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Objective: The study aims to investigate the role of dynamic [ 18 F]FDG PET/CT imaging by high-sensitivity PET/CT scanner for assessing patients with locally advanced non-small cell lung cancer (LA-NSCLC) who undergo induction immuno-chemotherapy, followed by concurrent hypo-fractionated chemoradiotherapy (hypo-CCRT) and consolidative immunotherapy., Methods: Patients with unresectable LA-NSCLC are prospectively recruited. Dynamic [ 18 F]FDG PET/CT scans are conducted at four timepoints: before treatment (Baseline), after induction immuno-chemotherapy (Post-IC), during hypo-CCRT (Mid-hypo-CCRT) and after hypo-CCRT (Post-hypo-CCRT). The primary lung tumors (PTs) are manually delineated, and the metabolic features, including the Patlak-Ki (Ki), maximum SUV (SUV max ), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been evaluated. The expressions of CD3, CD8, CD68, CD163, CD34 and Ki67 in primary lung tumors at baseline are assayed by immunohistochemistry. The levels of blood lymphocytes at four timepoints are analyzed with flow cytometry., Results: Fifteen LA-NSCLC patients are enrolled between December 2020 and December 2022. Baseline Ki of primary tumor yields the highest AUC values of 0.722 and 0.796 for predicting disease progression and patient death, respectively. Patients are classified into the High FDG Ki group (n = 8, Ki > 2.779 ml/min/100 g) and the Low FDG Ki group (n = 7, Ki ≤ 2.779 ml/min/100 g). The High FDG Ki group presents better progression-free survival (P = 0.01) and overall survival (P = 0.025). The High FDG Ki group exhibits more significant reductions in Ki after hypo-CCRT compared to the Low FDG Ki group. Patients with a reduction in Ki > 73.1% exhibit better progression-free survival than those with a reduction ≤ 73.1% in Ki (median: not reached vs. 7.33 months, P = 0.12). The levels of CD3 + T cells (P = 0.003), CD8 + T cells (P = 0.002), CD68 + macrophages (P = 0.071) and CD163 + macrophages (P = 0.012) in primary tumor tissues are higher in the High FDG Ki group. The High FDG Ki group has higher CD3 + CD8 + lymphocytes in blood at baseline (P = 0.108), post-IC (P = 0.023) and post-hypo-CCRT (P = 0.041) than the Low FDG Ki group., Conclusions: The metabolic features in the High FDG Ki group significantly decrease during the treatment, particularly after induction immuno-chemotherapy. The Ki value of primary tumor shows significant relationship with the treatment response and survival in LA-NSCLC patients by the combined immuno-chemoradiotherapy regimen., Trial Registration: ClinicalTrials.gov. NCT04654234. Registered 4 December 2020., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This phase I trial aimed to determine the maximum tolerated fraction dose (MTFD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer., Patients and Methods: Split-course hypo-RT and hypoboost combined with concurrent chemotherapy was administered at three dose levels (DL), using a stepwise dose-escalation protocol. The sophisticated esophagus-sparing technique was implemented to restrict the dose to the esophagus. Patients who did not experience disease progression or unresolved ≥grade 2 (G2+) toxicities after RT received cICI. Each DL aimed to treat six patients. The MTFD was defined as the highest DL at which ≤2 patients of the six who were treated experienced treatment-related G3+ toxicity and ≤1 patient experienced G4+ toxicity within 12 months post-RT., Results: Eighteen patients were enrolled, with six patients in each DL. All patients completed hypo-RT and concurrent chemotherapy, and 16 (88.9%) received at least one infusion of cICI, with a median of 10 infusions. Within the 12-month assessment period, one patient in DL1 experienced G3 pneumonitis, and one patient in DL3 developed G3 tracheobronchitis. The MTFD was not reached. The objective response rate was 100%. With a median follow-up of 20.9 months, the 1-year overall survival and progression-free survival rates were 94.4% and 83.3%, respectively., Conclusions: Utilizing the split-course hypo-RT and hypoboost approach, a fraction dose of 5 Gy to a total dose of 60 Gy, combined with concurrent chemotherapy and subsequent cICI, was well tolerated and yielded a promising objective response rate and survival outcomes., (©2024 American Association for Cancer Research.)

