Thoracic Radiotherapy Research Articles

Increased prevalence of coronary atherosclerosis in cancer survivors: a matched cross-sectional study with coronary CT angiography

Abstract Background Cancer and atherosclerosis share many risk factors. Although cardiovascular disease is highly prevalent among cancer survivors, it is unknown whether coronary atherosclerosis is present at a younger age in patients with a history of cancer. Purpose The purpose of this study is to evaluate the prevalence of coronary atherosclerosis in different age groups of patients with a history of cancer compared to matched controls. Methods Consecutive patients with a history of cancer aged >30 years who underwent evaluation for coronary artery disease with coronary computed tomography angiography (CCTA) between 2010 and 2023 were included in this cross-sectional study. Patients with a history of cancer were matched 1:2 to a control population without oncological history using propensity score matching. Patients were matched on age, gender, body mass index, hypercholesterolemia, hypertension, diabetes, use of statins and smoking status. The presence of atherosclerosis in the main coronary arteries was compared between the groups. Results The study population consisted of 313 patients with an oncological history and 626 matched control patients. The median age during CCTA scan was 59.4 [50.4-67.5] years and 66.1% of the patients were female. Coronary atherosclerosis was observed in 258 (82.4%) patients with a history of cancer compared to 461 (73.6%) control patients with a risk ratio of 1.12 [95% CI: 1.04-1.20], p<0.01. Mainly younger patients with a history of cancer aged between 30-59 years had a significant increased prevalence of coronary atherosclerosis with a risk ratio of 1.18 [1.04-1.33] compared to healthy controls (p=0.02). In our study population, thoracic radiotherapy was not associated with an increased prevalence of coronary atherosclerosis. Calcified plaques were observed more frequently in patients with a history of cancer (14.4% vs. 9.3% respectively, p=0.018). Conclusion Patients with a history cancer have a higher prevalence of coronary atherosclerosis as observed on CCTA compared to matched patients without cancer. This effect was most pronounced in younger patients aged 30-59 years. There is an unmet need to define strategies for cardiovascular disease monitoring and prevention in this growing patient population of patients with a history of cancer.Presence of coronary atherosclerosisRadiotherapy and atherosclerosis

Procedural findings and follow-up results of catheter ablation of atrial fibrillation in patients after radiation therapy for breast cancer

Abstract Backround Data on breast cancer radiation therapy (RT) associated atrial cardiomyopathy and its potential role in the pathophysiology of atrial fibrillation (AF) is very limited. Objectives To investigate the effect of breast cancer radiotherapy (RT) on atrial cardiomyopathy and its possible role in the pathophysiology of atrial fibrillation. What is the therapeutic success of antral pulmonary vein isolation (PVI) with possible substrate modifications (CFAE) in patients with breast cancer radiation therapy and paroxysmal or persistent atrial fibrillation. Methods We searched the institution’s data base for patients who received RT for breast cancer and underwent subsequently 3D mapping guided AF ablation. Intraprocedural mapping data and short- and long-term results of ablation were evaluated according to "no low voltage" and "low voltage" present. Low voltage amplitudes in bipolar electrograms were defined as <0.5 mV for endocardial maps created during SR and <0.3mV during AF. Ablation strategy comprised pulmonary vein isolation (PVI) ± additional substrate modification according to the mapping results. Follow Up (FU) was evaluated using repetitive 7-days Holter ECG and clinical visits. Results We included 45 patients (all female, 70.9±7.2 years) with paroxysmal or persistent AF (n=18 and n=27). In 3D mapping, 60% of the patients (27/45) showed left atrial low voltage (LV group) with the majority showing low voltage in the anterior wall of the left atrium (LA) in 18 of 45 patients (40%). PVI with ablation of complex fractionated signals (CFAE) was predominantly performed (18/27). After one ablation, 33.3% (9) of the patients in the LV group were recurrence-free and after an average of 1.9 ablations, freedom from recurrence was achieved in 21 patients with low voltage (77.8%). In 18 patients, no low voltage was detected (NLV group) and PVI only was performed in the majority (14/18). In this NLV group, 61.1% (11) of the patients were recurrence-free after one ablation and freedom from recurrence was achieved in 72.2% (13) after an average of 1.2 ablations. Conclusion Thoracic radiation therapy in patients with breast cancer can lead to low voltage in the LA with the predominant low voltage location being the anterior wall of the LA. An extended ablation strategy (PVI & CFAE) can show good treatment options in these patients with atrial fibrillation, with high freedom from recurrence after a mean of two ablation procedures.Freedom from recurrence after ablationCharacteristics of left atrium (LA)

First-line chemoimmunotherapy for patients with small-cell lung cancer and interstitial lung abnormality: CIP risk and prognostic analysis.

