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Frontiers in Immunology 2021Head and neck cancer (HNC) is the sixth most common malignancy worldwide; head and neck squamous cell carcinoma (HNSCC) account for the most cases of HNC. Past smoking...
Head and neck cancer (HNC) is the sixth most common malignancy worldwide; head and neck squamous cell carcinoma (HNSCC) account for the most cases of HNC. Past smoking and alcohol consumption are common risk factors of HNSCC; however, an increasing number of cases associated with human papillomavirus (HPV) infection have been reported in recent years. The treatment of HNSCC is integrated and multimodal including traditional surgery, radiotherapy, chemotherapy, and targeted therapy. Since pembrolizumab was approved in 2016, an increasing number of studies have focused on immunotherapy. However, not all of HNSCC patients have a better outcome on immunotherapy. Immunotherapy has been reported to be more effective in HPV-positive patients, but its molecular mechanism is still unclear. Some researchers have proposed that the high proportion of infiltrating immune cells in HPV-positive tumors and the difference in immune checkpoint expression level may be the reasons for their better response. As a result, a series of individualized immunotherapy trials have also been conducted in HPV-positive patients. This paper summarizes the current status of HNSCC immunotherapy, individualized immunotherapy in HPV-positive patients, and immune differences in HPV-positive tumors to provide new insights into HNSCC immunotherapy and try to identify patients who may benefit from immunotherapy.
Topics: Alphapapillomavirus; Antineoplastic Agents, Immunological; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Head and Neck Neoplasms; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Papillomavirus Infections; Progression-Free Survival; Randomized Controlled Trials as Topic; Squamous Cell Carcinoma of Head and Neck
PubMed: 34305889
DOI: 10.3389/fimmu.2021.652054 -
Journal of the National Cancer Institute Apr 2022The consensus molecular subtypes (CMSs) of colorectal cancer (CRC) capture tumor heterogeneity at the gene-expression level. Currently, a restricted number of molecular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The consensus molecular subtypes (CMSs) of colorectal cancer (CRC) capture tumor heterogeneity at the gene-expression level. Currently, a restricted number of molecular features are used to guide treatment for CRC. We summarize the evidence on the clinical value of the CMSs.
METHODS
We systematically identified studies in Medline and Embase that evaluated the prognostic and predictive value of CMSs in CRC patients. A random-effect meta-analysis was performed on prognostic data. Predictive data were summarized.
RESULTS
In local disease, CMS4 tumors were associated with worse overall survival (OS) compared with CMS1 (hazard ratio [HR] = 3.28, 95% confidence interval = 1.27 to 8.47) and CMS2 cancers (HR = 2.60, 95% confidence interval = 1.93 to 3.50). In metastatic disease, CMS1 consistently had worse survival than CMS2-4 (OS HR range = 0.33-0.55; progression-free survival HR range = 0.53-0.89). Adjuvant chemotherapy in stage II and III CRC was most beneficial for OS in CMS2 and CMS3 (HR range = 0.16-0.45) and not effective in CMS4 tumors. In metastatic CMS4 cancers, an irinotecan-based regimen improved outcome compared with oxaliplatin (HR range = 0.31-0.72). The addition of bevacizumab seemed beneficial in CMS1, and anti-epidermal growth factor receptor therapy improved outcome for KRAS wild-type CMS2 patients.
CONCLUSIONS
The CMS classification holds clear potential for clinical use in predicting both prognosis and response to systemic therapy, which seems to be independent of the classifier used. Prospective studies are warranted to support implementation of the CMS taxonomy in clinical practice.
