Cancer Control

Hu, Chunxiao; Wu, Jing; Liu, Yafeng; Zhou, Jiawei; Wang, Wenyang; Wang, Xueqin; Guo, Jianqiang; Wang, Qingsen; Zhang, Xin; Li, Danting; Xie, Jun; Ding, Xuansheng; Xing, Yingru; Hu, Dong

doi: 10.1177/10732748221076805pmid: 35209734

Objective To investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) of patients with non-small cell lung cancer (NSCLC) and their risk of developing brain metastases after adjusting for confounding factors. Methods A retrospective observational study of the general data of patients with NSCLC diagnosed from January 2016 to December 2020. Multivariate logistic regression was used to calculate the dominance ratio (OR) with 95% confidence interval (CI) for NLR and NSCLC brain metastases with subgroup analysis. Generalized summation models and smoothed curve fitting were used to identify whether there was a nonlinear relationship between them. Results In all 3 models, NLR levels were positively correlated with NSCLC brain metastasis (model 1: OR: 1.12, 95% CI: 1.01-1.23, P = .025; model 2: OR: 1.16, 95% CI: 1.04-1.29, P = .007; model 3: OR: 1.20, 95% CI: 1.05-1.37, P = .006). Stratified analysis showed that this positive correlation was present in patients with adenocarcinoma (LUAD) and female patients (LUAD: OR: 1.30, 95% CI: 1.10-1.54, P = .002; female: OR: 1.52, 95% CI: 1.05-2.20, P = .026), while there was no significant correlation in patients with squamous carcinoma (LUSC) and male patients (LUSC: OR:0.76,95% CI:0.38- 1.53, P = .443; male: OR:1.13, 95% CI:0.95-1.33, P = .159). Conclusion This study showed that elevated levels of NLR were independently associated with an increased risk of developing brain metastases in patients with NSCLC, and that this correlation varied by TYPE and SEX, with a significant correlation in female patients and patients with LUAD.

Ma, Grace X.; Zhu, Lin; Zhai, Shumenghui; Lin, Timmy R.; Tan, Yin; Johnson, Cicely; Fang, Carolyn Y.; Belinson, Jerome L.; Wang, Min Qi

doi: 10.1177/10732748221076813pmid: 35193408

Background Asian American women face disproportionate burden of cervical cancer (CC) than non-Hispanic white women in the U.S. The goal of this study was to assess the feasibility and impact of a culturally tailored intervention to promote Human papillomavirus (HPV) self-sampling test among hard-to-reach Asian American women. Methods We adopted the community-based participatory research (CBPR) approach to conduct this efficacy study. A total of 156 female participants (56 Chinese, 50 Korean, and 50 Vietnamese) were recruited from community-based organizations (CBOs) in the greater Philadelphia metropolitan area. The intervention components included HPV-related education, HPV self-sampling test kit and instructions, group discussions, and patient navigations, all available in Asian languages. We examined several outcomes, including the completion of HPV self-sampling, HPV-related knowledge, perceived social support, self-efficacy, and comfort with the self-sampling test at post-intervention assessment. Results The majority of Asian American women had low annual household income (62.3% earned less than $20,000) and low educational attainment (61.3% without a college degree). We found significant increase in participants’ knowledge on HPV (baseline: 2.83, post: 4.89, P <.001), social support (baseline: 3.91, post: 4.09, P < .001), self-efficacy (baseline: 3.05, post: 3.59, P < .001), and comfortable with HPV self-sample test (baseline: 3.62, post: 4.06, P < .001). Conclusion To the best of our knowledge, this is the first intervention study that promoted HPV self-sampling test among Asian American women. Our findings showed that CBPR culturally tailored intervention of self-sampling was highly effective in empowering low-income Asian American women to conduct HPV self-sampling tests.

