Efficacy of Prophylactic Cranial Irradiation in Early to Mid-stage Small Cell Lung Cancer Patients in the Era of Magnetic Resonance Imaging.

BACKGROUND: Recent advancements in magnetic resonance imaging (MRI) for staging have highlighted the critical question of the need for prophylactic cranial irradiation (PCI) in managing early to mid-stage small cell lung cancer (SCLC). This study assesses the impact of PCI on overall survival (OS) and intracranial control among patients with stage I-IIB SCLC. METHODS: Data from 148 stage I-IIB SCLC patients treated with thoracic radiation therapy (TRT) at two centers were examined. Patients were categorized based on PCI administration: 63 received PCI, while 85 did not. All underwent pretreatment MRI, achieving at least a partial response to therapy. A 1:1 propensity score matching analysis corrected for potential biases. RESULTS: Propensity scores were generated to 116 patients, considering patient demographics, disease progression, and treatment methods. Death was included as a competing risk. The 3-year brain metastases (BM) occurrence rate was significantly higher in patients who did not receive PCI (30.0%) compared to those who did (14.8%), however, the difference was not statistically significant (No PCI vs. PCI, hazard ratio [HR]: 2.08, 95% CI [0.93-4.55], P = .07). No significant effect of PCI on OS was observed [PCI vs. No PCI, HR: 0.80, 95% CI (0.45-1.43), P = .45]. A subgroup analysis of stage IIB patients showed a significant increase in BM risk and mortality for those not receiving PCI (No PCI vs. PCI, BM risk HR: 5.85, 95% CI: 1.83-18.87, P = .003; mortality HR: 2.78, 95% CI: 1.14-6.67, P = .02), with less pronounced effects in stages I-IIA. CONCLUSION: With modern MRI-based screening, PCI may markedly benefit stage IIB SCLC patients by reducing BM and improving OS after initial sensitive treatment. This benefit does not appear to extend to stage I-IIA patients.

Adjuvant therapy in renal cell carcinoma: Tyrosine kinase inhibitor versus immune checkpoint inhibitor.

BACKGROUND: To date, no meta-analysis has been conducted to compare the effectiveness and safety of adjuvant tyrosine kinase inhibitors (TKIs) and adjuvant immunotherapies (IMTs) in renal cell carcinoma (RCC) patients using reconstructed individual patient data (IPD). This study aims to fill that gap by assessing the efficacy and safety profiles of these treatments in such patients. METHODS: This study employed a systematic approach for identifying relevant literature from the PubMed and EMBASE databases. We included articles published in English from the inception of these databases until November 11, 2023, focusing specifically on appropriate phase III randomized controlled trials (RCTs). To reconstruct survival curves, we utilized a semiautomated tool, WebPlotDigitizer, in conjunction with a novel shiny application integrated with R software. For adverse events (AEs), the summary measures were incidences, expressed as a 95% confidence interval (CI), calculated using a random-effects model with a logit transformation. RESULTS: The analysis included 8 RCTs with a total of 9119 patients. Compared to adjuvant TKIs, adjuvant IMTs showed a similar disease-free survival (DFS) (hazard ratio [HR] 1.03, 95% CI [0.98-1.09], P = .281). However, the overall survival (OS) rates between the 2 groups couldn't be directly compared due to unmatched control groups in the IMT and TKI studies. Against placebo, adjuvant IMTs demonstrated superior DFS (HR 0.82, 95% CI [0.71-0.94], P = .004) but comparable OS (HR 0.79, 95% CI [0.59-1.06], P = .120). Against placebo, adjuvant TKIs showed superior DFS (HR 0.85, 95% CI [0.79-0.92], P < .0001) and marginally better OS (HR 0.89, 95% CI [0.80-0.996], P = .042). Regarding severe AEs and discontinuation rates due to AEs, adjuvant IMTs had a significantly lower incidence of severe AEs (25% [320/1282] vs 59% [2192/3716], odds ratio [OR] 0.23, 95% CI [0.20-0.27], P < .0001) and a markedly better discontinuation rate (39% [499/1282] vs 52% [2068/4018], OR 0.60, 95% CI [0.53-0.68], P < .0001) compared to TKIs. CONCLUSION: This paper presents a thorough analysis of DFS, OS, and treatment-related AEs across various groups in RCC patients, offering a valuable resource for clinicians in everyday practice. Our findings indicate that while adjuvant IMTs and adjuvant TKIs demonstrate similar DFS, IMTs are notably superior in terms of safety and compliance.