Topics: Bevacizumab; Biomarkers, Tumor; Colorectal Neoplasms; Gene Expression Profiling; Humans; Oxaliplatin; Prognosis
PubMed: 34077519
DOI: 10.1093/jnci/djab106 -
Cancers May 2024Modern advanced radiotherapy techniques have improved the precision and accuracy of radiotherapy delivery, with resulting plans being highly personalised based on... (Review)
Review
Modern advanced radiotherapy techniques have improved the precision and accuracy of radiotherapy delivery, with resulting plans being highly personalised based on individual anatomy. Adaptation for individual tumour biology remains elusive. There is an unmet need for biomarkers of intrinsic radiosensitivity that can predict tumour response to radiation to facilitate individualised decision-making, dosing and treatment planning. Over the last few decades, the use of high throughput molecular biology technologies has led to an explosion of newly discovered cancer biomarkers. Gene expression signatures are now used routinely in clinic to aid decision-making regarding adjuvant systemic therapy. They have great potential as radiotherapy biomarkers. A previous systematic review published in 2015 reported only five studies of signatures evaluated for their ability to predict radiotherapy benefits in clinical cohorts. This updated systematic review encompasses the expanded number of studies reported in the last decade. An additional 27 studies were identified. In total, 22 distinct signatures were recognised (5 pre-2015, 17 post-2015). Seventeen signatures were 'radiosensitivity' signatures and five were breast cancer prognostic signatures aiming to identify patients at an increased risk of local recurrence and therefore were more likely to benefit from adjuvant radiation. Most signatures (15/22) had not progressed beyond the discovery phase of development, with no suitable validated clinical-grade assay for application. Very few signatures (4/17 'radiosensitivity' signatures) had undergone any laboratory-based biological validation of their ability to predict tumour radiosensitivity. No signatures have been assessed prospectively in a phase III biomarker-led trial to date and none are recommended for routine use in clinical guidelines. A phase III prospective evaluation is ongoing for two breast cancer prognostic signatures. The most promising radiosensitivity signature remains the radiosensitivity index (RSI), which is used to calculate a genomic adjusted radiation dose (GARD). There is an ongoing phase II prospective biomarker-led study of RSI/GARD in triple negative breast cancer. The results of these trials are eagerly anticipated over the coming years. Future work in this area should focus on (1) robust biological validation; (2) building biobanks alongside large radiotherapy randomised controlled trials with dose variance (to demonstrate an interaction between radiosensitivity signature and dose); (3) a validation of clinical-grade cost-effective assays that are deliverable within current healthcare infrastructure; and (4) an integration with biomarkers of other determinants of radiation response.
PubMed: 38792019
DOI: 10.3390/cancers16101942 -
Andrology Sep 2017The impact of phosphodiesterase type 5 inhibitor (PDE5I) treatment modality (on-demand vs. daily), PDE5I half-life and time from surgery to PDE5I prescription on the... (Meta-Analysis)
Meta-Analysis Review
Erectile function recovery in men treated with phosphodiesterase type 5 inhibitor administration after bilateral nerve-sparing radical prostatectomy: a systematic review of placebo-controlled randomized trials with trial sequential analysis.
The impact of phosphodiesterase type 5 inhibitor (PDE5I) treatment modality (on-demand vs. daily), PDE5I half-life and time from surgery to PDE5I prescription on the achievement of drug-assisted erectile function (EF) recovery is uncertain. We systematically reviewed published randomized clinical trials (RCTs). We performed meta-analyses of data on 2317 men treated with PDE5Is after nerve-sparing radical prostatectomy (NSRP). A PubMed and SCOPUS search was performed for trials published from 1 January 1969 to 30 June 2016. PDE5Is are effective in achieving drug-assisted recovery of erectile function (EF). From a statistical standpoint, these studies were subjected to Trial Sequential Analysis to determine whether the pooled data were adequately powered to verify the study outcomes. On-demand treatment with PDE5Is was significantly better than daily treatment in recovering drug-assisted EF. This effect was maintained even when the drugs were stratified according with half-life. Although not based on head-to-head trials, Avanafil used on-demand was the most effective PDE5I in recovering drug-assisted EF. Whereas tadalafil was equally effective when used both on-demand and daily, vardenafil significantly improved drug-assisted EF recovery only when used on-demand. The start of PDE5I treatment six months or more after surgery compared to treatment started earlier did not negatively affect the rate of drug-assisted EF recovery or the possibility to have successful intercourse based on the Sexual Encounter Profile question-3 (SEP-3). Current trials do not support the hypothesis that PDE5I use recovers drug-unassisted EF, although chronic low-dose tadalafil administration may help to preserve erectile tissue integrity. Potential shortcomings in the trials design may partially explain these disappointing results and several questions concerning the recovery of drug-unassisted EF remain unanswered. Thus, there is a need for well-designed new RCTs requiring changes in the timing of PDE5I administration as well as in the dose and the treatment duration.
