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Journal of Clinical Oncology : Official... Dec 2017Purpose Treatment of oropharyngeal squamous cell carcinoma (OPSCC) is evolving toward risk-based modification of therapeutic intensity, which requires patient-specific...
Purpose Treatment of oropharyngeal squamous cell carcinoma (OPSCC) is evolving toward risk-based modification of therapeutic intensity, which requires patient-specific estimates of overall survival (OS) and progression-free survival (PFS). Methods To develop and validate nomograms for OS and PFS, we used a derivation cohort of 493 patients with OPSCC with known p16 tumor status (surrogate of human papillomavirus) and cigarette smoking history (pack-years) randomly assigned to clinical trials using platinum-based chemoradiotherapy (NRG Oncology Radiation Therapy Oncology Group [RTOG] 0129 and 0522). Nomograms were created from Cox models and internally validated by use of bootstrap and cross-validation. Model discrimination was measured by calibration plots and the concordance index. Nomograms were externally validated in a cohort of 153 patients with OPSCC randomly assigned to a third trial, NRG Oncology RTOG 9003. Results Both models included age, Zubrod performance status, pack-years, education, p16 status, and T and N stage; the OS model also included anemia and age × pack-years interaction; and the PFS model also included marital status, weight loss, and p16 × Zubrod interaction. Predictions correlated well with observed 2-year and 5-year outcomes. The uncorrected concordance index was 0.76 (95% CI, 0.72 to 0.80) for OS and 0.70 (95% CI, 0.66 to 0.74) for PFS, and bias-corrected indices were similar. In the validation set, OS and PFS models were well calibrated, and OS and PFS were significantly different across tertiles of nomogram scores (log-rank P = .003;< .001). Conclusion The validated nomograms provided useful prediction of OS and PFS for patients with OPSCC treated with primary radiation-based therapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Cohort Studies; Disease-Free Survival; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Nomograms; Organoplatinum Compounds; Oropharyngeal Neoplasms; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Randomized Controlled Trials as Topic; Squamous Cell Carcinoma of Head and Neck; Survival Rate
PubMed: 28777690
DOI: 10.1200/JCO.2016.72.0748 -
Archives of Pathology & Laboratory... Nov 2015The incidence of oropharyngeal squamous cell carcinoma has increased during the past decade and is related primarily to the human papillomavirus. This change in... (Review)
Review
CONTEXT
The incidence of oropharyngeal squamous cell carcinoma has increased during the past decade and is related primarily to the human papillomavirus. This change in etiology, from tobacco and alcohol to human papillomavirus, has resulted in improved survival for the disease. In the United States, open resection had largely been replaced by concurrent chemotherapy and/or radiotherapy by the early 2000s. The advent of transoral surgery has led to an increase in surgery as the primary treatment for both early- and advanced-stage oropharyngeal squamous cell carcinoma because it has potential advantages over open surgery and nonsurgical modalities.
OBJECTIVE
To provide an overview of transoral robotic surgery for oropharyngeal squamous cell carcinoma and contrast it with other surgical and nonsurgical modalities.
DATA SOURCES
Articles from 2000 to 2014 were accessioned on PubMed and reviewed for utility by the primary authors.
CONCLUSIONS
Transoral surgery has become more commonly used as a minimally invasive approach to treat oropharyngeal tumors. Other strategies, including radiation, chemotherapy with radiation, and open surgery, are still important treatment approaches. The treatment options for an individual patient rely on multiple factors, including the tumor location and size, features of the tumor, and patient comorbidities. The continued study of these techniques is important to match the patient with the most appropriate treatment.
Topics: Carcinoma, Squamous Cell; Humans; Oropharyngeal Neoplasms; Oropharynx; Quality of Life; Robotic Surgical Procedures; Treatment Outcome
PubMed: 26288397
DOI: 10.5858/arpa.2014-0573-RA -
Journal of Otolaryngology - Head & Neck... Jan 2017Epigenetic modifications are heritable changes in gene expression that do not directly alter DNA sequence. These modifications include DNA methylation, histone... (Review)
Review
Epigenetic modifications are heritable changes in gene expression that do not directly alter DNA sequence. These modifications include DNA methylation, histone post-translational modifications, small and non-coding RNAs. Alterations in epigenetic profiles cause deregulation of fundamental gene expression pathways associated with carcinogenesis. The role of epigenetics in oropharyngeal squamous cell carcinoma (OPSCC) has recently been recognized, with implications for novel biomarkers, molecular diagnostics and chemotherapeutics. In this review, important epigenetic pathways in human papillomavirus (HPV) positive and negative OPSCC are summarized, as well as the potential clinical utility of this knowledge.This material has never been published and is not currently under evaluation in any other peer-reviewed publication.