High methylation of the same promoter of lncRNA ZNF582-AS1/ZNF582 promotes malignant progression of esophageal cancer.

Aim: This study aimed to investigate the functions of ZNF582-AS1 and ZNF582 in esophageal cancer (EC). Materials & methods: Bioinformatics analysis, qRT-PCR and western blot were used to analyze the expression levels. Biological functions were evaluated using cell-counting kit 8, colony formation, Transwell assays and flow cytometry. FISH was used to detect subcellular localization, and methylation-specific PCR determined gene methylation levels. Animal experiments validated the impact on tumor progression. Results: ZNF582-AS1 and ZNF582 were highly methylated and downregulated in EC. Overexpression of ZNF582-AS1 up-regulated the expression of ZNF582, thereby inhibiting EC cell viability and metastasis, promoting apoptosis and inhibiting tumor growth. Conclusion: Low expression of ZNF582-AS1/ZNF582 mediated by DNA hypermethylation facilitates the malignant progression of EC.

Promoter hypermethylation silences ZNF582-AS1 and ZNF582, driving esophageal cancer progression, which has the potential for novel therapeutic strategies. # Methylation # Esophageal Cancer.

Enterprise service-oriented transformation and sustainable development driven by digital technology.

The deep integration of digital technology and the real economy not only affects the production and operation mode of enterprises, but also becomes the promoter of service-oriented transformation and the driving force of sustainable development. Based on the text analysis method, this paper uses the data of Chinese listed manufacturing enterprises from 2011 to 2020 to study the impact of digital technology application on the service-oriented transformation and sustainable development of enterprises. It is found that digital technology application significantly improves the environmental performance and economic performance of enterprises by driving their service-oriented transformation and technological innovation, and then enhances their sustainable development. The improvement effect of digital technology application on the sustainable development of resource-based enterprises and capital-intensive enterprises is more significant. The conclusion in this paper provides micro-evidence for understanding the role of digital technology in addressing environmental issues and sustainable development.

Prediction by a multiparametric magnetic resonance imaging-based radiomics signature model of disease-free survival in patients with rectal cancer treated by surgery.

Objective: The aim of this study was to assess the ability of a multiparametric magnetic resonance imaging (MRI)-based radiomics signature model to predict disease-free survival (DFS) in patients with rectal cancer treated by surgery. Materials and methods: We evaluated data of 194 patients with rectal cancer who had undergone radical surgery between April 2016 and September 2021. The mean age of all patients was 62.6 ± 9.7 years (range: 37-86 years). The study endpoint was DFS and 1132 radiomic features were extracted from preoperative MRIs, including contrast-enhanced T1- and T2-weighted imaging and apparent diffusion coefficient values. The study patients were randomly allocated to training (n=97) and validation cohorts (n=97) in a ratio of 5:5. A multivariable Cox regression model was used to generate a radiomics signature (rad score). The associations of rad score with DFS were evaluated using Kaplan-Meier analysis. Three models, namely a radiomics nomogram, radiomics signature, and clinical model, were compared using the Akaike information criterion. Result: The rad score, which was composed of four MRI features, stratified rectal cancer patients into low- and high-risk groups and was associated with DFS in both the training (p = 0.0026) and validation sets (p = 0.036). Moreover, a radiomics nomogram model that combined rad score and independent clinical risk factors performed better (Harrell concordance index [C-index] =0.77) than a purely radiomics signature (C-index=0.73) or clinical model (C-index=0.70). Conclusion: An MRI radiomics model that incorporates a radiomics signature and clinicopathological factors more accurately predicts DFS than does a clinical model in patients with rectal cancer.

Evaluation of the safety and efficacy of high-dose rate brachytherapy for radiorecurrent prostate cancer: a systematic review and meta-analysis.

