: To determine the proportion of radiationinduced pneumonitis and pericarditis in patients who have received Hypo-fractionated Radiation along with simultaneous integrated boost technique after breast conservative surgery using a prospective observational study from a tertiary hospital. MATERIALS & METHODS: The incidence of radiationinduced pneumonitis and pericarditis was evaluated in all adult patients with biopsy-proven early-stage unilateral breast cancer who underwent breast-conserving surgery followed by hypo-fractionated radiation with a simultaneous integrated boost technique. Baseline assessments including a six-minute walk test, highresolution computed tomography (HRCT), pulmonary function tests (PFTs), electrocardiography (ECG) and echocardiography (ECHO) were performed. At three months post-radiation treatment, patients underwent follow-up assessments with a six-minute walk test, ECG and ECHO. At six months post-radiation treatment, patients underwent further assessments with a six-minute walk test, ECG, ECHO, PFTs, and HRCT of the thorax. Data analysis was performed using SPSS version 19. RESULTS: Our study investigated the incidence of acute radiation-induced pneumonitis and pericarditis in patients treated with hypofractionated VMAT-SIB technique in 20 eligible early breast cancer patients. The study found that the technique is feasible and achieves encouraging dosimetric parameters, including well achieved ipsilateral lung and heart doses. The reduced treatment time of 3-4 weeks compared to the previous 6-7 weeks with sequential boost was also found to be desirable in resource-constrained settings. The incidence of acute radiation pneumonitis and pericarditis was acceptable and comparable to existing data, with 90% of patients experiencing grade 1 radiation pneumonitis according to CTCAE v5.0. Post-treatment pulmonary function tests showed significant changes, particularly in patients who had received neoadjuvant chemotherapy and nodal irradiation. The six-minute walk test and Borg scale also showed a significant positive correlation with pulmonary function tests. There was no significant pericarditis during the follow-up. The study proposes that the hypofractionated radiotherapy using VMAT-SIB is a suitable alternative to conventional fractionation, with acceptable acute toxicities, but longer follow-up is required to assess the impact on late toxicities. CONCLUSION: Our research has shown that hypofractionated adjuvant radiotherapy with SIB is a safe and feasible treatment for patients with early breast cancer. This treatment method doesn't pose any significant short-term risks to the lungs or heart, and the SIB technique provides better coverage, conformity and sparing of organs at risk. Additionally, patients have reported positive cosmetic outcomes with this treatment. However, to make more accurate conclusions, we need to conduct further studies with larger sample sizes and longer follow-up periods to evaluate the potential longterm side effects of this treatment using VMAT in whole breast radiation.

Deep-Learning Model Prediction of Radiation Pneumonitis Using Pretreatment Chest Computed Tomography and Clinical Factors.

Objectives: This study aimed to build a comprehensive deep-learning model for the prediction of radiation pneumonitis using chest computed tomography (CT), clinical, dosimetric, and laboratory data. Introduction: Radiation therapy is an effective tool for treating patients with lung cancer. Despite its effectiveness, the risk of radiation pneumonitis limits its application. Although several studies have demonstrated models to predict radiation pneumonitis, no reliable model has been developed yet. Herein, we developed prediction models using pretreatment chest CT and various clinical data to assess the likelihood of radiation pneumonitis in lung cancer patients. Methods: This retrospective study analyzed 3-dimensional (3D) lung volume data from chest CT scans and 27 features including dosimetric, clinical, and laboratory data from 548 patients who were treated at our institution between 2010 and 2021. We developed a neural network, named MergeNet, which processes lung 3D CT, clinical, dosimetric, and laboratory data. The MergeNet integrates a convolutional neural network with subsequent fully connected layers. A support vector machine (SVM) and light gradient boosting machine (LGBM) model were also implemented for comparison. For comparison, the convolution-only neural network was implemented as well. Three-dimensional Resnet-10 network and 4-fold cross-validation were used. Results: Classification performance was quantified by using the area under the receiver operative characteristic curve (AUC) metrics. MergeNet showed the AUC of 0.689. SVM, LGBM, and convolution-only networks showed AUCs of 0.525, 0.541, and 0.550, respectively. Application of DeLong test to pairs of receiver operating characteristic curves respectively yielded P values of .001 for the MergeNet-SVM pair and 0.001 for the MergeNet-LGBM pair. Conclusion: The MergeNet model, which incorporates chest CT, clinical, dosimetric, and laboratory data, demonstrated superior performance compared to other models. However, since its prediction performance has not yet reached an efficient level for clinical application, further research is required. Contribution: This study showed that MergeNet may be an effective means to predict radiation pneumonitis. Various predictive factors can be used together for the radiation pneumonitis prediction task via the MergeNet.

