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Purpose: This study aims to evaluate the risk factors of treatment-related pneumonitis (TRP) following thoracic radiotherapy/chemoradiotherapy combined with anti-PD‑1 monoclonal antibodies (mAbs) in patients with advanced esophageal squamous cell carcinoma (ESCC). Methods: We retrospectively reviewed 97 patients with advanced ESCC who were treated with thoracic radiotherapy/chemoradiotherapy combined with anti-PD‑1 mAbs. Among them, 56 patients received concurrent radiotherapy with anti-PD‑1 mAbs and 41 patients received sequential radiotherapy with anti-PD‑1 mAbs. The median prescribed planning target volume (PTV) dose was 59.4 Gy (range from 50.4 to 66 Gy, 1.8–2.2 Gy/fraction). Clinical characteristics, the percentage of lung volume receiving more than 5–50 Gy in increments of 5 Gy (V5–V50, respectively) and the mean lung dose (MLD) were analyzed as potential risk factors for TRP. Results: 46.4% (45/97), 20.6% (20/97), 20.6% (20/97), 4.1% (4/97), and 1.0% (1/97) of the patients developed any grade of TRP, grade 1 TRP, grade 2 TRP, grade 3 TRP, and fatal (grade 5) TRP, respectively. Anti-PD‑1 mAbs administered concurrently with radiotherapy, V5, V10, V15, V25, V30, V35, V40 and MLD were associated with the occurrence of grade 2 or higher TRP. Concurrent therapy (P = 0.010, OR = 3.990) and V5 (P = 0.001, OR = 1.126) were independent risk factors for grade 2 or higher TRP. According to the receiver operating characteristic (ROC) curve analysis, the optimal V5 threshold for predicting grade 2 or higher TRP was 55.7%. Conclusion: The combination of thoracic radiotherapy/chemoradiotherapy with anti-PD‑1 mAbs displayed a tolerable pulmonary safety profile. Although the incidence of TRP was high, grade 1–2 TRP accounted for the majority. Anti-PD‑1 mAbs administered concurrently with radiotherapy and the lung V5 were significantly associated with the occurrence of grade 2 or higher TRP. Therefore, it seems safer to control V5 below 55% in clinical, especially for the high-risk populations receiving concurrent therapy. [ABSTRACT FROM AUTHOR]

Radiotherapy is an essential part of treatment for many patients with thoracic cancers. However, proximity of the heart to tumour targets can lead to cardiac side effects, with studies demonstrating link between cardiac radiation dose and adverse outcomes. Although reducing cardiac dose can reduce associated risks, most cardiac constraint recommendations in clinical use are generally based on dose to the whole heart, as dose assessment at cardiac substructure levels on individual patients has been limited historically. Furthermore, estimation of an individual's cardiac risk is complex and multifactorial, which includes radiation dose alongside baseline risk factors, and the impact of systemic therapies. This review gives an overview of the epidemiological impact of cancer and cardiac disease, risk factors contributing to radiation‐related cardiotoxicity, the evidence for cardiac side effects and future directions in cardiotoxicity research. A better understanding of the interactions between risk factors, balancing treatment benefit versus toxicity and the ongoing management of cardiac risk is essential for optimal clinical care. The emerging field of cardio‐oncology is thus a multidisciplinary collaborative effort to enable better understanding of cardiac risks and outcomes for better‐informed patient management decisions. [ABSTRACT FROM AUTHOR]

Background: The therapeutic advantage of thoracic radiotherapy (tRT) as an adjunct to first‐line immunotherapy and chemotherapy in patients with extensive‐stage small cell lung cancer (ES‐SCLC) remains unclear. We sought to elucidate this in a retrospective cohort study comparing the effectiveness and safety of tRT in combination with first‐line immunotherapy and chemotherapy. Methods: Our retrospective study included patients with ES‐SCLC, treated at the West China Hospital between January 2019 and December 2022. They received first‐line immunotherapy and chemotherapy and were categorized into two cohorts based on the administration of tRT. The primary outcomes were overall survival (OS) and progression‐free survival (PFS). Cox regression analysis was utilized to identify potential independent predictors of prognosis and to compare the treatment outcomes across various patient subgroups. Treatment‐related toxicities across both cohorts were compared using the Chi‐squared test. Results: A total of 99patients were eligible for the study, out of which 55 received tRT. The medianduration of follow‐up was 39 months. Remarkably, patients who received tRTdemonstrated superior OS and PFS in comparison to those who did not (P < 0.05). Subgroup analysis further confirmed these findings. Multivariate analysisidentified treatment group and liver metastasis as independent prognosticfactors (P < 0.05). The incidence of grade 3‐4 adverse events showed nostatistically significant difference between the two cohorts. Conclusions: Thus, weconfirmed that the addition of tRT to the conventional regimen of first‐linechemotherapy and immunotherapy yields better survival outcomes without asignificant increase in toxicity. [ABSTRACT FROM AUTHOR]

Abstract Background First-line chemotherapy combined with bevacizumab is one of the standard treatment modes for patients with advanced non-small cell lung cancer (NSCLC). Thoracic radiotherapy (TRT) can provide significant local control and survival benefits to patients during the treatment of advanced NSCLC. However, the safety of adding TRT has always been controversial, especially because of the occurrence of radiation pneumonia (RP) during bevacizumab treatment. Therefore, in this study, we used an expanded sample size to evaluate the incidence of RP when using bevacizumab in combination with TRT. Patients and methods Using an institutional query system, all medical records of patients with NSCLC who received TRT during first-line chemotherapy combined with bevacizumab from 2017 to 2020 at Shandong Cancer Hospital and Institute were reviewed. RP was diagnosed via computed tomography and was classified according to the RTOG toxicity scoring system. The risk factors for RP were identified using univariate and multivariate analyses. The Kaplan–Meier method was used to calculate progression-free survival (PFS) and overall survival (OS). Results Ultimately, 119 patients were included. Thirty-eight (31.9%) patients developed Grade ≥ 2 RP, of whom 27 (68.1%) had Grade 2 RP and 11 (9.2%) had Grade 3 RP. No patients developed Grade 4 or 5 RP. The median time for RP occurrence was 2.7 months (range 1.2–5.4 months). In univariate analysis, male, age, KPS score, V20 > 16.9%, V5 > 33.6%, PTV (planning target volume)-dose > 57.2 Gy, and PTV-volume > 183.85 cm3 were correlated with the occurrence of RP. In multivariate analysis, male, V20 > 16.9%, and PTV-volume > 183.85 cm3 were identified as independent predictors of RP occurrence. The mPFS of all patients was 14.27 (95% CI, 13.1–16.1) months. The one-year and two-year PFS rates were 64.9% and 20.1%, respectively. The mOS of all patients was 37.09 (95% CI, 33.8–42.0) months. The one-year survival rate of all patients was 95%, and the two-year survival rate was 71.4%. Conclusions The incidence of Grade ≥ 2 RP in NSCLC patients who received both bevacizumab and TRT was 31.9%. Restricting factors such as V20 and PTV will help reduce the risk of RP in these patients. For patients who receive both bevacizumab and TRT, caution should be exercised when increasing TRT, and treatment strategies should be optimized to reduce the incidence of RP.

Purpose: The aim of this study was to investigate a first-site-metastasis pattern (FSMP) in unresectable stage III NSCLC after concurrent chemoradiotherapy (cCRT) with or without immune checkpoint inhibition (ICI). Methods: We defined three patient subgroups according to the year of initial multimodal treatment: A (2011–2014), B (2015–2017) and C (2018–2020). Different treatment-related parameters were analyzed. Observed outcome parameters were brain metastasis-free survival (BMFS), extracranial distant metastasis-free survival (ecDMFS) and distant metastasis-free survival (DMFS). Results: 136 patients treated between 2011 and 2020 were included with ≥ 60.0 Gy total dose and concurrent chemotherapy (cCRT); thirty-six (26%) received ICI. Median follow-up was 49.7 (range:0.7–126.1), median OS 31.2 (95% CI:16.4–30.3) months (23.4 for non-ICI vs not reached for ICI patients, p = 0.001). Median BMFS/ecDMFS/DMFS in subgroups A, B and C was 14.9/16.3/14.7 months, 20.6/12.9/12.7 months and not reached (NR)/NR/36.4 months (p = 0.004/0.001/0.016). For cCRT+ICI median BMFS was 53.1 vs. 19.1 months for cCRT alone (p = 0.005). Median ecDMFS achieved 55.2 vs. 17.9 (p = 0.003) and median DMFS 29.5 (95% CI: 1.4–57.6) vs 14.93 (95% CI:10.8–19.0) months (p = 0.031), respectively. Multivariate analysis showed that age over 65 (HR:1.629; p = 0.036), GTV ≥ 78 cc (HR: 2.100; p = 0.002) and V20 ≥ 30 (HR: 2.400; p = 0.002) were negative prognosticators for BMFS and GTV ≥ 78 cc for ecDMFS (HR: 1.739; p = 0.027). After onset of brain metastasis (BM), patients survived 13.3 (95% CI: 6.4–20.2) months and 8.6 months (95% CI: 1.6–15.5) after extracranial-distant-metastasis (ecDM). Patients with ecDM as FSMP reached significantly worse overall survival of 22.1 (range:14.4–29.8) vs. 40.1 (range:18.7–61.3) months (p = 0.034) in the rest of cohort. In contrast, BM as FSMP had no impact on OS. Conclusion: This retrospective analysis of inoperable stage III NSCLC patients revealed that age over 65, V20 ≥ 30 and GTV ≥ 78 cc were prognosticators for BMFS and GTV ≥ 78 cc for ecDMFS. ICI treatment led to a significant improvement of BMFS, ecDMFS and DMFS. ecDM as FSMP was associated with significant deterioration of OS, whereas BM as FSMP was not. [ABSTRACT FROM AUTHOR]