BACKGROUND: High-dose-rate brachytherapy (HDR-BT) plays an important role in the treatment of locally recurrent prostate cancer after definitive treatment. The objective of this study is to summarize the efficacy and toxicity of HDR-BT in these patients. METHODS: We performed a systematic review of PubMed and EMBASE from inception to July 2023. The primary endpoint was relapse-free survival (RFS) in different subgroups, and the secondary endpoint was gastrointestinal (GI) and genitourinary (GU) toxicity. A semi-automated tool (WebPlotDigitizer) and a new Shiny application combined with R software (R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria; https://www.R-project.org/ ) helped to reconstruct survival curves. RESULTS: Twenty-six studies met the inclusion criteria for quantitative analysis, including 1447 patients. A total of 761 patients from 13 studies were included in survival reconstruction, and the median RFS time was 61.2 months (57.6-72.0 months). The estimated 2­, 3­, and 5­year rates were 75.9% (95% confidence interval [CI] 72.8 ~ 79.2%), 66.7% (95% CI 63.0 ~ 70.5%), and 52.3% (95% CI 47.5 ~ 57.4%), respectively. Whole-gland irradiation with multiple fractions (≥ 2 F) resulted in better RFS compared with focal gland irradiation with fewer fractions (1 F mostly; hazard ratio [HR]: 0.60, 95% CI 0.47-0.77, p < 0.0001). According to the different median time from primary treatment to salvage therapy (TRS) and median age at recurrence, short median TRS (56-67.2 months vs. 70-120 months; HR 0.52, 95% CI 0.68-0.40; p < 0.0001) and younger median age (60-70 years vs. 71-75 years; HR 0.58, 95% CI 0.46-0.74; p < 0.0001) were positive factors for RFS. The cumulative incidences estimated for grade ≥ 3 acute and late GU toxicities were 1% (95% CI 0 ~ 1%) and 5% (95% CI 4 ~ 7%), respectively. Three patients (3/992) experienced grade ≥ 3 late GI toxicity, and no cases of grade ≥ 3 acute GI toxicity were reported. CONCLUSION: HDR-BT has a high safety profile and good RFS benefit for salvage treatment of radiorecurrent prostate cancer. In terms of RFS, whole-gland irradiation with multiple fractions seems to be better than focal gland irradiation with fewer fractions, while short TRS and younger age are good prognostic factors. In view of the low level of evidence in the included studies and the large heterogeneity of each study, these conclusions still need to be confirmed by randomized controlled trials.

Construction of brain metastasis prediction model in limited stage small cell lung cancer patients without prophylactic cranial irradiation.

INTRODUCTION: Small cell lung cancer (SCLC) is a highly aggressive lung cancer variant known for its elevated risk of brain metastases (BM). While earlier meta-analyses supported the use of prophylactic cranial irradiation (PCI) to reduce BM incidence and enhance overall survival, modern MRI capabilities raise questions about PCI's universal benefit for limited-stage SCLC (LS-SCLC) patients. As a response, we have created a predictive model for BM, aiming to identify low-risk individuals who may not require PCI. METHODS: A total of 194 LS-SCLC patients without PCI treated between 2009 and 2021 were included. We conducted both univariate and multivariate analyses to pinpoint the factors associated with the development of BM. A nomogram for predicting the 2- and 3-year probabilities of BM was then constructed. RESULTS: Univariate and multivariate analyses revealed several significant independent risk factors for the development of BM. These factors include TNM stage, the number of chemotherapy (ChT) cycles, Ki-67 expression level, pretreatment serum lactate dehydrogenase (LDH) levels, and haemoglobin (HGB) levels. These findings underscore their respective roles as independent predictors of BM. Based on the results of the final multivariable analysis, a nomogram model was created. In the training cohort, the nomogram yielded an area under the receiver operating characteristic curve (AUC) of 0.870 at 2 years and 0.828 at 3 years. In the validation cohort, the AUC values were 0.897 at 2 years and 0.789 at 3 years. The calibration curve demonstrated good agreement between the predicted and observed probabilities of BM. CONCLUSIONS: A novel nomogram has been developed to forecast the likelihood of BM in patients diagnosed with LS-SCLC. This tool holds the potential to assist healthcare professionals in formulating more informed and tailored treatment plans.

Efficacy of Adjuvant First-Generation TKIs versus Chemotherapy in Patients with Completely Resected EGFR-Mutant Non-Small Cell Lung Cancer: A Meta-Analysis.

