Thoracic Radiotherapy Research Articles

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.

Impact of lung adenocarcinoma subtypes on survival and timing of brain metastases.

Lung cancer is a devastating disease, with brain metastasis being one of the most common distant metastases of lung adenocarcinoma. This study aimed to investigate the prognostic characteristics of individuals with brain metastases originating from invasive lung adenocarcinoma of distinct pathological subtypes, providing a reference for the management of these patients. Clinical data from 156 patients with lung adenocarcinoma-derived brain metastases were collected, including age, sex, smoking status, Karnofsky Performance Status scores, pathological subtype, lymph node metastasis, tumor site, treatment mode, T stage, and N stage. Patients were classified into two groups (highly differentiated and poorly differentiated) based on their pathological subtypes. Propensity score matching was used to control for confounding factors. The prognostic value of pathological subtypes was assessed using Kaplan-Meier analysis and Cox proportional hazards regression modeling. Kaplan-Meier analysis indicated that patients in the moderately to highly differentiated group had better prognoses. Multivariate analysis revealed that being in the poorly differentiated group was a risk factor for poorer prognosis. Thoracic tumor radiation therapy, chemotherapy, and surgery positively influenced the time interval between lung cancer diagnosis and brain metastasis. The pathological subtypes of lung adenocarcinoma-derived brain metastases are associated with patient prognosis. Patients in the poorly differentiated group have worse prognoses compared to those in the moderately to highly differentiated group. Therefore, patients in the poorly differentiated group may require more frequent follow-ups and aggressive treatment.

Moving beyond mean heart dose: The importance of cardiac substructures in radiation therapy toxicity.

Normal tissue tolerance dose limits to the heart have been established to reduce the risk of radiation-induced cardiac disease (RICD). Dose constraints have been developed based on either the mean dose delivered to the whole heart (MHD) or the dose delivered to a specific volume, for example, volume of heart receiving equal to or greater than 30 Gy (V30). There is increasing evidence that the impact of thoracic radiation on cardiac morbidity and mortality has been underestimated. Consequently, there is a need to reduce the dose delivered to the heart in radical radiotherapy treatment planning. The pathophysiology of RICD may relate to dose to specific cardiac substructures (CS) rather than the traditionally observed MHD for common toxicities. The MHD or V30 Gy threshold dose rarely represents the true dose delivered to individual CS. Studies have shown the dose to specific areas may be more strongly correlated with overall survival (OS). With advances in modern radiotherapy techniques, it is vital that we develop robust, evidence-based dose limits for CS, to fully understand and reduce the risk of RICD, particularly in high-risk populations with cardiac risk factors. The following review will summarise the existing evidence of dose limits to CS, explain how dose limits may vary according to different disease sites or radiation techniques and propose how radiotherapy plans can be optimised to reduce the dose to these CS in clinical practice.

Advances in CT-based lung function imaging for thoracic radiotherapy.

The objective of this review is to examine the potential benefits and challenges of CT-based lung function imaging in radiotherapy over recent decades. This includes reviewing background information, defining related concepts, classifying and reviewing existing studies, and proposing directions for further investigation. The lung function imaging techniques reviewed herein encompass CT-based methods, specifically utilizing phase-resolved four-dimensional CT (4D-CT) or end-inspiratory and end-expiratory CT scans, to delineate distinct functional regions within the lungs. These methods extract crucial functional parameters, including lung volume and ventilation distribution, pivotal for assessing and characterizing the functional capacity of the lungs. CT-based lung ventilation imaging offers numerous advantages, notably in the realm of thoracic radiotherapy. By utilizing routine CT scans, additional radiation exposure and financial burdens on patients can be avoided. This imaging technique also enables the identification of different functional areas of the lung, which is crucial for minimizing radiation exposure to healthy lung tissue and predicting and detecting lung injury during treatment. In conclusion, CT-based lung function imaging holds significant promise for improving the effectiveness and safety of thoracic radiotherapy. Nevertheless, challenges persist, necessitating further research to address limitations and optimize clinical utilization. Overall, this review highlights the importance of CT-based lung function imaging as a valuable tool in radiotherapy planning and lung injury monitoring.