Patients with non-small-cell lung cancer (NSCLC) receiving immunotherapy face a potential risk of developing checkpoint inhibitor-related pneumonitis (CIP). However, there is no clear understanding of the specific link between interstitial lung abnormality (ILA) and CIP in patients with small-cell lung cancer (SCLC). In addition, the prognosis of SCLC patients with ILA who receive chemoimmunotherapy is uncertain. Our study aimed to investigate the effect of ILA on the occurrence of CIP in SCLC patients receiving first-line chemoimmunotherapy and to assess its relationship with prognosis. We conducted a retrospective analysis of SCLC patients who received chemoimmunotherapy as a first-line treatment between January 2018 and April 2024. The diagnosis of ILA was assessed by two experienced pulmonologists based on pretreatment chest computed tomography images. We investigated independent risk factors for CIP using logistic regression analysis and factors affecting PFS and OS using Cox regression analysis. A total of 128 patients with SCLC were included in the study. ILA was present in 41 patients (32.03%), and CIP occurred in 16 patients (12.50%). In multivariate logistic regression analysis, previous ILA (OR, 5.419; 95% CI, 1.574-18.652; p = 0.007) and thoracic radiation therapy (TRT) (OR, 5.259; 95% CI, 1.506-18.365; p = 0.009) were independent risk factors for CIP. ILA (HR, 2.083; 95% CI, 1.179-3.681; p = 0.012) and LDH (HR, 1.002; 95% CI, 1.001-1.002; p < 0.001) were statistically significant for increased mortality risk in multivariate Cox regression analysis. In SCLC patients receiving first-line chemoimmunotherapy, baseline ILA is a risk factor for CIP and is associated with poorer prognosis.

P1.09A.03 Concurrent Combination of EGFR-TKIs and Thoracic Radiation Therapy for Metastatic Non Small Cell Lung Cancer Patients

P1.09A.03 Concurrent Combination of EGFR-TKIs and Thoracic Radiation Therapy for Metastatic Non Small Cell Lung Cancer Patients

Thoracic Radiotherapy Improves the Survival in Patients With EGFR-Mutated Oligo-Organ Metastatic Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors: A Multicenter, Randomized, Controlled, Phase III Trial.

This multicenter, randomized, phase III clinical trial (Northern Radiation Oncology Group of China-002) focused on patients with oligo-organ metastatic non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations. We aimed to investigate whether first-line concurrent thoracic radiotherapy (TRT) and EGFR-tyrosine kinase inhibitors (TKIs), compared with TKIs alone, could achieve better survival. The patients in the TKI plus TRT group received 60 Gy to primary lung tumor and positive regional lymph nodes. Radiotherapy for metastases to other sites was determined by clinicians. The primary end point was the progression-free survival (PFS). Secondary end points included overall survival (OS) and treatment-related adverse events (TRAEs). The first and second interim analyses were performed in March 2021 and March 2022. Between April 14, 2016, and February 25, 2022, a total of 118 patients were enrolled. Compared with the TKI alone group, the TKI plus TRT group achieved significantly better PFS (hazard ratio [HR], 0.57; P = .004) and OS (HR, 0.62; P = .029). The median PFS was 10.6 months in the TKI alone group and 17.1 months in the TKI plus TRT group. The median OS was 26.2 months and 34.4 months in the TKI alone group and TKI plus TRT group, respectively. The TKI plus TRT group showed better local control but was associated with a higher incidence of severe TRAEs (11.9% v 5.1%). For patients with EGFR-mutated oligo-organ metastatic NSCLC treated with first-line EGFR-TKIs, concurrent TRT improves the PFS and OS, and TRAEs are acceptable and tolerable.