Metabolic profiling of murine radiation-induced lung injury with Raman spectroscopy and comparative machine learning.

Radiation-induced lung injury (RILI) is a dose-limiting toxicity for cancer patients receiving thoracic radiotherapy. As such, it is important to characterize metabolic associations with the early and late stages of RILI, namely pneumonitis and pulmonary fibrosis. Recently, Raman spectroscopy has shown utility for the differentiation of pneumonitic and fibrotic tissue states in a mouse model; however, the specific metabolite-disease associations remain relatively unexplored from a Raman perspective. This work harnesses Raman spectroscopy and supervised machine learning to investigate metabolic associations with radiation pneumonitis and pulmonary fibrosis in a mouse model. To this end, Raman spectra were collected from lung tissues of irradiated/non-irradiated C3H/HeJ and C57BL/6J mice and labelled as normal, pneumonitis, or fibrosis, based on histological assessment. Spectra were decomposed into metabolic scores via group and basis restricted non-negative matrix factorization, classified with random forest (GBR-NMF-RF), and metabolites predictive of RILI were identified. To provide comparative context, spectra were decomposed and classified via principal component analysis with random forest (PCA-RF), and full spectra were classified with a convolutional neural network (CNN), as well as logistic regression (LR). Through leave-one-mouse-out cross-validation, we observed that GBR-NMF-RF was comparable to other methods by measure of accuracy and log-loss (p > 0.10 by Mann-Whitney U test), and no methodology was dominant across all classification tasks by measure of area under the receiver operating characteristic curve. Moreover, GBR-NMF-RF results were directly interpretable and identified collagen and specific collagen precursors as top fibrosis predictors, while metabolites with immune and inflammatory functions, such as serine and histidine, were top pneumonitis predictors. Further support for GBR-NMF-RF and the identified metabolite associations with RILI was found as CNN interpretation heatmaps revealed spectral regions consistent with these metabolites.

Validated machine learning tools to distinguish immune checkpoint inhibitor, radiotherapy, COVID-19 and other infective pneumonitis.

BACKGROUND: Pneumonitis is a well-described, potentially disabling, or fatal adverse effect associated with both immune checkpoint inhibitors (ICI) and thoracic radiotherapy. Accurate differentiation between checkpoint inhibitor pneumonitis (CIP) radiation pneumonitis (RP), and infective pneumonitis (IP) is crucial for swift, appropriate, and tailored management to achieve optimal patient outcomes. However, correct diagnosis is often challenging, owing to overlapping clinical presentations and radiological patterns. METHODS: In this multi-centre study of 455 patients, we used machine learning with radiomic features extracted from chest CT imaging to develop and validate five models to distinguish CIP and RP from COVID-19, non-COVID-19 infective pneumonitis, and each other. Model performance was compared to that of two radiologists. RESULTS: Models to distinguish RP from COVID-19, CIP from COVID-19 and CIP from non-COVID-19 IP out-performed radiologists (test set AUCs of 0.92 vs 0.8 and 0.8; 0.68 vs 0.43 and 0.4; 0.71 vs 0.55 and 0.63 respectively). Models to distinguish RP from non-COVID-19 IP and CIP from RP were not superior to radiologists but demonstrated modest performance, with test set AUCs of 0.81 and 0.8 respectively. The CIP vs RP model performed less well on patients with prior exposure to both ICI and radiotherapy (AUC 0.54), though the radiologists also had difficulty distinguishing this test cohort (AUC values 0.6 and 0.6). CONCLUSION: Our results demonstrate the potential utility of such tools as a second or concurrent reader to support oncologists, radiologists, and chest physicians in cases of diagnostic uncertainty. Further research is required for patients with exposure to both ICI and thoracic radiotherapy.

