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AJNR. American Journal of Neuroradiology Jun 2024Long-term post-treatment surveillance imaging algorithms for head and neck squamous cell carcinoma are not standardized due to debates over optimal surveillance strategy... (Review)
Review
BACKGROUND
Long-term post-treatment surveillance imaging algorithms for head and neck squamous cell carcinoma are not standardized due to debates over optimal surveillance strategy and efficacy. Consequently, current guidelines do not provide long-term surveillance imaging recommendations beyond 6 months.
PURPOSE
We performed a systematic review to evaluate the impact of long-term imaging surveillance (i.e., imaging beyond 6 months following treatment completion) on survival in patients treated definitively for head and neck squamous cell carcinoma.
DATA SOURCES
A search was conducted on PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials, and Web of Science for English literature published between 2003 and 2024 evaluating the impact of long-term surveillance imaging on survival in patients with head and neck squamous cell carcinoma.
STUDY SELECTION
718 abstracts were screened and 9 underwent full-text review, with 2 articles meeting inclusion criteria. The Risk of Bias in Non-randomized Studies of Interventions assessment tool was used.
DATA ANALYSIS
A qualitative assessment without a pooled analysis was performed for the two studies meeting inclusion criteria.
DATA SYNTHESIS
No randomized prospective controlled trials were identified. Two retrospective two-arm studies were included comparing long-term surveillance imaging with clinical surveillance and were each rated as having moderate risk of bias. Each study included heterogeneous populations with variable risk profiles and imaging surveillance protocols. Both studies investigated the impact of long-term surveillance imaging on overall survival and came to a different conclusion with one study reporting a survival benefit for long-term surveillance imaging with FDG PET/CT in patients with stage III or IV disease or an oropharyngeal primary tumor and the other study demonstrating no survival benefit.
LIMITATIONS
Limited heterogeneous retrospective data available precludes definitive conclusions on the impact of long-term surveillance imaging in head and neck squamous cell carcinoma.
CONCLUSIONS
There is insufficient quality evidence regarding the impact of long-term surveillance imaging on survival in patients treated definitively for head and neck squamous cell carcinoma. There is a lack of standardized definition of long-term surveillance, variable surveillance protocols, and inconsistencies in results reporting, underscoring the need for a prospective multi-center registry assessing outcomes.
ABBREVIATIONS
HNSCC = Head and Neck Squamous Cell Carcinoma; RT= radiotherapy; NCCN = National Comprehensive Cancer Network; MPC = metachronous primary cancer; CR = complete response; OS = overall survival; CRT = chemoradiotherapy; HPV = human papillomavirus; PFS = progression-free survival; CFU = clinical follow up; NI-RADS = Neck Imaging Reporting and Data System.
PubMed: 38914430
DOI: 10.3174/ajnr.A8392 -
Cancers May 2024Human papillomavirus (HPV) is an important risk factor for oropharyngeal squamous cell carcinoma (OPSCC). HPV-positive (HPV+) cases are associated with a different... (Review)
Review
Human papillomavirus (HPV) is an important risk factor for oropharyngeal squamous cell carcinoma (OPSCC). HPV-positive (HPV+) cases are associated with a different pathophysiology, microstructure, and prognosis compared to HPV-negative (HPV-) cases. This review aimed to investigate the potential of magnetic resonance imaging (MRI) to discriminate between HPV+ and HPV- tumours and predict HPV status in OPSCC patients. A systematic literature search was performed on 15 December 2022 on EMBASE, MEDLINE ALL, Web of Science, and Cochrane according to PRISMA guidelines. Twenty-eight studies ( = 2634 patients) were included. Five, nineteen, and seven studies investigated structural MRI (e.g., T1, T2-weighted), diffusion-weighted MRI, and other sequences, respectively. Three out of four studies found that HPV+ tumours were significantly smaller in size, and their lymph node metastases were more cystic in structure than HPV- ones. Eleven out of thirteen studies found that the mean apparent diffusion coefficient was significantly higher in HPV- than HPV+ primary tumours. Other sequences need further investigation. Fourteen studies used MRI to predict HPV status using clinical, radiological, and radiomics features. The reported areas under the curve (AUC) values ranged between 0.697 and 0.944. MRI can potentially be used to find differences between HPV+ and HPV- OPSCC patients and predict HPV status with reasonable accuracy. Larger studies with external model validation using independent datasets are needed before clinical implementation.