Background: First-line chemotherapy combined with bevacizumab is one of the standard treatment modes for patients with advanced non-small cell lung cancer (NSCLC). Thoracic radiotherapy (TRT) can provide significant local control and survival benefits to patients during the treatment of advanced NSCLC. However, the safety of adding TRT has always been controversial, especially because of the occurrence of radiation pneumonia (RP) during bevacizumab treatment. Therefore, in this study, we used an expanded sample size to evaluate the incidence of RP when using bevacizumab in combination with TRT. Patients and methods: Using an institutional query system, all medical records of patients with NSCLC who received TRT during first-line chemotherapy combined with bevacizumab from 2017 to 2020 at Shandong Cancer Hospital and Institute were reviewed. RP was diagnosed via computed tomography and was classified according to the RTOG toxicity scoring system. The risk factors for RP were identified using univariate and multivariate analyses. The Kaplan–Meier method was used to calculate progression-free survival (PFS) and overall survival (OS). Results: Ultimately, 119 patients were included. Thirty-eight (31.9%) patients developed Grade ≥ 2 RP, of whom 27 (68.1%) had Grade 2 RP and 11 (9.2%) had Grade 3 RP. No patients developed Grade 4 or 5 RP. The median time for RP occurrence was 2.7 months (range 1.2–5.4 months). In univariate analysis, male, age, KPS score, V20 > 16.9%, V5 > 33.6%, PTV (planning target volume)-dose > 57.2 Gy, and PTV-volume > 183.85 cm3 were correlated with the occurrence of RP. In multivariate analysis, male, V20 > 16.9%, and PTV-volume > 183.85 cm3 were identified as independent predictors of RP occurrence. The mPFS of all patients was 14.27 (95% CI, 13.1–16.1) months. The one-year and two-year PFS rates were 64.9% and 20.1%, respectively. The mOS of all patients was 37.09 (95% CI, 33.8–42.0) months. The one-year survival rate of all patients was 95%, and the two-year survival rate was 71.4%. Conclusions: The incidence of Grade ≥ 2 RP in NSCLC patients who received both bevacizumab and TRT was 31.9%. Restricting factors such as V20 and PTV will help reduce the risk of RP in these patients. For patients who receive both bevacizumab and TRT, caution should be exercised when increasing TRT, and treatment strategies should be optimized to reduce the incidence of RP. [ABSTRACT FROM AUTHOR]

Abstract Background The therapeutic advantage of thoracic radiotherapy (tRT) as an adjunct to first‐line immunotherapy and chemotherapy in patients with extensive‐stage small cell lung cancer (ES‐SCLC) remains unclear. We sought to elucidate this in a retrospective cohort study comparing the effectiveness and safety of tRT in combination with first‐line immunotherapy and chemotherapy. Methods Our retrospective study included patients with ES‐SCLC, treated at the West China Hospital between January 2019 and December 2022. They received first‐line immunotherapy and chemotherapy and were categorized into two cohorts based on the administration of tRT. The primary outcomes were overall survival (OS) and progression‐free survival (PFS). Cox regression analysis was utilized to identify potential independent predictors of prognosis and to compare the treatment outcomes across various patient subgroups. Treatment‐related toxicities across both cohorts were compared using the Chi‐squared test. Results A total of 99patients were eligible for the study, out of which 55 received tRT. The medianduration of follow‐up was 39 months. Remarkably, patients who received tRTdemonstrated superior OS and PFS in comparison to those who did not (P

Introduction: 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) is recommended for staging and defining target volume in limited-stage SCLC, though the impact on outcomes compared with CT staging and elective nodal irradiation (ENI) is not well documented. We analyzed patients receiving 45 Gy/30 fractions in two randomized trials of thoracic radiotherapy (TRT) in limited-stage SCLC (HAST and THORA trials) to evaluate whether PET-CT for staging and radiotherapy planning reduces radiotoxicity and improves survival. Methods: Patients in HAST were staged with CT of the thorax and upper abdomen and brain magnetic resonance imaging of the brain. Patients in THORA were staged with PET-CT in addition. All patients were to receive four courses of platinum/etoposide chemotherapy and concurrent TRT starting three to four weeks after the first chemotherapy course. In HAST, target volumes included pathological lesions on CT plus ENI of lymph node stations 4–7 (bilateral). In THORA, target volumes were limited to PET-CT-positive lesions (selective nodal irradiation [SNI]). Results: A total of 149 patients were included (PET-CT/SNI: n = 76, CT/ENI: n=73); the median age was 64 years, 56% were women, 85% had PS 0 to 1, and 81% had stage III disease. The PET-CT/SNI group experienced less grade 3-4 esophagitis (18% versus 33%, p = 0.043), less grade >=1 pneumonitis (5% versus 16%, p = 0.028), and less dysphagia after TRT (mean scores on European Organisation for Research and Treatment of Cancer 13-item lung cancer module: 45 versus 72). There was no difference in median overall survival (24 versus 25 mo, p = 0.59) or progression-free survival (11 versus 11 mo, p = 0.23). Conclusions: Using PET-CT for staging and target volume definition of TRT reduces acute radiotoxicity but does not improve overall or progression-free survival in limited-stage SCLC.

Abstract Objective This study assessed the outcomes of elderly patients with limited‐stage small cell lung cancer (LS‐SCLC), which may be linked to the timing of thoracic radiotherapy (TRT) following chemotherapy. Methods Elderly patients (n = 78) with LS‐SCLC were divided into three groups depending on the timing of radiotherapy. The patients in the TRT group were stratified into early (TRT after 1–2 cycles of chemotherapy, n = 29), medium‐term (TRT after 3–4 cycles of chemotherapy, n = 33), and late (TRT after 5–6 cycles of chemotherapy, n = 16) TRT groups. The overall survival (OS) and progression‐free survival (PFS) were assessed and compared. Results The medium‐term TRT group demonstrated significantly longer mPFS (20.12 months) and better mOS (35.97 months) than those in the other groups (PFS: P = 0.021;OS: P = 0.035). A pairwise comparison of the three groups revealed that those who received medium‐term TRT exhibited significantly improved PFS than the early (mPFS: 20.12 vs. 10.36 mouths, P = 0.018) and late (mPFS: 20.12 vs. 9.17 months, P = 0.016) TRT. The medium‐term TRT group demonstrated significantly improved OS than the early TRT (mOS: 35.97 vs. 25.22 months, P = 0.007) but not in comparison with the late TRT (mOS: 35.97 vs. 21.63 months, P = 0.100). Conclusion In elderly patients with LS‐SCLC, the addition of TRT after 3–4 cycles of chemotherapy appears to be a viable and potentially beneficial treatment approach.

Abstract Background The optimal timing of thoracic radiotherapy (TRT) in driver‐gene‐negative metastatic non‐small cell lung cancer (mNSCLC) patients was retrospectively investigated based on survival and safety profile. Methods The efficacy and safety data of driver‐gene‐negative mNSCLC patients treated with TRT during maintenance after first‐line therapy was collected. Patients whose primary tumor and metastatic lesions remained no progression during maintenance and then received TRT were categorized as the NP (no progression) group, while patients who experienced slow progression during maintenance without reaching progressive disease and then received TRT were categorized as the SP (slow progression) group. The efficacy and adverse events of TRT were analyzed. Results In total, 149 driver‐gene‐negative mNSCLC patients treated with TRT during maintenance were enrolled into the study, with 119 in the NP group and 30 in the SP group. After a median follow‐up of 30.83 (range: 26.62–35.04) months, the median progression‐free survival (PFS) in the NP group was 11.13 versus 9.53 months in the SP group (HR 0.599, p = 0.017). The median overall survival (OS) in the NP group was 32.27 versus 25.57 months in the SP group (HR 0.637, p = 0.088). The median PFS after radiotherapy (rPFS) was 6.33 versus 3.90 months (HR 0.288, p 0.05). Conclusion The addition of TRT during the pre‐emptive no progression phase was associated with a significantly longer PFS than during the delayed slow progression phase and had an acceptable safety profile. Our results might support the earlier initiation of TRT after induction therapy for some patients with driver‐gene‐negative mNSCLC.

Abstract 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.

Abstract Background Platinum-etoposide chemotherapy combined with immune checkpoint inhibitors (ICIs) has been recommended as the first-line standard treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, the effect of thoracic radiotherapy (TRT) on these patients is still unknown. This study aimed to evaluate the efficacy and safety of TRT for ES-SCLC patients who responded to first-line ICIs and chemotherapy (CHT). Methods Patients who received 4 to 6 cycles of ICIs and CHT as first-line therapy at three hospitals between 2018 and 2022 were included in the analysis. All patients were divided into two groups based on whether they received TRT as first-line treatment, and propensity score matching (PSM) was performed to ensure that the characteristics of two groups were well-balanced. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was toxic effects. Results A total of 276 patients were included, and the median follow-up time was 22.3 (range, 4.0-53.73) months. After PSM, 197 patients were further analysed, and 99 of whom received TRT. The baseline characteristics were well-balanced between patients in the TRT and non-TRT groups. There were significant differences in PFS between the TRT and non-TRT groups, with the median PFS of 10.76 and 7.63 months, respectively (P = 0.014). Significantly improved OS was observed in the TRT group (21.67 vs. 16.6 months, P = 0.009). In addition, the use of TRT was an independent prognostic factor for PFS and OS of ES-SCLC patients receiving ICIs plus CHT. In terms of safety, no significant increase of any grades adverse event (AE) (P = 0.874) and G3-4 AE (P = 0.909) was observed for patients receiving TRT. Radiation esophagitis, gastrointestinal and hematologic toxicities were the most common AEs in TRT group, which were tolerable. And high-dose radiotherapy was associated with higher incidence of pneumonitis. Conclusion Addition of TRT showed significant survival benefits and well tolerability in ES-SCLC patients receiving platinum-etoposide CHT and ICIs, which could be a feasible first-line treatment strategy for ES-SCLC patients.

