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Objective:To investigate the value of preoperative enhanced CT combined with serum cytokeratin fragment 19 (CYFER21-1) and neuron-specific enolase (NSE) in the diagnosis of lymph node metastasis in patients with non-small cell lung cancer (NSCLC).Methods:160 patients with NSCLC admitted to Linyi Cancer Hospital from October 2018 to October 2021 were retrospectively selected. All patients received surgical treatment in our hospital, and 84 patients with lymph node metastasis (metastatic group) and 76 patients without lymph node metastasis (non-metastatic group) were confirmed after surgery. The features of enhanced CT images and serum CYFER21-1 and NSE levels were compared between the two groups before operation, and the value of each index in the diagnosis of lymph node metastasis in patients with NSCLC alone and in combination was analyzed by receiver operating characteristic (ROC) curve.Results:The proportions of patients with lesion diameter ≥3.0 cm, pleural depression, lymph node enlargement shown by CT, lymph node short diameter ≥10 mm, lymph node boundary ambiguity and lymph node enhancement in metastatic group were significantly higher than those in non-metastatic group, with statistical significance (all P<0.05). Serum CYFER21-1 and NSE levels in metastatic group were significantly higher than those in non-metastatic group, with statistical significance (all P<0.05). The area under curve (AUC) of CYFER21-1 and NSE levels in the diagnosis of lymph node metastasis in NSCLC patients were 0.652 and 0.845, respectively, and the diagnostic cut-off values were 4.81 ng/ml and 24.14 ng/ml, respectively. The sensitivity and specificity of CYFER21-1+ NSE+ enhanced CT in the diagnosis of lymph node metastasis in NSCLC patients were 91.67% and 94.74%. Conclusions:Preoperative enhanced CT is of certain clinical value in the diagnosis of lymph node metastasis in NSCLC patients. Combined with serum CYFER21-1 and NSE levels, enhanced CT can further improve the sensitivity and specificity of diagnosis.
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Objective:To analyze the effects of apatinib on quality of life and immune function in older adult patients with advanced non-small cell lung cancer.Methods:A total of 187 older adult patients with advanced non-small cell lung cancer admitted to Taizhou Cancer Hospital from January 2017 to January 2021 were included in this study. They were divided into the control group ( n = 93) and the observation group ( n = 94). The control group was treated with carboplatin combined with pemetrexed and the observation group was treated with apatinib based on carboplatin and pemetrexed. Sign and symptoms remission was compared between the observation and control groups. The levels of tumor markers, immune function, and quality of life score were compared between the two groups before and after treatment. Results:Total remission rate in the observation group was significantly higher than that in the control group (88.30% vs. 69.89%, χ2 = 9.59, P < 0.05). After treatment, carbohydrate antigen 125, carbohydrate antigen 50, and carcinoembryonic antigen in the observation group were (16.25 ± 5.47) μg/L, (15.23 ± 3.27) μg/L and (5.91 ± 2.66) mg/L, respectively, which were significantly lower than (21.49 ± 6.61) μg/L, (19.11 ± 3.48) μg/L and (10.14 ± 2.73) mg/L in the control group ( t = 5.91, 7.86, 10.73, all P < 0.05). The percentage of CD3 + and CD4 + cells, and the ratio of CD4 +/CD8 + cells in the observation group were (69.34 ± 8.85)%, (38.15 ± 6.52)%, (1.40 ± 0.33), respectively, which were significantly higher than (64.51 ± 8.74)%, (33.55 ± 6.33)%, (1.23 ± 0.25) in the control group ( t = -3.75, -5.36, -3.97, all P < 0.05). Quality of life score was increased in each group ( P < 0.001). The amplitude of increase in quality of life score was greater in the observation group compared with the control group ( P < 0.001). Conclusion:Apatinib can effectively reduce the level of tumor markers and improve immune function in older adult patients with advanced non-small cell lung cancer and improve quality of life.