Purpose: This study aimed to investigate the prognostic significance of pretreatment dynamic contrast-enhanced (DCE)-MRI parameters concerning tumor response following induction immunochemotherapy and survival outcomes in patients with locally advanced non-small cell lung cancer (NSCLC) who underwent immunotherapy-based multimodal treatments., Material and Methods: Unresectable stage III NSCLC patients treated by induction immunochemotherapy, concurrent chemoradiotherapy (CCRT) with or without consolidative immunotherapy from two prospective clinical trials were screened. Using the two-compartment Extend Tofts model, the parameters including K trans , K ep , V e , and V p were calculated from DCE-MRI data. The apparent diffusion coefficient was calculated from diffusion-weighted-MRI data. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to assess the predictive performance of MRI parameters. The Cox regression model was used for univariate and multivariate analysis., Results: 111 unresectable stage III NSCLC patients were enrolled. Patients received two cycles of induction immunochemotherapy and CCRT, with or without consolidative immunotherapy. With the median follow-up of 22.3 months, the median progression-free survival (PFS) and overall survival (OS) were 16.3 and 23.8 months. The multivariate analysis suggested that Eastern Cooperative Oncology Group score, TNM stage and the response to induction immunochemotherapy were significantly related to both PFS and OS. After induction immunochemotherapy, 67 patients (59.8%) achieved complete response or partial response and 44 patients (40.2%) had stable disease or progressive disease. The K trans of primary lung tumor before induction immunochemotherapy yielded the best performance in predicting the treatment response, with an AUC of 0.800. Patients were categorized into two groups: high-K trans group (n=67, K trans ＞164.3×10 -3 /min) and low-K trans group (n=44, K trans ≤164.3×10 -3 /min) based on the ROC analysis. The high-K trans group had a significantly higher objective response rate than the low-K trans group (85.1% (57/67) vs 22.7% (10/44), p<0.001). The high-K trans group also presented better PFS (median: 21.1 vs 11.3 months, p=0.002) and OS (median: 34.3 vs 15.6 months, p=0.035) than the low-K trans group., Conclusions: Pretreatment K trans value emerged as a significant predictor of the early response to induction immunochemotherapy and survival outcomes in unresectable stage III NSCLC patients who underwent immunotherapy-based multimodal treatments. Elevated K trans values correlated positively with enhanced treatment response, leading to extended PFS and OS durations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: We launched a prospective phase 2 clinical trial to explore the safety and efficacy of hypofractionated radiation therapy (hypo-RT) followed by hypofractionated boost (hypo-boost) combined with concurrent weekly chemotherapy in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC)., Methods and Materials: Patients with newly diagnosed LA-NSCLC with unresectable stage III disease were recruited between June 2018 and June 2020. Patients were treated with hypo-RT (40 Gy in 10 fractions) followed by hypo-boost (24-28 Gy in 6-7 fractions) combined with concurrent weekly chemotherapy (docetaxel 25 mg/m 2 and nedaplatin 25 mg/m 2 ). The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), locoregional failure-free survival (LRFS), distant metastasis-free survival (DMFS), objective response rate (ORR), and toxicities., Results: From June 2018 to June 2020, 75 patients were enrolled with a median follow-up duration of 28.0 months. The ORR of the whole cohort was 94.7%. Disease progression or death was recorded in 44 (58.7%) patients, with a median PFS of 21.6 months (95% confidence interval [CI], 15.6-27.6 months). The 1- and 2-year PFS rates were 81.3% (95% CI, 72.5%-90.1%) and 43.3% (95% CI, 31.5%-55.1%), respectively. The median OS, DMFS, and LRFS had not been reached at the time of the last follow-up. The 1- and 2-year OS rates were 94.7% (95% CI, 89.6%-99.8%) and 72.4% (95% CI, 62.0%-82.8%), respectively. The most frequent acute nonhematologic toxicity was radiation esophagitis. Grade (G) 2 and G3 acute radiation esophagitis were observed in 20 (26.7%) and 4 (5.3%) patients, respectively. Thirteen patients (13/75, 17.3%) had G2 pneumonitis and no G3-G5 acute pneumonitis occurred during follow-up., Conclusions: Hypo-RT followed by hypo-boost combined with concurrent weekly chemotherapy could yield satisfactory local control and survival outcomes with moderate radiation-induced toxicity in patients with LA-NSCLC. The new potent