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JAMA Oncology Oct 2023Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and...
The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019.
IMPORTANCE
Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning.
OBJECTIVE
To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates.
EVIDENCE REVIEW
The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019.
FINDINGS
In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia.
CONCLUSIONS AND RELEVANCE
In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.
Topics: Adult; Female; Humans; Male; Global Burden of Disease; Global Health; Incidence; Lip; Pharyngeal Neoplasms; Quality-Adjusted Life Years; Risk Factors; Tobacco Use
PubMed: 37676656
DOI: 10.1001/jamaoncol.2023.2960 -
The Cochrane Database of Systematic... Dec 2021Oral cavity and oropharyngeal cancers are the most common cancers arising in the head and neck. Treatment of oral cavity cancer is generally surgery followed by... (Review)
Review
BACKGROUND
Oral cavity and oropharyngeal cancers are the most common cancers arising in the head and neck. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients. This review updates one last published in 2011.
OBJECTIVES
To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal squamous cell carcinoma results in improved overall survival, improved disease-free survival and/or improved locoregional control, when incorporated as either induction therapy given prior to locoregional treatment (i.e. radiotherapy or surgery), concurrent with radiotherapy or in the adjuvant (i.e. after locoregional treatment with radiotherapy or surgery) setting.
SEARCH METHODS
An information specialist searched 4 bibliographic databases up to 15 September 2021 and used additional search methods to identify published, unpublished and ongoing studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and that evaluated the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration.
DATA COLLECTION AND ANALYSIS
For this update, we assessed the new included trials for their risk of bias and at least two authors extracted data from them. Our primary outcome was overall survival (time to death from any cause). Secondary outcomes were disease-free survival (time to disease recurrence or death from any cause) and locoregional control (response to primary treatment). We contacted trial authors for additional information or clarification when necessary.
MAIN RESULTS
We included 100 studies with 18,813 participants. None of the included trials were at low risk of bias. For induction chemotherapy, we reported the results for contemporary regimens that will be of interest to clinicians and people being treated for oral cavity and oropharyngeal cancers. Overall, there is insufficient evidence to clearly demonstrate a survival benefit from induction chemotherapy with platinum plus 5-fluorouracil prior to radiotherapy (hazard ratio (HR) for death 0.85, 95% confidence interval (CI) 0.70 to 1.04, P = 0.11; 7427 participants, 5 studies; moderate-certainty evidence), prior to surgery (HR for death 1.06, 95% CI 0.71 to 1.60, P = 0.77; 198 participants, 1 study; low-certainty evidence) or prior to concurrent chemoradiation (CRT) with cisplatin (HR for death 0.71, 95% CI 0.37 to 1.35, P = 0.30; 389 participants, 2 studies; low-certainty evidence). There is insufficient evidence to support the use of an induction chemotherapy regimen with cisplatin plus 5-fluorouracil plus docetaxel prior to CRT with cisplatin (HR for death 1.08, 95% CI 0.80 to 1.44, P = 0.63; 760 participants, 3 studies; low-certainty evidence). There is insufficient evidence to support the use of adjuvant chemotherapy over observation only following surgery (HR for death 0.95, 95% CI 0.73 to 1.22, P = 0.67; 353 participants, 5 studies; moderate-certainty evidence). Among studies that compared post-surgical adjuvant CRT, as compared to post-surgical RT, adjuvant CRT showed a survival benefit (HR 0.84, 95% CI 0.72 to 0.98, P = 0.03; 1097 participants, 4 studies; moderate-certainty evidence). Primary treatment with CRT, as compared to radiotherapy alone, was associated with a reduction in the risk of death (HR for death 0.74, 95% CI 0.67 to 0.83, P < 0.00001; 2852 participants, 24 studies; moderate-certainty evidence). AUTHORS' CONCLUSIONS: The results of this review demonstrate that chemotherapy in the curative-intent treatment of oral cavity and oropharyngeal cancers only seems to be of benefit when used in specific circumstances together with locoregional treatment. The evidence does not show a clear survival benefit from the use of induction chemotherapy prior to radiotherapy, surgery or CRT. Adjuvant CRT reduces the risk of death by 16%, as compared to radiotherapy alone. Concurrent chemoradiation as compared to radiation alone is associated with a greater than 20% improvement in overall survival; however, additional research is required to inform how the specific chemotherapy regimen may influence this benefit.
