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Auris, Nasus, Larynx Feb 2022Trans Oral Robotic Surgery (TORS) is a modality in the management of oropharyngeal squamous cell carcinoma(OPSCC). This study was planned to determine whether Selective...
OBJECTIVE
Trans Oral Robotic Surgery (TORS) is a modality in the management of oropharyngeal squamous cell carcinoma(OPSCC). This study was planned to determine whether Selective Neck Dissection (SND) is oncological safe procedure even in patients with lymph node metastases.
METHODS
OPSCC patients were divided into Modified Radical Neck Dissection (MRND) and SND groups. The outcome measures were overall survival (OS), disease-free survival (DFS) and regional recurrence free survival (RRFS).
RESULTS
Thirty-seven SNDs and 18 MRNDs were performed. Regional relapse rate was 6.1% in SND group whilst 18.8% in MRND group(p=0.19). The 5-year OS, DFS and RRFS rates' differences were not statistically significant between SND and MRND groups (p=0.40, p=0.42 and p=0.18, respectively). At multivariate analysis, advanced stage impacted the 5-year OS and DFS(HR=9.39, p<0.01 and HR=11.03, p=0.04).
CONCLUSIONS
The SND seems to be effective in a TORS framework. The indication should be accurately discussed by the multidisciplinary tumor board.
Topics: Aged; Carcinoma, Squamous Cell; Disease-Free Survival; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oropharyngeal Neoplasms; Proportional Hazards Models; Robotic Surgical Procedures; Survival Analysis
PubMed: 34092436
DOI: 10.1016/j.anl.2021.05.007 -
European Archives of... Mar 2023Treatment of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is rapidly evolving. Despite either surgery or radiotherapy (RT), with or... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Treatment of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is rapidly evolving. Despite either surgery or radiotherapy (RT), with or without chemotherapy (CT), being acceptable in intermediate and locally advanced diseases, there is uncertainty regarding the best treatment option for these patients. Therefore, we performed a network meta-analysis (NMA) to compare the relative efficacy of different treatments for HPV+ oropharyngeal carcinoma.
MATERIAL AND METHODS
Randomized clinical trials that enrolled adults with non-metastatic HPV+ oropharynx cancer and provided data about overall survival (OS) and/or progression-free survival (PFS) and/or locoregional control and distant metastases (LRC and DM) were included. Fixed- or random-effects models were fit using a Bayesian approach to NMA. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (CrIs). The primary outcome was OS.
RESULTS
A total of 844 citations were screened; 11 randomized clinical trials were included (HPV+ stage III-IV cancer, mainly oropharynx carcinomas). Nine treatment arms were compared. Radiotherapy (altered or standard fractionation) + triweekly cisplatin (HR 3.8; 95% CrIs 0.29-65 and 0.3; 95% CrIs 0.03-2.51) was superior to RT in term of OS (P score = 0.42 and 0.16). Radiotherapy with low and high cisplatin doses appeared similar (HR 1.57; 95% CrIs 0.19-12.72). Altered fractionation or standard RT + 3-weekly cisplatin are the 2 highest-ranked options in terms of PFS (P score = 0.35 and 0.34).
CONCLUSIONS
This meta-analysis confirms the role of cisplatin added to RT as the best option for HPV+ oropharyngeal carcinoma. RT+ 3-weekly cisplatin is likely to be the best radical treatment in terms of OS and PFS.
Topics: Adult; Humans; Bayes Theorem; Chemoradiotherapy; Cisplatin; Network Meta-Analysis; Oropharyngeal Neoplasms; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck; Randomized Controlled Trials as Topic
PubMed: 36261656
DOI: 10.1007/s00405-022-07710-2 -
Journal of Experimental & Clinical... Sep 2022Immune checkpoint inhibitors (ICI) are approved for treatment of recurrent or metastatic oropharyngeal head and neck squamous cell carcinoma in the first- and...
The immune microenvironment of HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma: a multiparametric quantitative and spatial analysis unveils a rationale to target treatment-naïve tumors with immune checkpoint inhibitors.
BACKGROUND
Immune checkpoint inhibitors (ICI) are approved for treatment of recurrent or metastatic oropharyngeal head and neck squamous cell carcinoma in the first- and second-line settings. However, only 15-20% of patients benefit from this treatment, a feature increasingly ascribed to the peculiar characteristics of the tumor immune microenvironment (TIME).