hypo-CCRT regimen significantly shortened treatment time and provided the potential opportunity for the combination of consolidative immunotherapy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: This study aimed to investigate the predictive value of metabolic features in response to induction immuno-chemotherapy in patients with locally advanced non-small cell cancer (LA-NSCLC), using ultra-high sensitivity dynamic total body [ 18 F]FDG PET/CT., Methods: The study analyzed LA-NSCLC patients who received two cycles of induction immuno-chemotherapy and underwent a 60-min dynamic total body [ 18 F]FDG PET/CT scan before treatment. The primary tumors (PTs) were manually delineated, and their metabolic features, including the Patlak-Ki, Patlak-Intercept, maximum SUV (SUV max ), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were evaluated. The overall response rate (ORR) to induction immuno-chemotherapy was evaluated according to RECIST 1.1 criteria. The Patlak-Ki of PTs was calculated from the 20-60 min frames using the Patlak graphical analysis. The best feature was selected using Laplacian feature importance scores, and an unsupervised K-Means method was applied to cluster patients. ROC curve was used to examine the effect of selected metabolic feature in predicting tumor response to treatment. The targeted next generation sequencing on 1021 genes was conducted. The expressions of CD68, CD86, CD163, CD206, CD33, CD34, Ki67 and VEGFA were assayed through immunohistochemistry. The independent samples t test and the Mann-Whitney U test were applied in the intergroup comparison. Statistical significance was considered at P < 0.05., Results: Thirty-seven LA-NSCLC patients were analyzed between September 2020 and November 2021. All patients received two cycles of induction chemotherapy combined with Nivolumab/ Camrelizumab. The Laplacian scores showed that the Patlak-Ki of PTs had the highest importance for patient clustering, and the unsupervised K-Means derived decision boundary of Patlak-Ki was 2.779 ml/min/100 g. Patients were categorized into two groups based on their Patlak-Ki values: high FDG Patlak-Ki (H-FDG-Ki, Patlak-Ki > 2.779 ml/min/100 g) group (n = 23) and low FDG Patlak-Ki (L-FDG-Ki, Patlak-Ki ≤ 2.779 ml/min/100 g) group (n = 14). The ORR to induction immuno-chemotherapy was 67.6% (25/37) in the whole cohort, with 87% (20/23) in H-FDG-Ki group and 35.7% (5/14) in L-FDG-Ki group (P = 0.001). The sensitivity and specificity of Patlak-Ki in predicting the treatment response were 80% and 75%, respectively [AUC = 0.775 (95%CI 0.605-0.945)]. The expression of CD3 + /CD8 + T cells and CD86 + /CD163 + /CD206 + macrophages were higher in the H-FDG-Ki group, while Ki67, CD33 + myeloid cells, CD34 + micro-vessel density (MVD) and tumor mutation burden (TMB) were comparable between the two groups., Conclusions: The total body [ 18 F]FDG PET/CT scanner performed a dynamic acquisition of the entire body and clustered LA-NSCLC patients into H-FDG-Ki and L-FDG-Ki groups based on the Patlak-Ki. Patients with H-FDG-Ki demonstrated better response to induction immuno-chemotherapy and higher levels of immune cell infiltration in the PTs compared to those with L-FDG-Ki. Further studies with a larger patient cohort are required to validate these findings., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The study aimed to compare the characteristics and prognosis between patients with second primary lung cancer following Hodgkin's lymphoma and those with primary lung cancer., Materials and Methods: Using the SEER 18 database, the characteristics and prognosis were compared between the second primary non-small cell lung cancer following Hodgkin's lymphoma (HL-NSCLC) (n = 466) and the first primary non-small cell lung cancer (n = 469,851)(NSCLC-1), as well as between the second primary small cell lung cancer following Hodgkin's lymphoma (n = 93) (HL-SCLC) and the first primary small cell lung cancer (n = 94,168) (SCLC-1). Comparisons of categorical variables were performed using Chi-square or Fisher's test. Continuous variables were compared using the Mann-Whitney U test. Overall survival (OS) was estimated using the Kaplan-Meier method, and the difference between groups was analyzed by log-rank test., Results: HL-NSCLC group had more males than NSCLC-1 group, and the median age of HL-NSCLC group was younger than that of NSCLC-1 group. Patients with HL-NSCLC showed inferior OS than those with NSCLC-1 (median: 10 months vs. 11 months, P = 0.006). Both HL-SCLC and SCLC-1 groups had poor prognosis, with median OS of 7 months (P = 0.4). The 3-year cumulative risks of death from any cause for patients with the