Topics: Chemoradiotherapy, Adjuvant; Humans; Mouth Neoplasms; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms
PubMed: 34929047
DOI: 10.1002/14651858.CD006386.pub4 -
International Journal of Radiation... Dec 2023Evidence of a volume-outcome association in cancer surgery has shaped the centralization of cancer services; however, it is unknown whether a similar association exists... (Meta-Analysis)
Meta-Analysis
PURPOSE
Evidence of a volume-outcome association in cancer surgery has shaped the centralization of cancer services; however, it is unknown whether a similar association exists for radiation therapy. The objective of this study was to determine the association between radiation therapy treatment volume and patient outcomes.
METHODS AND MATERIALS
This systematic review and meta-analysis included studies that compared outcomes of patients who underwent definitive radiation therapy at high-volume radiation therapy facilities (HVRFs) versus low-volume facilities (LVRFs). The systematic review used Ovid MEDLINE and Embase. For the meta-analysis, a random effects model was used. Absolute effects and hazard ratios (HRs) were used to compare patient outcomes.
RESULTS
The search identified 20 studies assessing the association between radiation therapy volume and patient outcomes. Seven of the studies looked at head and neck cancers (HNCs). The remaining studies covered cervical (4), prostate (4), bladder (3), lung (2), anal (2), esophageal (1), brain (2), liver (1), and pancreatic cancer (1). The meta-analysis demonstrated that HVRFs were associated with a lower chance of death compared with LVRFs (pooled HR, 0.90; 95% CI, 0.87- 0.94). HNCs had the strongest evidence of a volume-outcome association for both nasopharyngeal cancer (pooled HR, 0.74; 95% CI, 0.62-0.89) and nonnasopharyngeal HNC subsites (pooled HR, 0.80; 95% CI, 0.75-0.84), followed by prostate cancer (pooled HR, 0.92; 95% CI, 0.86-0.98). The remaining cancer types showed weak evidence of an association. The results also demonstrate that some centers defined as HVRFs are undertaking very few procedures per annum (<5 radiation therapy cases per year).
CONCLUSIONS
An association between radiation therapy treatment volume and patient outcomes exists for most cancer types. Centralization of radiation therapy services should be considered for cancer types with the strongest volume-outcome association, but the effect on equitable access to services needs to be explicitly considered.
Topics: Male; Humans; Nasopharyngeal Neoplasms; Head and Neck Neoplasms; Prostatic Neoplasms
PubMed: 37227363
DOI: 10.1016/j.ijrobp.2023.02.048 -
Strahlentherapie Und Onkologie : Organ... Sep 2023Reirradiation is a potentially useful option for many patients with recurrent cancer, aiming at cure or symptom palliation, depending on disease/recurrence type and... (Review)
Review
BACKGROUND
Reirradiation is a potentially useful option for many patients with recurrent cancer, aiming at cure or symptom palliation, depending on disease/recurrence type and stage. The purpose of this follow-up study to a previous review from 2016 was to summarize all recently published randomized trials. Points of interest again included identifcation of methodological strengths and weaknesses, practice-changing results, and open questions.
MATERIAL AND METHODS
Systematic review of trials published between 2015 and February 2023.
