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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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Objective:To explore the potential categories of post-operative supportive care demand trajectory for patients with non-small cell lung cancer (NSCLC), analyze the influencing factors, and propose targeted interventions.Methods:This was a prospective observational study. A convenient sampling method was used to select 177 NSCLC patients who received surgical treatment in Shanghai Lung Hospital Affiliated to Tongji University from January 2021 to February 2022. The Supportive Care Demand Scale for cancer patients was used to investigate the level of patients′supportive care demand 1 day before operation, 3 days after operation, 1 day before discharge, 1 week after discharge, 1 month after discharge, and 3 months after discharge, and the potential growth model was used to identify the trajectory category and multi category Logistic regression analysis was used to explore the influencing factors.Results:Three supportive care demand trajectories were fitted out in this study, which were the continuous high demand group (46.33%), the slowly decreasing demand group (30.51%), and the low decreasing demand group (23.16%). With the potential category group 3, low demand reduction group as the reference category, Logistic regression analysis showed that high psychological distress, low social support, high disease stage, high comorbidities were more likely to enter the continuous high demand group ( OR = 0.826 to 18.526, all P<0.05), and high education level (college education and above and high school) were more likely to enter the slowly decreasing demand group ( OR = 6.076, 4.199, both P<0.05). Conclusions:The demand track of NSCLC patients for supportive care after surgery has population heterogeneity. Clinical medical staff should provide personalized social support and emotional support for patients with high disease stage, more complications and low education level in the early postoperative period.
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Objective:To investigate the grouping characteristics of psychological state symptom clusters in patients with non-small cell lung cancer during programmed death 1 (PD-1) monoclonal antibody combined with chemotherapy, and to analyze the predictors of different symptom cluster characteristics.Methods:This study was a cross-sectional study. In the form of a questionnaire, 171 patients with non-small cell lung cancer who received PD-1 monoclonal antibody combined with chemotherapy in Gansu Wuwei Tumor Hospital from March 2019 to March 2021 were selected as the research object by convenient sampling method. The general data questionnaire, Pittsburgh Sleep Quality Index, Cancer-Related Fatigue Survey Scale, Hospital Anxiety and Depression Scale, Physical Activity Measurement Scale for Cancer Patients, Distress Thermometer, and Quality of Life Measurement Scale for Lung Cancer Patients were used for investigation. The latent class model was fitted based on the evaluation results of physical fatigue, anxiety, depression, sleep quality and psychological distress in patients with non-small cell lung cancer during treatment. Latent class model analysis was performed on the scale results to establish a category group model. Logistic regression analysis was used to compare the demographic characteristics, disease stage, classification, and personality characteristics of patients in each group, and to explore the predictive indicators between different categories.Results:According to the symptoms of fatigue, anxiety, depression, sleep disorder and psychological distress in patients with non-small cell lung cancer during PD-1 monoclonal antibody therapy combined with chemotherapy, they were divided into two different categories. The group with high psychological symptoms accounted for 44.44% (76/171) and the group with low psychological symptoms accounted for 55.56% (95/171). The scores of physiological status, social/family status, emotional status, functional status, additional attention and physical activity in the quality of life scale of lung cancer patients with low psychological symptoms were 11.28 ± 5.62, 17.57 ± 4.31, 11.14 ± 3.27, 14.83 ± 5.24, 14.76 ± 4.03 and 88.61 ± 17.38, respectively. The scores were higher than those in the high psychological symptom group 17.82 ± 4.43, 10.76 ± 3.63, 18.62 ± 6.06, 9.34 ± 3.13, 26.26 ± 3.23, 58.04 ± 15.41, the differences were statistically significant ( t values were 10.36-15.84, all P<0.05); logistic regression analysis showed that personality traits [extroverted ( OR=0.08, 95 % CI 0.03-0.23, P<0.05), intermediate ( OR=0.16, 95 % CI 0.08-0.33, P<0.05)] and physical activity in cancer patients ( OR=0.91, 95 % CI 0.88-0.93, P<0.05) were predictors for distinguishing high psychological symptom group. Conclusions:There are obvious classification characteristics of psychological symptom clusters in patients with non-small cell lung cancer during PD-1 monoclonal antibody combined with chemotherapy. Different psychological interventions and nursing care are given according to different psychological symptom characteristics during treatment to improve the quality of life of patients.