Associations Between Mean Lung Dose and Prevalence of Radiation Pneumonitis in Elderly Lung Cancer Patients.

BACKGROUND/AIM: Pneumonitis is a serious radiotherapy complication. This study, which is a prerequisite for a prospective trial, aimed to identify the prevalence of pneumonitis and risk factors in elderly patients with lung cancer. PATIENTS AND METHODS: Ninety-eight lung cancer patients aged ≥65 years were included. Seventeen factors were investigated regarding grade ≥2 pneumonitis at 24 weeks following radiotherapy. RESULTS: The prevalence of grade ≥2 pneumonitis at 24 weeks was 27.3%. On univariate analysis, a significant association was observed for mean (ipsilateral) lung dose (MLD; ≤13.0 vs. 13.1-20.0 vs. >20.0 Gy; 0% vs. 24.9% vs. 48.7%). Results were significant also for ≤13.0 vs. >13.0 Gy (0% vs. 37.1%) or ≤20.0 vs. >20.0 Gy (13.4% vs. 48.7%). MLD achieved significance on multivariate analysis. CONCLUSION: Elderly patients receiving MLDs >13.0 Gy, particularly >20.0 Gy, have a high risk of grade ≥2 pneumonitis. These results are important for designing a prospective trial.

Adjuvant treatment with Cordyceps sinensis for lung cancer: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps sinensis (CS) is a fungus parasitic on lepidopteran larvae which is often used to treat lung diseases and regulate immune function. AIM OF THE STUDY: This review aimed to evaluate the efficacy of CS in the adjuvant treatment of lung cancer. MATERIALS AND METHODS: As of June 2022, the electronic database search was conducted in PubMed, EMBASE, Cochrane Library, China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Database and China Science Journal Database (VIP database). Randomized clinical trials (RCTs) that evaluated the efficacy of CS as an adjuvant treatment for lung cancer were included. After the quality evaluation, meta-analysis was performed with Stata 16.0 software. RESULTS: A total of 12 RCTs with 928 patients were identified for this meta-analysis, which showed that as an adjuvant treatment, CS has the following advantages in the treatment of lung cancer: (1) Improved tumor response rate (TRR) (RR: 1.17， 95%CI: 1.05-1.29，P = 0.00); (2) improved immune function, including increased CD4 (MD: 4.98, 95%CI: 1.49-8.47, P = 0.01), CD8 (MD: 1.60, 95%CI: 0.40-2.81, P = 0.01, I2 = 0.00%), NK (MD: 4.17, 95%CI: 2.26-6.08, P = 0.00), IgA (MD: 1.29, 95%CI: 0.35-2.24, P = 0.01), IgG (MD: 3.95, 95%CI: 0.98-6.92, P = 0.01) and IgM (MD: 6.44, 95%CI: 0.63-12.26, P = 0.03); (3) improved patients' quality of life based on the mean ± SD of Karnofsky Performance Status (KPS) (MD: 8.20, 95%CI: 6.87-9.53, P = 0.00); (4) reduced the incidence of adverse drug reactions (ADRs), including the incidence of myelosuppression (RR: 0.38, 95%CI: 0.19-0.75, P = 0.01), leukopenia (RR: 0.76, 95%CI: 0.63-0.92, P = 0.00), and thrombocytopenia (RR: 0.52, 95%CI: 0.31-0.86, P = 0.01) (5) reduced the incidence of radiation pneumonitis (RR: 0.74, 95%CI: 0.62-0.88, P = 0.00). However, the number of improved patients based on KPS (RR: 1.47, 95%CI: 0.98-2.20, P = 0.06) were similar between two groups, liver and renal damage (RR: 0.32, 95%CI: 0.09-1.10, P = 0.07) and gastrointestinal adverse reactions (RR: 0.80, 95%CI: 0.47-1.37, P = 0.42) as well. Subgroup analysis showed that CS could increase the TRR in the treatment with 6 g/d and 21 days/3-4 cycles. CONCLUSION: Compared with conventional treatment, adjuvant treatment with CS of lung cancer not only improve TRR, QOL and immune function, but also reduce the incidence of ADRs and radiation pneumonitis. The optimal usage may be 6 g/d and 21 days/3 to 4 cycles. PROSPERO REGISTRATION NO: CRD42022333681.