Purpose This study aimed to compare the failure patterns before and after the introduction of immunotherapy and to determine the role of thoracic radiotherapy (TRT) in extensive-stage small-cell lung cancer (ES-SCLC) treatment. Materials and Methods We retrospectively reviewed 294 patients with ES-SCLC, of which 62.2% underwent chemotherapy alone, 13.3% underwent chemotherapy followed by consolidative TRT (TRT group), and 24.5% underwent chemotherapy with immune checkpoint inhibitor (ICI group). We performed propensity-score matching (PSM) to compare each treatment group. Results The median follow-up duration was 10.4 months. At the first relapse, in the cohort showing objective response, the proportion of cases showing intrathoracic progression was significantly lower in the TRT group (37.8%) than in the chemotherapy-alone (77.2%, p < 0.001) and the ICI (60.3%, p=0.03) groups. Furthermore, in the subgroup analysis, TRT showed benefits related to intrathoracic progression-free survival (PFS) in comparison with ICI in patients with less than two involved extrathoracic sites (p=0.008) or without liver metastasis (p=0.02) or pleural metastasis (p=0.005) at diagnosis. After PSM, the TRT group showed significantly better intrathoracic PFS than both chemotherapy-alone and ICI groups (p < 0.001 and p=0.04, respectively), but showed no significant benefit in terms of PFS and overall survival in comparison with the ICI group (p=0.17 and p=0.31, respectively). Conclusion In ES-SCLC, intrathoracic progression was the most dominant failure pattern after immunotherapy. In the era of chemoimmunotherapy, consolidative TRT can still be considered a useful treatment strategy for locoregional control. [ABSTRACT FROM AUTHOR]

Background: The optimal timing of thoracic radiotherapy (TRT) in driver‐gene‐negative metastatic non‐small cell lung cancer (mNSCLC) patients was retrospectively investigated based on survival and safety profile. Methods: The efficacy and safety data of driver‐gene‐negative mNSCLC patients treated with TRT during maintenance after first‐line therapy was collected. Patients whose primary tumor and metastatic lesions remained no progression during maintenance and then received TRT were categorized as the NP (no progression) group, while patients who experienced slow progression during maintenance without reaching progressive disease and then received TRT were categorized as the SP (slow progression) group. The efficacy and adverse events of TRT were analyzed. Results: In total, 149 driver‐gene‐negative mNSCLC patients treated with TRT during maintenance were enrolled into the study, with 119 in the NP group and 30 in the SP group. After a median follow‐up of 30.83 (range: 26.62–35.04) months, the median progression‐free survival (PFS) in the NP group was 11.13 versus 9.53 months in the SP group (HR 0.599, p = 0.017). The median overall survival (OS) in the NP group was 32.27 versus 25.57 months in the SP group (HR 0.637, p = 0.088). The median PFS after radiotherapy (rPFS) was 6.33 versus 3.90 months (HR 0.288, p < 0.001). The adverse events were tolerable and manageable in both groups without significant difference (p > 0.05). Conclusion: The addition of TRT during the pre‐emptive no progression phase was associated with a significantly longer PFS than during the delayed slow progression phase and had an acceptable safety profile. Our results might support the earlier initiation of TRT after induction therapy for some patients with driver‐gene‐negative mNSCLC. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the outcomes of elderly patients with limited‐stage small cell lung cancer (LS‐SCLC), which may be linked to the timing of thoracic radiotherapy (TRT) following chemotherapy. Methods: Elderly patients (n = 78) with LS‐SCLC were divided into three groups depending on the timing of radiotherapy. The patients in the TRT group were stratified into early (TRT after 1–2 cycles of chemotherapy, n = 29), medium‐term (TRT after 3–4 cycles of chemotherapy, n = 33), and late (TRT after 5–6 cycles of chemotherapy, n = 16) TRT groups. The overall survival (OS) and progression‐free survival (PFS) were assessed and compared. Results: The medium‐term TRT group demonstrated significantly longer mPFS (20.12 months) and better mOS (35.97 months) than those in the other groups (PFS: P = 0.021;OS: P = 0.035). A pairwise comparison of the three groups revealed that those who received medium‐term TRT exhibited significantly improved PFS than the early (mPFS: 20.12 vs. 10.36 mouths, P = 0.018) and late (mPFS: 20.12 vs. 9.17 months, P = 0.016) TRT. The medium‐term TRT group demonstrated significantly improved OS than the early TRT (mOS: 35.97 vs. 25.22 months, P = 0.007) but not in comparison with the late TRT (mOS: 35.97 vs. 21.63 months, P = 0.100). Conclusion: In elderly patients with LS‐SCLC, the addition of TRT after 3–4 cycles of chemotherapy appears to be a viable and potentially beneficial treatment approach. [ABSTRACT FROM AUTHOR]

Background: Platinum-etoposide chemotherapy combined with immune checkpoint inhibitors (ICIs) has been recommended as the first-line standard treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, the effect of thoracic radiotherapy (TRT) on these patients is still unknown. This study aimed to evaluate the efficacy and safety of TRT for ES-SCLC patients who responded to first-line ICIs and chemotherapy (CHT). Methods: Patients who received 4 to 6 cycles of ICIs and CHT as first-line therapy at three hospitals between 2018 and 2022 were included in the analysis. All patients were divided into two groups based on whether they received TRT as first-line treatment, and propensity score matching (PSM) was performed to ensure that the characteristics of two groups were well-balanced. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was toxic effects. Results: A total of 276 patients were included, and the median follow-up time was 22.3 (range, 4.0-53.73) months. After PSM, 197 patients were further analysed, and 99 of whom received TRT. The baseline characteristics were well-balanced between patients in the TRT and non-TRT groups. There were significant differences in PFS between the TRT and non-TRT groups, with the median PFS of 10.76 and 7.63 months, respectively (P = 0.014). Significantly improved OS was observed in the TRT group (21.67 vs. 16.6 months, P = 0.009). In addition, the use of TRT was an independent prognostic factor for PFS and OS of ES-SCLC patients receiving ICIs plus CHT. In terms of safety, no significant increase of any grades adverse event (AE) (P = 0.874) and G3-4 AE (P = 0.909) was observed for patients receiving TRT. Radiation esophagitis, gastrointestinal and hematologic toxicities were the most common AEs in TRT group, which were tolerable. And high-dose radiotherapy was associated with higher incidence of pneumonitis. Conclusion: Addition of TRT showed significant survival benefits and well tolerability in ES-SCLC patients receiving platinum-etoposide CHT and ICIs, which could be a feasible first-line treatment strategy for ES-SCLC patients. [ABSTRACT FROM AUTHOR]

Abstract Background The CREST study showed that the addition of thoracic radiotherapy (TRT) could improve the survival rate in patients with extensive stage small cell lung cancer (ES-SCLC), but whether TRT can bring survival benefit in the era of immunotherapy remains controversial. This study aimed to explore the efficacy and safety of adding TRT to the combination of PD-L1 inhibitors and chemotherapy. Methods The patients who received durvalumab or atezolizumab combined with chemotherapy as the first-line treatment of ES-SCLC from January 2019 to December 2021 were enrolled. They were divided into two groups, based on whether they received TRT or not. Propensity score matching (PSM) with a 1:1 ratio was performed. The primary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results A total of 211 patients with ES-SCLC were enrolled, of whom 70 (33.2%) patients received standard therapy plus TRT as first-line treatment, and 141 (66.8%) patients in the control group received PD-L1 inhibitors plus chemotherapy. After PSM, a total of 57 pairs of patients were enrolled in the analysis. In all patients, the median PFS (mPFS) in the TRT and non-TRT group was 9.5 and 7.2 months, respectively, with HR = 0.59 (95%CI 0.39–0.88, p = 0.009). The median OS (mOS) in the TRT group was also significantly longer than that in the non-TRT group (24.1 months vs. 18.5 months, HR = 0.53, 95%CI 0.31–0.89, p = 0.016). Multivariable analysis showed that baseline liver metastasis and the number of metastases ≥ 3 were independent prognostic factors for OS. Addition of TRT increased the incidence of treatment-related pneumonia (p = 0.018), most of which were grade 1–2. Conclusions Addition of TRT to durvalumab or atezolizumab plus chemotherapy significantly improves survival in ES-SCLC. Although it may leads to increased incidence of treatment-related pneumonia, a majority of the cases can be relieved after symptomatic treatment.

The immunotherapy combined chemotherapy has been the standard treatment strategy for extensive-stage small lung cancer (ES-SCLC). The CREST trial reported consolidative thoracic radiotherapy (cTRT) improved overall survival (OS) for ES-SCLC with intrathoracic residual after chemotherapy. In this study, patients with ES-SCLC who received immunotherapy were assigned to receive either TRT or no TRT. TRT significantly improved progression-free survival (PFS), local recurrence-free survival (LRFS) and OS with well tolerated toxicity. Further sub-cohort analysis, TRT significantly improved LRFS in patients with oligo-metastasis and without liver metastasis. [ABSTRACT FROM AUTHOR]

Background: Prior research suggests that cardiovascular autonomic dysfunction might be an early marker of cardiotoxicity induced by antitumor treatment and act as an early predictor of cardiovascular disease-related morbidity and mortality. The impact of thoracic radiotherapy on the parasympathetic and sympathetic nervous systems, however, remains unclear. Therefore, this study aimed to evaluate the short-term effects of thoracic radiotherapy on the autonomic nervous system, using deceleration capacity (DC), acceleration capacity (AC) of heart rate, and heart rate variability (HRV) as assessment tools. Methods: A 5 min electrocardiogram was collected from 58 thoracic cancer patients before and after thoracic radiotherapy for DC, AC, and HRV analysis. HRV parameters employed included the standard deviation of the normal-normal interval (SDNN), root mean square of successive interval differences (RMSSD), low frequency power (LF), high frequency power (HF), total power (TP), and the LF to HF ratio. Some patients also received systemic therapies alongside radiotherapy; thus, patients were subdivided into a radiotherapy-only group (28 cases) and a combined radiotherapy and systemic therapies group (30 cases) for additional subgroup analysis. Results: Thoracic radiotherapy resulted in a significant reduction in DC (8.5 [5.0, 14.2] vs. 5.3 [3.5, 9.4], p = 0.002) and HRV parameters SDNN (9.9 [7.03, 16.0] vs. 8.2 [6.0, 12.4], p = 0.003), RMSSD (9.9 [6.9, 17.5] vs. 7.7 [4.8, 14.3], p = 0.009), LF (29 [10, 135] vs. 24 [15, 50], p = 0.005), HF (35 [12, 101] vs. 16 [9, 46], p = 0.002), TP (74 [41, 273] vs. 50 [33, 118], p < 0.001), and a significant increase in AC (-8.2 [-14.8, -4.9] vs. -5.8 [-10.1, -3.3], p = 0.003) and mean heart rate (79.8 ± 12.6 vs. 83.9 ± 13.6, p = 0.010). Subgroup analysis indicated similar trends in mean heart rate, DC, AC, and HRV parameters (SDNN, RMSSD, LF, HF, TP) in both the radiotherapy group and the combined treatment group post-radiotherapy. No statistically significant difference was noted in the changes observed in DC, AC, and HRV between the two groups pre- and post-radiotherapy. Conclusion: Thoracic radiotherapy may induce cardiovascular autonomic dysfunction by reducing parasympathetic activity and enhancing sympathetic activity. Importantly, the study found that the concurrent use of systemic therapies did not significantly amplify or contribute to the alterations in autonomic function in the short-term following thoracic radiotherapy. DC, AC and HRV are promising and feasible biomarkers for evaluating autonomic dysfunction caused by thoracic radiotherapy. [ABSTRACT FROM AUTHOR]