latencies from HL to NSCLC of 0 to 5 years, >5 to 10 years, >10 to 15 years, >15 to 20 years, and>20 years were 71.8%, 82.6%, 86.8%, 85.7% and 78.5%, respectively(P = 0.020)., Conclusion: HL-NSCLC patients had worse prognosis than NSCLC-1 patients, while HL-SCLC patients shared similar characteristics and survival with SCLC-1 patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This study aimed to quantitatively assess [ 18 F]FDG uptake in primary tumor (PT) and metastatic lymph node (mLN) in newly diagnosed non-small cell lung cancer (NSCLC) using the total-body [ 18 F]FDG PET/CT and to characterize the dynamic metabolic heterogeneity of NSCLC., Methods: The 60-min dynamic total-body [ 18 F]FDG PET/CT was performed before treatment. The PTs and mLNs were manually delineated. An unsupervised K-means classification method was used to cluster patients based on the imaging features of PTs. The metabolic features, including Patlak-Ki, Patlak-Intercept, SUV mean , metabolic tumor volume (MTV), total lesion glycolysis (TLG), and textural features, were extracted from PTs and mLNs. The targeted next-generation sequencing of tumor-associated genes was performed. The expression of Ki67, CD3, CD8, CD34, CD68, and CD163 in PTs was determined by immunohistochemistry., Results: A total of 30 patients with stage IIIA-IV NSCLC were enrolled. Patients were divided into fast dynamic FDG metabolic group (F-DFM) and slow dynamic FDG metabolic group (S-DFM) by the unsupervised K-means classification of PTs. The F-DFM group showed significantly higher Patlak-Ki (P < 0.001) and SUV mean (P < 0.001) of PTs compared with the S-DFM group, while no significant difference was observed in Patlak-Ki and SUV mean of mLNs between the two groups. The texture analysis indicated that PTs in the S-DFM group were more heterogeneous in FDG uptake than those in the F-DFM group. Higher T cells (CD3 + /CD8 + ) and macrophages (CD68 + /CD163 + ) infiltration in the PTs were observed in the F-DFM group. No significant difference was observed in tumor mutational burden between the two groups., Conclusion: The dynamic total-body [ 18 F]FDG PET/CT stratified NSCLC patients into the F-DFM and S-DFM groups, based on Patlak-Ki and SUV mean of PTs. PTs in the F-DFM group seemed to be more homogenous in terms of [ 18 F]FDG uptake than those in the S-DFM group. The higher infiltrations of T cells and macrophages were observed in the F-DFM group, which suggested a potential benefit from immunotherapy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: High activity of Indoleamine 2,3-dioxygenase1 (IDO1) in lung cancer patients converts tryptophan (Trp), which is the essential amino acid for T-cell metabolism, to kynurenine (Kyn) and consequently suppresses anti-tumor immune responses. We aimed to track the dynamics of IDO1 activity in stage III non-small cell lung cancer (NSCLC) patients who received first-line radiotherapy (RT) and explore its association with survival outcomes., Materials and Methods: Systemic IDO1 activity was calculated by Kyn : Trp ratio. Plasma levels of Kyn and Trp in 113 thoracic RT-received stage III NSCLC patients were measured by high-performance liquid chromatography before the initiation of RT. The dynamic change of IDO1 activity was followed in 24 patients by measuring the Kyn : Trp ratio before, during, and after RT administration., Results: In 24 patients with dynamic tracking of plasma IDO1 activity, there were no significant alterations observed among the three time points (Friedman test, p = 0.13). The changing pattern of the Kyn : Trp ratio was divided into four groups: decreased consistently during RT, first increased, then decreased, increased consistently, first decreased then increased. Patients whose Kyn : Trp ratio kept decreasing or first increased then decreased were defined as the good-change group. The good-change status was identified as an independent positive factor for overall survival (OS) and progression-free survival (PFS) (p = 0.04; p = 0.01) in multivariate analysis among evaluated parameters. Patients with good change showed significantly superior local control than the bad-change group (p = 0.01, HR = 0.22). In 113 stage III NSCLC patients with pre-radiation Kyn : Trp ratio, a trend that high baseline IDO1 activity was associated with short OS was observed (p = 0.079)., Conclusion: Favorable change in IDO1 activity during RT was associated with superior OS, PFS, and local control. IDO1 activity is a promising biomarker for prognosis in stage III NSCLC patients., Competing Interests: 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., (Copyright © 2022 Wu, Wang, Chen, Qian, Xu, Zhang, Bi and Wang.)