Whole-blood RNA biomarkers for predicting survival in non-human primates following thoracic radiation

Radiation injury, either from radiotherapy or a mass-casualty event requires a health care system that can efficiently allocate resources to patients. We conducted a comprehensive transcriptome analysis of whole blood from a nonhuman primate model that received upper thoracic radiation (9.8–10.7 Gy). Blood samples were collected at multiple time points, extending up to 270 days post-irradiation with a minimum n = 6 for initial time points (Day 3-Day 40) and a total number of n = 28 primates. No males receiving the higher dose survived to Day 270. Using the Elastic Net model in R we found that pooling biomarkers from Day 3–21 increased our accuracy in discerning survival time, pleural effusion or dose compared to using biomarkers specific to a single day. For survival data, in predicting short term (less than 90 day), medium term (Day 91–269) or long-term survival (Day 270), prediction accuracy using only Day 3 data was 0.14 (95% Confidence Interval (CI) 0.1, 0.19) while pooled data for Male and Female was 0.76 (CI 0.69, 0.82). When pooled data was divided by biological sex, accuracy was 0.7 (CI 0.58, 0.8) for pooled data from Males and 0.84 (CI 0.76, 0.91) for Females. The development of RNA biomarkers as a tool to aid in clinical decision-making could significantly improve patient care in cases of radiation injury, whether from radiotherapy or mass-casualty events. Further validation and clinical translation of these findings could lead to improved patient care and management strategies in cases of radiation exposure.

Dose-Volume Constraints Parameters for Lung Tissue in Thoracic Radiotherapy Following Immune Checkpoint Inhibitor Treatment.

This study aims to identify risk factors associated with symptomatic radiation pneumonitis (RP, Grade ≥ 2) following immunotherapy preceding thoracic radiotherapy (ICI-TRT) and establish safe dose constraints. This retrospective study enrolled patients diagnosed with non-small-cell lung cancer (NSCLC) who underwent thoracic radiotherapy (TRT) following immune checkpoint inhibitors (ICIs) treatment. The primary endpoint was the occurrence of symptomatic RP (Grade ≥ 2), as defined by the Common Terminology Criteria for Adverse Events version 5.0. Clinical and lung dosimetric parameters were analyzed to determine their associations with symptomatic RP. Dosimetric parameters included mean lung dose (MLD) and the percentage of lung volume receiving ≥10 Gy (V10), ≥20 Gy (V20), ≥30 Gy (V30), and ≥40 Gy (V40). Receiver operating characteristic curves were used to predict the risk of developing symptomatic RP to establish optimal threshold values for each dosimetric predictor. Among the 118 patients included, the incidence of symptomatic RP was 25.4%. Tumor locations, intervals between immunotherapy and radiotherapy, and MLD, V10, V20, V30, and V40 were identified as independent risk factors for symptomatic RP. The area under the curve (AUC) values for MLD, V10, V20, V30, and V40 were 0.788 (95% confidence interval [CI] 0.704-0.873), 0.789 (95% CI 0.705-0.874), 0.791 (95% CI 0.706-0.876), 0.784 (95% CI 0.697-0.871), and 0.749 (95% CI 0.656-0.842), respectively. The optimal threshold values for MLD, V10, V20, V30, and V40 were 9.7 Gy, 26.3%, 15.9%, 13.3%, and 8.6%, respectively. These thresholds are lower than current guideline recommendations, and maintaining dosimetric parameters below these values resulted in a cumulative symptomatic RP incidence of <12%. The recommended dose thresholds for MLD, V10, V20, V30, and V40 are lower than the current guidelines, underscoring the importance of radiotherapy planning to minimize symptomatic RP occurrence in patients receiving ICI-TRT.

Brief Report of a New Anatomical Region at Risk in Thoracic Radiotherapy: From Discovery to Implementation

Increasing radiotherapy dose to select cardiac structures is associated with cardiac events and premature death. Previous studies have found a dose–response relationship for structures at the base of the heart.We have defined a new cardiac anatomical region at risk for radiotherapy by consensus opinion, based on image-based data-mining studies. The cardiac avoidance area comprises the superior vena cava, right atrium, aortic root, left main coronary artery, and proximal segments of the left anterior descending and right coronary arteries. We describe a contouring atlas for the cardiac avoidance area to facilitate implementation.