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Objective:To explore the predictive value of neutrophil to lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) of inflammatory markers of peripheral blood cells on the prognosis in the advanced non-small cell lung cancer (NSCLC) patients with immune therapy.Methods:The hematologic and clinical data of 58 patients with advanced non-small cell lung cancer who received the treatment of immune therapy in the First People's Hospital of Chuzhou of Anhui Province from January 2018 to June 2022 were retrospectively analyzed. X-tile software was used to calculate the optimal cut-off values of NLR and SII. All patients were divided into high and low groups according to the optimal cut-off values. The relationship between different NLR, SII and clinicopathological features, clinical efficacy, prognosis of the advanced non-small cell lung cancer patients with immune therapy were analyzed. Cox regression models were used to perform univariate and multivariate analyses of factors affecting patient prognosis.Results:The optimal cut-off values for NLR and SII were 3.2 and 546.5, respectively. There were statistically significant differences in regional lymph node metastasis ( χ2=5.03, P=0.025) and the number of metastatic sites ( χ2=11.60, P=0.001) between patients in the low-NLR group (NLR<3.2, n=26) and the high-NLR group (NLR≥3.2, n=32). There were statistically significant differences in location of the primary site ( χ2=8.34, P=0.004) between patients in the low-SII group (SII<546.5, n=28) and the high-SII group (SII≥546.5, n=30). The objective response rate (ORR) of the low-NLR group [50.00% (13/26) ] was higher than that of the high-NLR group [21.88% (7/32) ], and there was a statistically significant difference ( χ2=5.02, P=0.025) ; the disease control rate (DCR) of the low-NLR group [69.23% (18/26) ] was higher than that of the high-NLR group [50.00% (16/32) ], but there was no statistically significant difference ( χ2=2.19, P=0.139). The ORR of the low-SII group [53.57% (15/28) ] was higher than that of the high-SII group [26.67% (8/30) ]; The DCR of the low-SII group [67.86% (19/28) ] was higher than that of the high-SII group [33.33% (10/30) ], and there were statistically significant differences ( χ2=4.38 , P=0.036; χ2=6.91 , P=0.009). The median overall survival (OS) of patients in the low-NLR group (17.6 months) was longer than that of the high-NLR group (11.7 months), and there was a statistically significant difference ( χ2=11.07, P=0.001). The median OS of patients in the low-SII group (16.5 months) was longer than that of the high-SII group (12.3 months), and there was a statistically significant difference ( χ2=5.53, P=0.019). Univariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score ( HR=2.20, 95% CI: 1.10-4.39, P=0.025), brain metastases ( HR=3.24, 95% CI: 1.61-6.50, P=0.001), the number of transferred sites ( HR=2.83, 95% CI: 1.44-5.57, P=0.003), NLR ( HR=3.22, 95% CI: 1.56-6.66, P=0.002) and SII ( HR=2.18, 95% CI: 1.12-4.24, P=0.021) were all independent influence factors affecting the prognosis of the advanced non-small cell lung cancer patients with immune therapy; multivariate analysis showed that brain metastases ( HR=2.91, 95% CI: 1.22-6.94, P=0.016), NLR ( HR=2.88, 95% CI: 1.17-7.13, P=0.022) and SII ( HR=3.63, 95% CI: 1.40-9.39, P=0.008) were all independent risk factors affecting the prognosis of the advanced non-small cell lung cancer patients with immune therapy. Conclusion:NLR and SII can be used as important indicators for predicting the efficacy of immunotherapy in the advanced NSCLC and elevated NLR and SII can indicate poor prognosis of patients.
