OBJECTIVES: To propose a new method for optimizing radiotherapy planning for lung cancer by incorporating prognostic models that take into account individual patient information and assess the feasibility of treatment planning optimization directly guided by minimizing the predicted prognostic risk. METHODS: A mixed fluence map optimization objective was constructed, incorporating the outcome-based objective and the physical dose constraints. The outcome-based objective function was constructed as an equally weighted summation of prognostic prediction models for local control failure, radiation-induced cardiac toxicity, and radiation pneumonitis considering clinical risk factors. These models were derived using Cox regression analysis or Logistic regression. The primary goal was to minimize the outcome-based objective with the physical dose constraints recommended by the clinical guidelines. The efficacy of the proposed method for optimizing treatment plans was tested in 15 cases of non-small cell lung cancer in comparison with the conventional dose-based optimization method (clinical plan), and the dosimetric indicators and predicted prognostic outcomes were compared between different plans. RESULTS: In terms of the dosemetric indicators, D_95% of the planning target volume obtained using the proposed method was basically consistent with that of the clinical plan (100.33% vs 102.57%, P=0.056), and the average dose of the heart and lungs was significantly decreased from 9.83 Gy and 9.50 Gy to 7.02 Gy (t=4.537, P<0.05) and 8.40 Gy (t=4.104, P<0.05), respectively. The predicted probability of local control failure was similar between the proposed plan and the clinical plan (60.05% vs 59.66%), while the probability of radiation-induced cardiac toxicity was reduced by 1.41% in the proposed plan. CONCLUSIONS The proposed optimization method based on a mixed objective function of outcome prediction and physical dose provides effective protection against normal tissue exposure to improve the outcomes of lung cancer patients following radiotherapy.
Humans ; Lung Neoplasms/radiotherapy* ; Radiotherapy Planning, Computer-Assisted/methods* ; Prognosis ; Radiotherapy, Intensity-Modulated/methods* ; Carcinoma, Non-Small-Cell Lung/radiotherapy* ; Radiotherapy Dosage ; Female ; Male ; Middle Aged

BACKGROUND: The incidence of symptomatic radiation pneumonitis (RP) and its relationship with dose-volume histogram (DVH) parameters in non-small cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and concurrent once-daily thoracic radiotherapy (TRT) remain unclear. We aim to analyze the values of clinical factors and dose-volume histogram (DVH) parameters to predict the risk for symptomatic RP in these patients. METHODS: Between 2011 and 2019, we retrospectively analyzed and identified 85 patients who had received EGFR-TKIs and once-daily TRT simultaneously (EGFR-TKIs group) and 129 patients who had received concurrent chemoradiotherapy (CCRT group). The symptomatic RP was recorded according to the Common Terminology Criteria for Adverse Event (CTCAE) criteria (grade 2 or above). Statistical analyses were performed using SPSS 26.0. RESULTS: In total, the incidences of symptomatic (grade≥2) and severe RP (grade≥3) were 43.5% (37/85) and 16.5% (14/85) in EGFR-TKIs group vs 27.1% (35/129) and 10.1% (13/129) in CCRT group respectively. After 1:1 ratio between EGFR-TKIs group and CCRT group was matched by propensity score matching, chi-square test suggested that the incidence of symptomatic RP in the MATCHED EGFR-TKIs group was higher than that in the matched CCRT group (χ2=4.469, P=0.035). In EGFR-TKIs group, univariate and multivariate analyses indicated that the percentage of ipsilateral lung volume receiving ≥30 Gy (ilV30) [odds ratio (OR): 1.163, 95%CI: 1.036-1.306, P=0.011] and the percentage of total lung volume receiving ≥20 Gy (tlV20) (OR: 1.171, 95%CI: 1.031-1.330, P=0.015), with chronic obstructive pulmonary disease (COPD) or not (OR: 0.158, 95%CI: 0.041-0.600, P=0.007), were independent predictors of symptomatic RP. Compared to patients with lower ilV30/tlV20 values (ilV30 and tlV20cut-off point values) and COPD had a significantly higher risk for developing symptomatic RP, with a hazard ratio (HR) of 1.350 (95%CI: 1.190-1.531, P<0.001). CONCLUSIONS Patients receiving both EGFR-TKIs and once-daily TRT were more likely to develop symptomatic RP than patients receiving concurrent chemoradiotherapy. The ilV30, tlV20, and comorbidity of COPD may predict the risk of symptomatic RP among NSCLC patients receiving EGFR-TKIs and conventionally fractionated TRT concurrently.
Carcinoma, Non-Small-Cell Lung/radiotherapy* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/radiotherapy* ; Protein Kinase Inhibitors/adverse effects* ; Pulmonary Disease, Chronic Obstructive/complications* ; Radiation Pneumonitis/etiology* ; Radiotherapy Dosage ; Retrospective Studies