Topics: Erectile Dysfunction; Humans; Male; Penile Erection; Phosphodiesterase 5 Inhibitors; Prostatectomy; Randomized Controlled Trials as Topic
PubMed: 28787547
DOI: 10.1111/andr.12403 -
Frontiers in Oncology 2020Human papillomavirus (HPV) is a risk factor for squamous cell carcinoma of the head and neck (HNSCC). This study aimed to investigate the feasibility of IHC- p16INK4a...
Feasibility of Immunohistochemical p16 Staining in the Diagnosis of Human Papillomavirus Infection in Patients With Squamous Cell Carcinoma of the Head and Neck: A Systematic Review and Meta-Analysis.
Human papillomavirus (HPV) is a risk factor for squamous cell carcinoma of the head and neck (HNSCC). This study aimed to investigate the feasibility of IHC- p16INK4a (p16) as an alternative modality for diagnosing HPV infection. We searched PubMed, EMBASE, Web of Science, and Cochrane library for studies that evaluated the diagnostic accuracy of IHC-p16 staining. A total of 30 studies involving 2,963 patients were included from 2007 to 2019. The combined sensitivity was 0.94 (95% CI: 0.92-0.95); specificity, 0.90 (95% CI: 0.89-0.91); positive likelihood ratio (LR), 6.80 (95% CI: 5.63-8.21); negative LR, 0.10 (95% CI: 0.07-0.16); diagnostic odds ratio, 85.98 (95% CI: 55.57-133.03); and area under the curve value, 0.9550. Subgroup analysis showed that the IHC-p16 test was more consistent with the hybridization (ISH) test and has greater diagnostic value for oropharyngeal squamous cell carcinoma. The diagnostic efficacy of IHC-p16 varied among countries. In conclusion, IHC-p16 has high sensitivity and specificity for diagnosing HPV infection in HNSCC. The consistency of IHC-p16 findings with those of ISH indicate that their combination can be used to improve the specificity of diagnosis.
PubMed: 33324540
DOI: 10.3389/fonc.2020.524928 -
Scientific Reports Jun 2017Trastuzumab combined with chemotherapy is standard of care for HER2 positive advanced gastro-esophageal cancers. The reported prevalence of HER2 discordance between... (Meta-Analysis)
Meta-Analysis
Trastuzumab combined with chemotherapy is standard of care for HER2 positive advanced gastro-esophageal cancers. The reported prevalence of HER2 discordance between primary tumors and corresponding metastases varies, hampering uniform patient selection for HER2 targeted therapy. This meta-analysis explores the influence of HER2 assessment methods on this discordance and investigates the prevalence of HER2 discordance in gastro-esophageal adenocarcinomas. PubMed, Embase and Cochrane databases were searched until January 2016. Differences in discordance rate between strict and broad(er) definitions of HER2 status were assessed using random-effect pair-wise meta-analysis. Random-effect single-arm meta-analyses were performed to assess HER2 discordance and the prevalence of positive and negative conversion. A significantly lower discordance rate in HER2 status between primary tumors and corresponding metastases was observed using a strict vs. broad definition of HER2 status (RR = 0.58, 95%CI 0.41-0.82), with a pooled discordance rate of 6.2% and 12.2%, respectively. Using the strict definition of HER2 assessment pooled overall discordance was 7% (95%CI 5-10%). The lowest discordance rates between primary tumors and corresponding metastasis are observed when using a strict method of HER2 positivity. Treatment outcomes of different studies will be better comparable if selection of eligible patients for HER2 targeted therapy is based on this strict definition.