The improvement in treatment strategies and outcomes in small cell lung cancer (SCLC) has lagged behind other cancers. The addition of immune checkpoint inhibitors (ICIs), durvalumab and atezolizumab, to the platinum-based chemotherapy in frontline setting has improved the survival in extensive stage SCLC, (ES-SCLC), albeit modestly, and is now the new standard of care. Prior to advent of immunotherapy into the therapeutic armamentarium in ES-SCLC, consolidative thoracic radiotherapy (TRT) was associated with improved thoracic control and survival outcomes. In the era of ICIs, the role of TRT is not well defined, chiefly because TRT was not incorporated in any immunotherapy trials, secondly due to concerns regarding the increased risks of pneumonitis, and finally uncertain magnitude of benefit with this combined approach. In principle, radiation can increase in the immunogenicity of tumor and hence the activity of immune checkpoint blockade, thereby increasing efficacy both locally and distantly. Such an approach has been promising in non-small cell lung cancer with ICIs improving outcomes after concurrent chemoradiation, but remains unanswered in ES-SCLC. It is, thus, possible that the modest improvement in survival by addition of ICIs to chemotherapy in ES-SCLC can be further improved by the incorporation of consolidative TRT in selected patients. Several early phase trials and retrospective studies have suggested that such an approach may be feasible and safe. Prospective trials are ongoing to answer whether adding radiation therapy to chemoimmunotherapy will improve outcomes in ES-SCLC. [ABSTRACT FROM AUTHOR]

BackgroundWe conducted a 2-part study to evaluate the incorporation of veliparib, a PARP inhibitor, into chemoradiotherapy (CRT) for stage III non-small-cell lung cancer.Patients and methodsIn the phase I part, patients were treated successively at 3 dose levels of veliparib (40, 80, and 120 mg) twice daily during CRT. In the phase II part, patients were randomized to receive veliparib or placebo during thoracic radiotherapy with concurrent weekly carboplatin and paclitaxel, followed by 2 cycles of consolidation carboplatin and paclitaxel with veliparib or placebo. The study was prematurely discontinued owing to the emergence of adjuvant immunotherapy as standard of care.ResultsOf 21 patients enrolled in phase I, 2 patients developed dose-limiting toxicities (DLTs): 1 grade 3 esophagitis with dysphagia (at 40 mg) and 1 grade 3 esophagitis with dehydration (at 80 mg). No DLTs were seen at veliparib dose of 120 mg twice daily, which was selected for the phase II part that enrolled 31 eligible patients. Progression-free survival (PFS) was not different between the 2 arms (P = .20). For the veliparib and placebo arms, response rates were 56% and 69%, PFS at 1 year 47% and 46%, and overall survival at 1 year 89% and 54%, respectively.ConclusionVeliparib with CRT was feasible and well tolerated. Efficacy could not accurately be determined because of early study closure. Nonetheless, there is enthusiasm for the evaluation of PARP inhibitors in lung cancer as predictive biomarkers are being developed and combinations with immunotherapy are attractive.

Fengchun Mu,1,2,&ast; Bingjie Fan,1,&ast; Butuo Li,1 Wenru Qin,1 Haoqian Li,1,2 Chunni Wang,1 Bing Zou,1 Shijiang Wang,1 Linlin Wang1 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China; 2Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 271016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linlin Wang, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China, Tel +86-531-67626142, Fax +86-531-67626141, Email wanglinlinatjn@163.comPurpose: The present study aimed to evaluate the incidence rate of radiation pneumonitis (RP) in patients with advanced lung adenocarcinoma treated with first-generation (1G), second-generation (2G), or third-generation (3G) epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with thoracic radiotherapy (TRT).Patients and Methods: Patients with advanced lung adenocarcinoma simultaneously treated with 1G/2G/3G EGFR-TKIs and TRT between 2015– 2021 at Shandong Cancer Hospital and Institute were screened. The incidence rate of clinical and imaging RP was compared between the three groups.Results: A total of 200 patients treated with EGFR-TKIs were enrolled in this study, including 100 patients who were treated with 1G EGFR-TKIs, 50 patients who were treated with 2G EGFR-TKIs, and 50 patients who were treated with 3G EGFR-TKIs (patients matched in a 2:1:1 ratio for tumor characteristics). The overall incidence of clinical RP in the 1G, 2G, and 3G EGFR-TKI groups were 29%, 48%, and 28% (p=0.043), respectively, and that of imaging RP were 33%, 58%, and 36% (p=0.010), respectively. The incidence of RP with a clinical grade ≥ 3 in the three groups were 14%, 28%, and 12% (p=0.055), respectively, and that with an imaging grade ≥ 3 in the three groups were 11%, 32%, and 10% (p=0.002), respectively. The incidence of clinical RP was higher in the CFRT group than in the SBRT group, with an overall clinical grade of 38% vs 10% (p< 0.001) and imaging grade of 46% vs 10% (p< 0.001), respectively. In the multivariate analysis, only GTV volume was an independent predictive factor for all risks of clinical and imaging RP. V20 and grouping of 1G/2G/3G EGFR-TKIs were other independent predictive factors for the risk factors of RP for imaging grades.Conclusion: Compared with 2G EGFR-TKIs combined with TRT, 1G or 3G EGFR-TKIs combined with TRT achieved a lower incidence of RP.Keywords: EGFR-TKI, molecular targeted therapy, radiation pneumonitis, thoracic radiotherapy, lung adenocarcinoma

Background: The CREST study showed that the addition of thoracic radiotherapy (TRT) could improve the survival rate in patients with extensive stage small cell lung cancer (ES-SCLC), but whether TRT can bring survival benefit in the era of immunotherapy remains controversial. This study aimed to explore the efficacy and safety of adding TRT to the combination of PD-L1 inhibitors and chemotherapy. Methods: The patients who received durvalumab or atezolizumab combined with chemotherapy as the first-line treatment of ES-SCLC from January 2019 to December 2021 were enrolled. They were divided into two groups, based on whether they received TRT or not. Propensity score matching (PSM) with a 1:1 ratio was performed. The primary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results: A total of 211 patients with ES-SCLC were enrolled, of whom 70 (33.2%) patients received standard therapy plus TRT as first-line treatment, and 141 (66.8%) patients in the control group received PD-L1 inhibitors plus chemotherapy. After PSM, a total of 57 pairs of patients were enrolled in the analysis. In all patients, the median PFS (mPFS) in the TRT and non-TRT group was 9.5 and 7.2 months, respectively, with HR = 0.59 (95%CI 0.39–0.88, p = 0.009). The median OS (mOS) in the TRT group was also significantly longer than that in the non-TRT group (24.1 months vs. 18.5 months, HR = 0.53, 95%CI 0.31–0.89, p = 0.016). Multivariable analysis showed that baseline liver metastasis and the number of metastases ≥ 3 were independent prognostic factors for OS. Addition of TRT increased the incidence of treatment-related pneumonia (p = 0.018), most of which were grade 1–2. Conclusions: Addition of TRT to durvalumab or atezolizumab plus chemotherapy significantly improves survival in ES-SCLC. Although it may leads to increased incidence of treatment-related pneumonia, a majority of the cases can be relieved after symptomatic treatment. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the impact of treatment time and patterns in inoperable stage III non-small cell lung cancer (NSCLC) following concurrent chemoradiotherapy (cCRT) ± immune checkpoint inhibitors (ICIs). Methods: Patients were stratified by treatment year: A (2011–2014), B (2015–2017) and C (2018–2020). Tumor- and treatment-related characteristics regarding locoregional recurrence-free survival (LRRFS), progression-free survival (PFS) and overall survival (OS) were investigated. Results: One hundred and thirty-six consecutive patients were analyzed. All patients completed thoracic radiotherapy (TRT) to a total dose ≥ 60.0 Gy; 36 (26%) patients received ICI. Median PFS in subgroups A, B and C was 8.0, 8.2 and 26.3 months (p = 0.007). Median OS was 19.9 months, 23.4 months and not reached (NR), respectively. In group C, median LRRFS and PFS were 27.2 vs. NR; and 14.2 vs. 26.3 months in patients treated with and without ICI. On multivariate analysis planning target volume (PTV) ≥ 700 cc was a negative prognosticator of LRRFS (HR 2.194; p = 0.001), PFS (HR 1.522; p = 0.042) and OS (HR 2.883; p = 0.001); ICI was a predictor of LRRFS (HR 0.497; p = 0.062), PFS (HR 0.571; p = 0.071) and OS (HR 0.447; p = 0.1). In the non-ICI cohort, multivariate analyses revealed PTV ≥ 700 cc (p = 0.047) and a maximum standardized uptake value (SUVmax) ≥ 13.75 (p = 0.012) were predictors of PFS; PTV ≥ 700 cc (p = 0.017), SUVmax ≥ 13.75 (p = 0.002) and a total lung V20 ≥ 30% (V20 ≥ 30) (p < 0.05) were predictors of OS. Conclusions: Patients treated after 2018 had improved survival regardless of ICI use. Implementation of ICI resulted in further significant increase of all tested survival endpoints. PTV ≥ 700 cc and ICI were only prognosticators for LRRFS, PFS and OS in the analyzed cohort. [ABSTRACT FROM AUTHOR]