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Objective:To investigate the risk factors of moderate to severe pain in patients with non-small cell lung cancer within 3 days after lobectomy.Methods:The clinical data of 297 patients with non-small cell lung cancer who underwent lobectomy in the Department of Thoracic Surgery, Sun Yat-sen University Cancer Center from December 2020 to June 2021 were retrospectively analyzed. A numerical rating scale was used to score the most severe pain within 3 days after surgery. Pain score ≥ 4 was defined as moderate to severe pain. The risk factors for moderate to severe pain were analyzed by binary Logistic regression. General linear model repeated measures and linear mixed models were used to analyze the trend of risk factors influencing postoperative pain with time.Results:The incidence of moderate to severe pain was 34.2% (102/297), 59.8% (178/297), 66.4% (198/297), and 28.2% (84/297) on days 0, 1, 2, and 3 after surgery respectively. The risk for moderate to severe pain was significantly higher in patients undergoing thoracotomy than patients undergoing thoracoscopic surgery on days 1 ( OR = 1.99, P = 0.009), 2 ( OR = 3.08, P < 0.001), and 3 ( OR = 3.88, P < 0.001) after surgery. However, the risk for moderate to severe pain in patients undergoing thoracotomy was slightly, but not significantly, higher than that in patients undergoing thoracoscopic surgery ( OR = 1.53, P = 0.087). The risk for moderate to severe pain was higher in female patients than male patients on day 2 ( OR = 1.62, P = 0.077), and in particular on day 3 after surgery ( OR = 2.39, P = 0.002). Prophylactic use of parecoxib significantly reduced the risk of moderate to severe pain on day 0 ( OR = 0.32, P = 0.004), 1 ( OR = 0.20, P < 0.001), 2 ( OR = 0.36, P < 0.001) and 3 ( OR = 0.56, P = 0.047). Conclusion:The incidence of moderate to severe pain on days 1 and 2 after lobectomy was relatively high in patients with non-small cell lung cancer. Patients undergoing thoracotomy have a higher risk of moderate to severe pain than those who underwent thoracoscopic surgery. Female patients have a higher risk for moderate to severe pain on days 2 and 3 after surgery than male patients. Prophylactic use of parecoxib can decrease the risk for moderate to severe pain in patients with non-small cell lung cancer.
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Objective:To investigate the prognostic value of urinary interleukin(IL)-8 in elderly patients with non-small cell lung cancer (NSCLC).Methods:The clinical data of 110 elderly patients with NSCLC treated in Beijing Hepingli Hospital from January 2018 to January 2019 were collected, and the relationship between urinary IL-8 and clinicopathological characteristics were analyzed. The best cut-off value was determined by receiver operating characteristic (ROC) curve. The factors affecting the survival and prognosis of elderly patients with NSCLC were determined by univariable and multivariable Cox proportional hazards regression models.Results:The best cut-off value of urine interleukin-8 for predicting prognostic of elderly patients with NSCLC was 26.08 ng/L, the specificity was 80.00%, the sensitivity was 84.60%. The level of urine IL-8 was related to neutrophil cell count, clinical stage and serum IL-8 level ( P<0.05). The results of Cox multivariate analysis showed that the age ( HR = 4.810, P = 0.000), serum soluble fragment of cytokeratin 19(CYFRA211) ( HR = 2.728, P = 0.017), clinical stage ( HR = 2.090, P = 0.014), urine IL-8 ( HR = 4.451, P = 0.000) were independent risk factors for survival of elderly patients with NSCLC. Conclusions:Urine IL-8 is an independent prognostic risk factor of survival of elderly patients with NSCLC, it can be used as one of the indicators to evaluate the survival prognosis of patients.
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Objective:To explore the efficacy of sequential and concurrent chemoradiotherapy in the treatment of advanced non-small cell lung cancer (NSCLC) in the elderly, and to analyze the influencing factors of prognosis and outcome.Methods:The clinical data of 195 elderly patients with advanced NSCLC admitted to Beijing Shijingshan Hospitaland and Beijing Shijitan Hospital from March 2015 to March 2018 were retrospectively analyzed. They were divided into the concurrent chemoradiotherapy (100 cases) and the sequential chemoradiotherapy (95 cases) according to different chemoradiotherapy regiments. The short-term efficacy, 3-year survival, influencing factors of prognosis and toxic and adverse effects of the two groups were compared.Results:The objective response rate in the concurrent chemoradiotherapy group was significantly higher than that in the sequential chemoradiotherapy group: 61.00%(61/100) vs. 44.21%(42/95), there was statistically difference ( χ2 = 5.51, P<0.05). The 2-year and 3-year survival rate in the concurrent chemoradiotherapy group were 52.00% and 23.00%, which were significantly higher than those in the sequential chemoradiotherapy group: 32.60%, 11.60%, there were statistically differences ( P<0.05). Multivariate analysis results showed that smoking, Karnofsky score<70, TNM stage Ⅲb, short-term efficacy and treatment methods/sequential chemoradiotherapy were independent risk factors ( P<0.05). The incidence of radiation esophagitis, bone marrow suppression and lung function damage in the concurrent chemoradiotherapy group were higher than those in the sequential chemoradiotherapy group: 45.00%(45/100) vs. 27.37% (26/95), 36.00%(36/100) vs. 22.11%(21/95), 48.00%(48/100) vs. 26.32%(25/95), there were statistically differences ( χ2 = 6.54, 4.55, 9.78; P<0.05). Conclusions:Concurrent chemoradiotherapy can improve the short-term efficacy, and improve the 2-year and 3-year survival rates in advanced NSCLC in elderly patients, but the adverse effects are significantly enhanced.