RESULTS
We reviewed 7 additional trials, most of which addressed reirradiation of head and neck or brain tumours. The median number of patients was 60. Mirroring the previous review, trial design, primary endpoints and statistical hypotheses varied widely. The updated results only impact on decision making for reirradiation of nasopharynx cancer and glioma. Patients with one of these diseases, as well as other head and neck cancers, may benefit from reirradiation-induced local control, e.g. in terms of progression-free survival. For the first time, hyperfractionated radiotherapy emerged as preferred option for recurrent, inoperable nasopharynx cancer. Despite better therapeutic ratio with hyperfractionation, serious toxicity remains a concern after high cumulative total doses. Randomized trials are still lacking for prostate cancer and other sites.
CONCLUSION
Multicentric randomized trials on reirradiation are feasible and continue to refine the current standard of care for recurrent disease after previous radiotherapy. Ongoing prospective studies such as the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer (ESTRO-EORTC) observational cohort ReCare (NCT: NCT03818503) will further shape the clinical practice of reirradiation.
Topics: Male; Humans; Re-Irradiation; Prospective Studies; Follow-Up Studies; Neoplasm Recurrence, Local; Head and Neck Neoplasms; Nasopharyngeal Neoplasms
PubMed: 37500926
DOI: 10.1007/s00066-023-02118-1 -
Radiotherapy and Oncology : Journal of... Dec 2023Given the central role that radiation has in the management of head and neck squamous cell carcinoma of unknown primary origin, it is imperative to review how treatment...
PURPOSE
Given the central role that radiation has in the management of head and neck squamous cell carcinoma of unknown primary origin, it is imperative to review how treatment paradigms have been refined and continue to evolve in the modern era.
METHODS AND MATERIALS
This study was designed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. A literature search of peer-reviewed publications was undertaken to identify works pertaining to the use of radiation for squamous cell carcinoma of unknown primary origin presenting as cervical lymph node metastases. Articles published from January 2002 to January 2023 with full text available on PubMed and restricted to the English language and human subjects were included. The full bibliographies of identified articles were reviewed and irrelevant studies were removed.
RESULTS
While such breakthroughs as intensity-modulated radiotherapy, positron emission tomography, biomarker testing with immune-histochemistry, and minimally invasive surgical techniques such as transoral robotic surgery have fundamentally changed the approach to this disease in recent decades, controversies still exist with respect to the manner in which radiation is delivered. Although the incidence of head and neck unknown primary cancer is relatively low, questions regarding the necessity of comprehensive radiation using the age-old standard method of targeting the bilateral necks and entire pharyngeal axis to encompass all putative sites of mucosal disease persist.
CONCLUSIONS
Prospective evidence is lacking, and the available studies have been complicated by such factors as the relatively limited sample sizes, as well as the variability in work-up, treatment, inclusion criteria, and follow-up. Regardless, advances in science and technology have ushered in more precise approaches with a high degree of customization, particularly given the increased proportion of patients presenting with human papillomavirus-related disease.
Topics: Humans; Head and Neck Neoplasms; Human Papillomavirus Viruses; Meta-Analysis as Topic; Neoplasms, Unknown Primary; Papillomavirus Infections; Systematic Reviews as Topic
PubMed: 37844736
DOI: 10.1016/j.radonc.2023.109952 -
Journal of B.U.ON. : Official Journal... 2021Hypopharyngeal cervical esophageal carcinoma (HPCEC) is a group of highly malignant entities usually presenting at an advanced stage. Our purpose was to systematically...
PURPOSE
Hypopharyngeal cervical esophageal carcinoma (HPCEC) is a group of highly malignant entities usually presenting at an advanced stage. Our purpose was to systematically review and synthesize all available data on the management and outcomes of patients with these upper gastrointestinal malignancies.
METHODS
A systematic literature search of the PubMed and Cochrane databases was performed with respect to the PRISMA statement (end-of-search date: May 1st, 2017). Data on the study design, interventions, participants, and outcomes were extracted by two independent reviewers. Quality assessment of included studies was performed using the tool developed by the National Heart, Lung, and Blood Institute.
