Prognostic impact of oral microbiome on survival of malignancies: a systematic review and meta-analysis.

BACKGROUND: Recent studies have shown that there exists a significant correlation between oral microbiome and the occurrence of malignancies. However, the prognostic significance of oral microbiome for cancer patients remains unclear. The purpose of this meta-analysis is to evaluate the impact of oral microbiome on the survival of patients with malignant neoplasms. METHODS: We conducted a thorough literature search of PubMed, Embase, and Cochrane Library databases until September 2022. The hazard ratio (HR) with a corresponding 95% confidence interval (CI) was analyzed using Review Manager 5.4 software for survival outcomes, including overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and disease-free survival (DFS). RESULTS: A total of 15 studies, covering 5191 samples with various types of cancers, were selected based on specified inclusion and exclusion criteria. In both univariate and multivariate analysis, patients with low diversity of the oral microbiome, or those with Fusobacterium-high/positive, or P. gingivalis positive in cancer tissue displayed poorer OS (univariate HR = 1.74; 95% CI 1.15-2.62; P = 0.009; multivariate HR = 1.56; 95% CI 1.07-2.27; P = 0.02), DSS (univariate HR = 2.06; 95% CI 1.50-2.84; P < 0.00001; multivariate HR = 1.80; 95% CI 1.48-2.20; P < 0.00001), and PFS/DFS (univariate HR = 2.00; 95% CI 1.12-3.58; P = 0.002; multivariate HR = 1.78; 95% CI 1.05-3.02; P = 0.003). Subgroup analysis revealed that Fusobacterium positive or high abundance in cancer tissues was associated with poor OS in multivariate analysis but had no statistical differences in PFS or DFS in univariate and multivariate analysis. Additionally, P. gingivalis positive in cancer tissue was also associated with worse OS. CONCLUSIONS: Our meta-analysis suggests that the composition of the oral microbiome may play a significant role in predicting survival outcomes for cancer patients.

Impact of BMI on the survival outcomes of non-small cell lung cancer patients treated with immune checkpoint inhibitors: a meta-analysis.

OBJECTIVES: ICIs have become the standard treatment for advanced NSCLC patients. Currently, PD-L1 is the most widely useful biomarker to predict ICI efficacy, but the sensitivity and specificity are limited. Therefore, the useful predictive biomarkers of ICI efficacy is urgently needed. BMI is an internationally used measure of body health. Obesity may affect ICI efficacy by changing T cell functions. This meta-analysis aimed to clarify the relationship between BMI and survival outcomes of NSCLC patients treated with ICIs. METHODS: A systematic review was conducted to identify studies that assessed the association between BMI and survival outcomes in patients treated with ICIs. OS was the primary endpoint, and PFS was the secondary endpoint. Random-effect models or fixed-effect models were utilized to combine study effects according to the Cochran Q and I2 tests. RESULTS: Nine studies, including 4602 NSCLC patients treated with ICIs, that met the inclusion criteria were selected for this meta-analysis. There was no significant difference in PFS (HR 0.885; 95% CI 0.777-1.009, p = 0.068) or OS (HR 0.947; 95% CI 0.789-1.137, p = 0.560) between the low BMI group and the high BMI group. However, in the subgroup analysis, compared with normal-weight patients, overweight and obese patients achieved prolonged PFS (HR 0.862; 95% CI 0.760-0.978, p = 0.021) and OS (HR 0.818; 95% CI 0.741-0.902, p<0.0001). CONCLUSION: Overweight and obese NSCLC patients tend to achieve prolonged survival time with ICI regimens. Further prospective studies are needed to strengthen the association between ICI outcomes and BMI levels.

A deep learning model based on the attention mechanism for automatic segmentation of abdominal muscle and fat for body composition assessment.

Background: Quantitative muscle and fat data obtained through body composition analysis are expected to be a new stable biomarker for the early and accurate prediction of treatment-related toxicity, treatment response, and prognosis in patients with lung cancer. The use of these biomarkers can enable the adjustment of individualized treatment regimens in a timely manner, which is critical to further improving patient prognosis and quality of life. We aimed to develop a deep learning model based on attention for fully automated segmentation of the abdomen from computed tomography (CT) to quantify body composition. Methods: A fully automatic segmentation deep learning model was designed based on the attention mechanism and using U-Net as the framework. Subcutaneous fat, skeletal muscle, and visceral fat were manually segmented by two experts to serve as ground truth labels. The performance of the model was evaluated using Dice similarity coefficients (DSCs) and Hausdorff distance at 95th percentile (HD95). Results: The mean DSC for subcutaneous fat and skeletal muscle were high for both the enhanced CT test set (0.93±0.06 and 0.96±0.02, respectively) and the plain CT test set (0.90±0.09 and 0.95±0.01, respectively). Nevertheless, the model did not perform well in the segmentation performance of visceral fat, especially for the enhanced CT test set. The mean DSC for the enhanced CT test set was 0.87±0.11, while the mean DSC for the plain CT test set was 0.92±0.03. We discuss the reasons for this result. Conclusions: This work demonstrates a method for the automatic outlining of subcutaneous fat, skeletal muscle, and visceral fat areas at L3.