METHODS
Immune-related gene expression profiling (GEP) and multiplex immunofluorescence (mIF) including spatial proximity analysis, were used to characterize the TIME of 39 treatment-naïve oropharyngeal squamous cell carcinomas (OPSCC) and the corresponding lymph node metastases. GEP and mIF results were correlated with disease-free survival (DFS). HPV-positive tumors disclosed a stronger activation of several immune signalling pathways, as well as a higher expression of genes related to total tumor-infiltrating lymphocytes, CD8 T cells, cytotoxic cells and exhausted CD8 cells, than HPV-negative patients. Accordingly, mIF revealed that HPV-positive lesions were heavily infiltrated as compared to HPV-negative counterparts, with a higher density of T cells and checkpoint molecules. CD8+ T cells appeared in closer proximity to tumor cells, CD163+ macrophages and FoxP3+ cells in HPV-positive primary tumors, and related metastases. In HPV-positive lesions, PD-L1 expression was increased as compared to HPV-negative samples, and PD-L1+ tumor cells and macrophages were closer to PD-1+ cytotoxic T lymphocytes. Considering the whole cohort, a positive correlation was observed between DFS and higher levels of activating immune signatures and T cell responses, higher density of PD-1+ T cells and their closer proximity to tumor cells or PD-L1+ macrophages. HPV-positive patients with higher infiltration of T cells and macrophages had a longer DFS, while CD163+ macrophages had a negative role in prognosis of HPV-negative patients.
CONCLUSIONS
Our results suggest that checkpoint expression may reflect an ongoing antitumor immune response. Thus, these observations provide the rationale for the incorporation of ICI in the loco-regional therapy strategies for patients with heavily infiltrated treatment-naïve OPSCC, and for the combination of ICI with tumor-specific T cell response inducers or TAM modulators for the "cold" OPSCC counterparts.
Topics: B7-H1 Antigen; Carcinoma, Squamous Cell; Forkhead Transcription Factors; Head and Neck Neoplasms; Humans; Immune Checkpoint Inhibitors; Oropharyngeal Neoplasms; Papillomavirus Infections; Programmed Cell Death 1 Receptor; Spatial Analysis; Squamous Cell Carcinoma of Head and Neck; Tumor Microenvironment
PubMed: 36123711
DOI: 10.1186/s13046-022-02481-4 -
Hematology/oncology Clinics of North... Oct 2021Squamous cell carcinoma of the oropharynx (OPC) consists of human papillomavirus (HPV)-negative disease caused by tobacco and alcohol use, and HPV-positive disease... (Review)
Review
Squamous cell carcinoma of the oropharynx (OPC) consists of human papillomavirus (HPV)-negative disease caused by tobacco and alcohol use, and HPV-positive disease caused by the sexually transmitted infection HPV. These entities have unique but overlapping risk factors, epidemiologic trends, staging systems, and survival outcomes. HPV-positive tumor status confers a significant survival benefit compared with HPV-negative disease. OPC treatment entails a combination of surgery, radiation, and chemotherapy. Ongoing trials will determine whether treatment of HPV-related disease may be safely deintensified to decrease morbidity. Emerging HPV-related biomarkers are under study as tools to inform screening, diagnosis, treatment, and surveillance for HPV-positive OPC.
Topics: Alphapapillomavirus; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prognosis
PubMed: 34244016
DOI: 10.1016/j.hoc.2021.05.004 -
Current Oncology Reports Jul 2020The treatment of patients with squamous cell carcinoma of the oropharynx (OPSCC) remains controversial. HPV positivity is widely accepted as a favorable prognostic... (Review)
Review
PURPOSE OF REVIEW
The treatment of patients with squamous cell carcinoma of the oropharynx (OPSCC) remains controversial. HPV positivity is widely accepted as a favorable prognostic factor, and HPV+ OPSCC is considered a distinct pathological entity with dedicated NCCN guidelines and may deserve a more personalized therapeutic strategy. The possibility to reduce surgical invasiveness and acute and late toxicity of radiotherapy/chemotherapy has led to the new concept of de-escalation treatment strategies. In particular, several de-intensified approaches have been investigated with the aim to give patients less toxic treatments, while maintaining comparable results in terms of disease's control and survival. The aim of the present review is to systematically illustrate the current status of research in de-intensification surgical and non-surgical strategies in the treatment of the OPSCC.