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Patients with operable non-small cell lung cancer (NSCLC) receiving neoadjuvant or adjuvant chemotherapy have a very limited improvement in 5-year survival rate. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have made a breakthrough in the treatment of EGFR-mutant advanced NSCLC, which shed light for the exploration of perioperative targeted therapy in NSCLC patients. Significant progress has been made in the research of targeted therapy of the first and third generation EGFR-TKI in perioperative patients. The availability of novel potent and less toxic targeted therapy has brought new treatments for the operable NSCLC. This article reviews the progress and existing problems of adjuvant and neoadjuvant targeted therapy in NSCLC harboring EGFR mutation.
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Objective:To investigate the relationship between KRAS gene mutation, programmed death receptor ligand 1 (PD-L1) expression and prognosis of first-line concurrent chemoradiotherapy in patients with locally advanced non-small cell lung cancer.Methods:The clinical data of 50 patients with locally advanced non-small cell lung cancer who were admitted to Nanping First Hospital from January 2018 to December 2021 were retrospectively analyzed. All patients were treated with first-line concurrent chemoradiotherapy. Tissue samples of patients were obtained and paraffin embedded before treatment. Real-time fluorescence quantitative polymerase chain reaction was used to detect the type of KRAS gene mutation in tissues before treatment, and the expression of PD-L1 was determined by immunohistochemistry (the percentage of positive cells in tumor cells ≥1% was positive), and the relationship between KRAS gene status, PD-L1 expression and clinical characteristics and short-term efficacy of patients was analyzed. Patients were followed up for 1 year, and progression-free survival (PFS) curves were plotted by Kaplan-Meier method, and log-rank test was used for comparison. Univariate and multivariate Cox proportional hazards models were used to analyze the influencing factors of PFS.Results:Among the 50 patients, 11 (22.00%) were KRAS mutant, and 36 (72.00%) were PD-L1 positive. Among the 11 patients with KRAS mutation, there were 2 cases of codon 13 mutation and 9 cases of codon 12 mutation in exon 2. The objective response rate (ORR) and clinical control rate (DCR) were 76.00% (38/50) and 86.00% (43/50). There were no significant differences in patients' age, pathological type, TNM stage, ORR and DCR between KRAS mutant group and KRAS wild type group (all P > 0.05). The proportions of male patients [72.73% (8/11) vs. 38.46% (15/39)], patients with smoking history [90.91% (10/11) vs. 20.51% (8/39)] and patients with PD-L1 positive expression [100.00% (11/11) vs. 64.10% (25/39)] in KRAS mutant group were higher than those in KRAS wild type group (all P < 0.05). There were no significant differences in patients' age, pathological type, gender, smoking history, TNM stage, ORR and DCR between PD-L1 positive group and PD-L1 negative group (all P > 0.05). The median PFS time of patients in KRAS mutant group and wild type group was 8.75 and 11.32 months, and the difference in PFS between the two groups was statistically significant ( P = 0.039). The median PFS time of patients with PD-L1 positive and negative was 10.19 and 11.16 months, and there was no statistical significance in PFS between the two ( P = 0.116). Multivariate Cox regression analysis showed that KRAS gene mutation was an independent risk factor for PFS in patients with locally advanced NSCLC after first-line concurrent chemoradiotherapy ( HR = 1.449, 95% CI 1.071-1.196, P = 0.017). PD-L1 expression, smoking history and gender were not independent influencing factors for PFS (all P > 0.05). Conclusions:KRAS gene status is closely related to the prognosis of patients with locally advanced non-small cell lung cancer treated with first-line concurrent chemoradiotherapy, while PD-L1 expression is not.