Cancer bronchique à petites cellules de stade étendu : quoi de neuf ?

This article describes recent advances in the therapeutic management of extensive-stage small cell lung cancer, particularly the development of immune checkpoint inhibitors and new agents targeting DLL3. He also cites still debatable issues such as thoracic radiotherapy and prophylactic cerebral irradiation. Finally, therapeutic approaches targeting DNA damage repair abnormalities are discussed.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

EP.09A.05 Consolidative Thoracic Radiotherapy Induced Lymphopenia in Metastatic NSCLC Is Predicted by EDIC and Associated with Poor Clinical Outcomes

EP.09A.05 Consolidative Thoracic Radiotherapy Induced Lymphopenia in Metastatic NSCLC Is Predicted by EDIC and Associated with Poor Clinical Outcomes

MO25-5 Phase II study of 54 Gy accelerated hyperfractionated thoracic radiotherapy in limited-stage small-cell lung cancer

MO25-5 Phase II study of 54 Gy accelerated hyperfractionated thoracic radiotherapy in limited-stage small-cell lung cancer

P1.13A.06 Outcomes in LS SCLC Patients with Severe Acute Esophagitis During Chemotherapy and Concurrent Twice-Daily Thoracic Radiotherapy

P1.13A.06 Outcomes in LS SCLC Patients with Severe Acute Esophagitis During Chemotherapy and Concurrent Twice-Daily Thoracic Radiotherapy

EP.13D.08 Impact of Thoracic Radiotherapy on First-Line Treatment Outcomes in ES-SCLC Patients

EP.13D.08 Impact of Thoracic Radiotherapy on First-Line Treatment Outcomes in ES-SCLC Patients

EP.13C.08 Leukoencephalopathy and Brain Metastasis in LS-SCLC Patients with and without PCI after Curative Thoracic RT

EP.13C.08 Leukoencephalopathy and Brain Metastasis in LS-SCLC Patients with and without PCI after Curative Thoracic RT

Development of brain metastases in patients managed with non-curative thoracic radiotherapy for stage II/III non-small cell lung cancer

BackgroundThis retrospective study analyzed the incidence of subsequent brain metastases after palliative radiotherapy or chemoradiation in patients with stage II/III non-small cell lung cancer (NSCLC). Risk factors for brain metastases development and survival after diagnosis were evaluated.MethodsDifferent baseline parameters including but not limited to age, stage and target volume size were assessed. Outcomes were abstracted from electronic health records. Uni- and multivariate tests were performed.ResultsThe study included 102 patients and found an actuarial risk of brain metastases of 15% (standard error ± 4) at one year and 20% (± 5) at two years. The maximum time interval was 15 months from start of radiation treatment. A non-significant survival difference was observed (median 12 months without versus 8.3 months with brain metastases, p = 0.21). Incidence was higher in patients with N2/3 stage, larger planning target volume size, and younger age (univariately significant factors). Trends were seen for stage III and adenocarcinoma histology. The multivariate analysis confirmed age as the most important risk factor.ConclusionThe risk of brain metastases development was comparable to that reported in studies of curative chemoradiation. All events occurred within 15 months of follow-up, suggesting that long-term surveillance imaging may not be warranted. Patients younger than 60 years had a very high risk of brain metastases development.