BACKGROUND: Immunotherapy (IT) is recommended for the treatment of advanced non-small cell lung cancer (NSCLC), while brain radiotherapy (RT) is the mainstream treatment for patients with brain metastases (BM). This study aimed to investigate the efficacy and safety of combined use of RT and IT. METHODS: The date was limited to May 1, 2022, and literature searches were carried out in CNKI, Wanfang, PubMed, EMBASE and Cochrane databases. Heterogeneity was judged using the I2 test and P value. Publication bias was assessed using a funnel plot. The quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). Statistical analysis was performed using Stata 16.0 software. RESULTS: A total of 17 articles involving 2,636 patients were included. In the comparison of RT+IT group and RT group, no significant difference was found in overall survival (OS) (HR=0.85, 95%CI: 0.52-1.38, I2=73.9%, Pheterogeneity=0.001) and intracranial distance control (DBC) (HR=1.04, 95%CI: 0.55-1.05, I2=80.5%, Pheterogeneity<0.001), but the intracranial control (LC) in the RT+IT group was better than the RT group (HR=0.46, 95%CI: 0.22-0.94, I2=22.2%, Pheterogeneity=0.276), and the risk of radiation necrosis/treatment-related imaging changes (RN/TRIC) was higher than RT (HR=1.72, 95%CI: 1.12-2.65, I2=40.2%, Pheterogeneity=0.153). In the comparison between the RT+IT concurrent group and the sequential group, no significant difference was found in OS (HR=0.62, 95%CI: 0.27-1.43, I2=74.7%, Pheterogeneity=0.003) and RN/TRIC (HR=1.72, 95%CI: 0.85-3.47, I2=0%, Pheterogeneity=0.388) was different between the two groups. However, DBC in the concurrent treatment group was better than that in the sequential treatment group (HR=0.77, 95%CI: 0.62-0.96, I2=80.5%, Pheterogeneity<0.001). CONCLUSIONS RT combined with IT does not improve the OS of NSCLC patients with BM, but also increases the risk of RN/TRIC. In addition, compared with sequential RT and IT, concurrent RT and IT improved the efficacy of DBC.
Humans ; Lung Neoplasms/radiotherapy* ; Carcinoma, Non-Small-Cell Lung/radiotherapy* ; Brain Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Radiation Injuries

As the main type of lung cancer, non-small cell lung cancer (NSCLC) is a common cancer which is characterized by low 5-year survival rate and worse prognosis. Nowadays, some studies show that the low survival rate and worse prognosis are due to the resistance to radiotherapy caused by circRNA. Therefore, to find out the relationship between circRNA and radiotherapy resistance of NSCLC was imoprtant. According to research the relevant literatures, the relationship between circRNA and radiotherapy resistance of NSCLC was explored. CircRNA plays an important role in the invasion, metastasis, proliferation and treatment resistance of NSCLC. The radiation resistance of tumor cells induced by circRNA has become a crucial problem in radiotherapy. CircRNA plays an important role in the radiotherapy resistance of NSCLC.
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Carcinoma, Non-Small-Cell Lung/radiotherapy* ; Cell Proliferation ; Humans ; Lung Neoplasms/radiotherapy* ; MicroRNAs ; RNA, Circular

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. The pathogenesis of NSCLC involves complex gene networks that include different types of non-coding RNAs, such as long non-coding RNAs (lncRNAs). The role of lncRNAs in NSCLC is gaining an increasing interest as their function is being explored in various human cancers. Recently, a new oncogenic lncRNA, LINC00152 (cytoskeleton regulator RNA (CYTOR)), has been identified in different tumor types. In NSCLC, the high expression of LINC00152 in tumor tissue and peripheral blood samples has been shown to be associated with worse prognoses of NSCLC patients. Overexpression of LINC00152 has been confirmed to promote the proliferation, invasion, and migration of NSCLC cells in vitro, as well as increase tumor growth in vivo. This review discusses the role of LINC00152 in NSCLC.
Apoptosis ; Biomarkers, Tumor/blood* ; Carcinoma, Non-Small-Cell Lung/radiotherapy* ; Cell Cycle Checkpoints ; Computational Biology ; Epithelial-Mesenchymal Transition ; Humans ; Lung Neoplasms/radiotherapy* ; Prognosis ; RNA, Long Noncoding/physiology* ; Radiation Tolerance