BACKGROUND: The use of adjuvant first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) in patients with resected EGFR-mutant non-small cell lung cancer (NSCLC) remains controversial. Therefore, we performed a systematic review with meta-analysis to investigate the overall survival (OS) in patients with resected NSCLC. METHODS: Relevant studies were identified from the PubMed and EMBASE databases, and pooled hazard risks were obtained by random-effects models. RESULTS: Three prospective phase III and one phase II randomized controlled trials were identified, including a total of 839 patients who had undergone resection of EGFR-sensitive mutation in our analysis, 429 of whom received adjuvant first-generation TKIs therapy. For all patients with complete resection, adjuvant first-generation TKIs therapy was associated with improved disease-free survival (DFS) [hazard ratio (HR): 0.50, 95% confidence interval (CI): 0.30-0. 82] but not OS (HR: 0.78, 95% CI: 0.48-1.27) compared with adjuvant chemotherapy. In addition, we reconstructed the OS curves of the ADJUVANT and IMPACT studies, and the pooled 3- and 5-year OS rates of stage II-III patients in the TKI group and chemotherapy group were 80% vs. 79% and 66% vs. 64%, respectively. We also reconstructed the DFS curves based on the ADJUVANT, IMPACT, and EVIDENCE studies, and the pooled 1-, 3- and 5-year DFS rates of stage II-III patients in the TKI group and chemotherapy group were 87% vs. 70%, 49% vs. 37% and 28% vs. 29%, respectively. CONCLUSIONS: In patients with completely resected EGFR-mutant NSCLC, adjuvant first-generation TKIs may delay disease progression but still fail to improve long-term survival compared with conventional chemotherapy.

Efficacy of photobiomodulation therapy in the management of oral mucositis in patients with head and neck cancer: A systematic review and meta-analysis of randomized controlled trials.

Numerous studies have examined the effectiveness of photobiomodulation therapy (PBMT) in reducing chemoradiotherapy (CRT)-induced oral mucositis (OM) in patients with head and neck cancer (HNC). Despite this, there is an urgent need to update the meta-analyses on this topic. This meta-analysis aims to explore the impact of PBMT on CRT-induced OM in these patients. We conducted a systematic search in PubMed, Embase, Cochrane, LILACS, and Web of Science from January 2000 to October 2023. This search focused on randomized controlled trials (RCTs) that assessed the effects of PBMT on CRT-induced OM. The study included a total of 14 RCTs encompassing 869 patients with HNC. The incidence of OM in the PBMT group was significantly lower from the second week onwards compared to the control group (RR = 0.49, CI = 0.25-0.97, I2 = 71%, p = 0.04), and this was present until the seventh week (RR = 0.77, CI = 0.61-0.99, I2 = 89%, p = 0.04). Furthermore, the occurrence of severe mucositis in the PBMT group decreased from the third week (RR = 0.51, CI = 0.29-0.90, I2 = 12%, p = 0.02) until the conclusion of the intervention (RR = 0.45, CI = 0.24-0.85, I2 = 80%, p = 0.01). Additionally, PBMT showed beneficial effects in alleviating OM-related pain (WMD = -1.09, 95% CI = -1.38 to -0.880, I2 = 13%, p < 0.00001). The use of He-Ne or InGaAlP lasers with a power range of 10-25 mW demonstrated the most favorable outcomes in preventing and treating OM. PBMT has shown considerable efficacy in reducing the incidence, severity, and pain associated with OM in patients with HNC. Future studies are encouraged to further investigate the most effective parameters for PBMT in the management of OM.

Transplantation of human induced pluripotent stem cell derived keratinocytes accelerates deep second-degree burn wound healing.

BACKGROUND: Current evidence shows that human induced pluripotent stem cells (hiPSCs) can effectively differentiate into keratinocytes (KCs), but its effect on skin burn healing has not been reported. AIM: To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms. METHODS: An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926, and GSE27186 was established. A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs. The expression of KCs marker proteins was detected using immunofluorescence staining. A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created, and then phosphate buffered saline (PBS), hiPSCs-KCs, or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface. The wound healing, re-epithelialization, engraftment of hiPSCs-KCs into wounds, proinflammatory factor level, and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining, carboxifluorescein diacetate succinimidyl ester (CFSE) fluorescence staining, enzyme linked immunosorbent assay, and Western blotting on days 3, 7, and 14 after the injection, respectively. Moreover, the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry, EdU, Transwell, and damage repair assays. RESULTS: HiPSCs-KCs could express the hallmark proteins of KCs. COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs. Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area, an increase in wound re-epithelialization, a decrease in proinflammatory factors content, and an inhibition of NF-κB pathway activation compared to the PBS group. The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration, providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration. CONCLUSION: In deep, second-degree burn wounds, COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.