Topics: Adenocarcinoma; Antineoplastic Agents; Esophageal Neoplasms; Gene Amplification; Humans; Neoplasm Metastasis; Receptor, ErbB-2; Stomach Neoplasms; Trastuzumab; Treatment Outcome
PubMed: 28600510
DOI: 10.1038/s41598-017-03304-9 -
International Journal of Molecular... Jul 2021Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and... (Meta-Analysis)
Meta-Analysis
Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and genotoxicity associated with increased risk of cancer. This review aims to identify the genotoxicity biomarkers that are the most elevated in IR-exposed vs. unexposed health workers. A systematic review of the literature was performed to retrieve relevant studies with various biomarkers of genotoxicity. Subsequent meta-analyses produced a pooled effect size for several endpoints. The search procedure yielded 65 studies. Chromosome aberrations (CA) and micronuclei (MN) frequencies were significantly different between IR-exposed and unexposed workers (θ = 3.19, 95% CI 1.46-4.93; and θ = 1.41, 95% CI 0.97-1.86, for total aberrant cells and MN frequencies, respectively), which was not the case for ring chromosomes and nucleoplasmic bridges. Although less frequently used, stable translocations, sister chromatid exchanges (SCE) and comet assay endpoints were also statistically different between IR-exposed and unexposed workers. This review confirms the relevance of CA and MN as genotoxicity biomarkers that are consistently elevated in IR-exposed vs. unexposed workers. Other endpoints are strong candidates but require further studies to validate their usefulness. The integration of the identified biomarkers in future prospective epidemiological studies is encouraged.
Topics: Biomarkers; Chromosome Aberrations; DNA Damage; Dose-Response Relationship, Radiation; Health Personnel; Humans; Occupational Exposure; Radiation, Ionizing
PubMed: 34299125
DOI: 10.3390/ijms22147504 -
Molecular Diagnosis & Therapy Jul 2024HtrA1, HtrA2, HtrA3 and HtrA4 appear to be involved in the development of pathologies such as cancer. This systematic review reports the results of a literature search...
PURPOSE
HtrA1, HtrA2, HtrA3 and HtrA4 appear to be involved in the development of pathologies such as cancer. This systematic review reports the results of a literature search performed to compare the expression of HtrA family genes and proteins in cancer versus non-cancer tissues and cell lines, assess relationships between HtrA expression and cancer clinical features in cancer, and analyse the molecular mechanism, by which HtrA family affects cancer.
METHODS
The literature search was conducted according to the PRISMA statement among four databases (PubMed, Web of Science, Embase and Scopus).
RESULTS
A total of 38 articles met the inclusion criteria and involved the expression of HtrA family members and concerned the effect of HtrA expression on cancer and metastasis development or on the factor that influences it. Additionally, 31 reports were retrieved manually. Most articles highlighted that HtrA1 and HtrA3 exhibited tumour suppressor activity, while HtrA2 was associated with tumour growth and metastasis. There were too few studies to clearly define the role of the HtrA4 protease in tumours.
CONCLUSION
Although the expression of serine proteases of the HtrA family was dependent on tumour type, stage and the presence of metastases, most articles indicated that HtrA1 and HtrA3 expression in tumours was downregulated compared with healthy tissue or cell lines. The expression of HtrA2 was completely study dependent. The limited number of studies on HtrA4 expression made it impossible to draw conclusions about differences in expression between healthy and tumour tissue. The conclusions drawn from the study suggest that HtrA1 and HtrA3 act as tumour suppressors.
Topics: Humans; Neoplasms; High-Temperature Requirement A Serine Peptidase 1; Serine Endopeptidases; High-Temperature Requirement A Serine Peptidase 2; Gene Expression Regulation, Neoplastic; Mitochondrial Proteins
PubMed: 38717523
DOI: 10.1007/s40291-024-00712-2 -
Cancer Treatment Reviews Nov 2021Esophageal and gastric malignancies are associated with poor prognosis, in part due to development of recurrences or metastases after curative treatment. The...