Segmentation-guided Denoising Network for Low-dose CT Imaging.

BACKGROUND: To reduce radiation exposure and improve diagnosis in low-dose computed tomography, several deep learning (DL)-based image denoising methods have been proposed to suppress noise and artifacts over the past few years. However, most of them seek an objective data distribution approximating the gold standard and neglect structural semantic preservation. Moreover, the numerical response in CT images presents substantial regional anatomical differences among tissues in terms of X-ray absorbency. METHODS: In this paper, we introduce structural semantic information for low-dose CT imaging. First, the regional segmentation prior to low-dose CT can guide the denoising process. Second the structural semantical results can be considered as evaluation metrics on the estimated normal-dose CT images. Then, a semantic feature transform is engaged to combine the semantic and image features on a semantic fusion module. In addition, the structural semantic loss function is introduced to measure the segmentation difference. RESULTS: Experiments are conducted on clinical abdomen data obtained from a clinical hospital, and the semantic labels consist of subcutaneous fat, muscle and visceral fat associated with body physical evaluation. Compared with other DL-based methods, the proposed method achieves better performance on quantitative metrics and better semantic evaluation. CONCLUSIONS: The quantitative experimental results demonstrate the promising performance of the proposed methods in noise reduction and structural semantic preservation. While, the proposed method may suffer from several limitations on abnormalities, unknown noise and different manufacturers. In the future, the proposed method will be further explored, and wider applications in PET/CT and PET/MR will be sought.

Sarcopenia Was a Poor Prognostic Predictor for Patients With Advanced Lung Cancer Treated With Immune Checkpoint Inhibitors.

Background: It remains not well known whether skeletal muscle mass (SMM) loss has any impact on the effectiveness of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer. We aimed to evaluate the association between SMM and clinical outcome of patients with advanced lung cancer receiving ICIs as first line or second line. Materials and Methods: From March 1st, 2019 to March 31st, 2021 at our hospital, 34 patients with advanced lung cancer treated with first-line or second-line ICIs were enrolled retrospectively. The estimation of skeletal muscle index (SMI) for sarcopenia was assessed at the level of the third lumbar vertebra (L3) on computed tomography (CT) images obtained within 4 weeks before initiation of ICIs treatment. The impact of sarcopenia (low SMI) on progression free survival (PFS) was analyzed using Kaplan-Meier method and log-rank tests. The effect of various variables on PFS was evaluated using Cox proportional hazards regression model with univariate and multivariate analysis. The impact on treatment response including objective response rate (ORR) and disease control rate (DCR) and immunotherapy related adverse events (irAEs) between patients with and without sarcopenia was compared by the chi-squared test. The comparison of SMI value between patients with objective response (OR), disease control (DC) and those without OR and DC was used student t-test or Mann-Whitney U test. Results: Both in univariate and multivariate analysis, sarcopenia and treatment lines were the predictive factors for PFS (p < 0.05). Patients with sarcopenia had significantly shorter PFS than that of non-sarcopenic ones [6.57 vs. 16.2 months, hazard ratios (HR) = 2.947 and 3.542, and 95% confidence interval (CI): 1.123-13.183 and 1.11-11.308, p = 0.022 and 0.033]. No significant difference in ORR and irAEs was found. Patients with sarcopenia had lower DCR than those without sarcopenia. The mean SMI value of DCR group and non-DCR group was 32.94 ± 5.49 and 44.77 ± 9.06 cm2/m2, respectively (p = 0.008). Conclusion: Sarcopenia before immunotherapy might be a significant predictor for poor prognosis including shorter PFS and lower DCR in patients with advanced lung cancer treated with ICIs as first line or second line.

Treatment efficacy and prognosis analysis in locally advanced or metastatic colorectal cancer patients with hydronephrosis.