Purpose: To evaluate the association of gut microbiome signature and disease progression in locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) by fecal metagenome analysis., Methods: Metagenome-wide association studies on baseline fecal samples from 18 LA-NSCLC patients before CCRT and 13 controls from healthy first-degree relatives were performed. Among the 18 LA-NSCLC patients, six patients were defined as the long progression-free survival (long-PFS) group (PFS≥11 months) while another 12 were in the short-PFS group (PFS<11 months). Alpha diversity, taxonomic composition, and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathways were compared between groups., Results: The Firmicutes/Bacteroidetes value of long-PFS group was higher than those of short-PFS (p=0.073) and healthy individual groups (p=0.009). Meanwhile, long-PFS group had significantly higher diversities in Fungi, Archaea, and Viruses than short-PFS group. The KEGG pathways overrepresented in short-PFS group included fructose and mannose metabolism (p=0.028), streptomycin biosynthesis (p=0.028), acarbose and validamycin biosynthesis (p=0.013), ribosome biogenesis in eukaryotes (p=0.035), biosynthesis of vancomycin group antibiotics (p=0.004), apoptosis-fly (p=0.044), and tetracycline biosynthesis (p=0.044), while those overrepresented in long-PFS group included fatty acid biosynthesis (p=0.035), fatty acid metabolism (p=0.008), vancomycin resistance (p=0.008), longevity regulating pathway-worm (p=0.028), type II diabetes mellitus (p=0.004), and viral carcinogenesis (p=0.003). Further analysis of antibiotic resistome demonstrated that the short-PFS group had a trend with more antibiotic resistance genes than healthy control (p=0.070) and long-PFS groups (p=0.218). The vancomycin resistance sequences were significantly enriched in the long-PFS group compared to the short-PFS group (p=0.006)., Conclusions: The baseline gut microbiome composition and functionality might be associated with PFS in LA-NSCLC treated with CCRT. The outcome of CCRT might be modulated through bacterial metabolic pathways. The antibiotic resistance genes might play a role in disease progression and provide potential information on the relationship between the use of antibiotics and treatment efficacy of CCRT in LA-NSCLC., Competing Interests: 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., (Copyright © 2022 Xi, Liu, Qiu, Li, Xie, Guo, Wu, Liang, Wang, Wang, Chen, Xue, Ding, Zhang, Wu and Liu.)