Simple Summary: Around 30% of patients with stage III non-small cell lung cancer (NSCLC) receiving radical chemoradiotherapy will develop symptomatic brain metastases (BM) during the disease course. Identifying risk factors for BM can help improve the management of these patients. The aim of this current study was to identify clinical risk factors, including gross tumor volume (GTV) radiomics features, for developing BM in patients with radically treated stage III NSCLC. We found that age, NSCLC subtype, and GTV of lymph nodes (GTVn) were significant factors for BM. GTVn radiomics features provided higher predictive value than GTV of primary tumor (GTVp) and GTV. Therefore, GTVp and GTVn should be separated in clinical and research practice. Purpose: To identify clinical risk factors, including gross tumor volume (GTV) and radiomics features, for developing brain metastases (BM) in patients with radically treated stage III non-small cell lung cancer (NSCLC). Methods: Clinical data and planning CT scans for thoracic radiotherapy were retrieved from patients with radically treated stage III NSCLC. Radiomics features were extracted from the GTV, primary lung tumor (GTVp), and involved lymph nodes (GTVn), separately. Competing risk analysis was used to develop models (clinical, radiomics, and combined model). LASSO regression was performed to select radiomics features and train models. Area under the receiver operating characteristic curves (AUC-ROC) and calibration were performed to assess the models' performance. Results: Three-hundred-ten patients were eligible and 52 (16.8%) developed BM. Three clinical variables (age, NSCLC subtype, and GTVn) and five radiomics features from each radiomics model were significantly associated with BM. Radiomic features measuring tumor heterogeneity were the most relevant. The AUCs and calibration curves of the models showed that the GTVn radiomics model had the best performance (AUC: 0.74; 95% CI: 0.71–0.86; sensitivity: 84%; specificity: 61%; positive predictive value [PPV]: 29%; negative predictive value [NPV]: 95%; accuracy: 65%). Conclusion: Age, NSCLC subtype, and GTVn were significant risk factors for BM. GTVn radiomics features provided higher predictive value than GTVp and GTV for BM development. GTVp and GTVn should be separated in clinical and research practice. [ABSTRACT FROM AUTHOR]

Abstract In lung squamous cell carcinoma, KEAP1 mutations frequently coexist with TP53 mutations. A preclinical model showed that mutations leading to the activation of the KEAP1–NRF2 pathway contribute to clinical radioresistance. However, there have been few clinical reports on the association between the presence of KEAP1 and TP53 mutations in patients with lung squamous cell carcinoma. Here, we report the case of a 62‐year‐old patient with advanced lung squamous cell carcinoma with KEAP1 and TP53 mutations who experienced primary resistance to thoracic radiotherapy. She was administered pembrolizumab in combination with cytotoxic agents as the first‐line treatment and the best response was a partial response. However, the mediastinal lymph node metastases regrew 11 months after the chemotherapy. Thus, she received thoracic radiation therapy for localized lesions. However, the lesions within the radiation field had apparently progressed. Although she received subsequent chemotherapy, the lesion rapidly progressed. Treatment strategies including radiotherapy based on genetic stratification, such as KEAP1 and TP53 mutation status, should be implemented for lung squamous cell carcinoma.

Abstract Background Recently, the combination of the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab with first-line chemotherapy has demonstrated to improve outcome for patients with advanced small cell lung cancer (SCLC), leading to approval of this regimen. At the same time, accumulating (pre-)clinical data suggest synergisms of radiotherapy and immunotherapy via the radiation-mediated induction of anti-tumor immunogenicity. Combining the recent findings, the TREASURE trial aims at further enhancing response to upfront chemo-immunotherapy by the addition of thoracic radiotherapy (TRT). Methods/design The TREASURE trial is a randomized, multicenter, phase II clinical trial ( ClinicalTrials.gov identifier, NCT04462276). One hundred four patients suffering from extensive disease (ED) SCLC, with any response to the standard of care induction chemo-immunotherapy will be randomized to receive atezolizumab maintenance therapy with or without TRT. The primary endpoint of this study is overall survival (OS). Secondary endpoints include further measures of efficacy, safety, and the collection of biomarker samples. A safety interim analysis will take place after n = 23 patients receiving TRT have been observed for three months after the end of TRT. Discussion This trial will investigate whether treatment efficacy can be improved by adding TRT to atezolizumab maintenance therapy in ED SCLC patients with any response after chemo-immunotherapy. Safety and feasibility of such a regimen will be evaluated, and biomaterials for a translational research project will be collected. Together, the results of this trial will deepen our comprehension of how checkpoint inhibition and radiotherapy interact and contribute to the evolving landscape of SCLC therapy. Trial registration Clinicaltrials.gov identifier: NCT04462276 (Date of initial registration: 8th July 2020), https://clinicaltrials.gov/ct2/show/NCT04462276 Eudra-CT Number: 2019-003916-29 (Date of initial registration: 30th March 2020), https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-003916-29/DE

Background/Aim: Non-small-cell lung cancer (NSCLC) not amenable to curative treatment can be managed with palliative thoracic radiation or chemoradiation, however, with variable success. This study evaluated the prognostic impact of the LabBM score [serum lactate dehydrogenase (LDH), C-reactive protein, albumin, hemoglobin, platelets] in 56 patients who were scheduled to receive at least 10 fractions of 3 Gy. Patients and Methods: Uni- and multivariate analyses of prognostic factors for overall survival were employed in a retrospective singleinstitution study of stage II and III NSCLC. Results: The first multivariate analysis showed that hospitalization in the month before radiotherapy (p<0.001), concomitant chemoradiotherapy (p=0.03), and LabBM point sum (p=0.09) were the leading predictors of survival. A second model with individual blood tests rather than the sum score suggested that concomitant chemoradiotherapy (p=0.002), hemoglobin (p=0.01), LDH (p=0.04), and hospitalization before radiotherapy (p=0.08) played important roles. Surprisingly long survival was seen in patients without prior hospitalization who received concomitant chemoradiotherapy and had favorable LabBM score (0-1 points): median 24 months, 5-year rate 46%. Conclusion: Blood biomarkers provide relevant prognostic information. The LabBM score has 1) previously been validated in patients with brain metastases and 2) demonstrated encouraging results in a cohort irradiated for different palliative non-brain indications, e.g., bone metastases. It might be helpful in predicting survival in patients with nonmetastatic cancer, e.g., NSCLC stage II and III. [ABSTRACT FROM AUTHOR]

To assess the risk of cardiac toxicity following radical radiotherapy in advanced lung cancer patients. Patients with a diagnosis of stage III non-small cell lung cancer (NSCLC) receiving chemoradiotherapy were extracted from a population-based cohort in Ontario, Canada. The primary outcome of cardiac toxicity, defined as cardiac events or congestive heart failure, was assessed at 1 and 5 years following chemoradiotherapy. Secondary outcomes included overall survival, survival in relationship to post-treatment cardiac events and the effect of radiotherapy technique on cardiac toxicity. In total, 2031 NSCLC patients were included. The cumulative incidence of cardiac toxicity at 5 years was 20.3% (18.4–22.3). The median survival was 13.7 months in NSCLC patients who had a cardiac event post-chemoradiotherapy compared with 23.4 months in those who did not (P = 0.012). There was a trend towards increased cumulative cardiac toxicity (hazard ratio 3.37, P = 0.14) with three-dimensional conformal radiotherapy compared with intensity-modulated or volumetric arc radiotherapy techniques. The risk of cardiac events and congestive heart failure 5 years after radical thoracic radiotherapy appears high and survival is inferior at 1 year in those patients who experience a cardiac event post-treatment. More conformal radiotherapy techniques may help reduce cardiac toxicity. Further studies should investigate adaptive treatment planning and close monitoring and intervention in this high-risk group after chemoradiotherapy. • There may be an elevated risk of cardiac disease following radiotherapy for NSCLC. • The risk of death may be higher in patients who experience cardiac events after treatment for NSCLC. • Increasing age and male sex may also confer increased cardiac disease risk in NSCLC patients. • Treatment technique may have the potential to modify cardiac risk. [ABSTRACT FROM AUTHOR]

Introduction: Active Breathing Control (ABC) is a motion management strategy that facilitates reproducible breath-hold for thoracic radiotherapy (RT), which may reduce radiation dose to organs at risk (OARs). Reduction of radiation-induced toxicity is of high importance in younger patients. However, there is little published literature on the feasibility of ABC in this group. The purpose of this study was to report our experience of using ABC for paediatric and teenage patients. Methods: Patients ≤18 years referred for thoracic RT using ABC at our centre from 2013–2021 were identified. Electronic records were retrospectively reviewed to obtain information on diagnosis, RT dose and technique, OAR dosimetry, tolerability of ABC, post-treatment imaging and early toxicity rates. Results: 12 patients completed RT and were able to comply with ABC during planning and for the duration of RT. Median age was 15.5 years (10–18 years). Diagnoses were: Hodgkin lymphoma (n = 5), mediastinal B-cell lymphoma (n = 1), Ewing sarcoma (n = 5) and rhabdomyosarcoma (n = 1). For mediastinal RT cases (n = 6), median dose delivered was 30.6Gy(19.8–40Gy), median mean heart dose was 11.4Gy(4.8–19.4Gy), median mean lung dose was 9.9Gy(5.7–14.5Gy) and mean lung V20 was 10.9%. For ipsilateral RT cases, (n = 6), median hemithorax and total doses to primary tumour were 18Gy(15–20Gy) and 52.2Gy(36–60Gy) respectively. Median mean heart dose was 19.5Gy(10.6–33.2Gy) and median mean lung dose was 17.7Gy(16.3–30.5Gy). Mean bilateral lung V20 was 39.6%. Median mean contralateral lung dose was 5.2Gy(3.5–11.6Gy) and mean contralateral lung V20 was 1.5%. At a median follow-up of 36 months, only 1 patient had symptomatic radiation pneumonitis having received further thoracic RT following relapse. Conclusions: ABC is feasible and well tolerated in younger patients receiving RT. Children as young as 10 years are able to comply. Use of ABC results in OAR dosimetry which is comparable to similar data in adults and can facilitate RT for extensive thoracic sarcoma