PURPOSE: It is unclear whether adding concurrent chemotherapy (CT) to definitive radiotherapy (RT) following induction CT is a tolerable and cost effective treatment for non-small-cell lung cancer (NSCLC) patients aged 70 years or older with comorbidities. This study evaluated the actual clinical outcomes between concurrent chemoradiotherapy (CCRT) and RT alone following induction CT or not in patients (≥70 years) in a single institution’s clinical practice. MATERIALS AND METHODS: A total of 82 patients with unresectable stage III NSCLC between 2004 and 2016 were retrospectively analyzed. Their treatment tolerance and clinical outcomes such as overall survival (OS), locoregional recurrence (LRR), treatment toxicities and distant metastasis (DM) were evaluated. Early mortality rates were also evaluated as 4-month mortality after RT. RESULTS: Fifty-four patients received CCRT and 28 patients received RT alone. Induction CT before RT was performed for 68.5% and 50.0% in CCRT and RT alone groups. Treatment tolerance was significantly worse in CCRT (p = 0.046). The median survival was 21.1 and 18.1 months for CCRT and RT alone, which was not statistically significant. LRR and DM were also not different. Most early deaths after CCRT were attributed to non-cancer-related mortality. Acute esophagitis of grade ≥2 occurred more following CCRT (p = 0.017). In multivariate analysis, a Charlson Comorbidity Index (CCI) of ≥5 and a weight loss of ≥5% after RT were associated with poor OS. The factors adversely affecting 4-month survival were a CCI of ≥5 and CCRT. CONCLUSION: There were no significant differences in OS, LRR, and DM between CCRT and RT alone treatment in elderly patients. However, there was a poorer tolerance and higher incidence of acute esophagitis in the CCRT group. Specifically, when the patients had a CCI of ≥5, RT alone seems to be reasonable with a low probability of early death.
Aged ; Carcinoma, Non-Small-Cell Lung ; Chemoradiotherapy ; Comorbidity ; Drug Therapy ; Esophagitis ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; Lung ; Mortality ; Multivariate Analysis ; Neoplasm Metastasis ; Radiotherapy ; Recurrence ; Retrospective Studies ; Weight Loss

In metastatic non-small cell lung cancer (NSCLC), the role of radiotherapy (RT) has been limited to palliation to alleviate the symptoms. However, with the development of advanced RT techniques, recent advances in immuno-oncology therapy targeting programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) and targeted agents for epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation allowed new roles of RT in these patients. Within this metastatic population, there is a subset of patients with a limited number of sites of metastatic disease, termed as oligometastasis that can achieve long-term survival from aggressive local management. There is no consensus on the definition of oligometastasis; however, most clinical trials define oligometastasis as having 3 to 5 metastatic lesions. Recent phase II randomized clinical trials have shown that ablative RT, including stereotactic ablative body radiotherapy (SABR) and hypofractionated RT, to primary and metastatic sites improved progression-free survival (PFS) and overall survival (OS) in patients with oligometastatic NSCLC. The PEMBRO-RT study, a randomized phase II study comparing SABR prior to pembrolizumab therapy and pembrolizumab therapy alone, revealed that the addition of SABR improved the overall response, PFS, and OS in patients with advanced NSCLC. The efficacy of RT in oligometastatic lung cancer has only been studied in phase II studies; therefore, large-scale phase III studies are needed to confirm the benefit of local ablative RT in patients with oligometastatic NSCLC. Local intensified RT to primary and metastatic lesions is expected to become an important treatment paradigm in the near future in patients with metastatic lung cancer.
Carcinoma, Non-Small-Cell Lung ; Consensus ; Disease-Free Survival ; Humans ; Lung Neoplasms ; Lymphoma ; Phosphotransferases ; Radiotherapy ; Receptor, Epidermal Growth Factor