Topics: Antineoplastic Agents; Carcinoma, Squamous Cell; Epigenomics; Humans; Oropharyngeal Neoplasms
PubMed: 28143553
DOI: 10.1186/s40463-017-0185-3 -
Journal of Cancer Research and... Jan 2024To retrospectively access outcome, adverse events and prognostic factors in oropharyngeal carcinoma (OPC) patients treated with intensity-modulated radiotherapy (IMRT).
BACKGROUND
To retrospectively access outcome, adverse events and prognostic factors in oropharyngeal carcinoma (OPC) patients treated with intensity-modulated radiotherapy (IMRT).
METHODS
Ninety-eight OPC patients were treated between 2000 and 2015. Thirty-three patients received definitive and 65 adjuvant radiotherapy. Seventy-one percent had simultaneous chemotherapy. Patients were systematically followed up (mean 114 months, range 19-197 months). Statistical analysis used Kaplan-Meier method, Cox regression analysis, and log-rank test. Adverse events were classified according to common toxicity criteria version (CTCAE) 4.03.
RESULTS
The 1-, 5-, and 10-year overall survival rates in the adjuvant vs. definitive cohort were 90.8% vs. 66.7%, 67.4% vs. 33.1%, and 57.7% vs. 16.5%. Survival in the adjuvant cohort was significantly longer than in the definitive cohort (P < 0.00005). Patients <65 years had a significantly longer survival than older patients. Locoregional tumor control rates after 1-, 5-, and 10 years in the adjuvant vs. definitive cohort were 90.2% vs. 66.7%, 82.2% vs 45.4%, and 72.1% vs. 30.3%. Locoregional tumor control in the adjuvant cohort was significantly longer than in the definite cohort (P < 0.005). Distant metastases were diagnosed in 20.4% of all patients. Most patients had mild CTCAE grade 1 and 2 adverse events and mild late adverse events including xerostomia, dysphagia, and lymphedema.
CONCLUSION
Intensity-modulated radiotherapy for OPC is an important part of the treatment algorithm alone and in particular after surgery while the additional benefits of chemotherapy might be age dependent. Despite advanced tumor stages, nearly half of our patients were alive in the long term. The majority of patients had relatively mild chronic adverse events.
Topics: Humans; Radiotherapy, Intensity-Modulated; Retrospective Studies; Oropharyngeal Neoplasms; Radiotherapy, Adjuvant; Carcinoma
PubMed: 38554349
DOI: 10.4103/jcrt.jcrt_2178_22 -
Otolaryngologic Clinics of North America Dec 2020This article outlines the ways that transoral robotic surgery and transoral laser microsurgery relate to treatment de-escalation in the treatment of head and neck... (Review)
Review
This article outlines the ways that transoral robotic surgery and transoral laser microsurgery relate to treatment de-escalation in the treatment of head and neck cancer. Treatment de-escalation has particular importance in context of human papillomavirus-related oropharynx squamous cell carcinoma, which responds well to therapy but leaves many survivors with decades of treatment-related sequelae. We compare these less invasive transoral approaches with previously used open approaches to the oropharynx. We discuss the topic of treatment de-escalation in human papillomavirus-related disease and outline completed and ongoing clinical trials investigating the choice of primary treatment modality and de-escalation of adjuvant therapy.
Topics: Carcinoma, Squamous Cell; Humans; Laser Therapy; Microsurgery; Oropharyngeal Neoplasms; Papillomaviridae; Robotic Surgical Procedures
PubMed: 32917423
DOI: 10.1016/j.otc.2020.07.009 -
Clinical Oncology (Royal College of... May 2021To analyse outcomes and patterns of failure in patients with oropharyngeal carcinoma (OPC) treated with definitive volumetric modulated arc therapy with omission of...
Radiotherapy for Oropharyngeal Carcinoma With an Uninvolved Contralateral Neck: The Safety of Omission of Contralateral High Level II and Retropharyngeal Lymph Nodes From Elective Target Volumes.
AIMS
To analyse outcomes and patterns of failure in patients with oropharyngeal carcinoma (OPC) treated with definitive volumetric modulated arc therapy with omission of contralateral high level II lymph nodes (HLII) and retropharyngeal lymph nodes (RPLN) in the contralateral uninvolved neck.
