scholarly journals Automated Quantification of CD44, c-MET, EGFR, MTOR, and GLUT1 Expression in Head and Neck Squamous Cell Carcinoma: The Impact of p16 Status and Response to Chemoradiation

2020 ◽  
pp. 1-10
Author(s):  
George Wilson ◽  
Jessica D. Arden ◽  
Thomas J. Quinn ◽  
Thomas G. Wilson ◽  
Alaa Hanna ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Locoregional Control ◽  
Free Survival ◽  
Automated Quantification ◽  
Control Disease ◽  
Disease Free

This study assessed automated quantification of CD44, c-MET, MTOR, EGFR, and GLUT1 protein expression in a tissue microarray of 109 Stage II-IV p16 positive and negative head and neck squamous cell carcinomas (HNSCC) treated with definitive chemoradiation. Immunohistochemistry-based protein expression was quantified in an automated manner using digitally scanned images processed with Definiens Tissue Studio software to generate a histologic score (H-score, range 0-300) which was normalized for each biomarker. Biomarker expression levels were correlated with one another and with p16 status. Effects of biomarker and p16 status on locoregional control, disease-free survival, and overall survival were analyzed using Kaplan Meier and Cox proportional hazard modelling. There was a significant negative correlation between CD44 and p16 expression and significant positive correlations between CD44 and MTOR, CD44 and GLUT1, c-MET and MTOR, and MTOR and GLUT1. When patients were stratified by p16 status, the significant positive correlation between CD44 expression and MTOR remained for both the p16 positive and negative subsets, while correlations between CD44 and GLUT1 and c-MET and MTOR were seen in the p16 negative subset only. A significant correlation between MTOR and GLUT was seen overall and for the p16 positive subset. When the effects of biomarker expression on clinical endpoints were examined, histologic scores below the defined cut-points for CD44 and c-MET were each associated with improved locoregional control. Higher expressions of CD44, c-MET, EGFR, and GLUT1 were associated with inferior disease-free and overall survival. On multivariable analysis, p16 positivity remained independently associated with improved locoregional control, disease-free survival, and overall survival, high CD44 remained independently associated with inferior locoregional control, disease-free survival, and overall survival, and EGFR with inferior disease-free and overall survival. In conclusion, the use of an automated system to quantify IHC expression allowed objective correlation between biomarkers and stratification of patients, revealing that higher expressions of CD44, c-MET, EGFR, and GLUT1 were associated with poorer disease-free and overall survival.

scholarly journals Early Postoperative Paclitaxel Followed by Concurrent Paclitaxel and Cisplatin With Radiation Therapy for Patients With Resected High-Risk Head and Neck Squamous Cell Carcinoma: Report of the Phase II Trial RTOG 0024

2009 ◽  
Vol 27 (28) ◽  
pp. 4727-4732 ◽  
Author(s):  
David I. Rosenthal ◽  
Jonathan Harris ◽  
Arlene A. Forastiere ◽  
Randal S. Weber ◽  
John A. Ridge ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
High Risk ◽  
Head And Neck ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Disease Free Survival ◽  
Locoregional Control ◽  
Free Survival ◽  
Positive Margins ◽  
Disease Free

Purpose We sought to improve outcomes for patients with high-risk head and neck squamous cell cancer (HNSCC) after surgical resection by testing the feasibility and safety of early postoperative chemotherapy followed by concurrent chemoradiotherapy. Patients and Methods Eligible patients had resected, stages III to IV HNSCC with positive margins, extracapsular nodal extension, or multiple positive nodes. Paclitaxel (80 mg/m2) was given once weekly during postoperative weeks 2, 3, and 4 and was given before radiation therapy (RT). Paclitaxel (30 mg/m2) and cisplatin (20 mg/m2) were given once weekly during the last 3 weeks of RT (60 Gy over 6 weeks, beginning 4 to 5 weeks after surgery). The primary end points were treatment safety and tolerability compared with concurrent cisplatin (100 mg/m2 every 3 weeks) and RT, as tested in Radiation Therapy Oncology Group trial RTOG 9501. Results The median follow-up time for the 70 patients enrolled was 3.3 years (range, 0.6 to 4.4 years) for surviving patients. Tolerability of all treatment components was comparable to that of RTOG 9501 treatment, which is the current standard of care (compliance rate, 75%; 95% CI, 63% to 85%). One patient died, and seven patients experienced grade 4 nonhematologic toxicities. Rates of locoregional control, disease-free survival, and overall survival exceeded those of RTOG 9501 after adjustment for important prognostic variables (ie, positive margins, extracapsular extension, primary site, and performance status). Conclusion Chemotherapy soon after surgery followed by concurrent chemoradiotherapy therapy was feasible; tolerance was in line with standard postoperative chemoradiotherapy; and this regimen led to excellent rates of locoregional control and disease-free survival.