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Objective:To investigate the difference of dose distribution between intensity-modulated photon radiotherapy (IMRT) and intensity-modulated proton radiotherapy (IMPT) in patients with non-small cell lung cancer.Methods:The clinical data of 8 patients with stage Ⅱ-Ⅲ non-small cell lung cancer who received radiotherapy in Ion Medical center of the First Affiliated Hospital of University of Science and Technology of China from November 2020 to April 2022 were retrospectively analyzed. IMRT and IMPT radiotherapy plans were created for each patient separately, the main evaluation indicators were targeted area dose distribution parameters [homogeneity index (HI), conformity index (CI) and the percent volume of volume wrapped by 95% and 100% of prescription dose profile in the targeted area (V 95% and V 100%)], and the average dose (D mean) to the organ at risk and the percent volume of a certain relative biological effect (RBE) dose exposure [D mean, V 5 Gy(RBE) and V 20 Gy(RBE) of ipsilateral lung, D mean, V 5 Gy(RBE) and V 20 Gy(RBE) of bilateral lung, D mean, V 30 Gy(RBE) and V 40 Gy(RBE) of heart, maximum dose (D max) of spinal cord, and D mean of esophageal]. Results:In comparison with IMRT, IMPT reduced the levels of dose parameters in bilateral lung, ipsilateral lung, spinal cord, esophagus, and heart with statistically significant differences (all P < 0.05), especially in D mean of bilateral lung [(4.1±1.8) Gy (RBE) vs. (6.9±1.9) Gy (RBE)], V 5 Gy(RBE) [(15.9±7.1) % vs. (28.5±8.6)%], V 20 Gy(RBE) [(7.4±3.5)% vs. (10.1±3.5)%], and D mean of ipsilateral lung [(9.1±4.5) Gy (RBE) vs. (11.9±3.3) Gy (RBE)], all decreased significantly (all P < 0.001), but the differences in the levels of targeted area dose distribution parameters between them were not statistically significant (all P > 0.05). Conclusions:For patients with non-small cell lung cancer, IMPT is superior to IMRT in the protection of bilateral lung, ipsilateral lung, spinal cord, esophagus and heart.
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Objective:To explore the expression of OGDHL and AU element-rich RNA-binding protein 1 (AUF1) in patients with non-small cell lung cancer (NSCLC) and their correlation with the prognosis of patients.Methods:The clinical data of 96 patients with NSCLC who were diagnosed and underwent surgical treatment in Guang'an People's Hospital from February 2018 to February 2019 were retrospectively analyzed. The surgically resected NSCLC tissues and the paracancerous tissues (4 cm from the tumor edge) were taken, and the immunohistochemical staining was used to detect the protein expressions of OGDHL and AUF1 in all specimens. The relationship between OGDHL and AUF1 proteins and clinicopathological characteristics of NSCLC was analyzed. The 3-year overall survival (OS) rate of patients with different expressions of OGDHL and AUF1 proteins were compared by using Kaplan-Meier method. Multivariate Cox proportional hazards model was used to explore the influencing factors for the prognosis of NSCLC patients.Results:The high expression rate of OGDHL protein in the cancer tissues of NSCLC patients was lower than that in the paracancerous tissues [32.3% (31/96) vs. 62.5% (60/96), χ2 = 45.21, P < 0.001], and the high expression rate of AUF1 protein was higher than that in the paracancerous tissues [68.8% (66/96) vs. 34.4% (33/96), χ2 = 42.36, P < 0.001]. The high expression rate of OGDHL protein in patients with TNM stage Ⅰ-Ⅱ was higher than that in patients with stage Ⅲ-Ⅳ [39.1% (25/64) vs. 18.8% (6/32)], and the high expression rate of OGDHL protein in patients with lymph node metastasis was lower than that in patients without lymph node metastasis [10.3% (3/29) vs. 41.8% (28/67)] (both P < 0.05). The high expression rate of AUF1 protein in patients with stageⅠ-Ⅱ was lower than that in patients with stage Ⅲ-Ⅳ [59.4% (38/64) vs. 87.5% (28/32)], and the high expression rate of AUF1 protein in patients with lymph node metastasis was higher than that in patients without lymph node metastasis [86.2% (25/29) vs. 61.2% (41/67)] (both P < 0.05). The 3-year OS rate of all NSCLC patients was 62.50%. The 3-year OS rate of patients with high expression of OGDHL protein after surgery was higher than that of patients with low expression of OGDHL protein (80.66% vs. 53.33%, P < 0.05), and the 3-year OS rate of patients with high expression group of AUF1 protein after surgery was lower than that of patients with low expression of AUF1 protein (50.00% vs. 76.52%, P < 0.05). The difference in 3-year OS rate of patients with different TNM stage and lymph node metastasis was statistically significant (both P < 0.05), and the 3-year OS rate of patients with TNM stage Ⅲ-Ⅳ and lymph node metastasis was lower than that of patients with stage Ⅰ-Ⅱ and no lymph node metastasis (both P < 0.05). Low expression of OGDHL ( HR = 3.78, 95% CI 1.72-8.31) and high expression of AUF1 ( HR = 3.67, 95% CI 1.73-7.80) were both independent risk factors for the prognosis of NSCLC patients (both P < 0.001). Conclusions:The expression of OGDHL protein is decreased and the expression of AUF1 protein is increased in NSCLC tissues. The expression levels of OGDHL and AUF1 proteins are related to the prognosis of NSCLC patients.