Wang, Shaokang; Pan, Da; Chen, Zitong; Song, Guang; Han, Renqiang; Sun, Guiju; Su, Ming

doi: 10.1177/10732748221076824pmid: 35196897

Purpose This study aimed to provide a clear comparable figure of the trends in incidence and mortality rates of esophageal cancer (EC) in Huai’an District, Huai’an City, Jiangsu Province, China, a high-risk area for EC. Methods The data for age- and sex-specific incidence rates between 1998 and 2016, the mortality rates in 1990-2016 and the number of EC patients were obtained from Huai’an District Cancer Registry. Crude rates, Age-standardized rates (ASRs) by world standard population and truncated age-standardized rates of EC incidence and mortality were calculated. The joinpoint regression analysis was used to calculate the annual percent changes (APC), average annual percent changes (AAPC), and their 95% confidence intervals (CIs). Results Overall, 20,892 new EC cases and 20,806 EC deaths were registered in Huai’an District. ASR of EC incidence from 1998 to 2016 and mortality from 1990 to 2016 were 73.32/100,000 and 60.03/100,000, respectively. The ASR illustrated that the incidence of EC had significant downward trends in total, male and female (AAPC = −4.65, −4.90, and −5.51, respectively, p <.01). The age-specific incidence and mortality rates of EC increased dramatically in people over the age of 40, and peaked in people between the ages 70-74. In the subdivisions of Huai’an District, geographical diversities in the crude incidence and mortality rates of EC were found. Conclusion In summary, the incidence and mortality rates of EC showed downward trends in Huai’an District. However, the burden of EC still remained serious in this high-risk area. Cost-effective methods of intervention and health education should be enhanced for improving EC prevention.

Urrutia Argueta, Samuel; Basnet, Nishraj; Abdul-Kafi, Owais; Hanna, Nasser

doi: 10.1177/10732748221081383pmid: 36895164

IntroductionLung cancer remains the leading cause of cancer-related death in the United States. Low density CT (LDCT) has been shown to reduce mortality in high-risk populations. Recognizing and mitigating gaps in knowledge in early medical training could result in increased utilization of screening CT in high risk-populations.MethodsAn electronic survey was conducted among Internal Medicine (IM) residents at 4 academic programs in the Midwestern United States. A survey was distributed to evaluate knowledge about high-risk populations, mortality benefits, and a comparison in mortality benefits between LDCT and other screening modalities using number needed to screen (NNS). Results: There was a 46.6% (166/360) response rate. Residents correctly answered an average of 2.9/7 (43.1%) questions. PGY-1 (post-graduate year) and PGY-2 residents performed better than PGY-3 (P = .022). Only 1/3 rd of all respondents correctly identified the population needed to be screened. Over 80% of residents thought screening with LDCT had a cancer-specific mortality benefit but were evenly split (except Program 2 residents), on recognizing an all-cause mortality benefit with LDCT, (P = .016). Only 7.7% thought women benefited the most from LDCT. Self-assess and attained knowledge were similar among programs.ConclusionsLDCT is a noninvasive intervention with a substantial mortality reduction, especially in states with high rates of smoking, and is widely covered by insurers. With average knowledge score less than 50%, this study shows there is a substantial need to increase the knowledge of LCS in IM residency programs.

Olazagasti, Coral; Ehrlich, Matthew; Kohn, Nina; Aviles, Karen; Hoilett, Aldane; Seetharamu, Nagashree

doi: 10.1177/10732748221077959pmid: 35157547

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. The U.S. Preventive Services Task Force (USPSTF) and National Comprehensive Cancer Network (NCCN) recommend annual low-dose CT chest (LDCT) for LC screening in high-risk adults who meet appropriate criteria, which primarily focus on age and smoking history. Despite this, screening rates remain low and patients with LC are typically diagnosed at a later stage. We conducted a single-center retrospective analysis of patients with an established diagnosis of lung cancer to evaluate if screening guidelines were appropriately followed before the cancer diagnosis. Patients diagnosed with LC between 2016 and 2019 were included in the analysis. Charts were reviewed for demographics, detailed smoking history, as well as histology and stage of LC. Associations between categorical factors and screening were examined using the chi-square test. Associations between continuous and ordinal factors and screening were examined using the Mann–Whitney test. A total of 530 charts were reviewed, of which 52% met NCCN criteria and 35% met USPSTF criteria. Only 4.0% and 4.8% of patients who met NCCN and USPSTF criteria, respectively, underwent screening. There was a significant association between staging at diagnosis and screening with LDCT. All the patients who had screening CT scans were diagnosed at localized stages of lung cancer in both NCCN and USPSTF groups compared to 49.1% and 48% in eligible subjects that did not undergo screening, respectively. Our study showed that despite established guidelines for LC screening and insurance coverage, a vast majority of screening-eligible LC patients have never had LDCT. We found that patients who underwent screening as per guidelines were diagnosed at earlier stages of the disease. Ongoing efforts to increase awareness and adherence to LC screening guidelines are needed to improve early detection and reduce LC mortality.