Comparison of the seventh and eighth editions of the American Joint Committee on Cancer (AJCC) staging for oropharyngeal squamous cell carcinomas (OPSCC): A Surveillance, Epidemiology and End Results Program (SEER) database analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17538-e17538
Author(s):  
Sumita Trivedi ◽  
Haocan Song ◽  
Yuan Liu ◽  
Conor Ernst Steuer ◽  
William Stokes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Squamous Cell Carcinomas ◽  
Stage I ◽  
Seer Database ◽  
Free Survival ◽  
Ajcc Staging ◽  
Disease Free

e17538 Background: The recently released eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual, Head and Neck Section, incorporates significant changes to the prior seventh edition. The changes reflect the improved understanding of tumor biology, prognostic factors and molecular markers that effect outcomes in Head and Neck cancers. A key update restages OPSCC by human papilloma virus (HPV) positive and negative cancers as data demonstrated that these tumors have significantly different biology and outcomes. Methods: Using SEER data from 2004 – 2014, we identified male patients with squamous cell carcinomas of the tonsil, base of tongue and soft palate aged between 21 and 64 years old (those clinical characterizes were considered as surrogate markers for HPV positive status). We classified them by the AJCC 8th edition staging for HPV positive OPSCC and by AJCC 7th edition staging. The prediction performance by two staging editions were compared regarding overall survival (OS) and Disease free survival (DFS). Kaplan-Meier method and Cox proportional hazard model were applied, and the discrimination performance was measured by the concordance statistics (C-statistics). Results: A total of 8202 eligible patients were included in the analysis with a median follow up period of 51 months. 7415 (90.4%) patients had previously received radiation and 7038 (85.8%) patients had previously received chemotherapy. The median age of patients was 56 years. Distribution of stage I disease increased from 2% to 19.6% in AJCC 8th edition. 10-year overall survival (OS) for AJCC 8th stages I (74%), II (78%), III (55%) and IV (32%). Using Stage I as reference, the hazard ratio for stage II, III, and IV is 0.98 (95%CI: 0.87-1.09), 2.29 (95%CI: 2.04-2.57), and 5.88 (95%CI: 4.96-6.98). Similar results were noted for ten year disease free survival. The C-statistics measured overall discrimination for 8th edition is 0.68 and 0.63 for the 7th edition (P < 0.001). Conclusions: Based on this SEER analysis, the overall performance of discrimination improved from AJCC 7th to 8th edition; but in this study population, AJCC 8th edition does not distinguish stage I and II sufficiently as expected as it does for stages III and IV disease. Limitations of the SEER database include the surrogate for P16 status and under reported and incomplete data.

scholarly journals Prospective Evaluation of Sarcopenia in Head and Neck Cancer Patients Treated with Radiotherapy or Radiochemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 753
Author(s):  
Sébastien Thureau ◽  
Lucie Lebret ◽  
Justine Lequesne ◽  
Marine Cabourg ◽  
Simon Dandoy ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Squamous Cell ◽  
Nutritional Support ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Curative Intent ◽  
Free Survival ◽  
The Impact ◽  
Disease Free

Highlights: Sarcopenia is frequent in patients treated with radiation therapy (RT) or radiochemotherapy (RTCT) for head and neck squamous cell carcinomas. Sarcopenia is associated with poor disease-free survival and overall survival outcomes. Sarcopenia is not associated with a higher rate of treatment-related toxicity. Background: Sarcopenia occurs frequently with the diagnosis of head and neck squamous cell carcinoma (HNSCC). We aimed to assess the impact of sarcopenia on survival among HNSCC patients treated with radiotherapy (RT) or radiochemotherapy (RTCT). Methods: Patients treated between 2014 and 2018 by RT or RTCT with curative intent were prospectively included (NCT02900963). Optimal nutritional support follow-up, including weekly consultation with a dietician and an oncologist and daily weight monitoring, was performed. Sarcopenia was determined by measuring the skeletal muscles at the L3 vertebra on the planning CT scan for radiotherapy. For each treatment group (RT or RTCT), we assessed the prognostic value of sarcopenia for disease-free survival (DFS) and overall survival (OS) and its impact on treatment-related toxicity. Results: Two hundred forty-three HNSCC patients were included: 116 were treated by RT and 127 were treated by RTCT. Before radiotherapy, eight (3.3%) patients were considered malnourished according to albumin, whereas 88 (36.7%) patients were sarcopenic. Overall, sarcopenia was associated with OS and DFS in a multivariate analysis (HR 1.9 [1.1–3.25] and 1.7 [1.06–2.71], respectively). It was similar for patients treated with RT (HR 2.49 [1.26–4.9] for DFS and 2.24 [1.03–4.86] for OS), whereas for patients treated with RTCT sarcopenia was significantly associated with OS and DFS in univariate analysis only. Sarcopenia was not related to higher treatment-related toxicity. Conclusions: Pretherapeutic sarcopenia remains frequent and predicts OS and DFS for non-frail patients treated with curative intent and adequate nutritional support.

