Analysis of Risk Factors for Pulmonary Infections During Radiotherapy in Lung Cancer Patients.

Objective: To investigate the risk factors for lung infection in lung cancer patients undergoing radiotherapy. Methods: We selected 142 patients with lung cancer who underwent radiotherapy at our hospital from January 2020 to June 2021. The patients were divided into groups according to whether they had pulmonary infection during radiotherapy in our hospital, which was infected group (n=44) and the uninfected group (n=98), respectively. To observe the incidence of lung infection in lung cancer patients during radiotherapy. The distribution of pathogenic bacteria in patients with pulmonary infection was observed. Clinical data of the two groups were collected and compared. The risk factors of lung cancer patients complicated with lung infection were analyzed by binary Logistic regression. Results: All patients with lung cancer complicated with lung infection underwent relevant examination, and the results showed that they were all complicated infections, and the composition ratio of Klebsiella pneumoniae was the highest (31.82%), followed by Staphylococcus, Pseudomonas, and fungi, which accounted for 27.27%, 22.73%, and 18.18%, respectively. Binary Logistic regression analysis showed that age ≥60 years old, smoking history ≥30 years, radiotherapy duration of combined drug regimen > 2 weeks, pathogenic bacteria combined infection, albumin content < 30 g/L were risk factors for lung cancer patients during radiotherapy. Conclusion: Age ≥60 years old, smoking history ≥30 years old, radiotherapy duration of combined drug regimen > 2 weeks, pathogenic bacteria combined infection, albumin content < 30 g/L are the risk factors for lung cancer patients during radiotherapy. Clinical prevention and intervention should be based on the aforementioned independent risk factors to decrease the incidence of lung infections, thereby enhancing patient prognosis.

An updated network meta-analysis of EGFR-TKIs and combination therapy in the first-line treatment of advanced EGFR mutation positive non-small cell lung cancer.

Objectives: Tyrosine kinase inhibitors (TKIs) are a standard care option in patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation. TKI-based combination treatment modes show encouraging outcomes. However, it remains unknown which is the optimal treatment as the first-line regimen for these patients on overall survival (OS). Materials and methods: Randomized controlled trials and meeting abstracts that investigated EGFR-TKIs alone or in combination as front-line care for patients with NSCLC were systematically searched in relevant databases and reviewed. Fixed and random effects network meta-analysis models were used to estimate progression-free survival (PFS), OS, overall response rate, and grade three and higher adverse events (AEs). Surface under the cumulative ranking curves (SUCRAs) were used to rank treatment effects. Results: Eighteen studies covering six treatments and involving a total of 4389 patients were included in this network meta-analysis. On OS, the top three treatment were first-generation EGFR-TKIs (1G EGFR-TKIs) plus chemotherapy (SUCRA, 88.1%), osimertinib (SUCRA, 65.8%) and second-generation EGFR-TKIs (2GEGFR-TKIs) (SUCRA, 63.3%). On PFS, the top three treatments were osimertinib (SUCRA, 96.0%), 1G EGFR-TKIs plus chemotherapy (SUCRA, 67.1%), and 1G EGFR-TKIs plus antiangiogenesis (SUCRA, 48.2%). Two types of TKI-based combination therapy have significantly higher risk of grade three and higher AEs than TKI alone. Conclusion: 1G EGFR-TKIs plus chemotherapy and osimertinib seem to be the two better options as first-line care in advanced NSCLC patients with EGFR-mutation. Osimertinib caused the lowest incidence of AEs. However, TKIs-based combination therapy significantly increased AEs.

Late-course accelerated Hyperfractionation vs. Conventional Fraction Radiotherapy under precise technology plus Concurrent Chemotherapy for Esophageal Squamous Cell Carcinoma: comparison of efficacy and side effects.