Effect of anlotinib combined with ticeorgio for recurrent nasopharyngeal carcinoma: a case report.

For patients with locally unresectable recurrent nasopharyngeal carcinoma who relapsed after 2 years of radiotherapy, re-radiotherapy is also the preferred treatment. However, for patients relapsed within 2 years, the use of re-radiotherapy would be greatly limited by its adverse effects. Consequently, finding a new strategy to prolong the time of re-radiotherapy for locally recurrent nasopharyngeal carcinoma is very necessary to reduce the related side effects and improve the curative effect. Anlotinib is an orally available small molecule multi-target tyrosine kinase inhibitor that primarily inhibits VEGFR2/3, FGFR1-4, PDGFR α/ß, c-Kit, and Ret. However, whether recurrent nasopharyngeal carcinoma patients can be treated with anlotinib combined with ticeorgio (also called S-1) remains unknown. Herein, we report a nasopharyngeal carcinoma patient with local recurrence after radical radiotherapy who benefited from combination treatment of anlotinib with ticeorgio.

A nomogram to predict the cumulative risk for brain metastases in patients with limited-stage small cell lung cancer without prophylactic cranial irradiation.

OBJECTIVE: Patients with small cell lung cancer (SCLC) have a high risk of developing brain metastases (BM). Prophylactic cranial irradiation (PCI) is a standard therapy for limited-stage SCLC (LS-SCLC) patients who achieved complete or partial response after thoracic chemoradiotherapy (Chemo-RT). Recent studies have indicated that a subgroup of patients with a lower risk of BM can avoid PCI, and the present study therefore tries to construct a nomogram to predict the cumulative risk of development of BM in LS-SCLC patients without PCI. METHODS: After screening of 2298 SCLC patients who were treated at the Zhejiang Cancer Hospital from December 2009 to April 2016, a total of 167 consecutive patients with LS-SCLC who received thoracic Chemo-RT without PCI were retrospectively analyzed. The paper analyzed clinical and laboratory factors that may be correlated with BM, such as response to treatment, pretreatment serum neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) levels, and TNM stage. Thereafter, a nomogram was constructed to predict 3­ and 5­year intracranial progression-free survival (IPFS). RESULTS: Of 167 patients with LS-SCLC, 50 developed subsequent BM. Univariate analysis showed that pretreatment LDH (pre-LDH) ≥ 200 IU/L, an incomplete response to initial chemoradiation, and UICC stage III were positively correlated to a higher risk of BM (p < 0.05). Multivariate analysis identified pretreatment LDH level (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.08-3.34, p = 0.026), response to chemoradiation (HR 1.87, 95% CI 1.04-3.34, p = 0.035), and UICC stage (HR 6.67, 95% CI 1.03-49.15, p = 0.043) as independent predictors for the development of BM. A nomogram model was then established, and areas under the curve of 3­year and 5­year IPFS were 0.72 and 0.67, respectively. CONCLUSION: The present study has developed an innovative tool that is able to predict the individual cumulative risk for development of BM in LS-SCLC patients without PCI, which is beneficial for providing personalized risk estimates and facilitating the decision to perform PCI.

Survival benefit of prophylactic cranial irradiation in limited-stage small-cell lung cancer in modern magnetic resonance imaging staging: a systematic review and meta-analysis.