RESULTS
Thirty-four observational studies were included in this review. Overall, 20,409 patients with HPCECs were included. Mean patient age was 61.3 years. The most widely implemented therapeutic modalities were chemoradiation (38%), radiation alone (16%), and surgery plus radiation (13%). Overall, mean relapse rates were 15±2.6% for local recurrence, 14.7±2.6% for regional recurrence. and 10±2.3% for distant metastases. Cumulative mean 5- and 3-year survival rates were 20±2.6% and 22±2.6%, respectively, while mean 5-year disease-free survival rates were 22±2.3%. The most common complications were fistulae and pulmonary complications. Mean 30-day mortality rate was 7±2.2% and the mean long-term mortality rate was 22±3.3%.
CONCLUSIONS
Multimodal approaches are typically needed for the management of HPCECs. Radiotherapy is the mainstay of treatment for local tumors. Locally advanced non-metastatic tumors are typically managed with chemoradiation or a combination of pharyngolaryngoesophagectomy and chemoradiation. For metastatic carcinomas, an arsenal of surgical and medical treatment options can help relieve tumor burden and improve quality of life.
Topics: Esophageal Neoplasms; Female; Humans; Hypopharyngeal Neoplasms; Male; Middle Aged
PubMed: 33721430
DOI: No ID Found -
Medicine Jan 2022To evaluate the prognostic effect and clinical significance of epidermal growth factor receptor and its phosphorlated form (EGFR/p-EGFR) in nasopharyngeal carcinoma. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the prognostic effect and clinical significance of epidermal growth factor receptor and its phosphorlated form (EGFR/p-EGFR) in nasopharyngeal carcinoma.
METHODS
A systematic review and meta-analysis was designed. We visited PubMed, Embase, China National Knowledge Infrastructure Database, Database of Chinese sci-tech periodicals, WanFang Database, and China Biology Medicine disc to search for Chinese and English publications of prospective studies and retrospective studies investigating the association of EGFR/p-EGFR and nasopharyngeal carcinoma prognosis from inception to April 2021. The inclusion criteria were that the samples should be pathologically confirmed as nasopharyngeal carcinoma and the expression of EGFR/p-EGFR should be detected via immunohistochemistry; the study should analyze the prognostic significance of EGFR/p-EGFR in nasopharyngeal carcinoma; hazard ratio (HR) and 95% confidence interval (CI) should be reported in the study or could be derived from survival curves; and the outcomes of the study should include overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS).
RESULTS
A total of 18 studies evaluating 1451 samples were included. For studies that reported OS as an outcome, EGFR overexpression indicated worse OS of nasopharyngeal carcinoma patients. The heterogeneity between studies was high (I2 = 91%, P < .01), and a random-effect model was used to combine the effect size (HR = 1.71, 95% CI [1.21, 2.41], P < .01). Further sensitivity analysis and prespecified subgroup analysis were performed to detect the source of heterogeneity, and the results showed that the heterogeneity could not be eliminated. Publication bias assessed by funnel plots and Begg test and Egger test was low (Begg test: P = .846 and Egger test: P = .074). p-EGFR was not correlated with the OS of nasopharyngeal carcinoma patients (HR = 1.01, 95% CI [0.88, 1.15], P = .92). For studies that reported DFS, EGFR overexpression was associated with worse DFS in patients with nasopharyngeal carcinoma (HR = 2.53, 95% CI [1.84, 3.47], P < .01). For studies that reported PFS, EGFR overexpression was not correlated with the PFS of nasopharyngeal carcinoma patients (HR = 1.86, 95% CI [0.90, 3.82], P = .09). For studies that reported DMFS, EGFR overexpression was not correlated with the DMFS of nasopharyngeal carcinoma patients, and high heterogeneity between studies was detected (I2 = 97%, P < .01). A random-effect model was used to combine the effect size (HR = 1.80, 95% CI [0.56, 5.76], P = .32). A sensitivity analysis was conducted. Publication bias was detected to be low (Begg test: P = .817 and Egger test: P = .954). There was no correlation between p-EGFR overexpression and DMFS in patients with nasopharyngeal carcinoma (HR = 1.20, 95% CI [0.95, 1.52], P = .12).