An 18F-FDG PET/CT and Mean Lung Dose Model to Predict Early Radiation Pneumonitis in Stage III Non-Small Cell Lung Cancer Patients Treated with Chemoradiation and Immunotherapy.

Radiation pneumonitis (RP) that develops early (i.e., within 3 mo) (RPEarly) after completion of concurrent chemoradiation (cCRT) leads to treatment discontinuation and poorer survival for patients with stage III non-small cell lung cancer. Since no RPEarly risk model exists, we explored whether published RP models and pretreatment 18F-FDG PET/CT-derived features predict RPEarly Methods: One hundred sixty patients with stage III non-small cell lung cancer treated with cCRT and consolidative immunotherapy were analyzed for RPEarly Three published RP models that included the mean lung dose (MLD) and patient characteristics were examined. Pretreatment 18F-FDG PET/CT normal-lung SUV featured included the following: 10th percentile of SUV (SUVP10), 90th percentile of SUV (SUVP90), SUVmax, SUVmean, minimum SUV, and SD. Associations between models/features and RPEarly were assessed using area under the receiver-operating characteristic curve (AUC), P values, and the Hosmer-Lemeshow test (pHL). The cohort was randomly split, with similar RPEarly rates, into a 70%/30% derivation/internal validation subset. Results: Twenty (13%) patients developed RPEarly Predictors for RPEarly were MLD alone (AUC, 0.72; P = 0.02; pHL, 0.87), SUVP10, SUVP90, and SUVmean (AUC, 0.70-0.74; P = 0.003-0.006; pHL, 0.67-0.70). The combined MLD and SUVP90 model generalized in the validation subset and was deemed the final RPEarly model (RPEarly risk = 1/[1+e(- x )]; x = -6.08 + [0.17 × MLD] + [1.63 × SUVP90]). The final model refitted in the 160 patients indicated improvement over the published MLD-alone model (AUC, 0.77 vs. 0.72; P = 0.0001 vs. 0.02; pHL, 0.65 vs. 0.87). Conclusion: Patients at risk for RPEarly can be detected with high certainty by combining the normal lung's MLD and pretreatment 18F-FDG PET/CT SUVP90 This refined model can be used to identify patients at an elevated risk for premature immunotherapy discontinuation due to RPEarly and could allow for interventions to improve treatment outcomes.

Clinical outcomes of interstitial lung abnormalities: a systematic review and meta-analysis.

Interstitial lung abnormalities (ILA), incidental findings on computed tomography scans, have raised concerns due to their association with worse clinical outcomes. Our meta-analysis, which included studies up to April 2023 from PubMed/MEDLINE, Embase, and Cochrane Library, aimed to clarify the impact of ILA on mortality, lung cancer development, and complications from lung cancer treatments. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for outcomes. Analyzing 10 studies on ILA prognosis and 9 on cancer treatment complications, we found that ILA significantly increases the risk of overall mortality (RR 2.62, 95% CI 1.94-3.54; I2 = 90%) and lung cancer development (RR 3.85, 95% CI 2.64-5.62; I2 = 22%). Additionally, cancer patients with ILA had higher risks of grade 2 radiation pneumonitis (RR 2.28, 95% CI 1.71-3.03; I2 = 0%) and immune checkpoint inhibitor-related interstitial lung disease (RR 3.05, 95% CI 1.37-6.77; I2 = 83%) compared with those without ILA. In conclusion, ILA significantly associates with increased mortality, lung cancer risk, and cancer treatment-related complications, highlighting the necessity for vigilant patient management and monitoring.