BACKGROUND: The use of prophylactic cranial irradiation (PCI) in patients suffering from limited-stage small-cell lung cancer (LS-SCLC) remains controversial in modern brain magnetic resonance imaging (MRI) staging. To this end, a systematic review with meta-analysis was hereby performed to investigate the overall survival (OS) in these patients. METHODS: Relevant studies from the PubMed and EMBASE databases were reviewed, and pooled hazard risks were obtained using fixed-effects models. The PRISMA 2020 checklist was used. RESULTS: Fifteen retrospective studies were identified, with a total of 2,797 patients with LS-SCLC included in the analysis, 1,391 of which had received PCI. For all included patients, PCI was associated with improved OS [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.58-0.70]. The combination of subgroup analysis and sensitivity analysis suggested that the effect of PCI on OS was independent of primary tumor treatment, proportion of complete response (CR), median age, PCI dose, publication years, etc. Additionally, the OS curve of 1,588 patients having undergone thoracic radiotherapy (TRT) as the primary tumor treatment from 8 studies were reconstructed, and the pooled 2-, 3- and 5-year OS rates of limited stage patients were 59% vs. 42%, 42% vs. 29% and 26% vs. 19% (HR: 0.69, 95% CI: 0.61-0.77) in the PCI group and the no PCI group, respectively. Another reconstructed OS curve of 339 patients having undergone radical surgery as the primary tumor treatment from 2 studies presented better results, and the pooled 2-, 3- and 5-year OS rates of in the PCI group and the no PCI group were 85% vs. 71%, 70% vs. 56% and 52% vs. 39% (HR: 0.59, 95% CI: 0.40-0.87), respectively. CONCLUSIONS: This meta-analysis demonstrates a significant beneficial effect of PCI on the OS in patients with LS-SCLC in modern pretreatment MRI staging. However, considering the absence of a strict follow-up of brain MRI recommended by the guideline for the control group from most of the included studies, the superiority of PCI to the treatment strategy of no PCI plus brain MRI surveillance remains unclear.

Combination of Tumor Mutational Burden and DNA Damage Repair Gene Mutations with Stromal/Immune Scores Improved Prognosis Stratification in Patients with Lung Adenocarcinoma.

Background: Both the tumor environment and the genomic landscape of lung cancer may shape patient responses to treatments, including immunotherapy, but their joint impacts on lung adenocarcinoma (LUAD) prognosis are underexplored. Methods: RNA sequencing data and whole-exome sequencing results were downloaded from the TCGA database, and only LUAD-related data were included in this study. Based on gene expression data, the ESTIMATE algorithm was used to estimate stromal and immune scores, and CIBERSORT analysis was used for quantification of the relative abundances of immune cells. Somatic mutations were used for calculating tumor mutation burden (TMB). Specific mutations in genes involved in DNA damage repair (DDR) pathways were identified. The individual and joint associations of stromal and immune score, TMB, and DDR gene mutations with 5-year survival were analyzed by the Kaplan-Meier method and multivariate Cox model. Results: LUAD patients with a high (>highest 25%) stromal or immune score had prolonged survival as compared to those with a low (highest 25%) and low (

Prognostic Value of Lactate Dehydrogenase, Melanoma Inhibitory Protein, and S-100B Protein in Patients with Malignant Melanoma.

Objective: This investigation probed the prognostic potential for lactate dehydrogenase (LDH), melanoma inhibitory activity protein (MIA), and S-100B protein in cases of malignant melanoma. Methods: 84 cases were segregated into effective cohort (n = 64) and ineffective cohort (n = 20) depending on clinical efficacy. The cases were followed up for three years and segregated into mortality cohort (n = 29) and survival cohort (n = 55) depending upon 3-year survival. Serum LDH, MIA, and S-100B levels were compared across the effective and ineffective cohorts. Serum LDH, MIA, and S-100B levels in cases of different clinical stages were comparatively analyzed, with correlations of these indicators with the clinical stage being evaluated. ROC evaluated the prognostic potential of serum LDH, MIA, and S-100B. Cases were segregated into the high-level and low-level cohorts according to serum LDH, MIA, and S-100B levels, and the survival rates of cases were compared. Results: The levels of LDH, MIA, and S-100B in the effective cohort were significantly lower than those in the ineffective cohort. The AUC value of the composite indicator of serum LDH, MIA, and S-100B for effectiveness evaluation was (0.839). Serum LDH, MIA, and S-100B levels were positively linked to the clinical stage. AUC value of the composite indicator of serum LDH, MIA, and S-100B for prognosis evaluation prediction (0.942) was elevated compared to LDH (0.632), MIA (0.732), or S-100B (0.828) alone. Survival rate of cases of LDH ≥30.56 mg/L (57.14%, 32/56) was lower than that of cases of LDH <30.56 mg/L (82.14%, 23/28) (log-rank χ 2 = 4.672, P < 0.05). The survival rate of MIA ≥5.34 ng/mL cases was lower than that of MIA <5.34 ng/mL cases. The survival rate of cases of S-100B ≥ 1.03ug/L was lower than that of S-100B < 1.03ug/L. Conclusion: Serum LDH, MIA, and S-100B protein levels are linked to the clinical stage. The lactate dehydrogenase, melanoma inhibitory protein, and S-100B protein are of good clinical effectiveness and have the prognostic potential for cases of malignant melanoma.