RECENT FINDINGS
We categorized all completed and on-going trials on the basis of the specific de-escalated treatment protocol. Several de-intensified approaches have been investigated with the aim to give patients less toxic treatments, while maintaining comparable results in terms of disease's control and survival. Considering the conflicting results reported so far by preliminary studies, it is necessary to wait for the final results of the on-going trials to better clarify which is the best de-intensified strategy and which patients would really benefit from it.
Topics: Carcinoma, Squamous Cell; Chemoradiotherapy; Clinical Trials as Topic; Humans; Oropharyngeal Neoplasms; Radiotherapy; Radiotherapy Dosage
PubMed: 32643045
DOI: 10.1007/s11912-020-00948-1 -
Otolaryngology--head and Neck Surgery :... Jan 2021To investigate differences in epidemiology of oropharyngeal squamous cell carcinoma (OPSCC) with regards to human papillomavirus (HPV), race, and socioeconomic status...
OBJECTIVE
To investigate differences in epidemiology of oropharyngeal squamous cell carcinoma (OPSCC) with regards to human papillomavirus (HPV), race, and socioeconomic status (SES) using the National Cancer Database (NCDB).
STUDY DESIGN
Population-based cohort study.
SETTING
Racial and socioeconomic disparities in survival of OPSCC have been previously acknowledged. However, the distribution of HPV-related cancers and its influence on survival in conjunction with race and SES remain unclear.
SUBJECTS AND METHODS
All patients with OPSCC in the NCDB with known HPV status from 2010 to 2016 were included. Differences in presentation, HPV status, treatment, and outcomes were compared along racial and socioeconomic lines. Univariable and multivariable Cox regression survival analyses were performed.
RESULTS
In total, 45,940 patients met criteria. Most were male (38,038, 82.8%), older than 60 years (23,456, 51.5%), and white (40,156, 87.4%), and lived in higher median income areas (>$48,000, 28,587, 62.2%). Two-thirds were HPV positive (31,007, 67.5%). HPV-negative disease was significantly more common in lower SES (<$38,000, 2937, 41.5%, < .001) and among blacks (1784, 55.3%, < .001). Median follow-up was 33 months. Five-year overall survival was 81.3% (95% CI, 80.5%-82.1%) and 59.6% (95% CI, 58.2%-61.0%) in HPV-positive and HPV-negative groups, respectively. In univariable and multivariable analyses controlling for HPV status, age, stage, and treatment, black race (hazard ratio [HR], 1.22; 95% CI, 1.11-1.34; < .001) and low SES (HR, 1.58; 95% CI, 1.45-1.72; < .001) were associated with worse survival.
CONCLUSION
Significant differences in HPV status exist between socioeconomic and racial groups, with HPV-negative disease more common among blacks and lower SES. When controlling for HPV status, race and SES still influence outcomes in oropharyngeal cancers.
Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Humans; Insurance Coverage; Male; Middle Aged; Oropharyngeal Neoplasms; Papillomavirus Infections; Registries; Socioeconomic Factors; Survival Rate
PubMed: 32660368
DOI: 10.1177/0194599820935853 -
Journal (Canadian Dental Association) Dec 2022The aims of this study were to determine demographic profiles, tumour characteristics and treatment factors related to oral cavity and oropharyngeal cancer (OCC and OPC)...
OBJECTIVES
The aims of this study were to determine demographic profiles, tumour characteristics and treatment factors related to oral cavity and oropharyngeal cancer (OCC and OPC) and comparatively analyze these cancers in the adult population of Alberta, Canada, over 12 years.
METHODS
Demographic, tumour characteristics and treatment data regarding OCC and OPC incidence in Alberta residents ≥18 years in 2005-2017 were extracted from the Alberta Cancer Registry database. Age-standardized incidence and mortality rates (ASIR and ASMR) were computed.