Background: The accelerated reproliferation of esophageal squamous cell carcinoma (ESCC) after radiation contributes to conventional fraction radiotherapy (CFRT) failure. Late course accelerated hyperfractionated radiotherapy (LCAHFRT) can improve the long-term survival of esophageal cancer patients in China but is associated with a high rate of side effects due to the large exposure field of two-dimensional treatment and drug toxicity. Intensity-modulated radiotherapy (IMRT) can increase the tumor dose while decreasing the normal tissue dose. Therefore, we compared the outcomes and side effects of LCAHFIMRT plus concurrent chemotherapy (CT) and CFIMRT plus CT for ESCC. Methods and Materials: Between 2013 and 2016, 114 eligible patients with ESCC were recruited and randomly assigned to receive LCAHFIMRT+CT (58 patients) or CFIMRT+CT (56 patients) by a linear accelerator (6-MV X-ray) under image guidance. Two cycles of CT with cisplatin and docetaxel were also administered. Results: The complete response (CR) rates were 79.3% and 61.8% in the LCAHFIMRT+CT and CFIMRT+CT groups, respectively (P=0.041). The median duration of local control times was 31.0±1.9 months for the LCAHFIMRT+CT group and 24.0±3.3 months for the CFIMRT+CT groups,and the 1-, 2-, and 3-year local control rates were 86.2%, 63.8%, and 41.4% and 85.7%, 51.8%, and 32.1% for the LCAHFIMRT+CT and CFIMRT+CT groups (P=0.240), respectively. The median survival times were 34.0±1.1 months for the LCAHFIMRT+CT group and 28.0.0±3.7 months for the CFIMRT groups,and the 1-, 2-, and 3-year survival rates were 87.9%, 74.1%, and 44.8% and 87.5%, 60.7%, and 39.3% for the LCAHFIMRT+CT and CFIMRT+CT groups, respectively (P=0.405). The incidence of side effects was not significantly different between the two groups. Local recurrence and uncontrolled disease resulted in more deaths in the CFIMRT+CT group than in the LCAHFIMRT+CT group (58.9% vs. 39.7%) (P=0.040). Conclusion: For ESCC patients, LCAHFRT delivered by image-guided intensity-modulated techniques Plus Concurrent Chemotherapy with cisplatin and docetaxel keeps safety and high CR rate, as well as local control and long-term survival rates.

Heteroplasmy of mutant mitochondrial DNA A10398G and analysis of its prognostic value in non-small cell lung cancer.

Mitochondrial dysfunction is associated with pathogenic mitochondrial (mt)DNA mutations. The majority of mtDNA point mutations have a heteroplasmic status, which is defined as the coexistence of wild-type and mutated DNA within a cell or tissue. Previous findings demonstrated that certain mtDNA heteroplasmic mutations contribute to widely spread chronic diseases, including cancer, and alterations in the heteroplasmy level are associated with the clinical phenotype and severity of cancer. In the present study, the proportions of mutant mtDNA 10398G were assessed using amplification-refractory mutation system-quantitative polymerase chain reaction (PCR) assay in 129 non-small cell lung cancer (NSCLC) tissue samples. Wild-type and mutant sequences were separately amplified using allele-specific primers and, subsequently, the PCR products containing the mtDNA 10398 site were ligated into vectors to construct a standard plasmid DNA construct. The association between mtDNA A10398G and the prognosis of patients was analyzed by survival analysis and Cox proportional hazards model. For the patient cohort, the median follow-up time and overall survival time were 20.6 and 26.3 months, respectively. The ratios of mutant heteroplasmy ranged between 0.31 and 97.04%. Patients with a high degree of mutant mtDNA 10398G had a significantly longer overall survival time compared with those with a low degree of mutant mtDNA 10398G (28.7 vs. 22.5 months, respectively; P<0.05). In addition, multivariate analysis demonstrated that epidermal growth factor receptor mutation status, tumor stage and the possession of a low degree of mutant 10398G were the three most independent prognostic factors. In conclusion, the present study suggests that, among NSCLC patients, there are large shifts in mutant mtDNA 10398G heteroplasmy and a low degree of mutant mtDNA 10398G heteroplasmy may be a marker of poor prognosis in patients with NSCLC.