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Objective:To evaluate the safety of ensartinib in the treatment of anaplastic lymphoma kinase (ALK) -positive non-small cell lung cancer (NSCLC) in the real-world clinical setting.Methods:Clinical data of 2 221 patients with ALK-positive locally advanced or metastatic NSCLC who received ensartinib treatment (225 mg/d) from December 16, 2020 to December 16, 2021 were collected and analyzed to assess drug adverse reactions in all population including elderly patients (≥ 65 years old) .Results:Among the total 2 221 patients, 511 patients (23.01%) experienced adverse events, including 8 patients (0.36%) who experienced serious adverse events. Adverse events led to dose modification in 67 patients (3.02%) and discontinuation in 18 patients (0.81%). The common adverse events were rash (407/2 221, 18.33%), pruritus (41/2 221, 1.85%), constipation (41/2 221, 1.85%), and facial edema (31/2 221, 1.40%). Thirty-six patients (1.62%) experienced ≥grade 3 adverse events. After symptomatic treatment of 511 patients with adverse reactions, 50 patients (9.78%) were healed, 271 patients (53.03%) were improved, 120 patients (23.48%) were persisted, and 70 patients (13.71%) were unknown due to loss of follow-up or other reasons. Forty-three patients (1.94%) reported 57 unintended adverse reactions. Among the 599 elderly patients, 116 patients (19.37%) experienced adverse events, including 1 patient (0.17%) who experienced serious adverse events. Adverse events led to dose modification in 25 patients (4.17%) and discontinuation in 5 patients (0.83%). The common adverse events of elderly patients were rash (88/599, 14.69%), constipation (14/599, 2.34%), facial edema (12/599, 2.00%), and pruritus (10/599, 1.67%). Twelve patients (2.00%) experienced ≥grade 3 adverse events. Among the 116 elderly patients with adverse reactions following the symptomatic treatment, 11 patients (9.48%) were healed, 58 patients (50.00%) were improved, 28 patients (24.13%) were persisted, and 19 patients (16.39%) were unknown due to loss of follow-up or other reasons. During the treatment, 1 patient (0.05%) experienced grade 2 interstitial lung disease, and no patient died due to adverse events.Conclusion:Ensartinib has a favorable safety profile in the real-world populations, with the most frequent adverse events being rash, mostly mild, and low incidence of ≥grade 3 adverse events. Overall, adverse reactions were tolerable and manageable.
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Epidermal growth factor receptor (EGFR) -mutant advanced non-small cell lung cancer (NSCLC) was previously regarded as a cold tumor according to tumor immune microenvironment (TIME) . However, recent studies have found that EGFR-tyrosine kinase inhibitors (EGFR-TKIs) treatment can transform the host immunity from immunosuppressive to immunosupportive state, bringing new hope for immunotherapy. There are four main therapeutic strategies for patients after EGFR-TKIs acquired resistance: immunotherapy alone (Im) , immunotherapy plus chemotherapy (Im+C) , immunotherapy plus antiangiogenic drugs (Im+A) , and immunotherapy combined with antiangiogenic drugs and chemotherapy (Im+A+C) . Among them, the efficacy of Im is extremely limited, being significantly lower than that of chemotherapy alone, while there is still scarce evidence for the efficacy of Im+A with few clinical studies. The combination of Im+C and Im+A+C shows better efficacy than chemotherapy alone. Im+A+C has a superior clinical outcome to Im+C. Additionally, the EGFR L858R mutation subgroup benefits more from Im+C than the EGFR 19 del mutation subgroup. The T790M-negative subgroup has a greater benefit from Im+A+C than the T790M-positive subgroup. In general, the strategy of combining immunotherapy with chemotherapy and/or an antiangiogenic drug represents a novel and promising method for treating EGFR-mutant NSCLC after EGFR-TKI failure.