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Objective:To explore the clinical effect of osimertinib combined with bevacizumab in treatment of advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) T790M positive.Methods:A prospective study was conducted on 83 EGFR T790M-positive advanced NSCLC patients who were admitted to Anhui Chest Hospital from April 2018 to December 2020. The patients were randomly divided into the observation group and the control group using random number table method. Among them, 41 cases in the control group were treated with osimertinib, while 42 cases in the observation group were treated with osimertinib combined with bevacizumab. The clinical efficacy, tumor markers [carcinoembryonic antigen (CEA), serum neuron specific enolase (NSE)] levels, tumor vascular associated protein factor (S100β protein) level and adverse reactions between the two groups after 3 months of treatment were compared. Kaplan-Meier method was used to draw survival curves, and the 1-year survival status of patients in the two groups was compared.Results:The disease control rate in the observation group was 69.05% (29/42), which was higher than that in the control group [43.90% (18/41)] ( χ2 = 5.34, P = 0.021), but there was no statistical difference in the objective response rate between the two groups [33.33% (14/42) vs. 21.95% (9/41)] ( χ2 = 1.34, P = 0.247). After treatment, the serum levels of CEA [(19.9±3.6) μg/ml vs. (79.3±7.9) μg/ml, (27.8±4.8) μg/ml vs. (78.6±8.1) μg/ml] and NSE [(18.9±3.2) ng/ml vs. (27.2±5.0) ng/ml, (22.0±3.3) ng/ml vs. (26.1±4.8) ng/ml] in the observation group and control group were lower than those before treatment (all P < 0.05). There was no statistical difference in CEA and NSE levels between the two groups before treatment (both P > 0.05), and after treatment, the observation group was lower than the control group (both P < 0.001). The serum S100β levels of patients in the observation and control groups after treatment were all higher than those before treatment [(50±5) μg/ml vs.(44±5) μg/ml, (55±4) μg/ml vs. (45±6) μg/ml, both P = 0.001), and the difference in S100β level between the two groups before treatment was not statistically significant ( P > 0.05), and after treatment, the observation group was lower than the control group ( P < 0.001). Both groups of patients did not experience acute severe adverse reactions during the medication period. There were no statistical differences between the observation group and the control group in the incidence rates of nausea and vomiting [9.52% (4/42) vs. 7.32% (3/41)], constipation and diarrhea [4.76% (2/42) vs. 4.88% (2/41)], thrombocytopenia [9.52% (4/42) vs. 4.88% (2/41)], and liver function damage [7.14% (3/42) vs. 2.44% (1/41)] (all P > 0.05). The 1-year overall survival rate of the observation group was higher than that of the control group [68.3% (95% CI 47.9%-86.1%) vs. 41.0% (95% CI 22.4%-65.3%)], and the overall survival of the observation group was better than that of the control group ( χ2 = 2.60, P = 0.037). Conclusions:The combination of osimertinib and bevacizumab in treatment of EGFR T790M-positive advanced NSCLC can effectively regulate the levels of tumor related factors, with good efficacy and safety.
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Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. In recent years, with the rapid development of immunotherapy, checkpoint inhibitors, especially programmed death factor-1 (PD-1)/programmed death factor ligand-1 (PD-L1) inhibitors, have made breakthrough progress in the treatment of NSCLC, breaking the pattern of low efficiency and extensive resistance to targeted therapy of traditional chemoradiotherapy, bringing survival benefits to patients. This article reviews the clinical research progress of PD-1/PD-L1 inhibitors in advanced NSCLC.
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The application of immune checkpoint inhibitors (ICI) has rewritten the current treatment pattern of non-small cell lung cancer. However, single-agent ICI has disadvantages such as small benefit population and slow tumor cytoreduction effect. Therefore, various immunizations combined with other treatment methods are becoming clinical hotspots. Low-dose irradiation shows a significant anti-tumor synergistic effect through activating the body's immune system, and its potential for adjuvant immunotherapy has transformed traditional radiotherapy from local radical treatment to immune adjuvant. This article reviews the current research progress of ICI combined with low-dose irradiation in the treatment of non-small cell lung cancer.