CONCLUSION
In nasopharyngeal carcinoma patients, EGFR overexpression could be used as a biomarker that predicts poor OS and DFS, but not a prognostic biomarker for PFS and DMFS. The overexpression of p-EGFR was not shown to be associated with the prognosis of nasopharyngeal carcinoma patients and could not be used as a prognostic biomarker.
ETHICS AND DISSEMINATION
This study was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), and reported as stated by the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Neither ethical approval nor informed consent was required since this study was conducted based on previous publications.
INPLASY REGISTRATION NUMBER
INPLASY 202150010.
Topics: ErbB Receptors; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Prognosis
PubMed: 35060503
DOI: 10.1097/MD.0000000000028507 -
Supportive Care in Cancer : Official... Sep 2021Patients living with and beyond head and neck cancer (HNC) often have long-term, functional challenges as a result of treatment. A key functional challenge relates to... (Review)
Review
PURPOSE
Patients living with and beyond head and neck cancer (HNC) often have long-term, functional challenges as a result of treatment. A key functional challenge relates to eating and drinking; often associated with physical, emotional, and social difficulties. Eating and drinking with family members and friends can become a struggle, increasing the risk of social isolation and loneliness. This systematic review aims to identify and synthesise the literature on the experiences of social eating and drinking for patients following treatment for HNC.
METHODS
Six electronic databases (Pubmed, Web of Science, CINAHL, EMBASE, PsychINFO, and Scopus) were systematically searched using subject headings and free-text word searches in February 2020. Citation chaining and Google Scholar were used to identify grey literature. PRISMA procedures were followed.
RESULTS
Of 6910 records identified, 24 studies met the inclusion criteria. Synthesis of the research findings results in two major themes: (1) the experience of loss associated with social eating and drinking, and (2) adjusting and support to promote social eating and drinking.
CONCLUSION
Losses associated with social eating affect a patient's psychological and emotional well-being and impact on close relationships. To promote positive participation in social eating, patients were more likely to seek and receive support from someone within their close social network, rather than a healthcare professional. Family and friends are an essential source of support and are integral in facilitating engagement with social eating following treatment for HNC. Future interventions should promote family orientated resources, incorporating self-management strategies.
Topics: Alcohol Drinking; Drinking; Head and Neck Neoplasms; Humans; Nasopharyngeal Neoplasms; Qualitative Research; Quality of Life
PubMed: 33646367
DOI: 10.1007/s00520-021-06062-7 -
Neuroradiology Aug 2022Endoscopic biopsy is recommended for diagnosis of nasopharyngeal carcinoma (NPC). A proportion of lesions are hidden from endoscopic view but detected with magnetic... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Endoscopic biopsy is recommended for diagnosis of nasopharyngeal carcinoma (NPC). A proportion of lesions are hidden from endoscopic view but detected with magnetic resonance imaging (MRI). This systematic review and meta-analysis investigated the diagnostic performance of MRI for detection of NPC.
METHODS
An electronic search of twelve databases and registries was performed. Studies were included if they compared the diagnostic accuracy of MRI to a reference standard (histopathology) in patients suspected of having NPC. The primary outcome was accuracy for detection of NPC. Random-effects models were used to pool outcomes for sensitivity, specificity, and positive and negative likelihood ratio (LR). Bias and applicability were assessed using the modified QUADAS-2 tool.