Feng, Zhenxing; Yin, Yan; Liu, Bin; Zheng, Yafang; Shi, Dongsheng; Zhang, Hong; Qin, Jianwen

doi: 10.1177/10732748221076682pmid: 35212236

Background The FAT atypical cadherin 1/2/3/4 (FAT1/2/3/4) has been linked to the occurrence and development of various cancers. However, the prognostic and immunological role of FAT1/2/3/4 in non-small cell lung cancer (NSCLC) has not been clarified. Methods The association of FAT1/2/3/4 mutations with tumor mutation burden (TMB), tumor immunity in the microenvironment, and response to ICIs in NSCLC was investigated. Whole-exome sequencing data of lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) samples from the Cancer Genome Atlas (TCGA), and an immunotherapy data set comprising mutation and survival data of 75 NSCLC patients were analyzed. Two independent pan-cancer cohorts with large samples were used to validate the prognostic value of FAT1/2/3/4 mutations in immunotherapy. Results A high mutation rate of FAT1/2/3/4 (57.3%, 603/1052) was observed in NSCLC patients. TMB was significantly higher in samples with mutated FAT1/2/3/4 compared to samples with wildtype FAT1/2/3/4 (P < .05). FAT2 mutation was found to be an independent prognostic biomarker in LUAD. FAT1/2/3/4 were aberrantly expressed in LUAD and LUSC, and high FAT2 expression strongly correlated with high PD-L1 levels in LUAD. Moreover, LUAD patients with FAT1 mutations showed significantly high activated dendritic cells infiltration, whereas those with FAT2/3/4 mutations had high infiltration of CD8+ T-cells, M1 macrophages, activated memory CD4+ T-cells, and helper follicular T-cells. It was also observed that FAT1/2/4 mutations were significantly associated with better enhanced objective response and durable clinical benefit, whereas FAT1/2/3 mutations correlated with longer progression-free survival in ICI-treated NSCLC cohort. FAT1/4 mutations were related to better overall survival in pan-cancer patients treated with ICIs. Conclusions FAT family genes are potential prognostic and immunological biomarkers and correlate with response to ICIs in NSCLC.

Xiong, Yubo; Zhuang, Yifan; Zhong, Mengya; Qin, Wenjuan; Huang, Boyi; Zhao, Jiabao; Gao, Zhi; Ma, Jingsong; Wu, Zhengxin; Hong, Xuehui; Yue, Zhicao; Lu, Haijie

doi: 10.1177/10732748221081369pmid: 35220799

Introduction The PER2 (Period circadian regulator 2) gene is related to the circadian clock, and it has been deemed as a suppressor gene in osteosarcoma and lung carcinoma. However, the part of PER2 in CRC (colorectal cancer) needs to be further determined. Methods First, we collected clinical samples to detect PER2 expression in CRC. Then, we used cell transfection to knock down PER2 expression in CRC cell lines and performed a series of functional experiments to elucidate the effects of PER2 on CRC cells. We next verified whether PER2 affects the epithelial-mesenchymal transformation (EMT) process in CRC by conducting quantitative real-time PCR and western blotting. Results In the research, we revealed that the expression of PER2 decreased in CRC clinical samples. In addition, knocking down PER2 expression caused CRC cells to acquire malignant biological features. Finally, we found that PER2 knockdown may activate the Snail/Slug axis through inhibiting p53, therefore promote the activation of the EMT pathway. Conclusion In conclusion, low PER2 expression reinforces migration and activates EMT in CRC, suggesting that PER2 is closely related to CRC development and could be used as a potential treatment site in the clinic.