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Objective:To investigate the effect of immune checkpoint inhibitors combined with concurrent chemotherapy for non-small cell lung cancer (NSCLC) and the effect of this regimen on serum levels of tumor marker and immune cells of patients.Methods:The clinical data of 60 NSCLC patients in Xuzhou Cancer Hospital from February 2020 to February 2022 were retrospectively analyzed, and they were divided into chemotherapy combined with immune checkpoint inhibitor treatment group (combination treatment group) and conventional chemotherapy group by treatment methods, with 30 cases in each group. Before treatment and 6 weeks after treatment, the patients' serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), vascular endothelial growth factor (VEGF), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) were detected by chemiluminescence immunoassay, and the levels of serum tumorous M2 pyruvate kinase (TuM2-PK) and fatty acid synthase (FAS) were detected by double-antibody sandwich enzyme-linked immunosorbent assay. The levels of T cell subsets were measured by flow cytometry, and the quality of life of patients was evaluated according to the World Health Organization quality of life scale brief version (WHOQOL-BREF). The clinical efficacy, tumor markers levels, immune cells levels, quality of life and adverse reactions were compared between the two groups.Results:The overall effective rate of patients in the combination treatment group was 46.67% (14/30), which was higher than 20.00% (6/30) in the conventional chemotherapy group ( χ2 = 4.80, P = 0.029). The differences in serum CEA, CA125, VEGF, CYFRA21-1, TuM2-PK, FAS levels and the proportions of CD3 +, CD4 +, CD8 + T cells and WHOQOL-BREF scores between the two groups before treatment were not statistically significant (all P > 0.05); the levels of CEA, CA125, VEGF, CYFRA21-1, TuM2-PK, FAS and the proportion of CD8 + T cells at 6 weeks after treatment were lower than those before treatment in both groups (all P < 0.05), and the proportions of CD3 + and CD4 + T cells and WHOQOL-BREF scores were higher than those before treatment (all P < 0.05); the levels CEA, CA125, VEGF, CYFRA21-1, TuM2-PK and the proportions of CD8 + T cells in the combination treatment group at 6 weeks after treatment were higher than those in the conventional chemotherapy group at 6 weeks after treatment (all P < 0.001), and the proportions of CD3 + and CD4 + T cells and WHOQOL-BREF scores were higher than those in the conventional chemotherapy group at 6 weeks after treatment (all P < 0.05). The differences in the incidence of gastrointestinal reactions, alopecia, leukopenia, thrombocytopenia, and liver and kidney function impairment between the two groups were not statistically significant (all P > 0.05). Conclusions:Immune checkpoint inhibitors combined with chemotherapy in NSCLC patients are more effective than conventional chemotherapy, and the combined treatment can more effectively reduce the serum tumor marker levels of patients and enhance the anti-tumor immune effect, with the adverse reactions comparable to conventional chemotherapy.
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The morbidity and mortality of non-small cell lung cancer(NSCLC)are among the highest of all malignancies.The mechanisms concerning metronomic chemotherapy include anti-angiogenesis, immune microenvironment regulation, and cytotoxic effects, among others.As an alternative to traditional chemotherapy, metronomic chemotherapy has shown promising outcomes in the treatment of advanced NSCLC.Several clinical trials have explored the application of metronomic chemotherapy in the treatment of advanced NSCLC, either as a monotherapy or in combination with chemotherapy, anti-angiogenic therapy, targeted therapy or immunotherapy.This paper mainly reviews the mechanisms underlying metronomic chemotherapy and its clinical application in advanced NSCLC, in order to provide more evidence for the optimization of NSCLC treatment regimens.