Endostar acts as a pneumonitis protectant in patients with locally advanced non-small cell lung cancer receiving concurrent chemoradiotherapy.

BACKGROUND: CCRT is presently the standard treatment for LA-NSCLC. RP is one of the main obstacles to the completion of thoracic radiation therapy, resulting in limited survival benefits in NSCLC patients. This research aims to explore the role of Endostar in the occurrence of grade≥2 RP and clinical curative effect in LA-NSCLC patients. METHODS: This study retrospectively analyzed 122 patients with stage III NSCLC who received CCRT from December 2008 to December 2017, or Endostar intravenous drip concurrently with chemoradiotherapy (Endostar + CCRT group). Standard toxicity of the pneumonitis endpoint was also collected by CTCAE V5.0. We further summarized other available studies on the role of Endostar in the prognosis of NSCLC patients and the incidence of RP. RESULTS: There were 76 cases in the CCRT group and 46 cases in the CCRT+ Endostar group. In the CCRT+ Endostar group, the occurrence of grade ≥2 RP in patients with V20Gy ≥25% was significantly higher than that in patients with V20Gy < 25% (p = 0.001). In the cohorts with V20Gy < 25%, 0 cases of 29 patients treated with Endostar developed grade ≥2 RP was lower than in the CCRT group (p = 0.026). The re-analysis of data from other available studies indicated that Endostar plus CCRT could be more efficient and safely in the occurrence of grade≥2 RP with LA-NSCLC. CONCLUSIONS: When receiving CCRT for LA-NSCLC patients, simultaneous combination of Endostar is recommended to enhance clinical benefit and reduce pulmonary toxicity.

Successful salvage of a severe COVID-19 patient previously with lung cancer and radiation pneumonitis by mesenchymal stem cells: a case report and literature review.

During the COVID-19 pandemic, elderly patients with underlying condition, such as tumors, had poor prognoses after progressing to severe pneumonia and often had poor response to standard treatment. Mesenchymal stem cells (MSCs) may be a promising treatment for patients with severe pneumonia, but MSCs are rarely used for patients with carcinoma. Here, we reported a 67-year-old female patient with lung adenocarcinoma who underwent osimertinib and radiotherapy and suffered from radiation pneumonitis. Unfortunately, she contracted COVID-19 and that rapidly progressed to severe pneumonia. She responded poorly to frontline treatment and was in danger. Subsequently, she received a salvage treatment with four doses of MSCs, and her symptoms surprisingly improved quickly. After a lung CT scan that presented with a significantly improved infection, she was discharged eventually. Her primary disease was stable after 6 months of follow-up, and no tumor recurrence or progression was observed. MSCs may be an effective treatment for hyperactive inflammation due to their ability related to immunomodulation and tissue repair. Our case suggests a potential value of MSCs for severe pneumonia that is unresponsive to conventional therapy after a COVID-19 infection. However, unless the situation is urgent, it needs to be considered with caution for patients with tumors. The safety in tumor patients still needs to be observed.

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

OBJECTIVE: In 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. METHODS: Initially, 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. RESULTS: The 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. CONCLUSIONS: The 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.

Radiation pneumonitis after concurrent aumolertinib and thoracic radiotherapy in EGFR-mutant non-small cell lung cancer patients.