Purpose: This study aimed to explore the role of a modified criteria for assessing tumor response to concurrent chemoradiotherapy (CCRT) in locally advanced non-small cell lung cancer (LA-NSCLC), using the combined modalities of anatomical and functional MRI and CT., Materials and Methods: One hundred and fifty-three patients with LA-NSCLC who underwent CCRT with continuous chest MRI and CT follow-up were analyzed. The tumor response to CCRT was evaluated two months after the completion of CCRT. The RECIST criteria (CT imaging) and modified criteria (combined chest MRI and CT imaging) were compared and validated on follow-up imaging. The chest MRI scan analysis included T1C, T2fs, DWI imaging and the apparent diffusion coefficient values. Progression free survival (PFS) ≥ 18 months was used as a surrogate endpoint of complete response to analyze the accuracy of tumor response assessment., Results: Eight (5.2%) patients were considered to have complete response (CR) by the RECIST criteria while fifty-five (35.9%) were considered to have CR (CT + MRI) by the modified criteria. Using PFS ≥ 18 months as a surrogate for CR, the sensitivity and specificity of the modified criteria were 71.2% and 90.8% (AUC = 0.810, 95%CI 0.735-0.885), but were 9.1% and 97.7%, respectively, for the RECIST criteria (AUC = 0.534, 95%CI 0.441-0.627). The median PFS was 58.4 months for patients with CR (CT + MRI) and 9.7 months for those with non-CR (P < 0.001). Multivariate analysis showed that the tumor response evaluated by the modified criteria [CR (CT + MRI) vs. non-CR] was an independent factor for both PFS (HR 0.182, 95%CI 0.088-0.373, P < 0.001) and overall survival (HR 0.134, 95%CI 0.044-0.410, P < 0.001)., Conclusions: Combined multi-parameter MRI and CT imaging could improve the accuracy of tumor response assessment in LA-NSCLC patients after definitive CCRT, therefore contributed to the risk stratification and survival prediction for clinical practice., Competing Interests: Conflict of interest statement None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To develop a new radiobiological model and compare the efficacy of four concurrent chemotherapy regimens administered with radiotherapy in locally advanced non-small-cell lung cancer (LANSCLC) by in-field locoregional progression-free survival (LPFS)., Materials and Methods: 151 LANSCLC patients were reviewed and divided into 5 groups according to their concurrent chemotherapy regimens, including 24 patients treated with radiotherapy alone, 30 treated with concurrent 4-week etoposide-cisplatin (EP), 26 with 3-week pemetrexed-cisplatin (AP), 37 with weekly paclitaxel-cisplatin (TP) and 34 with weekly docetaxel-cisplatin (DP). In-field LPFS and toxicities were compared among groups. A novel tumor control probability (TCP) model, LQRGC, incorporating four "R"s of radiobiology, Gompertzian tumor growth and chemotherapeutic effect, was related to in-field LPFS. Chemo-induced biologically effective doses (BEDs) in LQRGC/TCP model were used to quantify the concurrent chemotherapeutic efficacy., Results: The median follow-up time was 54.5 months. The weekly DP and 4-week EP groups had favorable median in-field LPFS (EP:46.2 months, AP:30.3 months, TP:12.2 months, DP: not reached, radiotherapy alone: 12.2 months, p = 0.001). The 4-week EP group had a higher incidence of ≥grade 3 leukopenia (EP:76.7%, AP:15.4%, TP:24.3%, DP:14.7%, radiotherapy alone: 12.5%, p < 0.001) than the other four. The LQRGC/TCP model fitted well with the in-field LPFS with the average absolute and relative fitting errors of 6.36% and 12.12%. The chemo-induced BEDs of EP, AP, TP and DP were 5.17, 0.63, 1.89 and 2.52 Gy, respectively., Conclusion: The LQRGC/TCP model achieved promising fitting accuracy for in-field LPFS. As quantified by the model, the 4-week EP and weekly DP showed higher chemo-induced BEDs when concurrently administered with radiotherapy in LANSCLC., Competing Interests: Conflict of interest None., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: To explore the efficacy and toxicities of split-course hypo-fractionated radiotherapy with concurrent chemotherapy (HFRT-CHT) with intensity modulated radiotherapy (IMRT) technique in non-small cell lung cancer (NSCLC) patients with postoperative locoregional recurrence (LRR)., Materials and Methods: NSCLC patients were eligible if confirmed as LRR disease without distant metastasis after complete resection. HFRT-CHT using IMRT technique was administered with 51 Gy in 17 fractions or 40 Gy in 10 fractions as the first course followed by a break. Patients with no disease progression and no persistent Grade ≥2 toxicities had the