Expression patterns of Bmi-1 and p16 significantly correlate with overall, disease-specific, and recurrence-free survival in oropharyngeal squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is a fatal disease caused by complex interactions between environmental, genomic, and epigenetic alterations. In the current study, we aimed to identify clusters of genes whose promoter methylation status correlated with various tested clinical features. Molecular datasets of genetic and methylation analysis based on whole-genome sequencing of 159 OSCC patients were obtained from the The Cancer Genome Atlas (TCGA) data portal. Genes were clustered based on their methylation status and were tested for their association with demographic, pathological, and clinical features of the patients. Overall, seven clusters of genes were revealed that showed a significant association with the overall survival/recurrence free survival of patients. The top ranked genes within cluster 4, which showed the worst prognosis, primarily acted as paraneoplastic genes, while the genes within cluster 6 primarily acted as anti-tumor genes. A significant difference was found regarding the mean age in the different clusters. No significant correlation was found between the tumor staging and the different clusters. In conclusion, our result provided a proof-of-principle for the existence of phenotypic diversity among the epigenetic clusters of OSCC and demonstrated the utility of the use epigenetics alterations in devolving new prognostic and therapeutics tools for OSCC patients.

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NUCKS1 overexpression is a novel biomarker for recurrence-free survival in cervical squamous cell carcinoma

Tumor Biology ◽

10.1007/s13277-014-2035-5 ◽

2014 ◽

Vol 35 (8) ◽

pp. 7831-7836 ◽

Cited By ~ 18

Author(s):

Lina Gu ◽

Bairong Xia ◽

Lili Zhong ◽

Yuan Ma ◽

Lei Liu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cervical Squamous Cell Carcinoma ◽

Recurrence Free Survival ◽

Free Survival

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Randomized trial of radiotherapy with weekly cisplatin or cetuximab in low risk HPV associated oropharyngeal cancer (TROG 12.01): A Trans-Tasman Radiation Oncology Group study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.6012 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 6012-6012

Author(s):

Danny Rischin ◽

Madeleine T. King ◽

Lizbeth M. Kenny ◽

Sandro Porceddu ◽

Christopher Wratten ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Symptom Severity ◽

Oropharyngeal Cancer ◽

Symptom Burden ◽

Oropharyngeal Squamous Cell Carcinoma ◽

Low Risk ◽

Free Survival ◽

Weekly Cisplatin

6012 Background: The excellent prognosis of patients with low risk HPV associated oropharyngeal squamous cell carcinoma has led to concerns about overtreatment and excessive toxicity with radiotherapy and cisplatin, leading to interest in de-intensification trials. We investigated whether cetuximab, an EGFR targeting antibody, when combined with radiotherapy would result in a decrease in symptom burden and toxicity with similar efficacy when compared to weekly cisplatin. Methods: TROG 12.01, a randomised, multicentre trial involving 15 sites in Australia and New Zealand enrolled patients with HPV associated oropharyngeal squamous cell carcinoma, AJCC 7th edition Stage III (excluding T1-2N1) or stage IV (excluding T4 and/or N3 and/or N2b-c if smoking history >10 pack years and/or distant metastases). Patients were randomised (1:1) to receive radiotherapy (70Gy in 35 fractions) with either weekly cisplatin, 7 doses of 40mg/m2 or cetuximab, loading dose of 400mg/m2 followed by 7 weekly doses of 250 mg/m2. The primary outcome was symptom severity assessed by the MD Anderson Symptom Inventory Head and Neck Symptom Severity Scale from baseline to 13 weeks post completion of radiotherapy using the area under the time-severity curve (AUC). Sample size was 170 evaluable patients to provide at least 90% power to detect an effect size of 0.5, using a 2-sided test at 0.05 level of significance. Trial was registered on ClinicalTrials.gov: NCT01855451. Results: Between 17th June 2013 and 7th June 2018, 189 patients were enrolled and 182 were evaluable, with 92 on cisplatin arm and 90 on cetuximab included in the main analysis. The median follow-up was 4.1 years (0.4 - 5.3). Analyses were performed in all eligible randomised patients that commenced treatment (modified intention-to-treat population). There was no difference in the primary endpoint of symptom severity; difference in AUC cetuximab – cisplatin was 0.05 (95%CI: -0.19, 0.30), p= 0.66. The T-score (mean number of > grade 3 acute adverse events) was 4.35 (SD 2.48) in the cisplatin arm and 3.82 (SD 1.8) in the cetuximab arm, p= 0.108. The 3 -year failure-free survival rates were 93% (95% CI: 86-97%) in the cisplatin arm and 80% (95% CI: 70-87%) in the cetuximab arm (hazard ratio = 3.0 (95% CI: 1.2-7.7); p=0.015. The increase in failures in the cetuximab arm was evenly split between distant and locoregional failures. Conclusions: For patients with low risk HPV associated oropharyngeal cancer, radiotherapy and cetuximab had inferior failure-free survival without improvement in symptom burden or toxicity compared to radiotherapy and weekly cisplatin. Radiotherapy and cisplatin remains the standard of care. Clinical trial information: NCT01855451.