Serum lactate dehydrogenase predicts brain metastasis and survival in limited-stage small cell lung cancer patients treated with thoracic radiotherapy and prophylactic cranial irradiation.

BACKGROUND: Small cell lung cancer (SCLC) is characterized by a high risk of brain metastasis and poor survival. This study aims to assess the prognostic role of lactate dehydrogenase (LDH) in limited-stage small cell lung cancer (LS-SCLC) treated with thoracic radiotherapy (TRT) and prophylactic cranial irradiation (PCI). METHODS: This study retrospectively evaluated 197 consecutive patients who underwent TRT and PCI for LS-SCLC between November 2005 and October 2017. Both pretreatment and maximal serum LDH levels (mLDH) during treatment were checked, and an increased LDH level was defined as more than 240 IU/ml. Clinical factors were tested for associations with intracranial progression-free survival (IPFS) and overall survival (OS) after PCI. The Kaplan-Meier method was used to calculate survival rates, and multivariate Cox regression analyses were carried out to identify variables associated with survival. RESULTS: Of the total patients, 28 had higher pretreatment LDH levels and mLDH levels were increased in 95 patients during treatment. In patients in the normal and elevated mLDH groups, the 1­, 2­, and 5­year IPFS rates were 96.7% vs. 90.1%, 91.7% vs. 73.8%, and 87.8% vs. 61.0% (P < 0.01), respectively. Compared to those with normal LDH levels, patients with increased mLDH levels had a higher cumulative risk of intracranial metastasis (hazard ratio [HR] 3.87; 95% confidence interval [CI] 1.73-8.63; P < 0.01) and worse overall survival (HR 2.59; 95% CI 1.67-4.04; P < 0.01). The factors LDH level at baseline or changes between pretreatment level and maximum level during treatment failed to predict brain metastases or OS with statistical significance. In the multivariate analyses, both mLDH during treatment (HR 3.53; 95% CI 1.57-7.92; P = 0.002) and patient age ≥ 60 (HR 2.46; 95% CI 1.22-4.94; P = 0.012) were independently associated with worse IPFS. Factors significantly associated with worse OS included mLDH during treatment (HR 2.45; 95% CI 1.56-3.86; P < 0.001), IIIB stage (HR 1.75; 95% CI 1.06-2.88; P = 0.029), and conventional radiotherapy applied in TRT (HR 1.66; 95% CI 1.04-2.65; P = 0.034). CONCLUSION: The mLDH level during treatment predicts brain metastasis and survival in LS-SCLC patients treated with TRT and PCI, which may provide valuable information for identifying patients with poor survival outcomes and possible candidates for treatment intensification.

The multi-molecular mechanisms of tumor-targeted drug resistance in precision medicine.

Clinically, cancer drug therapy is still dominated by chemotherapy drugs. Although the emergence of targeted drugs has greatly improved the survival rate of patients with advanced cancer, drug resistance has always been a difficult problem in clinical cancer treatment. At the current level of medicine, most drugs cannot escape the fate of drug resistance. With the emergence and development of gene detection, liquid biopsy ctDNA technology, and single-cell sequencing technology, the molecular mechanism of tumor drug resistance has gradually emerged. Drugs can also be updated in response to drug resistance mechanisms and bring higher survival benefits. The use of new drugs often leads to new mechanisms of resistance. In this review, the multi-molecular mechanisms of drug resistance are introduced, and the overcoming of drug resistance is discussed from the perspective of the tumor microenvironment.

The application value of early postoperative pain management (EPPM) combined with skin temperature monitoring (STM) after flap repair of soft tissue defects in the lower limbs: a non-randomized controlled trial.