Prediction of new-onset atrial fibrillation in patients with non-small cell lung cancer treated with curative-intent conventional radiotherapy

BackgroundAtrial fibrillation (AF) is an important side effect of thoracic Radiotherapy (RT), which may impair quality of life and survival. This study aimed to develop a prediction model for new-onset AF in patients with Non-Small Cell Lung Cancer (NSCLC) receiving RT alone or as a part of their multi-modal treatment. Patients and MethodsPatients with stage I-IV NSCLC treated with curative-intent conventional photon RT were included. The baseline electrocardiogram (ECG) was compared with follow-up ECGs to identify the occurrence of new-onset AF. A wide range of potential clinical predictors and dose-volume measures on the whole heart and six automatically contoured cardiac substructures, including chambers and conduction nodes, were considered for statistical modeling. Internal validation with optimism-correction was performed. A nomogram was made. Results374 patients (mean age 69 ± 10 years, 57 % male) were included. At baseline, 9.1 % of patients had AF, and 42 (11.2 %) patients developed new-onset AF. The following parameters were predictive: older age (OR=1.04, 95 % CI: 1.013–1.068), being overweight or obese (OR=1.791, 95 % CI: 1.139–2.816), alcohol use (OR=4.052, 95 % CI: 2.445–6.715), history of cardiac procedures (OR=2.329, 95 % CI: 1.287–4.215), tumor located in the upper lobe (OR=2.571, 95 % CI: 1.518–4.355), higher forced expiratory volume in 1 s (OR=0.989, 95 % CI: 0.979–0.999), higher creatinine (OR=1.008, 95 % CI: 1.002–1.014), concurrent chemotherapy (OR=3.266, 95 % CI: 1.757 to 6.07) and left atrium Dmax (OR=1.022, 95 % CI: 1.012–1.032). The model showed good discrimination (area under the curve = 0.80, 95 % CI: 0.76–0.84), calibration and positive net benefits. ConclusionThis prediction model employs readily available predictors to identify patients at high risk of new-onset AF who could potentially benefit from active screening and timely management of post-RT AF.

A biomarker exploration in small-cell lung cancer for brain metastases risk and prophylactic cranial irradiation therapy efficacy

BackgroundSmall-cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis. Limited-stage (LS)-SCLC comprises only one-third of SCLC cases, resulting in limited molecularly targeted therapies and treatment options. Despite advances in thoracic and cranial irradiation leading to improved outcomes, a notable proportion of patients develop brain metastasis (BM), highlighting the importance of identifying high-risk patients for tailored screening and treatment strategies. Materials and MethodsWe analyzed baseline tumor biopsies from 180 LS-SCLC patients who received frontline definitive chemoradiotherapy (dCRT) using a 474-gene pan-cancer panel. The cumulative incidence of BM was calculated with death scored as a competing risk. Independent prognostic factors for BM risk were identified using the Fine-Gray model. ResultsAlterations in the cell cycle pathway, particularly RB1 mutations, were more common in patients with BM, while FLT4 mutations were more frequent in those without BM (P=0.002 and P=0.021, respectively). Significant risk factors for BM include smoking (subdistribution hazard ratio [SHR]: 1.73; 95 % confidence interval [CI]: 1.11–2.70; P=0.016), RB1 mutations (SHR: 2.19; 95 % CI: 1.27–3.81; P=0.005), and BCL3 amplification (SHR: 2.27; 95 % CI: 1.09–4.71; P=0.028). Conversely, prophylactic cranial irradiation (PCI) (SHR: 0.39; 95 % CI: 0.25–1.60; P<0.001), FLT4 mutations (SHR: 0.26; 95 % CI: 0.07–0.98; P=0.047), and NOTCH pathway alterations (SHR: 0.65; 95 % CI: 0.43–1.00; P=0.049) were associated with a lower incidence of BM in LS-SCLC. Notably, consolidation PCI therapy did not reduce the BM risk in patients with baseline RB1 mutations, with BM occurrence probabilities of 34.7 % at 20 months and 62.6 % at 40 months. ConclusionOur study yields valuable insights into the genetic characteristics of LS-SCLC patients with and without BM, aiding the development of personalized treatment strategies. Identifying risk factors associated with the incidence and timing of BM, within the standard regimen of dCRT followed by PCI, may help optimize clinical decision-making for LS-SCLC.

Feasibility Study of Nivolumab in Combination with Carboplatin Plus Paclitaxel and Concurrent Thoracic Radiation in Patients with Untreated Unresectable Locally Advanced Non-Small Cell Lung Cancer.