PURPOSE: Lung Cancer Subcommittee of Korean Radiation Oncology Group (KROG) has recently launched a prospective clinical trial (KROG 17-06) of hippocampus-sparing whole brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in treating multiple brain metastases from non-small cell lung cancer. In order to improve trial quality, dummy run studies among the participating institutions were designed. This work reported the results of two-step dummy run procedures of the KROG 17-06 study. MATERIALS AND METHODS: Two steps tested hippocampus contouring variability and radiation therapy planning compliance. In the first step, the variation of the hippocampus delineation was investigated for two representative cases using the Dice similarity coefficients. In the second step, the participating institutions were requested to generate a HS-WBRT with SIB treatment plan for another representative case. The compliance of the treatment plans to the planning protocol was evaluated. RESULTS: In the first step, the median Dice similarity coefficients of the hippocampus contours for two other dummy run cases changed from 0.669 (range, 0.073 to 0.712) to 0.690 (range, 0.522 to 0.750) and from 0.291 (range, 0.219 to 0.522) to 0.412 (range, 0.264 to 0.598) after providing the hippocampus contouring feedback. In the second step, with providing additional plan priority and extended dose constraints to the target volumes and normal structures, we observed the improved compliance of the treatment plans to the planning protocol. CONCLUSION: The dummy run studies demonstrated the notable inter-institutional variability in delineating the hippocampus and treatment plan generation, which could be decreased through feedback from the trial center.
Brain ; Carcinoma, Non-Small-Cell Lung ; Compliance ; Hippocampus ; Lung Neoplasms ; Neoplasm Metastasis ; Prospective Studies ; Radiation Oncology ; Radiotherapy

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), indexes of systemic inflammation, have been associated with worse survival for many types of cancer. The aim of this study is to investigate the impact of NLR and PLR on overall survival (OS) and to explore the value of changes in the NLR and PLR with treatment as a response indicator in non-small cell lung cancer (NSCLC). METHODS: A total of 68 NSCLC patients in Peking University Third Hospital were eligible for retrospective analysis between April 2008 and April 2015. The pretreatment and posttreatment NLR and PLR in all patients were calculated based on complete blood counts. Potential prognostic factors such as age, gender, performance status, histology, stage, response to chemotherapy, NLR and PLR were analyzed. NLR and PLR were assessed at baseline and during chemotherapy treatment. OS was calculated by the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to determine the associations of the PLR, NLR and clinical features with OS. RESULTS: Among the 68 cases, the values of the posttreatment NLR after two cycles of chemotherapy (NLR2) and the pretreatment NLR (NLR0) were (2.69±2.06) and (3.94±2.12), respectively. NLR2 was significantly lower than NLR0 (P=0.000). There was no difference between the pretreatment PLR (PLR0) and the posttreatment PLR after two cycles of chemotherapy (PLR2) (P<0.05). NLR2 significantly correlated with the response of first line treatment with two or four cycles of chemotherapy. The proportion of high NLR2 in the patients with progression disease was 100.0%, significantly higher than the proportion of high NLR2 in the patients with partial response or stable disease. NLR0, PLR0 and NLR2 were significantly correlated with the OS (P<0.05), but not with age, performance status, histology, stage, status and regimens of treatment (P>0.05). According to univariate analysis, the OS was significantly associated with NLR0, PLR0, NLR2, the response of 2 and 4 cycles of first line chemotherapy, status and regimens of second line treatment (P<0.05), but not with stage, status of third line or beyond treatment and radiotherapy (P>0.05). The multivariate analysis showed that NLR0 (P=0.004), the response with 4 cycles of first line chemotherapy (P=0.022) and status of second line treatment (P=0.007) were independent prognostic indicators in the 68 patients. CONCLUSIONS The study showed that NLR0 was well connected with outcomes and NLR2 was well connected with the response to first line chemotherapy in patients with advanced non-small cell lung cancer. Therefore, NLR may be a biomarker for predicting the outcomes and response of first line chemotherapy and a potential target for management of non-small cell lung cancer.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; pathology ; radiotherapy ; Disease-Free Survival ; Female ; Humans ; Leukocyte Count ; Lung Neoplasms ; blood ; drug therapy ; pathology ; radiotherapy ; Lymphocytes ; cytology ; drug effects ; Male ; Middle Aged ; Neutrophils ; cytology ; drug effects ; Retrospective Studies ; Treatment Outcome

A few study has proven that about 90% of local control rates might be benefit from stereotactic body radiotherapy (SBRT) for patients with medically inoperable stage I non-small cell lung cancer (NSCLC), it is reported SBRT associated overall survival and tumor specific survival is comparable with those treated with surgery. SBRT has been accepted as the first line treatment for inoperable patients with peripheral located stage I NSCLC. However, the role of SBRT in centrally located lesions is controversial for potential toxic effects from the adjacent anatomical structure. This paper will review the definition, indication, dose regimens, dose-volume constraints for organs at risk, radiation technology, treatment side effect of centrally located NSCLC treated with SBRT and stereotactic body proton therapy.
Carcinoma, Non-Small-Cell Lung ; pathology ; radiotherapy ; Humans ; Lung Neoplasms ; pathology ; radiotherapy ; Neoplasm Staging ; Radiotherapy ; instrumentation ; methods