BACKGROUND: Flap repair is often required when repairing soft tissue defects in the lower limbs. Although early postoperative pain management (EPPM) can improve postoperative comfort and rest efficiency, and reduce the probability of complications, it cannot detect tissue blood circulation disorders in time. The purpose of this study was to explore the application value of EPPM combined with skin temperature monitoring (STM) after flap repair of soft tissue defects in the lower limbs. METHODS: We retrospectively collected the data of 101 patients who underwent lower limb soft tissue defect flap repair, which were divided into the EPPM group (n=50 cases) and the EPPM-STM group (n=51 cases). The EPPM group was given early postoperative pain management, and the EPPM-STM group was given additional skin temperature monitoring on the basis of the EPPM group. The clinical effect, reoperation rate, flap survival rate, pain score, postoperative quality of life and mental resilience, and complications were analyzed and compared. RESULTS: The average healing time of the EPPM-STM group was significantly lower compared with the EPPM group, and the serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) levels were significantly lower after the intervention (t=7.418, 3.447, 7.472; P<0.001, =0.001, <0.001). Compared with the EPPM group, the reoperation rate and complication rate in the EPPM-STM group were significantly lower, and the flap survival rate was significantly higher (χ2=6.966, 7.358; P=0.008, 0.007). The pain scores of the EPPM-STM group were significantly lower than those of the EPPM group after intervention (At 3 days: t=4.723; P<0.001. At 5 days: t=5.261; P<0.001), while the mental resilience and quality of life scores were significantly higher (t=-12.942, -9.975; P<0.001, <0.001). Logistic regression analysis showed that the postoperative management methods and the area of the flap defect were independent risk factors that affected the survival of the flap (t=7.358, 4.819; P=0.007, 0.028). CONCLUSIONS: EPPM combined with STM can increase the speed of postoperative healing, increase the survival rate of skin flaps, reduce the rate of reoperation and complications, and improve the quality of life and mental resilience of patients who undergo flap repair.

Whole-Brain Radiotherapy Combined With Anlotinib for Multiple Brain Metastases From Non-small Cell Lung Cancer Without Targetable Driver Mutation: A Single-Arm, Phase II Study.

BACKGROUND: Existing evidence demonstrates that radiotherapy and antiangiogenic drugs have synergistic antitumour effects and may be a promising treatment option for patients with solid tumour. Thus, we performed a phase II trial to evaluate the efficacy and safety of whole-brain radiotherapy (WBRT) combined with anlotinib for multiple brain metastases (BMs) from non-small cell lung cancer (NSCLC) without targetable driver mutations. METHODS: Patients with multiple BMs (⩾3) from NSCLC without targetable driver mutations who failed to respond to at least first-line chemotherapy were enrolled. Eligible patients received WBRT (30 Gy/10 f, 5 f/week) and anlotinib (12 mg/day, day 1-14 of 21 days per cycle, 2 cycles) until disease progression or treatment intolerance. The primary endpoint was intracranial objective response rate (iORR) and secondary endpoints included intracranial progression-free survival (iPFS), disease control rate (DCR), overall survival (OS), and safety. RESULTS: Between April 2019 and March 2021, 21 patients were enrolled in the trial, of which 12 were aged ⩾60 years (57.1%), 13 were men (61.9%), 7 had an Eastern Cooperative Oncology Group Performance Status score of 0 to 1 (81.0%), 18 had adenocarcinoma (85.7%), and 11 had ⩾6 BMs (52.4%). Of the 21 evaluable patients, the iORR was 66.7% (1 complete response + 13 partial response [PR]), and 28.6% (7PR) had extracerebral lesions. The DCRs for intracerebral and extracerebral lesions were 90.5% and 81.0%, respectively. The iPFS and OS were 10.3 months (95% confidence interval [CI]: 0-24.8 months) and 13.4 months (95% CI: 0-27.9 months), respectively. The most frequently observed toxicities were loss of appetite (61.9%), hypertension (52.4%), fatigue (47.6%), diarrhoea (28.6%), vomiting (19.0%), dizziness (42.9%), and headache (33.3%). None of the patients developed grade 4 or higher grade adverse reactions. CONCLUSIONS: Anlotinib combined with WBRT is effective and well tolerated in patients with multiple BMs (⩾3) from NSCLC without targetable driver mutations. Therefore, further validation studies are required.Clinical trial registration number: ChiCTR 1900027769.