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Published By Springer (Biomed Central Ltd.)

1471-2407, 1471-2407

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Linda Rainey ◽  
Daniëlle van der Waal ◽  
Louise S. Donnelly ◽  
Jake Southworth ◽  
David P. French ◽  
...  

Abstract Background The Predicting Risk of Cancer at Screening (PROCAS) study provided women who were eligible for breast cancer screening in Greater Manchester (United Kingdom) with their 10-year risk of breast cancer, i.e., low (≤1.5%), average (1.5–4.99%), moderate (5.-7.99%) or high (≥8%). The aim of this study is to explore which factors were associated with women’s uptake of screening and prevention recommendations. Additionally, we evaluated women’s organisational preferences regarding tailored screening. Methods A total of 325 women with a self-reported low (n = 60), average (n = 125), moderate (n = 80), or high (n = 60) risk completed a two-part web-based survey. The first part contained questions about personal characteristics. For the second part women were asked about uptake of early detection and preventive behaviours after breast cancer risk communication. Additional questions were posed to explore preferences regarding the organisation of risk-stratified screening and prevention. We performed exploratory univariable and multivariable regression analyses to assess which factors were associated with uptake of primary and secondary breast cancer preventive behaviours, stratified by breast cancer risk. Organisational preferences are presented using descriptive statistics. Results Self-reported breast cancer risk predicted uptake of (a) supplemental screening and breast self-examination, (b) risk-reducing medication and (c) preventive lifestyle behaviours. Further predictors were (a) having a first degree relative with breast cancer, (b) higher age, and (c) higher body mass index (BMI). Women’s organisational preferences for tailored screening emphasised a desire for more intensive screening for women at increased risk by further shortening the screening interval and moving the starting age forward. Conclusions Breast cancer risk communication predicts the uptake of key tailored primary and secondary preventive behaviours. Effective communication of breast cancer risk information is essential to optimise the population-wide impact of tailored screening.


BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Yaodong Zhou ◽  
Tao Yu ◽  
Yixin Zhang ◽  
Liqiang Qian ◽  
Qing Xia

Abstract Background As segmentectomy had become commonly used for Non-Small Cell Lung Cancer (NSCLC) treatment, which had the advantages of radical operation, however, it remains controversial owing to procedural complexity and risk of increased complications compared with wedge resection. We evaluated operative and postoperative outcomes of simple segmentectomy compared to wedge resection in ground-glass opacity (GGO) diameter between 2 cm and 3 cm NSCLC. Methods We retrospectively reviewed 1600 clinical GGO diameter between 2 cm and 3 cm NSCLC patients who received simple segmentectomy and wedge resection between Jan 2011 and Jan 2015. Participants were matched 1:1 on their propensity score for two groups. Clinic-pathologic, operative, and postoperative results of two groups were compared. Results After using propensity score methods to create a matched cohort of participants with simple segmentectomy group similar to that wedge resection, there were no significant differences detected in tumor size, margin distance, histology, age, sex, preoperative comorbidities and preoperative pulmonary function. Overall complications in simple segmentectomy group were more than wedge resection group (21% vs 3%, p = 0.03). Median operative time (110.6 vs. 71.2 min; p = 0.01) and prolonged air leakage (12% vs. 3%; p = 0.02) was significantly longer in the simple segmentectomy group. There was no difference in recurrence free survival (RFS) and overall survival (OS) of 5-years between simple segmentectomy group and wedge resection group. Postoperative pulmonary function in simple segmentectomy group recovered more slowly than wedge resection group. Conclusion Wedge resection may have comparable efficacy as simple segmentectomy for GGO diameter between 2 cm and 3 cm NSCLC, but lead to less complications, less surgical procedure and faster recovery of pulmonary function.


BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Tamara Babic ◽  
Sandra Dragicevic ◽  
Marko Miladinov ◽  
Zoran Krivokapic ◽  
Aleksandra Nikolic