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Objective:To investigate the predictive value of the epithelial cell proliferation(ECP)pathway genes for the prognosis of elderly non-small cell lung cancer patients treated with immunotherapy.Methods:A total of 106 elderly patients aged 70 years and over receiving immunotherapy in the POPLAR and OAK clinical trials were retrospectively analyzed in October 2022.According to the mutation status, patients were divided into an ECP pathway-related gene mutation group(ECP mutation group, n=25)and an ECP pathway-related gene non-mutation group(ECP non-mutation group, n=81). The primary endpoints were overall survival(OS)and progression-free survival(PFS). Differences in survival and efficacy between the two groups were compared, and subgroup analysis was performed on clinical factors and genes involved in the pathway.Pyclone was used to calculate the distribution of major clones and subclones in each patient, and differences in survival were compared.Results:Survival outcomes were worse in the ECP(+ )group than in the ECP(-)group(mOS: 10.9 months vs.17.1 months, HR=1.84, 95% CI: 1.09-3.08, P<0.05; mPFS: 2.8 months vs.4.2 months, HR=1.58, 95% CI: 1.00-2.51, P<0.05). Of all mutations in ECP pathway-related genes, mutations in the RB1 gene had a significant prognostic effect on all patients, with the negative prognostic effect especially prominent in ECP(+ )patients.Compared with ECP(-)patients, ECP(+ )patients had a shorter mOS(6.9 months vs.12.6 months, HR=3.14, 95% CI: 1.10-8.97, P=0.024). Ten patients had clonal mutations and 15 patients had sub-clonal mutations in ECP pathway-related genes and the former had a shorter mPFS than the latter(1.3 months vs.5.3 months, HR=3.23, 95% CI: 1.25-8.37, P=0.011). Conclusions:Gene mutations in the epithelial cell proliferation pathway are a negative prognostic factor in elderly non-small cell lung cancer patients receiving immunotherapy, and mutations located in the clonal cluster have a stronger impact on the prognosis.
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Objective:To investigate the efficacy and safety of recombinant human endostatin(Endostar)combined with platium-contained chemotherapeutic agents in advanced non-small cell lung cancer(NSCLC)patients over 60 years old.Methods:93 advanced NSCLC patients from January 2019 to June 2021 were selected as the research objects.The patients received three days of continuous intravenous infusion of Endostar(210 mg for 72 hours)combined with platinum-containing chemotherapy.The efficacy and toxicities were evaluated according to Response Evaluation Criteria in Solid Tumors(RECIST)version1.1 and National Cancer Institute Common Terminology Criteria for Adverse Events(NCI-CTCAE version 4.0), respectively.Follow-up data were obtained to perform the Kaplan-Meier survival analysis.Results:In our study, the objective remission rate(ORR)and disease control rate(DCR)were 38.7% and 78.5%, respectively.The median progression-free survival(PFS)and overall survival(OS)were 6.8 months and 16.5 months, respectively.A Multivariate analysis showed that tumor staging and TP53 mutation were independent prognostic factors related to PFS and OS in advanced NSCLC patients.Adverse reactions related to Endostar during treatment included arrhythmia in 2 cases(2.2%), myocardial ischemia in 1 case(1.07%)and bloody sputum in 1 case(1.07%), all of which were Grade 1 or Grade 2.Conclusions:The application of three days continuous intravenous infusion of Endostar combined with platium-contained chemotherapeutic agents is worthy to be recommended for clinical application in elderly patients with advanced NSCLC due to its high effective rate and survival advantage, as well as good safety.
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Objective:To investigate the value of pre-therapy 18F-FDG PET/CT radiomic models in differentiating epidermal growth factor receptor (EGFR) exon 19 deletion from exon 21 L858R missense in patients with non-small cell lung cancer (NSCLC). Methods:A total of 172 patients with EGFR mutant NSCLC (54 males, 118 females, age: (56.2±12.5) years) in the Fourth Hospital of Hebei Medical University between January 2015 and November 2019 were retrospectively included. Exon 19 mutation was found in 75 patients and exon 21 mutation was identified in 97 patients. The patients were divided into training set ( n=121) and validation set ( n=51) in a 7∶3 ratio by using random number table. The LIFEx 4.00 package was used to extract texture features of PET/CT images of lesions. The least absolute shrinkage and selection operator (LASSO) algorithm was used for feature screening. Three machine learning models, namely logistic regression (LR), random forest (RF), and support vector machine (SVM) models, were constructed based on the selected optimal feature subsets. The ROC curve analysis was performed to assess the predictive performance of those models. Finally, decision curve analysis (DCA) was used to evaluate the clinical value of the models. Results:Nine radiomics features, including 6 PET features (histogram (HISTO)_Kurtosis, SHAPE_Sphericity, gray level run length matrix (GLRLM)_ low gray-level run emphasis (LGRE), GLRLM_ run length non-uniformity (RLNU), neighborhood grey level different matrix (NGLDM)_Contrast, gray level zone length matrix (GLZLM)_ short-zone low gray-level emphasis (SZLGE)), and 3 CT features (gray level co-occurrence matrix (GLCM)_Correlation, GLRLM_ run percentage (RP), NGLDM_Contrast), were screened by LASSO algorithm. Three machine learning models had similar predictive performance in the training and validation sets: AUCs for the RF model were 0.79, 0.77, and those for the SVM model were 0.76, 0.75, for the LR model were 0.77, 0.75. The DCA showed that the 3 machine learning models had good net benefits and clinical values in predicting EGFR mutation subtypes.Conclusion:18F-FDG PET/CT radiomics provide a non-invasive method for the identification of EGFR exon 19 deletion and exon 21 L858R missense mutations in patients with NSCLC, which may help the clinical decision-making and the formulation of individualized treatment plan.