Liao, Jun; Huang, Yihua; Gan, Jiadi; Pang, Lanlan; Ali, Wael A. S.; Yang, Yunpeng; Chen, Likun; Zhang, Li; Fang, Wenfeng

doi: 10.1177/10732748221081360pmid: 35201951

Objectives Osimertinib has exhibited promising central nervous system (CNS) efficacy in Epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) patients. In real-world clinical practice, patients would turn to plasma genotyping or take osimertinib blindly after CNS progression on previous tyrosine kinase inhibitors (TKIs). However, the efficacy of osimertinib in those patients according to their T790M mutational status has not been explored. Materials and methods Twenty-five patients who received osimertinib due to intracranial progressions with stable extracranial diseases after early-generation EGFR-TKI treatment were collected from 1032 EGFR-mutated NSCLC. Plasma samples were analyzed for EGFR mutations using next-generation sequencing (NGS) or polymerase chain reaction (PCR). Results Among the 25 patients, 17 patients took plasma genotyping before osimertinib treatment with 8 patients EGFR T790M mutation-positive and the rest started osimertinib blindly. The median progression-free survival (PFS) was 8.0 months (95% confidence interval [CI]: 6.12-9.94) and median intracranial PFS (iPFS) was 14.4 months (95% CI: 7.27-21.59) for the total population. No statistical difference was found in PFS and iPFS among patients with different EGFR T790M mutational statuses. Intracranial disease control rate (DCR) was 100.0% for 14 patients with evaluable intracranial lesions despite different T790M mutational statuses. DCR for extracranial lesions and overall lesions were 100.0%, 66.7%, and 87.5% for patients with T790M, no T790M, and unknown T790M mutational status, respectively. Conclusion For EGFR-mutated NSCLC patients with only intracranial progressions after previous TKI treatments, osimertinib is a promising treatment option regardless of T790M mutational status from plasma genotyping.

Bielecka-Wajdman, Anna M; Ludyga, Tomasz; Smyk, Daria; Smyk, Wojciech; Mularska, Magdalena; Świderek, Patrycja; Majewski, Wojciech; Mullins, Christina Susanne; Linnebacher, Michael; Obuchowicz, Ewa

doi: 10.1177/10732748221075468pmid: 35225010

Objective Current research indicates that weakness of glucose metabolism plays an important role in silencing of invasiveness and growth of hypoxic tumors such as GBM. Moreover, there are indications that DXM, frequently used in treatment, may support GBM energy metabolism and provoke its recurrence. Methods We carried out in vitro experiments on the commercial T98G cell line and two primary GBM lines (HROG02, HROG17) treated with TMZ and/or DXM in physiological oxygen conditions for GBM (2.5% oxygen) and for comparison, in standard laboratory conditions (20% oxygen). The influence of different glucose levels on selected malignancy features of GBM cells-cellular viability and division, dynamic of cell culture changes, colony formation and concentration of InsR have been elevated. Results Under 2.5% oxygen and high glucose concentration, an attenuated cytotoxic effect of TMZ and intensification of malignancy features in all glioblastoma cell lines exposed to DXM was seen. Furthermore, preliminary retrospective analysis to assess the correlation between serum glucose levels and Ki-67 expression in surgical specimens derived from patients with GBM (IV) treated with radio-chemotherapy and prophylactic DXM therapy was performed. Conclusion The data suggest a link between the in vitro study results and clinical data. High glucose can influence on GBM progression through the promotion of the following parameters: cell viability, dispersal, InsR expression and cell proliferation (Ki-67). However, this problem needs more studies and explain the mechanism of action studied drugs.

Yao, Peng; Lu, Yubao; Cai, Zongyan; Yu, Tianci; Kang, Yuchen; Zhang, Yu; Wang, Xulong

doi: 10.1177/10732748221076683pmid: 35179996

Currently, although the improvement of surgical techniques and the development of chemotherapy drugs have brought a certain degree of development to the treatment of osteosarcoma, the treatment of osteosarcoma has many shortcomings, and its treatment is limited. MiRNAs and exosomes can be used as diagnostic tools, and they play an important role in the occurrence and chemotherapy resistance of osteosarcoma. Therefore, providing a new method for the treatment of osteosarcoma is the key to solving this problem. To systematically summarize the research status of exoskeleton drug-loaded miRNA in osteosarcoma, we identified and evaluated 208 studies and found that exosome-carrying miRNA can be used as an index for the diagnosis and prognosis of osteosarcoma and share a certain relationship with chemosensitivity. In addition, exosomes can also be used as a carrier of genetic drugs able to regulate the progression of osteosarcoma. Based on the above findings, we propose suggestions for the future development of this field, aiming to bring new ideas for the early diagnosis and treatment of osteosarcoma.