BACKGROUND: The superior efficacy of concurrent thoracic radiotherapy (TRT) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been proven in locally advanced and advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, the high incidence of radiation pneumonitis (RP) reduced by concurrent TRT and TKIs has attracted widespread attention. Thus, this study was designed to investigate the rate and risk factors for RP in EGFR-positive NSCLC patients simultaneously treated with aumolertinib and TRT. METHODS: We retrospectively evaluated stage IIIA-IVB NSCLC patients treated with concurrent aumolertinib and TRT between May 2020 and December 2022 at Shandong Cancer Hospital and Institute, Shandong, China. RP was diagnosed by two senior radiologists and then graded from 1 to 5 according to the Common Terminology Criteria for Adverse Events v5.0. All risk factors were evaluated by univariate and multivariate logistic regression analyses. RESULTS: A total of 49 patients were included, the incidence of grade ≥ 2 RP was 42.9%. Grade 2 and 3 RP were observed in 28.6% and 14.3% of patients, respectively. Grade 4 to 5 RP were not observed. the gross total volume (GTV) ≥ 21 ml and ipsilateral lung V20 ≥ 25% were risk factors for RP. The median progression-free survival (PFS) in the first-line therapy group and second-line therapy group were 23.5 months and 17.2 months, respectively (p = 0.10). CONCLUSIONS: Better local control is achieved with concurrent TRT and aumolertinib, and special attention should be given to controlling ipsilateral lung V20 and GTV to reduce the risk of RP.

Dual-energy computed tomography in the early evaluation of acute radiation pneumonia.

OBJECTIVE: To investigate the value of dual-energy dual-source computed tomography (DSCT) in evaluating pulmonary perfusion changes before and after radiotherapy for esophageal cancer, and its clinical use in the early diagnosis of acute radiation pneumonia (ARP). METHODS: We selected 45 patients with pathologically confirmed esophageal cancer who received radiotherapy (total irradiation dose of 60 Gy). Dual-energy DSCT scans were performed before and after radiotherapy and the normalized iodine concentrations (NIC) in the lung fields of the areas irradiated with doses of > 20 Gy, 10-20 Gy, 5-10 Gy, and < 5 Gy were measured. We also checked for the occurrence of ARP in the patients, and the differences in NIC values and NIC reduction rates before and after radiotherapy were calculated and statistically analyzed. RESULTS: A total of 16 of the 45 patients developed ARP. The NIC values in the lung fields of all patients decreased at different degrees after radiotherapy, and the NIC values in the area where ARP developed, decreased significantly. The rate of NIC reduction and incidence rate of ARP increased gradually with the increasing irradiation dose, and the inter-group difference in NIC reduction rate was statistically significant (P < 0.05). Based on the receiver operating characteristic (ROC) curve analysis, the areas under the curves of NIC reduction rate versus ARP occurrence in the V5-10 Gy, V10-20 Gy, and V> 20 Gy groups were 0.780, 0.808, and 0.772, respectively. Sensitivity of diagnosis was 81.3%, 75.0%, and 68.8% and the specificity was 65.5%, 82.8%, and 79.3%, when taking 12.50%, 16.50%, and 26.0% as the diagnostic thresholds, respectively. The difference in NIC values in the lung fields of V<5 Gy before and after radiotherapy was not statistically significant (P > 0.05). CONCLUSION: The dual-energy DSCT could effectively evaluate pulmonary perfusion changes after radiotherapy for esophageal cancer, and the NIC reduction rate was useful as a reference index to predict ARP and provide further reference for decisions in clinical practice.

Lung Mean Dose Prediction in Transarterial Radioembolization (TARE): Superiority of [166Ho]-Scout Over [99mTc]MAA in a Prospective Cohort Study.