RESULTS
Among 3448 OCC and OPC cases, mean (standard deviation) age at diagnosis was 63.9 (14.4) and 60.1 (10.2) years, respectively. There was a male predilection for both OCC (58.2%) and OPC (81.7%). With some fluctuations, ASIR remained the same for OCC but increased for OPC. ASMR increased for both. The most common site for OCC was tongue and for OPC tonsil. Squamous cell carcinoma was the most common diagnosis for OCC and OPC. Involvement of at least 1 lymph node was observed in 38.5% of OCC and 85.8% of OPC cases. For 45.2% of OCC and 82.3% of OPC cases, diagnosis occurred at stage IV. The most common initial treatments for OCC were surgery, alone or combined with radiation, whereas radiation with chemotherapy was the main treatment modality for OPC.
CONCLUSION
The incidence of OPC in younger males was higher than that of OCC. Although incidence of OPC per 100 000 population increased over the 12-year study period, it remained largely unchanged for OCC. For both cancers, initial diagnoses were made at advanced stages, with almost twice as many stage IV OPC cases than OCC cases.
Topics: Adult; Male; Humans; Mouth Neoplasms; Alberta; Oropharyngeal Neoplasms; Incidence
PubMed: 37098276
DOI: No ID Found -
The Lancet. Digital Health Jun 2023Pretreatment identification of pathological extranodal extension (ENE) would guide therapy de-escalation strategies for in human papillomavirus (HPV)-associated... (Randomized Controlled Trial)
Randomized Controlled Trial
Screening for extranodal extension in HPV-associated oropharyngeal carcinoma: evaluation of a CT-based deep learning algorithm in patient data from a multicentre, randomised de-escalation trial.
BACKGROUND
Pretreatment identification of pathological extranodal extension (ENE) would guide therapy de-escalation strategies for in human papillomavirus (HPV)-associated oropharyngeal carcinoma but is diagnostically challenging. ECOG-ACRIN Cancer Research Group E3311 was a multicentre trial wherein patients with HPV-associated oropharyngeal carcinoma were treated surgically and assigned to a pathological risk-based adjuvant strategy of observation, radiation, or concurrent chemoradiation. Despite protocol exclusion of patients with overt radiographic ENE, more than 30% had pathological ENE and required postoperative chemoradiation. We aimed to evaluate a CT-based deep learning algorithm for prediction of ENE in E3311, a diagnostically challenging cohort wherein algorithm use would be impactful in guiding decision-making.
METHODS
For this retrospective evaluation of deep learning algorithm performance, we obtained pretreatment CTs and corresponding surgical pathology reports from the multicentre, randomised de-escalation trial E3311. All enrolled patients on E3311 required pretreatment and diagnostic head and neck imaging; patients with radiographically overt ENE were excluded per study protocol. The lymph node with largest short-axis diameter and up to two additional nodes were segmented on each scan and annotated for ENE per pathology reports. Deep learning algorithm performance for ENE prediction was compared with four board-certified head and neck radiologists. The primary endpoint was the area under the curve (AUC) of the receiver operating characteristic.
FINDINGS
From 178 collected scans, 313 nodes were annotated: 71 (23%) with ENE in general, 39 (13%) with ENE larger than 1 mm ENE. The deep learning algorithm AUC for ENE classification was 0·86 (95% CI 0·82-0·90), outperforming all readers (p<0·0001 for each). Among radiologists, there was high variability in specificity (43-86%) and sensitivity (45-96%) with poor inter-reader agreement (κ 0·32). Matching the algorithm specificity to that of the reader with highest AUC (R2, false positive rate 22%) yielded improved sensitivity to 75% (+ 13%). Setting the algorithm false positive rate to 30% yielded 90% sensitivity. The algorithm showed improved performance compared with radiologists for ENE larger than 1 mm (p<0·0001) and in nodes with short-axis diameter 1 cm or larger.
INTERPRETATION
The deep learning algorithm outperformed experts in predicting pathological ENE on a challenging cohort of patients with HPV-associated oropharyngeal carcinoma from a randomised clinical trial. Deep learning algorithms should be evaluated prospectively as a treatment selection tool.
FUNDING
ECOG-ACRIN Cancer Research Group and the National Cancer Institute of the US National Institutes of Health.
Topics: Humans; Human Papillomavirus Viruses; Retrospective Studies; Papillomavirus Infections; Deep Learning; Extranodal Extension; Oropharyngeal Neoplasms; Algorithms; Carcinoma; Tomography, X-Ray Computed
PubMed: 37087370
DOI: 10.1016/S2589-7500(23)00046-8 -
The Annals of Otology, Rhinology, and... Mar 2022To analyze the oncologic outcomes and risk factors for recurrence in patients who underwent surgery for oropharyngeal squamous cell carcinoma (OPSCC), and in whom...