PubMed: 38893224
DOI: 10.3390/cancers16112105 -
Medicine International 2024The present systematic review evaluated the effectiveness of anti-EGFR therapy in combination with radiotherapy (RT) or with chemoradiation compared with the existing...
The present systematic review evaluated the effectiveness of anti-EGFR therapy in combination with radiotherapy (RT) or with chemoradiation compared with the existing standard of care for the treatment of locally advanced head and neck squamous cell carcinoma (LAHNSCC). The PubMed, SCOPUS, EMBASE and COCHRANE databases were searched and 12 phase III randomized controlled trials were included. The effectiveness of the anti-EGFR monoclonal antibody cetuximab was evaluated in nine trials. Nimotuzumab (one trial), zalutumumab (one trial) and panitumumab (one trial) were the monoclonal antibodies evaluated in the remaining three trials. One study tested the effectiveness of adding cetuximab to radical RT and found that patients with LAHNSCC exhibited improvement in locoregional control (LRC), overall survival (OS) and progression-free survival (PFS) compared with those of patients treated with RT alone. A total of three studies tested the effectiveness of adding an anti-EGFR agent to chemoradiation. Of these, a single institution study in which patients received cisplatin at 30 mg/m weekly, instead of the standard doses of 100 mg/m every 3 weeks or 40 mg/m every week, reported significant improvement in PFS with the addition of nimotuzumab to chemoradiotherapy without an improvement in overall survival. However, the other two studies indicated that, when added to standard chemoradiation, the anti-EGFR monoclonal antibodies cetuximab or zalutumumab did not improve survival outcomes. Two phase III trials evaluated RT plus an anti-EGFR agent compared with chemoradiation alone. Of these, one study reported inferior outcomes with cetuximab-RT in terms of OS and LRC, whereas the other study with panitumumab plus RT failed to prove the non-inferiority. Two trials evaluated induction chemotherapy followed by cetuximab-RT compared with chemoradiotherapy and reported no benefits in terms of OS or PFS. Furthermore, one study evaluated induction chemotherapy followed by cetuximab-RT compared with induction chemotherapy followed by chemoradiotherapy and found no improvement in OS or PFS. Finally, three phase III trials tested the effectiveness of cetuximab plus RT in the treatment of human papillomavirus-positive oropharyngeal carcinoma, and found it to be inferior compared with cisplatin-RT in terms of OS, PFS and failure-free survival. Based on the aforementioned findings, it is difficult to conclude that anti-EGFR therapy in any form has an advantage over conventional chemoradiation in the treatment of LAHNSCC.
PubMed: 38873325
DOI: 10.3892/mi.2024.165 -
Prognostic role of lymph node micrometastasis in oral and oropharyngeal cancer: A systematic review.Oral Oncology Jul 2024An estimated 20% of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) have micrometastases (Mi) or isolated tumor cells (ITC) in the cervical lymph... (Review)
Review
BACKGROUND
An estimated 20% of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) have micrometastases (Mi) or isolated tumor cells (ITC) in the cervical lymph nodes that evade detection by standard histological evaluation of lymph node sections. Lymph node Mi and ITC could be one reason for regional recurrence after neck dissection. The aim of this study was to review the existing data regarding the impact of Mi on the survival of patients with OOSCC.
METHODS
PubMed and the Cochrane Library were searched for articles reporting the impact of Mi and ITC on patient survival. Two authors independently assessed the methodological quality of retrieved studies using the Downs and Black index. Data were also extracted on study type, number of included patients, mode of histological analysis, statistical analysis, and prognostic impact.
RESULTS
Sixteen articles with a total of 2064 patients were included in the review. Among the 16 included studies, eight revealed a statistically significant impact of Mi on at least one endpoint in the Kaplan-Meier and/or multivariate analysis. Three studies regarded Mi as Ma, while five studies found no impact of Mi on survival. Only one study demonstrated an impact of ITC on patient's prognosis in the univariate but not in the multivariate analysis.
CONCLUSION
The majority of cases included in the review were patients with oral cancer. The findings provide low-certainty evidence that Mi negatively impacts survival. Data on ITC were scarcer, so no conclusions can be drawn about their effect on survival. The lower threshold to discriminate between Mi and ITC should be defined for OOSCC since the existing thresholds are based on data from different tumors. The histological, immunohistological, and anatomical characteristics of Mi and ITC in OOSCC as well as the effect of radiotherapy on Mi should be further investigated separately for oral and oropharyngeal carcinomas.