In lung squamous cell carcinoma, KEAP1 mutations frequently coexist with TP53 mutations. A preclinical model showed that mutations leading to the activation of the KEAP1–NRF2 pathway contribute to clinical radioresistance. However, there have been few clinical reports on the association between the presence of KEAP1 and TP53 mutations in patients with lung squamous cell carcinoma. Here, we report the case of a 62‐year‐old patient with advanced lung squamous cell carcinoma with KEAP1 and TP53 mutations who experienced primary resistance to thoracic radiotherapy. She was administered pembrolizumab in combination with cytotoxic agents as the first‐line treatment and the best response was a partial response. However, the mediastinal lymph node metastases regrew 11 months after the chemotherapy. Thus, she received thoracic radiation therapy for localized lesions. However, the lesions within the radiation field had apparently progressed. Although she received subsequent chemotherapy, the lesion rapidly progressed. Treatment strategies including radiotherapy based on genetic stratification, such as KEAP1 and TP53 mutation status, should be implemented for lung squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: Curative thoracic radiotherapy (CTRT) with concurrent chemotherapy has been considered as standard treatment approach for stage-III non-small cell lung cancer (NSCLC). The hematological and esophageal toxicities that have been encountered during CTRT would affect the immunonutritional status of the patients. The aim of this study is to evaluate the prognostic value of the change in pre- and post-treatment prognostic nutritional index (PNI) in stage-III NSCLC patients. Methods: Eighty seven consecutive stage III NSCLC patients' data were collected. Pre-radiotherapy (RT) and post-RT PNI values were calculated and the impact of prognostic value of PNI change on overall survival (OS) was evaluated by univariate and multivariate Cox regression analyses. A cutoff value of PNI change was obtained by receiver operator characteristic (ROC) curve analysis. Results: The cutoff value was found to be a 22% decrease in PNI by ROC curve analysis in terms of effect on OS. The median OS of low and high PNI decrease groups were 22.5 and 16.5 months respectively (P = 0,001). In univariate and multivariate analyses PNI decrease of = 22% was found to be an independent poor prognostic factor for OS (P = 0.012) and hazard ratio (95% confidence interval)= 2.05 (1.16-3.62). Conclusion: The PNI change would be a convenient parameter to assess the immunonutritional status of the patient at the end of CTRT. A decrease of more than 22% of PNI value may predict poor prognosis. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the prognostic potential of the pre-radiotherapy systemic immune-inflammation index (SII) for the survival of advanced lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutations, which might provide a basis for optimizing the comprehensive treatment scheme. Methods: A total of 111 lung adenocarcinoma patients with EGFR mutations, who received thoracic radiotherapy, were included in this retrospective study. The primary endpoint of the study was based on the overall survival (OS) of patients. The receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value of each immune inflammation index. Kaplan–Meier analysis was performed for the comparison of OS. The Cox proportional-hazard model was used for the multivariate and univariate regression analyses to determine the correlations of prognostic factors with the disease. Results: SII was divided into the high SII group (≥ 620.2; 45.95%) and the low SII group (SII < 620.2; 54.05%) based on the optimal cutoff values. The median OS rates were 53.3 and 33.3 months in the low and high SII groups, respectively, showing statistically significant differences (hazard ratio (HR) = 0.459; 95% CI 0.286–0.736; P < 0.001). The multivariate analysis showed that, after adjusting for the significant covariates, the SII values were independently associated with the improved OS of the patients (adjusted HR = 0.444; 95% CI 0.279–0.709; P = 0.001). The low NLR values were associated with the better OS of patients (HR = 0.509; 95% CI 0.326–0.792; P = 0.005) and vice versa (HR = 0.422; 95% CI 0.213–0.836; P < 0.001). The patients in the low LMR group before radiotherapy exhibited longer OS as compared to those in the high LMR group (HR = 0.497; 95% CI 0.308–0.802; P = 0.001). Conclusions: This study showed that these inflammatory indices might have an important prognostic potential for advanced lung adenocarcinoma patients with EGFR mutations, receiving thoracic radiotherapy and might provide a basis for the individualized treatment of these patients. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE. 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). METHODS. 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. RESULTS. 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. CONCLUSIONS. 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. [ABSTRACT FROM AUTHOR]

Thoracic radiotherapy decisions in patients with interstitial lung disease (ILD) are complex due to concerns about severe or even fatal radiation pneumonitis. This systematic review analysed the published evidence regarding the incidence of radiation pneumonitis and mortality after thoracic radiotherapy and investigated clinical and dosimetric predictors of radiation pneumonitis in lung cancer patients with ILD. A systematic search was carried out in PubMed, Medline, Embase and the Cochrane database for articles published between January 2000 and April 2021. Two authors independently screened eligible studies that met our predefined criteria. Studies were assessed for design and quality and a qualitative data synthesis was carried out. The search strategy resulted in 1750 articles. After two rounds of screening, 24 publications were included. The median overall incidence of grade ≥3 radiation pneumonitis was 19.7% (range 8–46%). The incidence was greater in conventional radical radiotherapy-treated patients (median 31.8%) compared with particle beam therapy- or stereotactic ablative radiotherapy-treated patients (median 12.5%). The median rate of grade 5 radiation pneumonitis was 11.9% (range 0–60%). The presence of ILD was an independent predictor of severe radiation pneumonitis. Severe radiation pneumonitis was more common in the presence of usual interstitial pneumonia (UIP) pattern or idiopathic pulmonary fibrosis (IPF) than non-UIP or non-IPF subtype. Several other clinical predictors were reported in the literature. V5, V10, V20 and mean lung dose were the most common dosimetric predictors for severe radiation pneumonitis, often with stricter dose constraints than conventionally used. Patients with lung cancer associated with ILD had a poorer overall survival compared with patients without ILD. In conclusion, patients with lung cancer associated with ILD have a poor prognosis. They are at high risk of severe and even fatal radiation pneumonitis. Careful patient selection is necessary, appropriate high-risk consenting and strict lung dose-volume constraints should be used, if these patients are to be treated with thoracic radiotherapy. • Patients with lung cancer associated with ILD have a poor prognosis. • They are at increased risk of severe and even fatal radiation pneumonitis. • Patients must be counselled and appropriately consented regarding the increased risks when planning thoracic radiotherapy. • Careful patient selection & strict lung dose volume constraints should be chosen if treated with thoracic radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Small cell lung cancer (SCLC) is characterized by a high risk of brain metastasis and poor survival. This study aims to assess the prognostic role of lactate dehydrogenase (LDH) in limited-stage small cell lung cancer (LS-SCLC) treated with thoracic radiotherapy (TRT) and prophylactic cranial irradiation (PCI).Methods: This study retrospectively evaluated 197 consecutive patients who underwent TRT and PCI for LS-SCLC between November 2005 and October 2017. Both pretreatment and maximal serum LDH levels (mLDH) during treatment were checked, and an increased LDH level was defined as more than 240 IU/ml. Clinical factors were tested for associations with intracranial progression-free survival (IPFS) and overall survival (OS) after PCI. The Kaplan-Meier method was used to calculate survival rates, and multivariate Cox regression analyses were carried out to identify variables associated with survival.Results: Of the total patients, 28 had higher pretreatment LDH levels and mLDH levels were increased in 95 patients during treatment. In patients in the normal and elevated mLDH groups, the 1‑, 2‑, and 5‑year IPFS rates were 96.7% vs. 90.1%, 91.7% vs. 73.8%, and 87.8% vs. 61.0% (P < 0.01), respectively. Compared to those with normal LDH levels, patients with increased mLDH levels had a higher cumulative risk of intracranial metastasis (hazard ratio [HR] 3.87; 95% confidence interval [CI] 1.73-8.63; P < 0.01) and worse overall survival (HR 2.59; 95% CI 1.67-4.04; P < 0.01). The factors LDH level at baseline or changes between pretreatment level and maximum level during treatment failed to predict brain metastases or OS with statistical significance. In the multivariate analyses, both mLDH during treatment (HR 3.53; 95% CI 1.57-7.92; P = 0.002) and patient age ≥ 60 (HR 2.46; 95% CI 1.22-4.94; P = 0.012) were independently associated with worse IPFS. Factors significantly associated with worse OS included mLDH during treatment (HR 2.45; 95% CI 1.56-3.86; P < 0.001), IIIB stage (HR 1.75; 95% CI 1.06-2.88; P = 0.029), and conventional radiotherapy applied in TRT (HR 1.66; 95% CI 1.04-2.65; P = 0.034).Conclusion: The mLDH level during treatment predicts brain metastasis and survival in LS-SCLC patients treated with TRT and PCI, which may provide valuable information for identifying patients with poor survival outcomes and possible candidates for treatment intensification. [ABSTRACT FROM AUTHOR]

Background: Therapies based on the combination of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) are transforming the treatment landscape of esophageal cancer. Nevertheless, the available data on adverse events (AEs) mainly stemmed from several prospective clinical trials and retrospective studies, in which, AE data are often handled and reported with less rigor than the primary beneficial outcomes of the study. Thus, we conducted a systematic review to investigate the toxicity spectrum of these novel regimens. Method: We searched for all prospective clinical trials investigating the role of ICIs combined with TRT published between January 2010 and August 2022. Study articles and conference proceedings involving esophageal cancers and reporting the overall incidence or details of treatment-related AEs (trAEs) were synthesized to determine the toxicity profile of combination treatment. We compared trAEs between cancer type, programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, and between sequential and concurrent administration of ICIs and TRT to identify potentially high-risk patients. Results: We obtained toxicity data from 14 clinical trials involving 863 patients. The pooled overall incidence was 88.97% for any-grade trAEs and 18.48% for high-grade trAEs. The three most frequent non-hematologic any-grade trAEs were reactive cutaneous capillary endothelial proliferation (RCCEP, 63.80%), esophagitis (51.54%), and fatigue (33.63%). Meanwhile, RCCEP (15.69%) was the most common non-hematologic high-grade trAE, followed by nausea (4.91%) and anorexia (3.81%). The occurrence rates of any-grade and high-grade pneumonitis were 10.82% and 0.66%, respectively. In subgroup analysis, the toxicity profiles of PD-1 and PD-L1 inhibitors were mostly similar, except for any-grade pneumonitis (15.20% vs 4.88%, p=0.03) and high-grade leukopenia (6.25% vs 59.09%, p=0.00). In addition, concurrent treatment seemed to have a higher incidence of any-grade trAEs (95.20% vs 70.85%, p=0.03) compared with sequential treatment. ESCC seems to have higher incidence of any-grade hypothyroidism (22.55% vs 8.96%, p=0.049) compared to EAC. Conclusion: Our study is the first systematic review to provide a toxicity profile of trAEs in esophageal cancer patients who received ICIs combined with TRT. Most AEs of this combination treatment are tolerable, although the incidence of any-grade trAEs was higher in the concurrent group. The difference in anygrade pneumonitis between PD-1 and PD-L1 inhibitor groups needs further validation in a large clinical trial. [ABSTRACT FROM AUTHOR]