Electrolyte disorders assessment in solid tumor patients treated with anti-EGFR monoclonal antibodies: a pooled analysis of 25 randomized clinical trials.

The role of anti-epithelial growth factor receptor monoclonal antibodies (anti-EGFR MoAbs) in treatment-related electrolyte disorders is still controversial. Therefore, we conducted a meta-analysis of published randomized controlled trials (RCTs) to evaluate the incidences and overall risks of all-grade and grade 3/4 electrolyte disorder events. We searched relevant clinical trials from PubMed, EMBASE, and Web of Knowledge databases, meeting proceedings of American Society of Clinical Oncology and the European Society of Medical Oncology, as well as ClinicalTrials.gov. Eligible studies included phases II, III, and IV RCTs. Statistical analysis was performed to calculate the summary incidence, relative risk (RR), and 95 % confidence intervals (CIs) using fixed effects or random effects models based on the heterogeneity of included studies. A total of 16,411 patients from 25 RCTs were included in this meta-analysis. The all-grade incidence of hypomagnesemia related to anti-EGFR MoAbs was 34.0 % (95 % CI 28.0-40.5 %), and that for hypokalemia and hypocalcemia were 14.5 % (95 % CI 8.2-24.4 %) and 16.8 % (95 % CI 14.2-19.7 %), respectively. Compared with chemotherapy alone in colorectal cancer, addition of cetuximab increased the risk of grade 3/4 hypomagnesemia and grade 3/4 hypokalemia with RRs of 7.14 (95 % CI 3.13-16.27, p < 0.001) and 2.19 (95 % CI 1.14-4.23, p = 0.019). Additionally, colorectal cancer patients in panitumumab cases were more vulnerable to grade 3/4 hypomagnesemia and hypokalemia (RR 18.29, 95 % CI 7.29-48.41, p < 0.001, and RR 3.3, 95 % CI 1.32-8.25, p = .011). Treatment with anti-EGFR MoAbs is associated with significantly higher risks of electrolyte disorders such as hypomagnesemia, hypomagnesemia, and hypocalcemia, especially in colorectal cancer. Rigorous monitoring and early treatment of electrolyte disorders are proposed.

Predictive value of excision repair cross-complementation group 1 expression for platinum-based chemotherapy and survival in gastric cancer: a meta-analysis.

PURPOSE: The predictive value of excision repair cross-complementation group 1 (ERCC1) gene for survival and response to platinum-based chemotherapy in gastric cancer (GC) remains controversial. We performed a meta-analysis to clarify the precise estimation of the prognostic and predictive effect of ERCC1. METHODS: A systematic literature search was conducted using PubMed, ScienceDirect, Wiley and American Society of Clinical Oncology (ASCO) before March 2014. Studies analyzing survival data and/or chemotherapy response in GC by ERCC1 status were identified. The principal outcome measures were hazard ratios (HRs) for survival and relative risks (RRs) for chemotherapy response. Pooled HRs and RRs were calculated using fixed- or random-effects models according to the heterogeneity. RESULTS: Twenty-one studies involving 1,628 patients met our inclusion criteria. High ERCC1 expression was significantly associated with shorter overall survival (OS) and lower response to chemotherapy in advanced GC patients receiving palliative chemotherapy (HR 1.83; 95 % CI 1.45-2.31; P < 0.001; RR 0.49; 95 % CI 0.38-0.62; P < 0.001). There was no significant difference in survival between high and low ERCC1 expression in adjuvant setting (OS: HR 1.38; 95 % CI 0.77-2.45; P = 0.276; EFS 0.72; 95 % CI 0.38-1.33; P = 0.291). Some evidence of heterogeneity and possible publication bias were discovered in few meta-analyses. CONCLUSIONS: High ERCC1 expression might be an adverse prognostic and a drug-resistance predictive factor for advanced GC patients. However, further studies with consistent ERCC1 assessment methodology are needed.