The effect of hydronephrosis, a common complication of metastatic colorectal cancer (CRC), on the treatment outcome and prognosis of locally advanced or metastatic CRC remains to be elucidated. The present study investigated the clinical characteristics, outcomes, and prognoses of patients with locally advanced or metastatic colorectal cancer (CRC) with hydronephrosis. Clinical data of patients with locally advanced or metastatic CRC who were attending Peking University Shenzhen Hospital and Shenzhen Cancer Hospital between January 2016 and December 2020 were retrospectively collected. A total of 52 patients with hydronephrosis based on CT or MRI findings were selected, and their clinical characteristics, treatment outcomes, and survival times were analyzed. Of the 52 patients, 33 were male (63.5%), and the median age was 49 years (range, 31-76 years). A total of 15 (28.8%) patients with CRC had synchronous hydronephrosis and the remaining 37 patients had metachronous hydronephrosis. Ureters were either compressed by peritoneal or abdominal cavity metastatic lymph nodes in 34 cases (65.4%) or by direct tumor invasion in 18 cases (34.6%). However, objective response rate (ORR) was higher in the group in which ureters were compressed by peritoneal or abdominal cavity metastatic lymph nodes; ORR, disease control rate and median progression-free survival (PFS) between the two groups were not statistically different. (P>0.05). The median survival period was only 27.0 months (95% CI, 20.549-33.451) in patients complicated with malignant hydronephrosis. Univariate and multivariate analyses showed that CA19-9 might be a prognostic factor for locally advanced and metastatic CRC patients with hydronephrosis. Metachronous metastatic CRC has a high incidence rate of complicated hydronephrosis. Targeted drugs in combination with chemotherapy improve the treatment efficacy and prognosis of patients. Notably, the present study found that CA19-9 level might be a prognostic factor in CRC patients with hydronephrosis.

Brigatinib treated ALK positive lung squamous cell carcinoma after failed chemotherapy: A case report.

The definitive efficacy of anaplastic lymphoma kinase (ALK) inhibitors in ALK positive lung squamous cell carcinoma (sqCC) patients remain unclear. Here, we report a case in which brigatinib had a therapeutic effect on ALK-positive lung squamous cell carcinoma. The patient in this report was diagnosed with ALK-positive lung squamous cell carcinoma with brain metastases, and received brigatinib after failure of first-line chemotherapy. Response duration was approximately 11 months, with tolerable side effects. In conclusion, a good clinical effect was achieved in a patient with ALK positive lung squamous cell carcinoma who received treatment with an ALK inhibitor.

Prognostic Impact of Sarcopenia on Clinical Outcomes in Malignancies Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

BACKGROUND: The effect of sarcopenia on the clinical outcomes of patients with malignant neoplasms receiving immune checkpoint inhibitors (ICIs) is unclear. The aim of this study was to evaluate the effect and survival of patients with malignancies and sarcopenia receiving ICIs. METHODS: We systematically searched related studies in PubMed, Embase, and Cochrane Library up to March 2021 according to the inclusion and exclusion criteria. Information pertaining to the hazard ratio (HR) corresponding to 95% confidence interval (CI) of overall survival (OS) and progression-free survival (PFS) as determined by univariate and multivariate analyses; the odds ratio (OR) corresponding to the 95% CI of the disease control rate (DCR) and objective response rate (ORR); and immune-related adverse events (irAEs) was collected and analyzed using the RevMan 5.4 software. Study heterogeneity and sensitivity were also assessed. RESULTS: A total of 19 studies were finalized that included 1763patients with lung, gastrointestinal, and head and neck cancers as well as those with melanoma, renal cell carcinoma, urothelial carcinoma, pancreatic cancer, and soft tissue sarcoma. According to univariate and multivariate analyses, patients with sarcopenia at pre-immunotherapy had poorer PFS and OS than those without. HRs and the corresponding 95% CI of PFS were 1.91(1.55-2.34, p <0.00001) and 1.46 (1.20-1.78, p =0.0001), respectively, and HRs and the corresponding 95% CI of OS were 1.78 (1.47-2.14, p <0.00001) and 1.73 (1.36-2.19, p <0.0001), respectively. Patients with sarcopenia showed poor PFS and OS during treatment. In addition, patients with sarcopenia had worse ORR (OR 0.46, 95% CI 0.28-0.74, p = 0.001) and DCR (OR 0.44, 95% CI 0.31-0.64, p<0.0001); however, the incidence of irAEs of any grade and high-grade in patients with sarcopenia did not increase, OR and the corresponding 95% CI were 0.58(0.30-1.12, p = 0.10) and 0.46(0.19-1.09, p = 0.08). Further, we performed subgroup analysis, skeletal muscle mass index (SMI) and psoas muscle mass index (PMI) stratification. In the SMI group, patients with sarcopenia had poor ORR, DCR, PFS, and OS than those without. In the PMI group, sarcopenia had poor ORR,DCR, and was a poor prognostic factor for PFS and OS according to univariate analysis but had no effect on PFS and OS according to multivariate analysis. CONCLUSIONS: Patients with malignancies and sarcopenia at pre-immunotherapy or follow-up visits had poorer clinical outcomes than those without, and sarcopenia was a poor predictive factor of ICI immunotherapy outcomes.