PURPOSE: Radiation pneumonitis is a serious complication of radioembolization. In holmium-166 ([166Ho]) radioembolization, the lung mean dose (LMD) can be estimated (eLMD) using a scout dose with either technetium-99 m-macroaggregated albumin ([99mTc]MAA) or [166Ho]-microspheres. The accuracy of eLMD based on [99mTc]MAA (eLMDMAA) was compared to eLMD based on [166Ho]-scout dose (eLMDHo-scout) in two prospective clinical studies. MATERIALS AND METHODS: Patients were included if they received both scout doses ([99mTc]MAA and [166Ho]-scout), had a posttreatment [166Ho]-SPECT/CT (gold standard) and were scanned on the same hybrid SPECT/CT system. The correlation between eLMDMAA/eLMDHo-scout and LMDHo-treatment was assessed by Spearman's rank correlation coefficient (r). Wilcoxon signed rank test was used to analyze paired data. RESULTS: Thirty-seven patients with unresectable liver metastases were included. During follow-up, none developed symptoms of radiation pneumonitis. Median eLMDMAA (1.53 Gy, range 0.09-21.33 Gy) was significantly higher than median LMDHo-treatment (0.00 Gy, range 0.00-1.20 Gy; p < 0.01). Median eLMDHo-scout (median 0.00 Gy, range 0.00-1.21 Gy) was not significantly different compared to LMDHo-treatment (p > 0.05). In all cases, eLMDMAA was higher than LMDHo-treatment (p < 0.01). While a significant correlation was found between eLMDHo-scout and LMDHo-treatment (r = 0.43, p < 0.01), there was no correlation between eLMDMAA and LMDHo-treatment (r = 0.02, p = 0.90). CONCLUSION: [166Ho]-scout dose is superior in predicting LMD over [99mTc]MAA, in [166Ho]-radioembolization. Consequently, [166Ho]-scout may limit unnecessary patient exclusions and avoid unnecessary therapeutic activity reductions in patients eligible for radioembolization. TRAIL REGISTRATION: NCT01031784, registered December 2009. NCT01612325, registered June 2012.

Diagnosis and management of pneumonitis following chemoradiotherapy and immunotherapy in stage III non-small cell lung cancer.

BACKGROUND: In inoperable stage III NSCLC, the standard of care is chemoradiotherapy and adjuvant durvalumab (IO) for 12 months. Pneumonitis is the commonest toxicity leading to discontinuation of IO. A failure to distinguish between expected radiation-induced changes, IO pneumonitis and infection can lead to unnecessary durvalumab discontinuation. We investigated the use of a structured multidisciplinary review of CT-scans, radiation dose distributions and clinical symptoms for the diagnosis of IO pneumonitis. METHODS: A retrospective study was conducted at an academic medical center for patients treated for stage III NSCLC with chemoradiotherapy and adjuvant durvalumab between 2018 and 2021. An experienced thoracic radiologist reviewed baseline and follow-up chest CT-scans, systematically scored radiological features suspected for pneumonitis using a published classification system (Veiga C, Radioth Oncol 2018), and had access to screenshots of radiation dose distributions. Next, two experienced thoracic oncologists reviewed each patients' case record, CT-scans and radiation fields. A final consensus diagnosis incorporating views of expert clinicians and the radiologist was made. RESULTS: Among the 45 included patients, 14/45 (31.1%) had a pneumonitis scored in patient records and durvalumab was discontinued in 11/45 cases (24.4%). Review by the radiologist led to a diagnosis of immune-related pneumonitis only in 6/45 patients (13.3%). Review by pulmonary oncologists led to a diagnosis of immune-related pneumonitis in only 4/45 patients (8.9%). In addition a suspicion of an immune-related pneumonitis was rejected in 3 separate patients (6.7%), after the thoracic oncologists had reviewed the patients' radiation fields. CONCLUSIONS: In patients treated using the PACIFIC regimen, multidisciplinary assessment of CT-scans, radiation doses and patient symptoms, resulted in fewer diagnoses of immune-related pneumonitis (8.9%). Our study underscores the challenges in accurately diagnosing either IO-related or radiation pneumonitis in patients undergoing adjuvant immunotherapy after chemoradiotherapy and highlights the need for multidisciplinary review in order to avoid inappropriate cessation of adjuvant IO.

A dynamic nomogram predicting symptomatic pneumonia in patients with lung cancer receiving thoracic radiation.