Despite advancements in diagnosing and treating non-small cell lung cancer (NSCLC), the prognosis remains poor. Immune checkpoint inhibitors have shown promise in enhancing survival rates. Therefore, this study aimed to investigate the safety of nivolumab administration with concurrent chemoradiation therapy (CCRT) in patients with unresectable locally advanced NSCLC. Twelve patients with unresectable locally advanced NSCLC at Kansai Medical University Hospital and Izumi City General Medical Center were enrolled from May 2018 to September 2020. They received nivolumab (360 mg) tri-weekly twice, weekly carboplatin (AUC 2 min × mg/mL) and paclitaxel (40 mg/m2) for 6 weeks, and thoracic radiotherapy (60 Gy/30 fractions), followed by maintenance nivolumab therapy (360 mg, tri-weekly) for 6 months. The primary endpoint was incidence of dose-limiting toxicities (DLTs), and the secondary endpoints included safety, response rate, progression-free survival (PFS), overall survival (OS), 2-year survival rate, and treatment completion rate. Three patients completed the protocol. Nine discontinued due directly to interstitial pneumonia (three) and pneumonia (one). Ten patients (83.3%) experienced a grade 3 or higher event, of which three (25%) experienced a grade 4 or higher event, and of these, one (8.3%) experienced a grade 5 event. Three patients experienced DLTs. Concurrent nivolumab with CCRT was tolerated in unresectable locally advanced NSCLC, which offers potential treatment benefits.

Pyrroloquinoline Quinone Alleviates Mitochondria Damage in Radiation-Induced Lung Injury in a MOTS-c-Dependent Manner.

Radiation-induced lung injury (RILI) is a prevalent complication of thoracic tumor radiotherapy and accidental radiation exposure. Pyrroloquinoline quinone (PQQ), a novel vitamin B, plays a crucial role in delaying aging, antioxidation, anti-inflammation, and antiapoptosis. This study aims to investigate the protective effect and mechanisms of PQQ against RILI. C57BL/6 mice were exposed to a 20 Gy dose of X-ray radiation on the entire thorax with or without daily oral administration of PQQ for 2 weeks. PQQ effectively mitigated radiation-induced lung tissue damage, inflammation, oxidative stress, and epithelial cell apoptosis. Additionally, PQQ significantly inhibited oxidative stress and mitochondrial damage in MLE-12 cells. Mechanistically, PQQ upregulated the mRNA and protein levels of MOTS-c in irradiated lung tissue and MLE-12 cells. Knockdown of MOTS-c by siRNA substantially attenuated the protective effects of PQQ on oxidative stress, inflammation, and apoptosis. In conclusion, PQQ alleviates RILI by preserving mitochondrial function through a MOTS-c-dependent mechanism, suggesting that PQQ may serve as a promising nutraceutical intervention against RILI.

A phase II study of weekly carboplatin and concurrent radiotherapy in older adults with locally advanced non-small cell lung cancer (LOGIK1902).

Concurrent chemoradiotherapy is the standard therapy for locally advanced non-small cell lung cancer (NSCLC). However, there is little evidence supporting its use in older adults. Low-dose daily carboplatin combined with thoracic radiotherapy is considered a standard regimen for this population. To establish a simple and feasible carboplatin administration method, we conducted a study of weekly carboplatin and concurrent radiotherapy for older adults with locally advanced NSCLC. This prospective, single-arm, multicenter, phase II clinical trial included patients aged ≥75 years with unresectable stage III NSCLC and Eastern Cooperative Oncology Group performance status 0-1. Patients received chemoradiotherapy (60 Gy/30 fractions plus concurrent weekly carboplatin at an area under curve of 2 mg mL-1 min-1). The primary endpoint was the overall response rate (ORR). Key secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. From July 2020 to June 2022, 37 patients were enrolled from 15 institutions, and 36 patients were evaluable for efficacy and safety. The ORR was 63.9% (95% confidence interval [CI] = 47.6-77.5). Median PFS was 14.6 months (95% CI = 9.1-18.1). Median OS was 25.5 months (95% CI = 17.4-not reached). Grade 4 leucopenia, neutropenia, and thrombocytopenia were observed in one patient (2.8%) each. Weekly carboplatin and concurrent radiation therapy was safe in older adults with locally advanced NSCLC, and promising activity was observed.