Topics: Humans; Oropharyngeal Neoplasms; Mouth Neoplasms; Prognosis; Neoplasm Micrometastasis; Lymphatic Metastasis; Lymph Nodes; Carcinoma, Squamous Cell
PubMed: 38823172
DOI: 10.1016/j.oraloncology.2024.106808 -
European Journal of Surgical Oncology :... May 2024Transoral Robotic Surgery (TORS) and radiotherapy are considered oncologically equivalent primary treatment options for early-stage HPV-positive oropharyngeal squamous...
Quality of life outcomes comparing primary Transoral Robotic Surgery (TORS) with primary radiotherapy for early-stage oropharyngeal squamous cell carcinoma: A systematic review and meta-analysis.
BACKGROUND
Transoral Robotic Surgery (TORS) and radiotherapy are considered oncologically equivalent primary treatment options for early-stage HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). Quality of Life (QoL) and Patient Reported Outcome Measures (PROMs) are therefore imperative in supporting clinical decision-making and optimising patient-centred care. The aim of this article is to evaluate how these primary treatment modalities compare in terms of QoL.
MATERIALS AND METHODS
Systematic review and meta-analysis of studies comparing primary TORS and primary radiotherapy for OPSCC using validated QoL tools. Swallowing and global QoL were the primary endpoints with secondary endpoints including all other QoL domains. An inverse variance random-effects model was employed to calculate the weighted estimate of the treatment effects across trials.
RESULTS
A total of six studies collectively reporting on 555 patients were included (n = 236 TORS and n = 319 radiotherapy). Meta-analysis showed no significant difference for swallowing (mean difference = -0.24, p = 0.89) and global QoL (mean difference = 4.55, p = 0.14). For the remaining QoL domains (neck/shoulder impairment, neurotoxicity, voice, xerostomia, speech, and distress), the scarcity of data did not permit meta-analysis. However, the existing data showed no significant difference for any except for xerostomia where TORS appears favourable in the sole study reporting on this.
CONCLUSIONS
TORS and radiotherapy appear to be comparable primary treatment options for early stage OPSCC when it comes to QoL. However, a substantial proportion of patients in the TORS group received adjuvant (chemo)radiotherapy rendering it difficult to establish the 'true' QoL outcomes following surgery alone. There are also minimal studies reporting QoL outcomes beyond swallowing and global QoL. Further research is therefore needed, including more randomised trials adequately powered to detect differences in QoL outcomes.
PubMed: 38795678
DOI: 10.1016/j.ejso.2024.108434 -
PeerJ 2024To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal... (Meta-Analysis)
Meta-Analysis
Systematic evaluation and meta-analysis of the prognosis of down-staging human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma using cetuximab combined with radiotherapy instead of cisplatin combined with radiotherapy.
OBJECTIVE
To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (HPV OPSCC).
DESIGN
Meta-analysis and systematic evaluation.
DATA SOURCES
The PubMed, Embase, Web of Science, and Cochrane library databases were searched up to June 8, 2023, as well as Clinicaltrials.gov Clinical Trials Registry, China Knowledge Network, Wanfang Data Knowledge Service Platform, and Wiprojournal.com.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomized controlled trials reporting results of standard regimens of cetuximab + radiotherapy vs cisplatin + radiotherapy in treating HPV OPSCC were included. The primary outcomes of interest were overall survival (OS), progression-free survival (PFS), local regional failure rate (LRF), distant metastasis rate (DM), and adverse events (AE).
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data and assessed the risk of bias of the included studies. The HR and its 95% CI were used as the effect analysis statistic for survival analysis, while the OR and its 95% CI were used as the effect analysis statistic for dichotomous variables. These statistics were extracted by the reviewers and aggregated using a fixed-effects model to synthesise the data.
RESULTS
A total of 874 relevant papers were obtained from the initial search, and five papers that met the inclusion criteria were included; a total of 1,617 patients with HPV OPSCC were enrolled in these studies. Meta-analysis showed that OS and PFS were significantly shorter in the cetuximab + radiotherapy group of patients with HPV OPSCC compared with those in the conventional cisplatin + radiotherapy group (HR = 2.10, 95% CI [1.39-3.15], = 0.0004; HR = 1.79, 95% CI [1.40-2.29], < 0.0001); LRF and DM were significantly increased (HR = 2.22, 95% CI [1.58-3.11], < 0.0001; HR = 1.66, 95% CI [1.07-2.58], = 0.02), but there was no significant difference in overall grade 3 to 4, acute and late AE overall (OR = 0.86, 95% CI [0.65-1.13], = 0.28).