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Development and Validation of a CT Based Radiomics Nomogram for the Prediction of Local Recurrence-free Survival in Esophageal Squamous Cell Carcinoma Patients Receiving Definitive Chemoradiotherapy

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2019.06.116 ◽

2019 ◽

Vol 105 (1) ◽

pp. S131

Author(s):

L. Zhao ◽

J. Gong ◽

Y. Liao ◽

W. Qin ◽

M. Shi

Keyword(s):

Squamous Cell Carcinoma ◽

Local Recurrence ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Recurrence Free Survival ◽

Definitive Chemoradiotherapy ◽

Free Survival ◽

Development And Validation ◽

Local Recurrence Free Survival

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Transoral Surgery Alone for Human-Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma

Ear Nose & Throat Journal ◽

10.1177/014556131309200211 ◽

2013 ◽

Vol 92 (2) ◽

pp. 76-83 ◽

Cited By ~ 35

Author(s):

Steven M. Olsen ◽

Eric J. Moore ◽

Rebecca R. Laborde ◽

Joaquin J. Garcia ◽

Jeffrey R. Janus ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Human Papillomavirus ◽

Robotic Surgery ◽

Cell Carcinoma ◽

Neck Dissection ◽

Transoral Robotic Surgery ◽

Recurrence Free Survival ◽

Free Survival ◽

Kaplan Meier ◽

Disease Specific

The aim of this retrospective study was to describe the oncologic and functional results of treating oropharyngeal squamous cell carcinoma with transoral robotic surgery and neck dissection as monotherapy. A review was performed, including all patients who underwent transoral robotic surgery and neck dissection as the only means of therapy for oropharyngeal carcinoma from March 2007 to July 2009 at a single tertiary care academic medical center. We reviewed all cases with ≥ 24-month follow-up. Functional outcomes included tracheostomy dependence and oral feeding ability. Oncologic outcomes were stratified by human papillomavirus (HPV) status and tobacco use and included local, regional, and distant disease control, as well as disease-specific and recurrence-free survival. Eighteen patients met study criteria. Ten patients (55.6%) were able to eat orally in the immediate postoperative period, and 8 (44.4%) required a temporary nasogastric tube for a mean duration of 13.6 days (range 3 to 24 days) before returning to an oral diet. No patient required placement of a gastrostomy tube, and all patients are tracheostomy-tube–free. Among the HPV-positive nonsmokers (12/18, 66.7%), Kaplan-Meier estimated 3-year local, regional, and distant control rates were 90.9%, 100%, and 100%, respectively. Kaplan-Meier estimated disease-specific survival and recurrence-free survival were 100% and 90.9%, respectively. No complications occurred.

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Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus–Associated Oropharyngeal Squamous Cell Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.19.01007 ◽

2019 ◽

Vol 37 (29) ◽

pp. 2661-2669 ◽

Cited By ~ 24

Author(s):

Bhishamjit S. Chera ◽

Robert J. Amdur ◽

Rebecca Green ◽

Colette Shen ◽

Gaorav Gupta ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Human Papillomavirus ◽

Adverse Events ◽

Cell Carcinoma ◽

Squamous Cell ◽

Patient Reported Outcomes ◽

Oropharyngeal Squamous Cell Carcinoma ◽

Post Treatment ◽

Free Survival ◽

Patient Reported

PURPOSE To report the results of a phase II clinical trial of de-intensified chemoradiotherapy for patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma. MATERIALS AND METHODS Major inclusion criteria were (1) having American Joint Committee on Cancer (AJCC) 7th edition T0-T3, N0-N2c, M0 (AJCC 8th edition T0-T3, N0-N2, M0), (2) being p16 positive, and (3) reporting minimal or remote smoking history. Treatment was limited to 60 Gy intensity-modulated radiotherapy with concurrent intravenous cisplatin 30 mg/m2 once per week. Patients with T0-T2 N0-1 (AJCC 7th edition) did not receive chemotherapy. All patients had a 10- to 12-week post-treatment positron emission tomography/computed tomography to assess for neck dissection. The primary end point was 2-year progression-free survival. Secondary end points included 2-year local-regional control, distant metastasis-free survival and overall survival, and patient-reported outcomes (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events). RESULTS One hundred fourteen patients were enrolled (median follow-up of 31.8 months), with 81% having a minimum follow-up of 2 years. Eighty percent of patients had 10 or fewer tobacco pack-years. Two-year local-regional control, distant metastasis-free survival, progression-free survival, and overall survival were as follows: 95%, 91%, 86%, and 95%, respectively. Mean pre- and 2-year post-treatment European Organisation for Research and Treatment of Cancer quality of life scores were as follows: global, 79/84 (lower worse); swallowing, 8/9 (higher worse); and dry mouth, 14/45 (higher worse). Mean pre- and 2-year post-treatment patient-reported outcomes version of the Common Terminology Criteria for Adverse Events scores (0 to 4 scale, higher worse) were as follows: swallowing, 0.5/0.7, and dry mouth, 0.4/1.3. Thirty-four percent of patients required a feeding tube (median, 10.5 weeks; none permanent). There were no grade 3 or higher late adverse events. CONCLUSION Clinical outcomes with a de-intensified chemoradiotherapy regimen of 60 Gy intensity-modulated radiotherapy with concurrent low-dose cisplatin are favorable in patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma. Neither neoadjuvant chemotherapy nor routine surgery is needed to obtain favorable results with de-escalation.

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