Prognostic impact of sarcopenia on immune-related adverse events in malignancies received immune checkpoint inhibitors: a systematic review and meta-analysis.

BACKGROUND: Whether sarcopenia has an impact on immune-related adverse events (irAEs) in patients with malignant neoplasms receiving immune checkpoint inhibitors (ICIs) is not consistent. This study aimed to evaluate the impact of sarcopenia on all grades of irAEs. METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched for related studies up to May 2021. Eligible studies were included according to the PICOS criteria. The risk of bias of the included studies was assessed according to the Newcastle-Ottawa Scale (NOS). The odds ratio (OR), corresponding to the 95% confidence interval (CI) of all grades of irAEs, was collected and analyzed, and a further subgroup analysis of serious adverse events was conducted. All analyses were conducted using the RevMan 5.4 software downloaded from the Cochrane website. The heterogeneity and sensitivity of the study were assessed. RESULTS: Of the 135 references identified, only 8 studies were analyzed, including 519 patients comprising 250 with sarcopenia and 269 without sarcopenia. No obvious bias was observed in the included studies. An increased incidence of irAEs was not observed in patients with sarcopenia at pre-immunotherapy compared to those without sarcopenia. The OR and corresponding 95% CI were 0.97 and 0.62-1.53, respectively (P=0.90), with low heterogeneity (P=0.17, I2 =32%). Further, severe adverse events were analyzed in three studies, and the results showed that sarcopenia was not related to irAEs (P=0.97). CONCLUSIONS: Malignancies with sarcopenia at pre-immunotherapy may not increase the incidence of irAEs, and sarcopenia may not be a predictive factor for irAEs.

Trastuzumab with FLOT Regimen for the Perioperative Treatment of Resectable HER2 + Advanced Gastric Cancer: A Retrospective Study.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of trastuzumab, combined with the FLOT regimen, in the perioperative treatment of resectable HER-2-positive advanced gastric cancer. METHODS: Overall, 45 patients were divided into two groups; 29 patients in the experimental group were treated with trastuzumab combined with FLOT and 16 patients in the control group were treated with FLOT alone. The primary endpoint was objective response rate (ORR), and the secondary endpoints were disease control rate (DCR), tumor regression grade (TRG), surgical margin, side effects, and overall survival. RESULTS: In the experimental and control groups, ORR was 72.4% and 43.8% (p=0.226), DCR was 89.7% and 87.5%, R0 resection rate was 96.5% and 93.7%, total/subtotal tumor regression grade was 17.2% and 6.3%, partial tumor regression grade was 27.6% and 18.7% (p=0.468), and 2-year survival rate was 78.1% and 73.9% (p=0.932), respectively. The common side effects were agranulocytosis and vomiting. There was no significant difference between the two groups. CONCLUSION: Trastuzumab combined with FLOT has a good curative effect and safety profile in the perioperative treatment of patients with resectable HER-2-positive advanced gastric cancer. In addition, trastuzumab + FLOT had the same result as FLOT alone, as there was no significant benefit with the addition of T in the group studied.

Single Nucleotide Polymorphisms in the Acylphosphatase 2 Gene and The SNP-SNP Interactions on the Risk of Breast Cancer in Chinese Han Women.