CONCLUSIONS
Cisplatin + radiotherapy remains the standard treatment for HPV OPSCC. According to the 7th edition AJCC/UICC criteria, low-risk HPV OPSCC patients with a smoking history of ≤ 10 packs/year and non-pharyngeal tumors not involved in lymphatic metastasis had similar survival outcomes with cetuximab/cisplatin + radiotherapy. However, further clinical trials are necessary to determine whether cetuximab + radiotherapy can replace cisplatin + radiotherapy for degraded treatment in individuals who meet the aforementioned characteristics, particularly those with platinum drug allergies.
PROSPERO REGISTRATION NUMBER
CRD42023445619.
Topics: Humans; Cetuximab; Oropharyngeal Neoplasms; Cisplatin; Chemoradiotherapy; Papillomavirus Infections; Prognosis; Squamous Cell Carcinoma of Head and Neck; Neoplasm Staging; Papillomaviridae; Antineoplastic Agents, Immunological; Progression-Free Survival; Human Papillomavirus Viruses
PubMed: 38784388
DOI: 10.7717/peerj.17391 -
Clinical Otolaryngology : Official... May 2024Patients presenting with head and neck squamous cell carcinoma of unknown primary (HNSCCUP) remain challenging clinical scenarios as large variation exists in practices... (Review)
Review
INTRODUCTION
Patients presenting with head and neck squamous cell carcinoma of unknown primary (HNSCCUP) remain challenging clinical scenarios as large variation exists in practices used to locate the primary.
OBJECTIVE
The objective of this systematic review is to review of the literature and offer recommendations for oropharyngeal biopsies in HNSCCUP.
METHOD
Pubmed, Medline and Embase were searched to identify studies from inception to October 2021. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed.
RESULTS
A total of 483 articles were included and screened, 41 studies met the inclusion criteria, including over 3400 patients from the original articles (122 of these patients were reported on in two sequential articles by a single author - table 1) and 4 large metaanalyses including 1852 patients. The primary site identification rate following random biopsies or deep tissue biopsies is less than 5% in most studies. The mean detection rate following ipsilateral tonsillectomy is 34%; two pooled analyses indicate that the mean detection rate following tongue base mucosectomy is 64%, with this figure rising when the tonsils are negative.
CONCLUSIONS
High level evidence is lacking, with heterogeneity in the reported studies. Published meta-analyses are based on retrospective data. There is little evidence supporting the practice of random/non-directed oropharyngeal biopsies. Available evidence supports palatine tonsillectomy and tongue base mucosectomy compared to deep tissue biopsies.
PubMed: 38773941
DOI: 10.1111/coa.14168 -
Acta Otorhinolaryngologica Italica :... Jun 2024Studies have demonstrated that tonsillectomy may alter the risk of oropharyngeal cancer (OPC). We systematically reviewed the evidence and pooled data to examine such an... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Studies have demonstrated that tonsillectomy may alter the risk of oropharyngeal cancer (OPC). We systematically reviewed the evidence and pooled data to examine such an association.
METHODS
PubMed, Embase, and Scopus were searched up to 25 April 2023. Studies reporting an association between tonsillectomy and oropharyngeal cancer risk at any site were included.
RESULTS
Five studies were eligible. All examined the risk of tonsillar and base of the tongue (BOT) cancer with prior history of tonsillectomy. On meta-analysis of the data, prior history of tonsillectomy was associated with a significantly decreased risk of tonsillar cancer. The second meta-analysis showed that history of tonsillectomy did not significantly alter the risk of BOT cancer. However, after exclusion of one study, the results showed an increased risk of BOT cancer with a history of tonsillectomy.
CONCLUSIONS
The scarce data available in the literature suggests that tonsillectomy may reduce the risk of tonsillar cancer but does not alter the risk of BOT cancer. Further studies are needed to explore the association between tonsillectomy and the risk of OPC.