OBJECTIVE
To analyze the oncologic outcomes and risk factors for recurrence in patients who underwent surgery for oropharyngeal squamous cell carcinoma (OPSCC), and in whom adjuvant therapy was not recommended or was declined.
METHODS
Retrospective cohort study of patients with OPSCC who were treated with transoral surgery only at a tertiary care academic medical center from April 2010 to March 2019.
RESULTS
Seventy-four patients met inclusion criteria. In 16, adjuvant therapy was recommended but declined. There were 8 recurrences, of which 6 had been given recommendations for adjuvant therapy. Of the 8 recurrences, 2 died, 2 are alive with disease, and 4 were successfully salvaged. Five patients died of unrelated causes. Lymphovascular invasion (LVI, = .016) had a significant impact on recurrence, while other pathologic features of the primary tumor such as size, location, human papillomavirus (HPV) status, and margin status did not. Margins were classified as "positive" in 4 patients, "close" in 54, and "negative" in 16. There were 3 local recurrences (4.1%), each of whom had declined adjuvant therapy. Lymph node features such as N-stage ( = .0004), number of positive nodes ( = .0005), and presence of extra-nodal extension (ENE, = .0042) had a statistically significant impact on relapse. Smoking history and surgical approach showed no significant impact on recurrence.
CONCLUSION
Patients who undergo surgery for HPV-positive OPSCC with negative margins, no PNI, no LVI, and ≤1 positive lymph node without ENE have low risk for recurrence. These patients can likely be safely treated with surgery alone. Patients with these risk factors who decline adjuvant therapy are at risk for recurrence, and should be monitored.
Topics: Aged; Carcinoma, Squamous Cell; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Papillomaviridae; Retrospective Studies; Risk Factors; Survival Rate; Treatment Failure
PubMed: 34056954
DOI: 10.1177/00034894211021287 -
Radiotherapy and Oncology : Journal of... Jan 2020The aim was to evaluate in oropharyngeal carcinoma the: (1) incidence and predictors of retropharyngeal (RP) lymph node (LN) involvement, (2) pattern of...
INTRODUCTION
The aim was to evaluate in oropharyngeal carcinoma the: (1) incidence and predictors of retropharyngeal (RP) lymph node (LN) involvement, (2) pattern of ipsilateral/bilateral/contralateral-only RP LNs (3) location of RP LNs in relation to contouring guidelines.
METHODS
Single centre retrospective analysis of 402 patients with oropharyngeal carcinoma treated non-surgically between 2010 and 2017. All patients had a baseline FDG PET-CT and contrast-enhanced MRI and/or CT. All cases with reported abnormal RP LNs underwent radiology review.
RESULTS
Abnormal RP LNs were identified in 40/402 (10%) of patients. On multivariate analysis, RP LN involvement was associated with posterior pharyngeal wall/soft palate primaries (OR 10.13 (95% CI 2.29-19.08), p = 0.002) and contralateral cervical LN involvement (OR 2.26 (95% CI 1.05-4.86), p = 0.036). T stage, largest LN size, levels of ipsilateral LN level involvement, HPV and smoking status did not predict risk. 5/402 (1.2%) patients had bilateral RP involvement. 3/402 patients (0.7%) had contralateral-only RP LNs. All patients with contralateral RP LNs had contralateral neck nodes or primary cancers extending across midline. In 5/40 (12.5%) cases with involved RP LNs, the RP LNs were superior to hard palate/upper edge of body of C1 vertebra.
CONCLUSIONS
RP LNs were identified in 10% of oropharyngeal carcinoma patients, and were associated with contralateral neck disease and/or posterior pharyngeal wall/soft palate primary. Contralateral RP LN involvement was rare and associated with contralateral neck disease and/or primary crossing midline, suggesting potential for omission from target volumes for selected patients. Involvement of RP LNs close to the skull base highlights the need for generous elective outlining.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Incidence; Lymph Nodes; Lymphatic Metastasis; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Oropharyngeal Neoplasms; Positron Emission Tomography Computed Tomography; Retrospective Studies; Young Adult
PubMed: 31431388
DOI: 10.1016/j.radonc.2019.07.021