American Radium Society Appropriate Use Criteria on Cardiac Toxicity Prevention and Management After Thoracic Radiotherapy

IntroductionThe multidisciplinary American Radium Society Thoracic Committee was assigned to create appropriate use criteria on cardiac toxicity prevention and management for patients undergoing radiotherapy. MethodsA systematic review of the current literature was conducted. Case variants of patients with thoracic malignancies undergoing radiation were created based on presence or absence of cardiovascular risk factors and treatment-related risks assessed by dose exposure to the heart/cardiac substructures. Modified Delphi methodology was used to evaluate the variants and procedures, with less than or equal to three rating points from median defining agreement/consensus. ResultsA total of six variants were evaluated. The panel felt that patients with cardiac comorbidities at high risk for radiation-related cardiac toxicity should undergo a prescreening cardiac-focused history and physical (H&P) examination, electrocardiogram, cardiac imaging including an echocardiogram, and referral to a cardiologist/cardio-oncologist. Recommendations for those without cardiac comorbidities at low risk for cardiac toxicity were to undergo a baseline H&P examination only. Conversely, those without cardiac comorbidities but at high risk for radiation-related cardiac toxicity were recommended to undergo a prescreening electrocardiogram, in addition to a H&P examination. For patients with cardiac comorbidities at low risk for cardiac toxicity, the panel felt that prescreening and postscreening tests may be appropriate. ConclusionsThe American Radium Society Thoracic appropriate use criteria panel has developed multidisciplinary consensus guidelines for cardiac toxicity prevention, surveillance, and management after thoracic radiotherapy based on cardiac comorbidities at presentation and risk of radiation-related cardiac toxicity.

A retrospective evaluation of therapeutic efficacy and safety of chemoradiotherapy in older patients (aged ≥ 75 years) with limited-disease small cell lung cancer: insights from two institutions and review of the literature.

The standard treatment for patients in good general condition with limited-disease small cell lung cancer (LD-SCLC) is concurrent platinum/etoposide chemotherapy and thoracic radiotherapy (TRT). However, the efficacy and safety of chemoradiotherapy (CRT) in older patients with LD-SCLC has not been fully explored; moreover, the optimal treatment for this patient group remains unclear. This study aimed to investigate the feasibility and efficacy of CRT in older patients with LD-SCLC. From April 2007 to June 2021, consecutive older patients (aged ≥ 75 years) with stage I to III SCLC who received concurrent or sequential CRT at two institutions were retrospectively evaluated for efficacy and toxicity of CRT. A total of 32 older patients underwent concurrent (n = 19) or sequential (n = 13) CRT for LD-SCLC. The median ages of the patients in the concurrent and sequential CRT groups were 77 (range: 75-81) years and 79 (range: 76-92) years, respectively. The median number of chemotherapeutic treatment cycles was four (range, 1-5), and the response rate was 96.9% in all patients (94.7% in concurrent and 100% in sequential CRT groups). The median progression-free survival (PFS) and median overall survival (OS) for all patients were 11.9 and 21.1 months, respectively. The median PFS was 13.0 and 9.0 months in the concurrent CRT and sequential CRT groups, respectively, with no statistically significant difference (p = 0.67). The median OS from the initiation of CRT was 19.2 and 23.5 months in the concurrent and sequential CRT groups, respectively (p = 0.46). The frequencies of Grade ≥ 3 hematological adverse events were as follows: decreased white blood cell count, 20/32 (62.5%); decreased neutrophil count, 23/32 (71.9%); anemia, 6/32 (18.8%); decreased platelet count, 7/32 (21.9%); and febrile neutropenia, 3/32 (9.4%). Treatment-related deaths occurred in one patient from each group. Although hematological toxicities, particularly reduced neutrophil count, were severe, CRT showed favorable efficacy in both concurrent and sequential CRT groups. However, concurrent CRT may not be feasible for all older patients with LD-SCLC; accordingly, sequential CRT may be considered as a treatment of choice for these patients. Further prospective trials are warranted to identify optimal treatment strategies for this patient group.

Single-arm trial of neoadjuvant ipilimumab plus nivolumab with chemoradiotherapy in patients with resectable and borderline resectable lung cancer: the INCREASE study

BackgroundIn non-small cell lung cancer (NSCLC), chemoradiotherapy (CRT) yields pathological complete response (pCR) rates of approximately 30%. We investigated using ipilimumab plus nivolumab (IPI-NIVO) with neoadjuvant CRT in resectable, and...

1791P Thoracic radiotherapy plus maintenance durvalumab after first-line carboplatin and etoposide plus durvalumab in extensive-stage disease small cell lung cancer (ED-SCLC): A multicenter single-arm open-label phase II trial (SAKK 15/19)tle

1791P Thoracic radiotherapy plus maintenance durvalumab after first-line carboplatin and etoposide plus durvalumab in extensive-stage disease small cell lung cancer (ED-SCLC): A multicenter single-arm open-label phase II trial (SAKK 15/19)tle

1799P Efficacy and safety of integrating consolidative thoracic radiotherapy with immunochemotherapy in ES-SCLC: A real-world retrospective analysis

1799P Efficacy and safety of integrating consolidative thoracic radiotherapy with immunochemotherapy in ES-SCLC: A real-world retrospective analysis

278: Simultaneous PET/MRI to assess acute cardiotoxicity after chemotherapy and thoracic radiotherapy

278: Simultaneous PET/MRI to assess acute cardiotoxicity after chemotherapy and thoracic radiotherapy