MATERIALS AND METHODS
Patients with OPC treated between January 2016 and July 2019 were retrospectively identified. In the absence of contralateral neck disease, institutional protocols allowed omission of contralateral HLII and contralateral RPLN in the additional absence of ipsilateral RPLN, soft palate/posterior pharyngeal wall primary.
RESULTS
In total, 238 patients with OPC and an uninvolved contralateral neck received definitive (chemo)radiotherapy with bilateral neck treatment. The median follow-up was 30.6 months. Two-year local control, regional control and overall survival were 91.0, 91.6 and 86.5%, respectively. Contralateral HLII were omitted in 159/238 (66.8%) patients; this included 106 patients in whom the primary tumour was at/crossed the midline. The contralateral RPLN region was omitted from elective target volumes for 175/238 (73.5%); this included 114 patients with a primary tumour at/crossed the midline. The mean contralateral parotid dose when contralateral HLII and RPLN were both omitted was 24.4 Gy, compared with 28.3 Gy without HLII/RPLN omission (P < 0.001). Regional progression occurred in 18/238 (7.6%) patients, all involving the ipsilateral neck with one bilateral. There were no recurrences in the contralateral HLII or RPLN regions.
CONCLUSION
In patients with OPC and an uninvolved contralateral neck receiving bilateral (chemo)radiotherapy, the omission of contralateral RPLN and HLII from elective target volumes was safe and could lead to reduced contralateral parotid doses.
Topics: Carcinoma; Humans; Lymph Nodes; Neoplasm Staging; Oropharyngeal Neoplasms; Retrospective Studies
PubMed: 33358282
DOI: 10.1016/j.clon.2020.12.007 -
Annals of Oncology : Official Journal... Nov 2014Squamous cell carcinoma of the head and neck (SCCHN) was traditionally associated with smoking and alcohol use; however, human papillomavirus (HPV) infection has... (Review)
Review
BACKGROUND
Squamous cell carcinoma of the head and neck (SCCHN) was traditionally associated with smoking and alcohol use; however, human papillomavirus (HPV) infection has recently been implicated as a novel risk factor for oropharyngeal tumors. Furthermore, HPV-associated oropharyngeal carcinoma (OPC) appears to be a distinct entity with different epidemiology, biology, and clinical outcomes.
METHODS
Here, we comprehensively review the existing data regarding HPV status and prognostic or predictive outcomes in both the locoregionally advanced (LA) and recurrent/metastatic (RM) disease setting and discuss ongoing trials that may eventually impact the treatment of patients with HPV-positive (HPV+) SCCHN.
RESULTS
A body of retrospective and prospective data established an association between HPV+ OPC and better survival, particularly for LA disease. Current data on RM disease are limited, but they also suggest prognostic significance for HPV.
CONCLUSIONS
Better outcomes in HPV+ LA disease may allow for less aggressive treatment in the future, and several trials are evaluating deintensified regimens in patients with HPV+, LA OPC; it should be emphasized that deintensification strategies are appropriate only in a clinical research setting and only for selected subgroups of HPV+ patients. In addition, HPV-targeted strategies, such as vaccines, are currently undergoing clinical evaluation. On the other hand, the prognostic impact of HPV in RM disease requires further validation before any modifications in treatment can be made. Likewise, the predictive significance of HPV status in both disease settings remains to be defined.
CLINICAL TRIAL NUMBERS
NCT00226239, NCT00301028, NCT00387127, NCT00410826, NCT00503997, NCT00514943, NCT00544414, NCT00768664, NCT00939627, NCT01084083, NCT01302834, NCT01687413, NCT01706939.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Carcinoma, Squamous Cell; Cetuximab; Clinical Trials as Topic; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Panitumumab; Papillomaviridae; Prognosis; Retrospective Studies; Risk Factors; Squamous Cell Carcinoma of Head and Neck
PubMed: 25057165
DOI: 10.1093/annonc/mdu265 -
Cell Reports. Medicine Nov 2023Tumor-infiltrating HPV16-E2-specific CD8 T cells have been detected in HPV16-induced oropharyngeal squamous cell carcinoma (OPSCC). Whether intratumoral CD4 T cells...