second course of 15 Gy in 5 fractions or 28 Gy in 7 fractions as a boost. The primary endpoint was progression-free survival (PFS)., Results: Fifty-eight patients were enrolled and analyzed. With a median follow-up of 23.9 months for all, the 2-year and 3-year PFS rate was 59.7 % and 46.4 %, the 2-year and 3-year OS rate was 72.5 % and 52.2 %, respectively, and a favorable objective response rate of 95.9 % was obtained after the whole courses protocol. Grade 3 acute pneumonitis and esophagitis occurred in 2 (3.4 %) and 7 (12.1 %) patients, and fatal pneumonitis was reported in one case (1.7 %). Exploratory subgroup analysis showed that performance status (PS) (PS 0 vs. 1: 2-year PFS, 88.1 % vs. 46.9 %,P = 0.001; 2-year OS, 100 % vs. 59.4 %, P < 0.001), recurrence site (single vs. multiple: 2-year PFS, 93.8 % vs. 47.4 %, P = 0.008; 2-year OS, 100 % vs. 63.0 %, P = 0.001), and gross tumor volume (GTV) (<50cm 3 vs. ≥ 50cm 3 : 2-year PFS, 70.6 % vs. 46.2 %, P = 0.024; 2-year OS, 85.6 % vs. 57.4 %, P = 0.034) were significantly associated with PFS and OS., Conclusion: Split-course HFRT-CHT with IMRT technique achieved promising disease control and satisfactory survival with moderate toxicities in postoperative LRR of NSCLC. Good PS, a single recurrence site and GTV<50cm 3 tended to have prolonged PFS and OS. Early detection of LRR may improve the efficacy of HFRT-CHT., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Baseline lung immune prognostic index (LIPI) was reported as a potential predictive biomarker of immune checkpoint inhibitor treatment and a prognostic biomarker for metastatic non-small cell lung cancer (NSCLC). However, it remains unclear whether LIPI is associated with outcomes in locally advanced NSCLC (LA-NSCLC)., Materials/methods: Patients with LA-NSCLC receiving radiotherapy between 2000 to 2017 were retrospectively reviewed. Based on pretreatment dNLR and LDH level made up LIPI per previous publications, patients were divided into good group (0 score) and intermediate-poor group (1 or 2 scores). Propensity score matching (PSM) was conducted to balance confounding variables., Results: A total of 1079 patients were eligible for analysis. Patients with intermediate-poor pretreatment LIPI had inferior overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) than those with good LIPI. Multivariate analysis suggested that LIPI was an independent prognostic marker for OS (hazard ratio [HR] = 1.19, 95% CI: 1.02-1.40), PFS (HR = 1.18, 95% CI: 1.02-1.36), and LRRFS (HR = 1.22, 95% CI: 1.05-1.41) in patients with inoperable LA-NSCLC. PSM analysis further verified that intermediate-poor LIPI was an independent prognostic factor for shorter survivals (OS, PFS and LRRFS)., Conclusions: LIPI is a simple and promising prognostic marker for patients with unresectable LA-NSCLC. Further prospected studies are warranted to validated these findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Consistent results are lacking as regards the comparative effectiveness of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) versus conventional intensity-modulated radiotherapy in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). Therefore, we conducted a retrospective analysis to demonstrate the role of SIB-IMRT for patients., Methods: Patients who had histologically confirmed NSCLC, stage III disease and received thoracic IMRT between 2014 and 2016 were retrospectively reviewed. The survival, toxicities and dose to organs at risk (OAR) were compared among patients irradiated with different techniques. The SIB-IMRT plans were designed to deliver 45-59.4Gy (median: 50.4Gy) to PTV while simultaneously delivering 50-70Gy (median: 59.92Gy) to PGTV. As for conventional IMRT plans, a total dose of 50-70Gy (median: 60Gy) was delivered to PTV., Results: 426 patients with stage III NSCLC were eligible for analysis, including 128 with SIB-IMRT and 298 with conventional IMRT. The SIB-IMRT group had more stage IIIB disease (69.5% vs. 53%, P = 0.002), larger planning treatment volumes (median: 504 ml vs. 402 ml, P<0.001), and a larger planning treatment volume/volume of lung ratio (median, 0.18 vs. 0.12, P<0.001). The median OS of the SIB-IMRT and conventional IMRT groups were 34.5 and 31.7 months, with the 2-year rate of 60.4 and 59%, respectively (P = 0.797). No difference in PFS, LRFS or DMFS was observed between the two techniques. Patients treated with SIB-IMRT got similar lung and esophageal toxicities versus those with conventional IMRT., Conclusions: SIB-IMRT may be an effective and safe option for patients with locally advanced NSCLC, especially for those with large mass or wide lymph node metastasis.