Topics: Humans; Oropharyngeal Neoplasms; Risk Assessment; Risk Factors; Tonsillar Neoplasms; Tonsillectomy
PubMed: 38712770
DOI: 10.14639/0392-100X-N2790 -
Clinical Otolaryngology : Official... Apr 2024This systematic review aims to evaluate the role of biopsies in non-oropharyngeal subsites in patients with cervical metastasis from head and neck squamous cell... (Review)
Review
INTRODUCTION
This systematic review aims to evaluate the role of biopsies in non-oropharyngeal subsites in patients with cervical metastasis from head and neck squamous cell carcinoma of unknown primary (HNSCCUP).
METHODS
This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Articles that encompassed non-oropharyngeal biopsies in HNSCCUP as part of the diagnostic work-up were selected and analysed.
RESULTS
A comprehensive search strategy was used to search relevant literature in PubMed from inception to October 2021. Eleven articles out of 860 were included, comprising 990 patients. There are no randomised control trials comparing the outcomes of survival and or locoregional control between patients who have or have not undergone non-targeted biopsies of non-oropharyngeal sub-sites for HNSCCUP. Several retrospective studies which showed an extremely low yield from random biopsies (range of yield, 0%-9%) of non-oropharyngeal subsites. Even targeted biopsies showed a low yield (range of yield, 0.6%-16.6%) from non-oropharyngeal subsites. The primary site identified for Epstein-Barr virus (EBV) positive cervical lymph nodes with an unknown primary is mainly the nasopharynx (51.7%). Narrow band imaging (NBI) (sensitivity range, 64%-91%) helps in the detection of primaries to target biopsies in non-oropharyngeal subsites.
CONCLUSIONS
On the basis of this systematic review, it is not appropriate to offer biopsies of clinically and radiologically normal upper aerodigestive tract mucosa at non-oropharyngeal sites. Offer nasopharyngeal biopsies when the cervical node sampling reveals EBV-positive metastasis. Where available, NBI should be used to help detect and target biopsies in non-oropharyngeal subsites.
PubMed: 38664927
DOI: 10.1111/coa.14157 -
Clinical Otolaryngology : Official... Jul 2024About 17% of patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC), which is mainly comprised of oropharyngeal SCC (OPSCC),... (Review)
Review
OBJECTIVES
About 17% of patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC), which is mainly comprised of oropharyngeal SCC (OPSCC), will experience disease recurrence, which is often considered incurable when manifested at a metastatic and/or recurrent stage. We conducted a critical qualitative systematic review. Our objectives were to provide an overview of the molecular landscape of recurrent/metastatic HPV-positive HNSCC as well as novel molecular biomarkers.
DESIGN
A literature review was conducted to identify studies reporting on the molecular characteristics of recurrent/metastatic HPV-positive HNSCC, novel molecular biomarkers and treatment options. The reviews of abstracts, full articles, and revision of the included studies, followed by data extraction and quality assessment were performed by three independent assessors. All primary literature, such as retrospective, prospective, and clinical trials as well as basic research studies were considered, and the final search was conducted at the end of February 2023. The level of evidence was rated using the guidelines published by the Oxford Centre for Evidence-based Medicine and quality was assessed using the Newcastle-Ottawa Scale criteria.
RESULTS AND CONCLUSIONS
The literature search resulted in the identification of 1991 articles. A total of 181 full articles were screened, and 66 articles were included in this analysis. Several studies reported that recurrent/metastatic HPV-positive HNSCC had higher rates of TP53 mutation and were genomically similar to HPV-negative HNSCC. The detection of circulating tumour tissue-modified HPV DNA (ctHPVDNA) as a specific biomarker has shown promising results for monitoring treatment response and recurrence in the subset of HPV-positive HNSCC. In addition, evidence for targeted therapy in recurrent/metastatic HPV-positive HNSCC has emerged, including agents that inhibit overexpressed EGFR. Studies of combination immunotherapy are also underway. Our review outlines the latest evidence on the distinct molecular profiles of recurrent/metastatic HPV-positive HNSCC as well as the clinical potential of ctHPVDNA testing in routine practice. More controlled and longitudinal studies are needed to identify additional molecular targets and to assess the performance and benefits of novel molecular biomarkers in clinical practice.
Topics: Humans; Neoplasm Recurrence, Local; Squamous Cell Carcinoma of Head and Neck; Papillomavirus Infections; Head and Neck Neoplasms; Biomarkers, Tumor; Papillomaviridae
PubMed: 38658385
DOI: 10.1111/coa.14161