RESULTS
Nine studies were included involving 1736 patients of whom 337 were diagnosed with NPC. MRI demonstrated a pooled sensitivity of 98.1% (95% CI 95.2-99.3%), specificity of 91.7% (95% CI 88.3-94.2%), negative LR of 0.02 (95% CI 0.01-0.05), and positive LR of 11.9 (95% CI 8.35-16.81) for detection of NPC. Most studies were performed in regions where NPC is endemic, and there was a risk of selection bias due to inclusion of retrospective studies and one case-control study. There was limited reporting of study randomization strategy.
CONCLUSION
This study demonstrates that MRI has a high pooled sensitivity, specificity, and negative predictive value for detection of NPC. MRI may be useful for lesion detection prior to endoscopic biopsy and aid the decision to avoid biopsy in patients with a low post-test probability of disease.
Topics: Case-Control Studies; Humans; Magnetic Resonance Imaging; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Retrospective Studies; Sensitivity and Specificity
PubMed: 35499636
DOI: 10.1007/s00234-022-02941-w -
Frontiers in Immunology 2023Optimal biomarkers to select patients who will benefit most from immunotherapy remain lacking in nasopharyngeal cancer (NPC). This systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Optimal biomarkers to select patients who will benefit most from immunotherapy remain lacking in nasopharyngeal cancer (NPC). This systematic review and meta-analysis aimed to evaluate the association between various biomarkers and clinical outcomes in NPC patients treated with immune checkpoint inhibitors (ICIs).
METHODS
Systematic searches of PubMed, Embase, Cochrane Library, and Web of Science databases were performed up to October 2022. Studies evaluating the association between biomarkers and intended outcomes of ICIs were included. The pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals (CIs) were calculated, respectively, for the objective response rate (ORR) and progression-free survival (PFS) under fixed or random-effect models.
RESULTS
A total of 15 studies involving 1,407 patients were included. The pooled analysis indicated that NPC patients with lower plasma Epstein-Barr virus (EBV) DNA level at baseline (OR = 2.14, 95% CI: 1.46-3.14, < 0.001), decreased EBV DNA load during immunotherapy (OR = 4.57, 95% CI: 2.24-9.34, = 0.002) and higher programmed cell death-ligand 1 (PD-L1) expression (OR = 2.35, 95% CI: 1.36-4.09, = 0.002) had superior ORR than the counterparts. No significant differences of ORR were observed between positive PD-L1 expression and negative PD-L1 expression (OR = 1.50, 95% CI: 0.92-2.45, = 0.104), as well as higher tumor mutation burden (TMB) and lower TMB (OR = 1.62, 95% CI: 0.41-6.44, = 0.494). Patients with lower plasma EBV DNA level at baseline obtained a significant benefit on PFS than those with higher plasma EBV DNA level (HR = 0.52, 95% CI: 0.42-0.63, < 0.001). There were no differences in PFS between decreased EBV DNA load and increased EBV DNA load during immunotherapy (HR = 0.51, 95% CI: 0.22-1.17, = 0.109), higher PD-L1 expression and lower PD-L1 expression (HR = 0.65, 95% CI: 0.42-1.01, = 0.054), positive PD-L1 expression and negative PD-L1 expression (HR = 0.90, 95% CI: 0.64-1.26, = 0.531), lower TMB and higher TMB (HR = 0.84, 95% CI: 0.51-1.38, = 0.684).
CONCLUSION
Lower baseline plasma EBV DNA level, decreased plasma EBV DNA during immunotherapy, and higher PD-L1 expression are reliable biomarkers predicting better response to ICIs treatment. Lower baseline plasma EBV DNA level was also associated with longer PFS. It is warranted to further explore and better illuminate the utility of these biomarkers in future clinical trials and real-world practice.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022324434.
Topics: Humans; Immune Checkpoint Inhibitors; Nasopharyngeal Neoplasms; Epstein-Barr Virus Infections; B7-H1 Antigen; Biomarkers, Tumor; Herpesvirus 4, Human; Nasopharyngeal Carcinoma
PubMed: 37063822
DOI: 10.3389/fimmu.2023.1146898