Abstract Background Transcripts with alternative 5′-untranslated regions (UTRs) result from the activity of alternative promoters and they can determine gene expression by influencing its stability and translational efficiency, thus executing complex regulation of developmental, physiological and pathological processes. Transcriptional regulation of human SMAD4, a key tumor suppressor deregulated in most gastrointestinal cancers, entails four alternative promoters. These promoters and alternative transcripts they generate remain unexplored as contributors to the SMAD4 deregulation in cancer. The aim of this study was to investigate the relative abundance of the transcript SMAD4–201 in colorectal cell lines and tissues in order to establish if its fluctuations may be associated with colorectal cancer (CRC). Methods Relative abundance of SMAD4–201 in total SMAD4 mRNA was analyzed using quantitative PCR in a set of permanent human colon cell lines and tumor and corresponding healthy tissue samples from patients with CRC. Results The relative abundance of SMAD4–201 in analyzed cell lines varied between 16 and 47%. A similar relative abundance of SMAD4–201 transcript was found in the majority of analyzed human tumor tissue samples, and it was averagely 20% lower in non-malignant in comparison to malignant tissue samples (p = 0.001). Transcript SMAD4–202 was not detectable in any of the analyzed samples, so the observed fluctuations in the composition of SMAD4 transcripts can be attributed to transcripts other than SMAD4–201 and SMAD4–202. Conclusion The expression profile of SMAD4–201 in human tumor and non-tumor tissue samples may indicate the translational potential of this molecule in CRC, but further research is needed to clarify its usability as a potential biomarker for early diagnosis.


BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
John Sharp ◽  
Vinay Prasad

Abstract Importance It is unknown whether and to what degree trials submitted to the US FDA to support drug approval adhere to NCCN guideline-recommended care in their baseline and surveillance CNS imaging protocols. Objective We sought to characterize the frequency with which the trials cited in US FDA drug approvals for first line advanced NSCLC between 2015 and 2020 deviated from NCCN guideline-recommended care for baseline and surveillance CNS imaging. Design, setting, and participants Retrospective observational analysis using publicly available data of (1) list of trials cited by the FDA in drug approvals for first line advanced NSCLC from 2015 to 2020 (2) individual trial protocols (3) published trial data and supplementary appendices (4) archived versions of the NCCN guidelines for NSCLC from 2009 to 2018 (the years during which the trials were enrolling). Main outcomes and measures Estimated percentage of trials for first line advanced NSCLC leading to FDA approval which deviated from NCCN guideline-recommended care with regards to CNS baseline and surveillance imaging. Results A total of 14 studies that had been cited in FDA drug approvals for first line advanced NSCLC met our inclusion criteria between January 1, 2015 and September 30, 2020. Of these trials, 8 (57.1%) deviated from NCCN guidelines in their baseline CNS imaging requirement. The frequency of re-assessment of CNS disease was variable amongst trials as well, with 9 (64.3%) deviating from NCCN recommendations. Conclusions and relevance The trials supporting US FDA drug approvals in first line advanced NSCLC often have CNS imaging requirements that do not adhere to NCCN guidelines. Many trials permit alternative, substandard methods and the proportion of patients undergoing each modality is uniformly not reported. Nonstandard CNS surveillance protocols are common. To best serve patients with advanced NSCLC in the US, drug approvals by the FDA must be based on trials that mirror clinical practice and have imaging requirements consistent with current US standard of care.


BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Giuditta Chiloiro ◽  
Davide Cusumano ◽  
Luca Boldrini ◽  
Angela Romano ◽  
Lorenzo Placidi ◽  
...  

Abstract Background Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC). Since response to radiotherapy (RT) is dose dependent in rectal cancer, dose escalation may lead to higher complete response rates. The possibility to predict patients who will achieve complete response (CR) is fundamental. Recently, an early tumour regression index (ERI) was introduced to predict pathological CR (pCR) after nCRT in LARC patients. The primary endpoints will be the increase of CR rate and the evaluation of feasibility of delta radiomics-based predictive MRI guided Radiotherapy (MRgRT) model. Methods Patients affected by LARC cT2-3, N0-2 or cT4 for anal sphincter involvement N0-2a, M0 without high risk features will be enrolled in the trial. Neoadjuvant CRT will be administered using MRgRT. The initial RT treatment will consist in delivering 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum and 45 Gy in 25 fractions on the drainage nodes. Chemotherapy with 5-fluoracil (5-FU) or oral capecitabine will be administered continuously. A 0.35 Tesla MRI will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated: if ERI will be inferior than 13.1, the patient will continue the original treatment; if ERI will be higher than 13.1 the treatment plan will be reoptimized, intensifying the dose to the residual tumor at the 11th fraction to reach 60.1 Gy. At the end of nCRT instrumental examinations are to be performed in order to restage patients. In case of stable disease or progression, the patient will undergo surgery. In case of major or complete clinical response, conservative approaches may be chosen. Patients will be followed up to evaluate toxicity and quality of life. The number of cases to be enrolled will be 63: all the patients will be treated at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. Discussion This clinical trial investigates the impact of RT dose escalation in poor responder LARC patients identified using ERI, with the aim of increasing the probability of CR and consequently an organ preservation benefit in this group of patients. Trial registration ClinicalTrials.gov Identifier: NCT04815694 (25/03/2021).


BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Michele Sassano ◽  
Marco Mariani ◽  
Gianluigi Quaranta ◽  
Roberta Pastorino ◽  
Stefania Boccia

Abstract Background Risk prediction models incorporating single nucleotide polymorphisms (SNPs) could lead to individualized prevention of colorectal cancer (CRC). However, the added value of incorporating SNPs into models with only traditional risk factors is still not clear. Hence, our primary aim was to summarize literature on risk prediction models including genetic variants for CRC, while our secondary aim was to evaluate the improvement of discriminatory accuracy when adding SNPs to a prediction model with only traditional risk factors. Methods We conducted a systematic review on prediction models incorporating multiple SNPs for CRC risk prediction. We tested whether a significant trend in the increase of Area Under Curve (AUC) according to the number of SNPs could be observed, and estimated the correlation between AUC improvement and number of SNPs. We estimated pooled AUC improvement for SNP-enhanced models compared with non-SNP-enhanced models using random effects meta-analysis, and conducted meta-regression to investigate the association of specific factors with AUC improvement. Results We included 33 studies, 78.79% using genetic risk scores to combine genetic data. We found no significant trend in AUC improvement according to the number of SNPs (p for trend = 0.774), and no correlation between the number of SNPs and AUC improvement (p = 0.695). Pooled AUC improvement was 0.040 (95% CI: 0.035, 0.045), and the number of cases in the study and the AUC of the starting model were inversely associated with AUC improvement obtained when adding SNPs to a prediction model. In addition, models constructed in Asian individuals achieved better AUC improvement with the incorporation of SNPs compared with those developed among individuals of European ancestry. Conclusions Though not conclusive, our results provide insights on factors influencing discriminatory accuracy of SNP-enhanced models. Genetic variants might be useful to inform stratified CRC screening in the future, but further research is needed.


BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Maribel Salas ◽  
Margaret Mordin ◽  
Colleen Castro ◽  
Zahidul Islam ◽  
Nora Tu ◽  
...  

Abstract Background To identify and describe the breast cancer–specific health-related quality of life (HRQoL) instruments with evidence of validation in the breast cancer population for potential use in patients treated for breast cancer (excluding surgery). Methods We conducted a systematic literature review using PubMed, Embase, and PsycINFO databases to identify articles that contain psychometric properties of HRQoL instruments used in patients with breast cancer. Relevant literature from January 1, 2009, to August 19, 2019, was searched. Articles published in English that reported psychometric properties (reliability, validity) of HRQoL instruments were identified. Results The database search yielded 613 unique records; 131 full-text articles were reviewed; 80 articles presented psychometric data for instruments used in breast cancer (including generic measures). This article reviews the 33 full articles describing psychometric properties of breast cancer-specific HRQoL instruments: EORTC QLQ-C30, EORTC QLQ-BR23, FACT-B, FBSI, NFBSI-16, YW-BCI36, BCSS, QuEST-Br, QLICP-BR, INA-BCHRQoL, and two newly developed unnamed measures, one by Deshpande and colleagues (for use in India) and one by Vanlemmens and colleagues (for use among young women and their partners). The articles that described the EORTC QLQ-C30, QLQ-BR23, and FACT-B centered on validating translations, providing additional support for content validity, and demonstrating acceptability of electronic patient-reported outcome administration. Psychometric properties of the measures were acceptable. Several new measures have been developed in Asia with an emphasis on development on cultural relevance/sensitivity. Others focused on specific populations (i.e., young women with breast cancer). Conclusions Historically, there have been limited options for validated measures to assess HRQoL of patients with breast cancer. A number of new measures have been developed and validated, offering promising options for assessing HRQoL in this patient population. This review supports the reliability and validity of the EORTC QLQ-C30 and FACT-B; new translations and electronic versions of these measures further support their use for this population.


BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Teng Huang ◽  
Jiaheng Li ◽  
San Ming Wang

Abstract Background Bladder cancer is one of the most mortal cancers. Bladder cancer has distinct gene expression signature, highlighting altered gene expression plays important roles in bladder cancer etiology. However, the mechanism for how the regulatory disorder causes the altered expression in bladder cancer remains elusive. Core promoter controls transcriptional initiation. We hypothesized that mutation in core promoter abnormality could cause abnormal transcriptional initiation thereby the altered gene expression in bladder cancer. Methods In this study, we performed a genome-wide characterization of core promoter mutation in 77 Spanish bladder cancer cases. Results We identified 69 recurrent somatic mutations in 61 core promoters of 62 genes and 28 recurrent germline mutations in 20 core promoters of 21 genes, including TERT, the only gene known with core promoter mutation in bladder cancer, and many oncogenes and tumor suppressors. From the RNA-seq data from bladder cancer, we observed  altered expression of the core promoter-mutated genes. We further validated the effects of core promoter mutation on gene expression by using luciferase reporter gene assay. We also identified potential drugs targeting the core promoter-mutated genes. Conclusions Data from our study highlights that core promoter mutation contributes to bladder cancer development through altering gene expression.


BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Shigemasa Takamizawa ◽  
Tatsunori Shimoi ◽  
Natsuko Satomi-Tsushita ◽  
Shu Yazaki ◽  
Toshihiro Okuya ◽  
...  

Abstract Background Eribulin or capecitabine monotherapy is the next cytotoxic chemotherapy option for patients with metastatic or recurrent breast cancer who have previously received an anthracycline or a taxane. However, it is unclear what factors can guide the selection of eribulin or capecitabine in this setting, and prognostic factors are needed to guide appropriate treatment selection. The neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor for eribulin-treated patients, although it is unclear whether it is a prognostic factor for capecitabine-treated patients. Therefore, we analysed the ability of the NLR to predict oncological outcomes among patients who received capecitabine after previous anthracycline or taxane treatment for breast cancer. Methods We retrospectively reviewed the medical records of patients with metastatic or recurrent breast cancer who had previously received anthracycline or taxane treatment at the National Cancer Center Hospital between 2007 and 2015. Patients were included if they received eribulin or capecitabine monotherapy as first-line, second-line, or third-line chemotherapy. Analyses of overall survival (OS) and progression-free survival (PFS) were performed according to various factors. Results Between 2007 and 2015, we identified 125 eligible patients, including 46 patients who received only eribulin, 34 patients who received only capecitabine, and 45 patients who received eribulin and capecitabine. The median follow-up period was 19.1 months. Among eribulin-treated patients, an NLR of <3 independently predicted better OS. Among capecitabine-treated patients, an NLR of <3 independently predicted better PFS but not better OS. In addition, a lymphocyte-to-monocyte ratio of ≥5 was associated with better PFS and OS. Conclusions To the best of our knowledge, this is the first study to evaluate whether the NLR is a prognostic factor for capecitabine-treated patients with metastatic or recurrent breast cancer. However, the NLR only independently predicted PFS in this setting, despite it being a useful prognostic factor for other chemotherapies.


BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Astrid Louise Bjørn Bennedsen ◽  
Luyi Cai ◽  
Rune Petring Hasselager ◽  
Aysun Avci Özcan ◽  
Khadra Bashir Mohamed ◽  
...  

Abstract Background The immune system recognizes and destroys cancer cells. However, cancer cells develop mechanisms to avoid detection by expressing cell surface proteins. Specific tumour cell surface proteins (e.g. HLA-G, PD-L1, CDX2) either alone or in combination with the relative presence of immune cells (CD3 and CD8 positive T-cells) in the tumour tissue may describe the cancer cells’ ability to escape eradication by the immune system. The aim was to investigate the prognostic value of immunohistochemical markers in patients with colon cancer. Methods We conducted a retrospective study including patients diagnosed with pT3 and pT4 colon cancers. Immunohistochemical staining with HLA-G, PD-L1, CDX2, CD3, and CD8 was performed on tissue samples with representation of the invasive margin. PD-L1 expression in tumour cells and immune cells was reported conjointly. The expression of CD3 and CD8 was reported as a merged score based on the expression of both markers in the invasive margin and the tumour centre. Subsequently, a combined marker score was established based on all of the markers. Each marker added one point to the score when unfavourable immunohistochemical features was present, and the score was categorized as low, intermediate or high depending on the number of unfavourable stains. Hazard ratios for recurrence, disease-free survival and mortality were calculated. Results We included 188 patients undergoing colon cancer resections in 2011–2012. The median follow-up was 41.7 months, during which 41 (21.8%) patients had recurrence and 74 (39.4%) died. In multivariable regression analysis positive HLA-G expression (HR = 3.37, 95%CI [1.64–6.93]) was associated with higher recurrence rates, while a preserved CDX2 expression (HR = 0.23, 95%CI [0.06–0.85]) was associated with a lower risk of recurrence. An intermediate or high combined marker score was associated with increased recurrence rates (HR = 20.53, 95%CI [2.68–157.32] and HR = 7.56, 95%CI [1.06–54.16], respectively). Neither high expression of PD-L1 nor high CD3-CD8 score was significantly associated with recurrence rates. Patients with a high CD3-CD8 score had a significantly longer DFS and OS. Conclusions In tumour cells, expression of HLA-G and loss of CDX2 expression were associated with cancer recurrence. In addition, a combination of certain tumour tissue biomarkers was associated with colorectal cancer recurrence.


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