Tumor-infiltrating HPV16-E2-specific CD8 T cells have been detected in HPV16-induced oropharyngeal squamous cell carcinoma (OPSCC). Whether intratumoral CD4 T cells target HPV16 E2 and if HPV16-E2-specific immunity contributes to better clinical outcome is unknown. In a prospective HPV16 OPSCC cohort, we regularly detect HPV16-E2-specific CD4 and CD8 intratumoral T cells, albeit at lower frequencies than the co-infiltrating HPV16-E6/E7-specific T cells. These HPV16-reactive T cells produce multiple cytokines when activated, indicating their polyfunctionality. Importantly, their combined intratumoral presence predicts superior survival, emphasizing the value of HPV16-E2-specific T cells in anti-tumor immunity and suggests its use as a target antigen for immunotherapy.
Topics: Humans; Human papillomavirus 16; CD8-Positive T-Lymphocytes; Prospective Studies; Papillomavirus Infections; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms
PubMed: 37924817
DOI: 10.1016/j.xcrm.2023.101262 -
CA: a Cancer Journal For Clinicians 1995An examination of the oral cavity and oropharynx in asymptomatic patients at high risk requires an orderly visual inspection of the entire oral and oropharyngeal mucosa... (Comparative Study)
Comparative Study Review
An examination of the oral cavity and oropharynx in asymptomatic patients at high risk requires an orderly visual inspection of the entire oral and oropharyngeal mucosa with particular attention to the tongue, floor of mouth, soft palate, uvula, tonsillar pillars, and the lingual aspects of the retromolar trigones. Completion and clear documentation of the entire examination should be recorded. Detected lesions that do not resolve in a reasonable length of time--two to three weeks--require intense and assiduous investigation. The following specifics should be considered. 1. Alcohol drinkers and cigarette smokers, especially those 40 years of age and older, are at very high risk for the development of upper aerodigestive tract and lung squamous carcinomas. 2. The floor of the mouth, the ventrolateral tongue, and the soft palate complex are the high-risk sites within the oral cavity and oropharynx. 3. Persistent mucosal erythroplasia rather than leukoplakia is the earliest visual sign of oral and oropharyngeal carcinoma. These lesions should not be regarded merely as precancerous changes. The evidence indicates that these lesions in high-risk sites should be considered to be invasive carcinoma or carcinoma in situ unless proven otherwise by biopsy. 4. Toluidine blue staining is a useful diagnostic adjunct, particularly as a method of ruling out false-negative clinical impressions. It may also be used as a rinse in high-risk patients to encompass the entire oral mucosa after a negative clinical examination and as a guide to improve biopsy yields. 5. If oral or oropharyngeal cancer is identified, evaluations of the larynx, hypopharynx, esophagus, and lungs should be performed to rule out multiple primary cancers.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Alcohol Drinking; Biopsy; Carcinoma; Carcinoma in Situ; Carcinoma, Squamous Cell; Female; Humans; Leukoplakia, Oral; Male; Mouth Neoplasms; Oropharyngeal Neoplasms; Palatal Neoplasms; Risk Factors; Smoking; Staining and Labeling; Time Factors
PubMed: 7583906
DOI: 10.3322/canjclin.45.6.328 -
Cancer May 2014The discovery that the human papilloma virus (HPV) is associated with a high and increasing percentage of oropharyngeal squamous cell carcinomas (SCCs) is among the most... (Comparative Study)
Comparative Study Review
The discovery that the human papilloma virus (HPV) is associated with a high and increasing percentage of oropharyngeal squamous cell carcinomas (SCCs) is among the most significant advances in the field of head and neck oncology. HPV-positive oropharyngeal cancer (HPVOPC) has clinical, etiologic, pathologic, and molecular features that distinguish it from HPV-negative disease. Increasingly, HPVOPC is being diagnosed in clinical practice because of the easy availability of p16 immunohistochemistry, a surrogate marker of HPV. The superior prognosis of HPVOPC has led to a reexamination of treatment approaches, and clinical trials are currently investigating strategies to deintensify treatment to reduce acute and late toxicity while preserving efficacy. This is of particular interest in low-risk patients. Unfortunately, patients with HPV-negative tumors still have high rates of locoregional failure and more efficacious treatments are required. This review of oropharyngeal SCC focuses on current and investigational treatment strategies in patients with both HPV-positive and HPV-negative oropharyngeal SCC.
Topics: Carcinoma, Squamous Cell; Chemoradiotherapy; DNA, Viral; Human papillomavirus 16; Humans; Induction Chemotherapy; Neoplasm Staging; Oropharyngeal Neoplasms; Papillomavirus Infections; Prognosis; Treatment Outcome
PubMed: 24578320
DOI: 10.1002/cncr.28595