PURPOSE: The most common and potentially fatal side effect of thoracic radiation therapy is radiation pneumonitis (RP). Due to the lack of effective treatments, predicting radiation pneumonitis is crucial. This study aimed to develop a dynamic nomogram to accurately predict symptomatic pneumonitis (RP ≥ 2) following thoracic radiotherapy for lung cancer patients. METHODS: Data from patients with pathologically diagnosed lung cancer at the Zhongshan People's Hospital Department of Radiotherapy for Thoracic Cancer between January 2017 and June 2022 were retrospectively analyzed. Risk factors for radiation pneumonitis were identified through multivariate logistic regression analysis and utilized to construct a dynamic nomogram. The predictive performance of the nomogram was validated using a bootstrapped concordance index and calibration plots. RESULTS: Age, smoking index, chemotherapy, and whole lung V5/MLD were identified as significant factors contributing to the accurate prediction of symptomatic pneumonitis. A dynamic nomogram for symptomatic pneumonitis was developed using these risk factors. The area under the curve was 0.89(95% confidence interval 0.83-0.95). The nomogram demonstrated a concordance index of 0.89(95% confidence interval 0.82-0.95) and was well calibrated. Furthermore, the threshold values for high- risk and low- risk were determined to be 154 using the receiver operating curve. CONCLUSIONS: The developed dynamic nomogram offers an accurate and convenient tool for clinical application in predicting the risk of symptomatic pneumonitis in patients with lung cancer undergoing thoracic radiation.

The Impact of PM2.5 on Radiation-induced Pneumonitis in Patients With Breast Cancer.

BACKGROUND/AIM: Exposure to particulate matter (PM) air pollution is known to adversely affect respiratory disease, but no study has examined its effect on radiation-induced pneumonitis (RIP) in patients with breast cancer. PATIENTS AND METHODS: We conducted a retrospective review of 2,736 patients with breast cancer who received postoperative radiation therapy (RT) between 2017 and 2020 in a single institution. The distance between the PM measurement station and our institution was only 3.43 km. PM data, including PM2.5 and PM10, were retrieved from the open dataset in the official government database. RESULTS: Overall incidence rate of RIP was 1.74%. After adjusting for age, RT technique, regional irradiation, fractionation and boost, the average value of PM2.5 was significantly associated with a higher risk of RIP (p=0.047) when patients received ≥20 fractions of RT. Specifically, PM2.5 ≥35 (µg/m3) showed a significantly higher risk of RIP (p=0.019) in patients with ≥20 fractions of RT. CONCLUSION: This is the first study to reveal the association between PM2.5 and RIP in patients with breast cancer who received 20 fractions or more of postoperative RT. We demonstrated that high PM2.5 levels around the RT institution were associated with RIP, suggesting that reducing PM air pollution may be a modifiable risk factor.

Selection of the appropriate treatment for the combination of interstitial lung disease and lung cancer: A retrospective observational study.

Interstitial lung disease (ILD) independently heightens the risk of lung cancer (LC), often necessitating chemoradiotherapy (CRT) due to advanced disease stages. However, CRT may compromise survival through complications such as ILD exacerbation or radiation pneumonitis. The aim of this study was to determine the optimal surgical or nonsurgical treatment approaches for patients with concurrent ILD and LC. Over a 10-year period, a retrospective evaluation was conducted on 647 patients with confirmed diagnoses of LC and ILD from a total of 4541 patients examined in the polyclinic. This assessment included a comprehensive review of demographic, treatment, and survival records. Study groups included those treated for both ILD and LC with surgical treatment (ST), chemotherapy (CT), radiotherapy (RT), or CRT. A control group comprised ILD-only cases. In the whole sample of 647 patients with complete data, the length of stay in hospital and respiratory intensive care unit was significantly shorter in the ST group and longer in the CT group. Significant differences in discharge status (P < .001) were observed, with higher recovery rates in the ST and RT groups. The CT group showed an increased rate of transfer to other centers, in-hospital mortality was determined to be higher in the CRT group, and the control group exhibited no change in discharge. No statistically significant difference was determined between the groups with respect to the 24- and 48-month survival rates (P = .100). Although no disparity was found in 2- and 4-year survival rates, there were seen to be advantages in survival and quality of life with the addition of radiotherapy to regions aligning with surgical margins for LC patients with ILD, evaluated as radiological N0, undergoing wedge resection. This underscores the need for personalized treatment strategies to balance effective cancer control and to minimize ILD-related complications.