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Objective:To explore the clinical efficacy of CT-guided 125I seed implantation in patients with oligometastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) activating mutations (EGFRm+ ) without progression after first-line EGFR-tyrosine kinase inhibitors (TKIs) treatment. Methods:From January 2015 to January 2019, 89 eligible patients (38 males, 51 females; age: (62±11) years) in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. They were divided into 2 groups according to different treatment methods. The 125I seeds were implanted for oligometastatic lesions and/or primary tumors without progression after first-line EGFR-TKIs therapy in local consolidation treatment group (Group A, n=32). The maintenance treatment group (Group B, n=57) only received EGFR-TKIs until disease progression. The progression-free survival (PFS) and overall survival (OS) of the 2 groups were estimated by Kaplan-Meier curves, and were compared by using log-rank test. Complications in Group A were observed. Results:The follow-up time of the group A and group B were 36.5(31.0, 43.3) months and 30.0(24.0, 35.0) months respectively. The median PFS and OS in group A were 15.0(95% CI: 12.8-17.2 ) months and 37.0(95% CI: 33.9-40.1) months, both of which were significantly longer than those in group B (12.0(95% CI: 10.9-13.1) months and 31.0(95% CI: 28.9-33.1) months; χ2 values: 8.80, 7.15, P values: 0.003, 0.007). In Group A, the total incidence of complications in CT-guided 125I seed implantation was 21.9%(7/32), and the common complications and adverse events were pneumothorax and hemoptysis. Only 1 patient underwent chest tube insertion, and the rest were treated with conservative treatment. No operation related death occurred. Conclusion:CT-guided 125I seed implantation is safe and feasible for patients with EGFRm+ oligometastatic NSCLC without progression after first-line EGFR-TKIs treatment, and can prolong the PFS and OS of patients.
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Objective:To assess the predictive efficacy of 18F-FDG PET/CT-based radiomics models for the mutation status of Kirsten rats sarcoma viral oncogene homolog (KRAS) in patients with non-small cell lung cancer (NSCLC). Methods:From January 2016 to January 2021, the 18F-FDG PET/CT images and KRAS testing of 258 NSCLC patients (180 males, 78 females; age: 33-91 years) in the First Affiliated Hospital of the Air Force Military Medical University were retrospectively analyzed. Patients were randomly divided into training set ( n=180) and validation set ( n=78) in the ratio of 7∶3. Tumor lesions on PET and CT images were drawn respectively, and the radiomics features of PET and CT lesions were extracted. The radiomics features were screened by least absolute shrinkage and selection operator (LASSO). CT radiomics score (RS) model, PET/CT RS model and composite models of PET/CT RS combined with screened clinical information were eventually developed. ROC curves were used to assess the predictive efficacy of these models. Results:The CT RS model included 4 radiomics features and the PET/CT RS model included 4 CT radiomics features and 8 PET radiomics features. The CT RS model and the PET/CT RS model both had significant differences in RS between KRAS mutant and wild-type patients in the training set and validation set ( z values: from -8.30 to -4.10, all P<0.001). In predicting KRAS mutations, the composite model of PET/CT RS combined with age showed AUCs of 0.879 and 0.852 in the training and validation sets respectively, which were higher than those of the CT RS model (0.813 and 0.770) and the PET/CT RS model (0.858 and 0.834). The accuracy of the composite model of PET/CT RS combined with age were 81.67%(147/180) and 79.49%(62/78) in the training set and validation set respectively, which were also higher than those of the CT RS model (75.00%(135/180) and 74.36%(58/78)) and the PET/CT RS model (78.89%(142/180) and 78.21%(61/78)). Conclusion:Models based on radiomics features can predict KRAS gene mutation status, and the composite model combining PET/CT RS and age can improve the prediction performance.
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The morbidity and mortality of lung cancer rank first in the world. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) can significantly prolong survival of patients with advanced non-small cell lung cancer (NSCLC). 18F-FDG PET/CT can evaluate EGFR mutation status and EGFR-TKI efficacy. This article reviews the role of 18F-FDG PET/CT in predicting EFGR mutation, the efficacy and survival prognosis evaluation of EGFR-TKI therapy, as well as the development of latest EGFR-TKI PET imaging agents.