Abstract Introduction Online MR-guided radiotherapy (MRgRT) is a relatively novel advancement in the field of radiation oncology, ensuring superior soft-tissue visualisation, allowing for online plan adaptation to anatomical and functional interfractional changes and improved motion management. Platinum-based chemoradiation followed by durvalumab is the recommended treatment for stage IIB(N1)/III NSCLC. However, this is only the case for patients with favourable risk factors and sufficient pulmonary function and reserve. Methods Herein, we present a technical report on tumour motion and breathing curve analyses of the first patient with node-positive stage IIB NSCLC and severely compromised pulmonary function and reserve [total lung capacity (TLC) 8.78L/132% predicted, residual volume (RV) 6.35L/271% predicted, vital capacity (VC) max 2.43L/58% predicted, FEV1 1.19L/38% predicted, DLCO-SB corrected for hemoglobin 2.76 mmol/min/kPa/30% predicted] treated in a prospective observational study with moderately hypofractionated MRgRT to a total dose of 48.0 Gy/16 daily fractions on the MRIdian system (Viewray Inc, Oakwood, USA). Results Radiotherapy was well tolerated with no relevant toxicity. First follow-up imaging at 3 months post-radiotherapy showed a partial remission. The distinctive features of this case are the patient’s severely compromised pulmonary function and the first online MR-guided accelerated hypofractionated radiotherapy treatment for primary node-positive NSCLC. Conclusions This technical report describes the first patient treated in a prospective observational study evaluating the feasibility of this relatively novel technology in stage IIB(N1)/III disease, proposing a clinical pathway for the management of high-risk patients.

The etiology of radiation-induced pulmonary fibrosis is not clearly understood yet, and effective interventions are still lacking. This study aimed to identify genes responsive to irradiation and compare the genome expression between the normal lung tissues and irradiated ones, using a radiation-induced pulmonary fibrosis mouse model. We also aimed to map the mRNA alterations as a predictive model and a potential mode of intervention for radiation-induced pulmonary fibrosis. Thirty C57BL/6 mice were exposed to a single dose of 16 Gy or 20 Gy thoracic irradiation, to establish a mouse model of radiation-induced pulmonary fibrosis. Lung tissues were harvested at 3 and 6 months after irradiation, for histological identification. Global gene expression in lung tissues was assessed by RNA sequencing. Differentially expressed genes were identified and subjected to functional and pathway enrichment analysis. Immune cell infiltration was evaluated using the CIBERSORT software. Three months after irradiation, 317 mRNAs were upregulated and 254 mRNAs were downregulated significantly in the low-dose irradiation (16 Gy) group. In total, 203 mRNAs were upregulated and 149 were downregulated significantly in the high-dose irradiation (20 Gy) group. Six months after radiation, 651 mRNAs were upregulated and 131 were downregulated significantly in the low-dose irradiation group. A total of 106 mRNAs were upregulated and 4 downregulated significantly in the high-dose irradiation group. Several functions and pathways, including angiogenesis, epithelial cell proliferation, extracellular matrix, complement and coagulation cascades, cellular senescence, myeloid leukocyte activation, regulation of lymphocyte activation, mononuclear cell proliferation, immunoglobulin binding, and the TNF, NOD-like receptor, and HIF-1 signaling pathways were significantly enriched in the irradiation groups, based on the differentially expressed genes. Irradiation-responsive genes were identified. The differentially expressed genes were mainly associated with cellular metabolism, epithelial cell proliferation, cell injury, and immune cell activation and regulation. [ABSTRACT FROM AUTHOR]

OBJECTIVE The purpose of the study was to evaluate the treatment field deviations in lung cancer patients treated with thoracic radiotherapy (RT) performed using different immobilization devices into three different set-up positions and the influencing factors. METHODS Thirty lung cancer patients having palliative thoracic RT indication were randomized into three different set-up positions using different immobilization devices (Group I: arm along the body, Group II: lung board, and Group III: arm supported board). The treatment field center deviation was measured on sternal (X and Y axis) and axillary (z and θ axis) cross. In addition, parameters such as age, pain, pulmonary function test, set-up time, the temperature difference between the treatment room and the outside environment, and patient education level that may cause set-up were evaluated. RESULTS Mean intra-fraction field center deviations of 5.66±4.15 mm were observed in the right (z) axis (p=0.049) and 5.53±4.81 mm in the left (z) axis (p=0.015) in Group II which were statistically significantly larger than the deviations in other groups. A statistically significant correlation was found between the indoor and outdoor temperature difference and set-up time. CONCLUSION Both set-up positions of Groups I and III, gave better results than the position of Group II. According to our results, if a lung board will be used, adding the arm supporting accessory will be necessary. Random errors can be minimized and the set-up quality improved by using appropriate immobilization devices, minimizing the total set-up time and balancing the in and outdoor temperature by air conditioning system. [ABSTRACT FROM AUTHOR]

Background: Recently, the combination of the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab with first-line chemotherapy has demonstrated to improve outcome for patients with advanced small cell lung cancer (SCLC), leading to approval of this regimen. At the same time, accumulating (pre-)clinical data suggest synergisms of radiotherapy and immunotherapy via the radiation-mediated induction of anti-tumor immunogenicity. Combining the recent findings, the TREASURE trial aims at further enhancing response to upfront chemo-immunotherapy by the addition of thoracic radiotherapy (TRT).Methods/design: The TREASURE trial is a randomized, multicenter, phase II clinical trial ( ClinicalTrials.gov identifier, NCT04462276). One hundred four patients suffering from extensive disease (ED) SCLC, with any response to the standard of care induction chemo-immunotherapy will be randomized to receive atezolizumab maintenance therapy with or without TRT. The primary endpoint of this study is overall survival (OS). Secondary endpoints include further measures of efficacy, safety, and the collection of biomarker samples. A safety interim analysis will take place after n = 23 patients receiving TRT have been observed for three months after the end of TRT.Discussion: This trial will investigate whether treatment efficacy can be improved by adding TRT to atezolizumab maintenance therapy in ED SCLC patients with any response after chemo-immunotherapy. Safety and feasibility of such a regimen will be evaluated, and biomaterials for a translational research project will be collected. Together, the results of this trial will deepen our comprehension of how checkpoint inhibition and radiotherapy interact and contribute to the evolving landscape of SCLC therapy.Trial Registration: Clinicaltrials.gov identifier: NCT04462276 (Date of initial registration: 8th July 2020), https://clinicaltrials.gov/ct2/show/NCT04462276 Eudra-CT Number: 2019-003916-29 (Date of initial registration: 30th March 2020), https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-003916-29/DE. [ABSTRACT FROM AUTHOR]

Background: Trophoblast cell-surface antigen 2 (TROP2) is expressed on the surface of trophoblast cells and many malignant tumor cells. However, data on TROP2 expression in advanced lung cancer are insufficient, and its changes have not been fully evaluated. Methods: We assessed the prevalence and changes in TROP2 expression in patients with lung cancer who received anti-cancer treatments using immunohistochemical (IHC) analysis with an anti-TROP2 antibody (clone: SP295). IHC scores were graded from 0 to 3; grade ≥ 2 was considered positive for TROP2 expression. We defined a difference in IHC score, before and after anti-cancer treatments, as the change in TROP2 expression. Results: Before anti-cancer treatment, TROP2 expression was observed in 89% (143/160) of the patients and was significantly more common in adenocarcinoma and squamous cell carcinoma than in neuroendocrine carcinoma (P < 0.001). After anti-cancer treatment, TROP2 expression was observed in 87% (139/160) of the patients. The distribution of TROP2 expression in post-treatment samples was analogous to that in pre-treatment samples when compared using the Wilcoxon signed-rank test (P = 0.509). However, an increase in TROP2 expression was seen in 19 (12%), and a decrease in 20 (13%) patients. Patients treated with targeted therapy showed significantly higher changes in TROP2 expression (P = 0.019) and thoracic radiotherapy was more likely to increase TROP2 expression than chemotherapy alone. Conclusion: Although some anti-cancer treatments might alter the TROP2 expression, TROP2 was expressed in most lung cancer specimens before and after anti-cancer treatments. These results support the development of TROP2-directed therapy against advanced lung cancer in various treatment lines. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are therapeutic agents for advanced and metastatic non-small cell lung cancer (NSCLC) with high clinical antitumor efficacy. However, immune-related adverse events occur in 20% of these patients and often requiring treatment with immunosuppressive agents, such as corticosteroids. Consequently, this may increase the risk of patients to opportunistic infections. Pneumocystis jirovecii pneumonia (PJP), a rare but serious opportunistic infection typically observed in patients with human immunodeficiency virus, can also occur in cancer patients undergoing long-term glucocorticoid treatment., Case Summary: We report a case of a 56-year-old male with squamous NSCLC treated with triplimab combined with paclitaxel, carboplatin, and radical thoracic radiation therapy. Following this regimen, he developed acute kidney injury (AKI) with elevated creatinine levels. After concurrent radical chemoradiotherapy ended, he developed a grade 3 immune-related AKI. High-dose corticosteroids were administered to treat AKI, and renal function gradually recovered. Corticosteroids were reduced to a dose of 10 mg prednisone equivalent daily eight weeks later; however, he developed severe pneumonia with spontaneous pneumothorax. Next-generation sequencing of the bronchoscopic lavage revealed PJP co-infection with herpes simplex virus 1 and cytomegalovirus. The inflammation was more severe in areas exposed to radiation. Piperacillin-tazobactam, acyclovir, sulfamethoxazole, and trimethoprim were used to control the infection. The patient recovered, and immunotherapy was terminated., Conclusion: PJP is rare but can occur in patients with ICI adverse events and should be differentiated from tumor progression or immune-related adverse events. Thoracic radiation may increase risk, necessitating careful monitoring and prevention., Competing Interests: Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: Palliative thoracic radiotherapy is a key treatment option for symptom management in advanced lung cancer. Continuous symptom monitoring is critical to ensuring optimal therapeutic outcomes and preserving patients' well-being. This systematic review aimed to explore patients' symptom experiences during palliative thoracic radiotherapy for advanced lung cancer., Methods: Following PRISMA guidelines, we conducted a comprehensive search of MEDLINE, EMBASE, CINAHL, Cochrane, and PsycINFO from database inception through August 31, 2023. Eligible studies included those examining the prevalence and severity of symptoms and side effects experienced by adult patients undergoing palliative thoracic radiotherapy for advanced lung cancer, regardless of treatment duration or dosage. Methodological quality was assessed using the standardized QualSyst tool, and data were synthesized narratively., Results: A total of 8 studies met the inclusion criteria. Thirteen symptoms were reported prior to radiotherapy, with cough being the most common (62%). Symptom severity ranged from mild to severe, with dyspnoea recording the highest average score. Distress was not measured during this phase. Post-radiotherapy, fatigue was the most prevalent symptom (69%), followed by cough (64%) and dyspnoea (50%). Symptom severity varied across studies, with improvements noted in cough, dyspnoea, chest pain, and haemoptysis. Moderating factors influencing symptom prevalence and variation included performance status, weight loss, cancer stage, objective tumour response, and radiation-induced pulmonary changes., Conclusions: Symptom control through palliative thoracic radiotherapy demonstrates variability in both frequency and severity of symptoms. Systematic monitoring is essential for identifying persistent symptoms and determining the need for more targeted supportive care interventions., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)