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Objective:To investigate the real-world efficacy of osimertinib and icotinib in metastatic non-small cell lung carcinoma (NSCLC) patients.Methods:A retrospective analysis was performed on clinical data of 151 newly-diagnosed patients with epidermal growth factor receptor (EGFR) -positive advanced NSCLC in Renmin Hospital of Wuhan University from March 2018 to May 2022. The patients were divided into osimertinib group ( n=53) and icotinib group ( n=98) according to treatment method. The objective response rate (ORR) , disease control rate (DCR) , progression-free survival (PFS) and overall survival (OS) were compared between the two groups. The factors influencing prognosis were analyzed by using Cox regression models. Subgroup analysis was performed according to metastatic site and EGFR mutation type. Results:ORR was 56.6% (30/53) and 59.2% (58/98) for patients in the osimertinib group and icotinib group, respectively, with no statistically significant difference ( χ2=0.09, P=0.759) . DCR was 83.0% (44/53) and 91.8% (90/98) for patients in the osimertinib group and icotinib group, respectively, with no statistically significant difference ( χ2=2.68, P=0.102) . The median PFS was 11.7 months and 11.8 months for patients in the osimertinib group and icotinib group, respectively, with no statistically significant difference ( χ2=0.06, P=0.802) . The median OS was not reached for patients in both the osimertinib group and icotinib group, with no statistically significant difference ( χ2<0.01, P=0.969) . The results of multivariate analysis showed that adrenal metastases ( HR=1.89, 95% CI: 1.04-3.41, P=0.036) was an independent prognostic factor for PFS. Gender ( HR=2.22, 95% CI: 1.08-4.58, P=0.031) and adrenal metastases ( HR=4.87, 95% CI: 1.76-13.46, P=0.002) were independent prognostic factors for OS. The results of the subgroup analysis showed that in patients with pleural metastases (median PFS: 11.7 months vs. 9.3 months, median OS: not reached vs. not reached) , adrenal metastases (median PFS: 8.7 months vs. 5.6 months, median OS: 20.0 months vs. 15.3 months) , 19DEL mutations (median PFS: 14.5 months vs. 13.3 months, median OS: not reached vs. 40.7 months) , the osimertinib group tended to have better survival outcomes. Conversely, in patients with contralateral lung metastases (median PFS: 8.3 months vs. 11.2 months, median OS: not reached vs. 40.7 months) , bone metastases (median PFS: 11.7 months vs. 11.8 months, median OS: not reached vs. 34.5 months) , liver metastases (median PFS: 8.7 months vs. 9.1 months, median OS: not reached vs. 23.8 months) , brain metastases (median PFS: 11.7 months vs. 15.3 months, median OS: 22.4 months vs. 35.3 months) and 21L858R mutations (median PFS: 9.5 months vs. 10.0 months, median OS: 22.4 months vs. not reached) , the icotinib group tended to have better survival outcomes, but with no statistically significant differences (all P>0.05) . Conclusion:Both osimertinib and icotinib have good therapeutic efficacy in patients with EGFR-positive advanced NSCLC, thus can be used as first-line treatment options.
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MET exon14 (METex14) skipping mutation is an independent driver gene in non-small cell lung cancer (NSCLC) . About 3%-4% of NSCLC patients carry METex14 skipping mutation. These patients have poor prognoses and poor responses to traditional chemotherapy and immunotherapy. Highly selective MET inhibitors such as capmatinib, tepotinib, savolitinib have shown good efficacy and safety data in clinical trials, which bring new treatment options for patients with METex14 skipping mutations.
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Lung cancer remains the leading cause of cancer-related deaths in men and women worldwide, and 85% of these patients have non-small cell lung cancer. In recent years, the clinical use of targeted drug therapy and immune checkpoint inhibitors has dramatically changed the treatment landscape for advanced NSCLC. The mechanism and the value of targeted therapies have been a hot topic of research, as KRAS is one of the earliest discovered and most frequently mutated oncogenes, which is activated by binding to GTP and triggers a series of cascade reactions in cell proliferation and mitosis. The KRAS protein acts as a molecular switch and is activated by binding to GTP, triggering a series of cascade responses in cell proliferation and mitosis. Clinically, patients with KRAS mutated NSCLC have poor response to systemic medical therapy and poor prognosis. Since the first report of KRAS gene in 1982, research on KRAS targeted therapeutics has been slow, and previous studies such as farnesyltransferase inhibitors and downstream protein inhibitors of KRAS signaling pathway have not achieved the expected results, making KRAS long defined as a "non-druggable target". The deeper understanding of the crystal structure of KRAS has led to the discovery of potential therapeutic sites for KRAS and the development of several drugs directly targeting KRAS, especially KRAS G12C inhibitors such as AMG510 (sotorasib) and MRTX849 (adagrasib), which have shown encouraging results in clinical trials. In recent years, studies on the therapeutic efficacy of immune checkpoint inhibitors for KRAS-mutated NSCLC have made some progress. In this review, we systematically introduce the basic understanding of RAS gene and clinical characteristics of KRAS mutated NSCLC patients, summarize the medical treatments for KRAS mutated NSCLC, including chemotherapy, anti-vascular drug therapy and tumor immunotherapy, and focus on the review and outlook of the research progress of KRAS targeted therapy.
Subject(s)
Male , Humans , Female , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/genetics , Proto-Oncogene Proteins p21(ras)/therapeutic use , Genes, ras , Immune Checkpoint Inhibitors/therapeutic use , Guanosine Triphosphate/therapeutic use , MutationABSTRACT
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.