Esophageal and gastric malignancies are associated with poor prognosis, in part due to development of recurrences or metastases after curative treatment. The transforming growth factor β (TGF-β) pathway might play a role in the development of treatment resistance. In this systematic review, we provide an overview of preclinical studies investigating the role of TGF-β in esophageal and gastric malignancies. We systematically searched MEDLINE/PubMed and EMBASE for eligible preclinical studies describing the effect of TGF-β or TGF-β inhibition on hallmarks of cancer, such as proliferation, migration, invasion, angiogenesis and immune evasion. In total, 2107 records were screened and 45 articles were included, using mouse models and 45 different cell lines. TGF-β failed to induce apoptosis in twelve of sixteen tested cell lines. TGF-β could either decrease (five cell lines) or increase proliferation (seven cell lines) in gastric cancer cells, but had no effect in esophageal cancer cells. In all esophageal and all but two gastric cancer cell lines, TGF-β increased migratory, adhesive and invasive capacities. In vivo studies showed increased metastasis in response to TGF-β treatment. Additionally, TGF-β was shown to induce vascular endothelial growth factor production and differentiation of cancer-associated fibroblasts and regulatory T-cells. In conclusion, we found that TGF-β enhances hallmarks of cancer in most gastric and esophageal cancer cell lines, but not in all. Therefore, targeting the TGF-β pathway could be an attractive strategy in patients with gastric or esophageal cancer, but additional clinical trials are needed to define patient groups who would benefit most.
Topics: Animals; Esophageal Neoplasms; Humans; Mice; Stomach Neoplasms; Transforming Growth Factor beta
PubMed: 34536730
DOI: 10.1016/j.ctrv.2021.102285 -
International Journal of Hyperthermia :... Nov 2018In pancreatic cancer, which is therapy resistant due to its hypoxic microenvironment, hyperthermia may enhance the effect of radio(chemo)therapy. The aim of this...
OBJECTIVE
In pancreatic cancer, which is therapy resistant due to its hypoxic microenvironment, hyperthermia may enhance the effect of radio(chemo)therapy. The aim of this systematic review is to investigate the validity of the hypothesis that hyperthermia added to radiotherapy and/or chemotherapy improves treatment outcome for pancreatic cancer patients.
METHODS AND MATERIALS
We searched MEDLINE and Embase, supplemented by handsearching, for clinical studies involving hyperthermia in pancreatic cancer patients. The quality of studies was evaluated using the Oxford Centre for Evidence-Based Medicine levels of evidence. Primary outcome was treatment efficacy; we calculated overall response rate and the weighted estimate of the population median overall survival (m) and compared these between hyperthermia and control cohorts.
RESULTS
Overall, 14 studies were included, with 395 patients with locally advanced and/or metastatic pancreatic cancer of whom 248 received hyperthermia. Patients were treated with regional (n = 189), intraoperative (n = 39) or whole-body hyperthermia (n = 20), combined with chemotherapy, radiotherapy or both. Quality of the studies was low, with level of evidence 3 (five studies) and 4. The six studies including a control group showed a longer m in the hyperthermia groups than in the control groups (11.7 vs. 5.6 months). Overall response rate, reported in three studies with a control group, was also better for the hyperthermia groups (43.9% vs. 35.3%).
CONCLUSIONS
Hyperthermia, when added to chemotherapy and/or radiotherapy, may positively affect treatment outcome for patients with pancreatic cancer. However, the quality of the reviewed studies was limited and future randomised controlled trials are needed to establish efficacy.
Topics: Aged; Female; Humans; Hyperthermia, Induced; Male; Middle Aged; Pancreatic Neoplasms; Prognosis
PubMed: 29168401
DOI: 10.1080/02656736.2017.1401126