Background and Purpose: On the basis of the promising clinical study results, thoracic radiotherapy (TRT)1 has become an integral part of treatment of synchronous oligometastatic non--small cell lung cancer (SOM-NSCLC). However, some of them experienced rapid disease progression after TRT and showed no significant survival benefit. How to screen out such patients is a more concerned problem at present. In this study, we developed a risk-prediction model by screening hematological and clinical data of patients with SOM-NSCLC and identified patients who would not benefit from TRT. Materials and Methods: We investigated patients with SOM-NSCLC between 2011 and 2019. A formula named Risk-Total was constructed using factors screened by LASSO-Cox regression analysis. Stabilized inverse probability treatment weight analysis was used to match the clinical characteristics between TRT and non-TRT groups. The primary endpoint was overall survival (OS). Results: We finally included 283 patients divided into two groups: 188 cases for the training cohort and 95 for the validation cohort. Ten prognostic factors included in the Risk-Total formula were age, N stage, T stage, adrenal metastasis, liver metastasis, sensitive mutation status, local treatment status to metastatic sites, systemic inflammatory index, CEA, and Cyfra211. Patients were divided into low- and high-risk groups based on risk scores, and TRT was found to have improved the OS of low-risk patients (46.4 vs. 31.7 months, P = 0.083; 34.1 vs. 25.9 months, P = 0.078) but not that of high-risk patients (14.9 vs. 11.7 months, P = 0.663; 19.4 vs. 18.6 months, P = 0.811) in the training and validation sets, respectively. Conclusion: We developed a prediction model to help identify patients with SOMNSCLC who would not benefit from TRT, and TRT could not improve the survival of highrisk patients. [ABSTRACT FROM AUTHOR]

Purpose: Whilst survival benefits of thoracic radiotherapy (TRT) followed by immune checkpoint inhibitor (ICI) have been reported in patients with lung cancer, the potential high risk of treatment-related pneumonitis remains a concern. Asians may be more sensitive to lung toxicity than other races. This retrospective study intended to provide a comprehensive pneumonitis profile of TRT followed by ICI and investigate the risk factors from a Chinese cohort of lung cancer. Methods and Materials: From January 2016 to July 2021, 196 patients with lung cancer who received TRT prior to ICI were retrospectively analyzed. Treatment-related pneumonitis, including checkpoint inhibitor pneumonitis (CIP), radiation pneumonitis (RP), and radiation recall pneumonitis (RRP), were recorded and graded through medical records and chest computed tomography. Characteristics predictive of pneumonitis were assessed using logistic regression models, and the receiver operating characteristic analyses were performed to identify optimal cut points for quantitative variables. Results: With a median follow-up of 18 months, a total of 108 patients (55.1%) developed treatment-related pneumonitis during ICI therapy, with an incidence of 25.5% for grade 2 or higher (G2+) and 4.1% for G3+. The overall rates of CIP, RP and RRP were 8.2% (n=16), 46.9% (n=92) and 7.1% (n=14), respectively. With a total mortality rate of 1.5%, vast majority of the patients recovered from pneumonitis or remained stable. No patients died of RRP. Half of the patients with G2+ RP who withheld ICI therapy restarted ICI safely after resolution of RP. The history of chronic pulmonary diseases (P =0.05), mean lung dose (MLD, P =0.038), percent volume of lung receiving ≥5 Gy (V5, P =0.012) and percent volume of lung receiving ≥20 Gy (V20, P =0.030) predicted the occurrence of RRP in univariate analyses. Interval between TRT and ICI less than 3 months was an independent predictor for G2+ treatment-related pneumonitis in a multivariate model (Odds ratio OR=2.787, P =0.004). Conclusions: Treatment-related pneumonitis, especially RRP, is acceptable and manageable in the setting of TRT followed by ICI in this Asian population. Dosimetric parameters MLD, V5 and V20 may improve the predictions of RRP in clinical practice. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to investigate the feasibility and efficacy of image‐guided moderately hypofractionated thoracic radiotherapy (hypo‐IGRT) in patients with non–small cell lung cancer (NSCLC) with poor performance status and severely limited pulmonary function and reserve. Methods: Consecutive inoperable patients who had node‐positive, stage IIB‐IIIC (TNM, 8th edition) or recurrent NSCLC, had an Eastern Cooperative Oncology Group performance status ≥1, and had a forced expiratory volume in 1 second (FEV1) ≤1.0 L, had a single‐breath diffusing capacity of the lung for carbon monoxide (DLCO‐SB) ≤40% and/or on long‐term oxygen therapy were analyzed. All patients received hypofractionated IGRT to a total dose of 42.0 to 49.0 Gy/13 to 16 fractions (2.8‐3.5 Gy/fraction) (equivalent dose in 2‐Gy fractions/biologically effective dose [α/β = 10] = 45.5‐55.1 Gy/54.6‐66.2 Gy) alone. Patients were monitored closely for nonhematological toxicity, which was classified per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Results: Between 2014 and 2021, 47 consecutive patients with a median age of 72 years (range, 52.2‐88 years) were treated. At baseline, the median FEV1, vital capacity, and DLCO‐SB were 1.17 L (range, 0.69‐2.84 L), 2.34 L (range, 1.23‐3.74 L), and 35% predicted (range, 13.3%‐69.0%), respectively. The mean and median planning target volumes were 410.8 cc (SD, 267.1 cc) and 315.4 cc (range, 83.4‐1174.1 cc). With a median follow‐up of 28.9 months (range, 0.5‐90.6 months) after RT, the median progression‐free survival (PFS)/overall survival (OS) and 6‐ and 12‐month PFS/OS rates were 10.4 months (95% CI, 7‐13.8 months)/18.3 months (95% CI, 9.2‐27.4 months), 70%/89.4%, and 38.8%/66%, respectively. Treatment was well tolerated with only 1 case each of grade 3 pneumonitis and esophagitis. No toxicity greater than grade 3 was observed. Conclusions: Patients with inoperable node‐positive NSCLC, a poor performance status, and severely limited lung function can be safely and effectively treated with individualized moderately hypofractionated IGRT. The achieved survival rates for this highly multimorbid group of patients were encouraging. In this article, the knowledge gap between the management of patients with unfavorable risk factors and severely limited pulmonary function and reserve (forced expiratory volume in 1 second ≤1 L and/or single‐breath diffusing capacity of the lung for carbon monoxide ≤40% predicted and/or on long‐term oxygen therapy) is addressed. In light of encouraging results, a clinical pathway is proposed for the management of these high‐risk patients. [ABSTRACT FROM AUTHOR]

Background: Thoracic radiotherapy (TRT) with concurrent chemotherapy is the standard treatment of limited-stage small-cell lung cancer (LS-SCLC). However, there is still a controversy surrounding the treatment strategy especially optimal dosing and fractionation schedule. Current practice patterns among Chinese oncologists are unknown. Materials and Methods: We surveyed 212 Chinese oncologists using a questionnaire including 50 questions designed by experienced oncologists. Questions covered demographic data, treatment recommendations, and self-assessed knowledge of guidelines or key clinical trials for SCLC. The chi-square test and Fisher's exact test were utilized to describe the result of the study. Results: The response rate was 97% (207/212). Of all the respondents, 69% preferred TRT QD, 29% preferred BID, and 2% chose HFRT. For those who prefer TRT QD, 72% preferred a total dose of 60 Gy, followed by 15% opting for 66 Gy, 12% for <60 Gy, and 1% for 70 Gy. Of those who prefer BID, 79% preferred a total dose of 45 Gy, with 4% choosing 30 Gy, 8% choosing 50 Gy, 7% choosing 54 Gy, and 2% choosing >54 Gy. Regarding PCI, 82% of participants believed that PCI should be performed when treatment is completed and 13% believed that PCI should begin immediately after concurrent chemoradiotherapy. As for other therapies, 26% of participants choose concurrent anti-angiogenic therapy during SCLC treatment, and 49% recommended small-molecule TKI as the main anti-angiogenic therapy. Conclusion: Substantial variation exists in how Chinese oncologists approach TRT dosing and fractionation for LS-SCLC. Almost 70% of respondents reported administering TRT QD more often in daily work. The most common doses were 60 Gy QD and 45 Gy BID. [ABSTRACT FROM AUTHOR]