INTRODUCTION: The purpose of this study was to investigate the impact of single nucleotide polymorphisms (SNPs) in the acylphosphatase 2 gene and the SNP-SNP interactions on breast cancer (BC) risk in Chinese Han women. PATIENTS AND METHODS: A logistic regression model was used to examine the association between SNPs and BC risk. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Generalized multifactor dimensionality reduction was employed to analyze the SNP-SNP interaction. RESULTS: Logistic regression analysis showed that BC risk was significantly higher in carriers with the rs1682111-A allele than those with the TT genotype (TA + AA vs. TT; adjusted OR, 1.47; 95% CI, 1.21-1.92). In addition, we also found that BC risk was significantly higher in carriers with the rs10439478-C allele than those with the AA genotype (AC + CC vs. AA); adjusted OR, 1.67; 95% CI, 1.29-2.11. We found a significant 2-locus model (P = .0010) involving rs1682111 and rs10439478; the cross-validation consistency of this model was 10 of 10, and the testing accuracy was 60.11%. Participants with the TA or AA of rs1682111 and the AC or CC of rs10439478 genotype have the highest BC risk, compared with subjects with the TT of rs1682111 and the AA of rs10439478 genotype (OR, 2.52; 95% CI, 1.67-3.44), after covariate adjustment for gender, age, age at menarche, number of children, and body mass index. CONCLUSIONS: Minor allele of rs1682111 and rs10439478 and its interaction were associated with increased BC risk.

An Interdisciplinary Nutrition Support Team Improves Clinical and Hospitalized Outcomes of Esophageal Cancer Patients with Concurrent Chemoradiotherapy.

BACKGROUND: The prevalence of malnutrition is very high in patients with cancer. The purpose of this study was to investigate whether or not a nutrition support team (NST) could benefit esophageal cancer patients undergoing chemoradiotherapy (CRT). METHODS: Between June 2012 and April 2014, 50 esophageal cancer patients undergoing concurrent CRT were randomly assigned into two groups: The NST group and the control group. The nutritional statuses of 25 patients in the NST group were managed by the NST. The other 25 patients in the control group underwent the supervision of radiotherapy practitioners. At the end of the CRT, nutritional status, the incidence of complications, and completion rate of radiotherapy were evaluated. Besides, the length of hospital stay (LOS) and the in-patient cost were also compared between these two groups. RESULTS: At the completion of CRF, the nutritional status in the NST group were much better than those in the control group, as evidenced by prealbumin (ALB), transferrin, and ALB parameters (P = 0.001, 0.000, and 0.000, respectively). The complication incidences, including bone marrow suppression (20% vs. 48%, P = 0.037) and complications related infections (12% vs. 44%, P = 0.012), in the NST group were lower and significantly different from the control group. In addition, only one patient in the NST group did not complete the planned radiotherapy while 6 patients in the control group had interrupted or delayed radiotherapy (96% vs. 76%, P = 0.103). Furthermore, the average LOS was decreased by 4.5 days (P = 0.001) and in-patient cost was reduced to 1.26 ± 0.75 thousand US dollars person-times (P > 0.05) in the NST group. CONCLUSIONS: A NST could provide positive effects in esophageal cancer patients during concurrent CRT on maintaining their nutrition status and improving the compliance of CRF. Moreover, the NST could be helpful on reducing LOS and in-patient costs.

[Impact of glutamine, eicosapntemacnioc acid, branched-chain amino acid supplements on nutritional status and treatment compliance of esophageal cancer patients on concurrent chemoradiotherapy and gastric cancer patients on chemotherapy].

OBJECTIVE: To explore the effects of glutamine, eicosapntemacnioc acid (EPA) and branched-chain amino acids supplements in esophageal cancer patients on concurrent chemoradiotherapy and gastric cancer patients on chemotherapy. METHODS: From April 2013 to April 2014, a total of 104 esophageal and gastric carcinoma patients on chemotherapy or concurrent chemoradiotherapy were recruited and randomly divided into experimental and control groups. Both groups received dietary counseling and routine nutritional supports while only experimental group received supplements of glutamine (20 g/d), EPA (3.3 g/d) and branched-chain amino acids (8 g/d). And body compositions, blood indicators, incidence of complications and completion rates of therapy were compared between two groups. RESULTS: After treatment, free fat mass and muscle weight increased significantly in experiment group while decreased in control group (P < 0.05). And albumin, red blood cell count, white blood cell count and blood platelet count remained stable in experiment group while declined significantly in control group. During treatment, compared to control group, the incidences of infection-associated complication were lower (6% vs 19%, P < 0.05) and the completion rates of therapy were significantly higher in experiment group (96% vs 83%, P < 0.05). CONCLUSION: Supplements of glutamine, EPA and branched-chain amino acids can help maintain nutrition status, decrease the complications and improve compliance for esophageal cancer patients on concurrent chemo-radiotherapy and gastric cancer patients on postoperative adjuvant chemotherapy.