scholarly journals Comparison of salvage surgery for recurrent or residual head and neck squamous cell carcinoma

2019 ◽  
Vol 50 (3) ◽  
pp. 288-295 ◽  
Author(s):  
Takashi Maruo ◽  
Sadamoto Zenda ◽  
Takeshi Shinozaki ◽  
Toshifumi Tomioka ◽  
Wataru Okano ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Oropharyngeal Cancer ◽  
Salvage Surgery ◽  
Disease Free Survival ◽  
Chemoradiation Therapy ◽  
Locoregional Control ◽  
Free Survival ◽  
Concomitant Chemoradiation ◽  
Disease Free

Abstract Objective Concomitant chemoradiation therapy is a standard treatment for head and neck cancer. Thus, salvage surgery has become a necessary treatment. The aim of the study was to evaluate the results of salvage surgery by each site of the head and neck, especially the oropharynx, hypopharynx and larynx. Methods This was a retrospective, single-institute study. The primary endpoint was overall survival. Secondary endpoints were disease-free survival, the locoregional control rate after salvage surgery, the indication rate for salvage surgery, the reasons for contraindications to salvage surgery, the post-operative complication rate and the predictors of survival. Results Three-year overall survival after salvage surgery was 58.8% in the salvage surgery group and 8.59% in the other treatment group (P &lt; 0.0001). Regarding overall survival and disease-free survival after salvage surgery, there was no difference among sites. Regarding locoregional control rate among sites, there was no significant difference. The oropharyngeal cancer group had the lowest rate of salvage primary resection. Surgical margin and local and regional recurrence or residual disease were predictors on univariate and multivariate analyses. Conclusions Salvage surgery is effective for recurrent or residual cases after concomitant chemoradiation therapy. For oropharyngeal cancer, local control is important, and for oropharyngeal cancer and hypopharyngeal cancer, distant metastasis is important.

scholarly journals Mucosal Melanoma of the Head and Neck: Tata Memorial Hospital Experience

2010 ◽  
Vol 1 (3) ◽  
pp. 141-145 ◽  
Author(s):  
Vedang Murthy ◽  
Ashwini Budrukkar ◽  
Gupta Tejpal ◽  
Jai Prakash Agarwal ◽  
Suruchi Singh ◽  
...  
Keyword(s):  
Head And Neck ◽  
Surgical Resection ◽  
Adjuvant Radiotherapy ◽  
Disease Free Survival ◽  
Mucosal Melanoma ◽  
Locoregional Control ◽  
Free Survival ◽  
Tata Memorial Hospital ◽  
Aggressive Tumor ◽  
Disease Free

Abstract Background Primary mucosal melanoma of the head and neck (MMHN) is a rare, aggressive tumor of neural-crest origin. Despite universal progress in cancer care, the prognosis of MMHN continues to remain dismal. Aims To analyze and report the outcomes of primary head and neck mucosal melanomas treated at Tata Memorial Hospital. Methods Retrospective chart review of all patients with a diagnosis of nonocular MMHN presenting to the institute between 1995 to 2003. Locoregional control and disease-free survival were used as outcome measures. Results 42 patients presenting within the study period with nonocular MMHN (oral-55%, sinonasal-40%, and pharyngeal-5%) at a median age of 53 years constituted the demographic cohort. 11 (26%) patients not amenable to any active anticancer treatment were treated with best supportive care alone and excluded from outcome analysis. 26 patients underwent surgery with complete resection of tumor. Seven (27%) also received adjuvant radiotherapy due to the adverse histopathologic features. Two patients were treated with radical radiotherapy due to unresectability, two patients received palliative chemotherapy, while one patient was treated with definitive chemoradiotherapy. With a mean follow-up of 11 months (range 1-58 months), the 3-year locoregional control and disease-free survival was 41% and 12% respectively. Age, sex, site of primary, tumor stage, surgical resection, margin status, depth of infiltration, and adjuvant radiotherapy did not affect outcome significantly. Conclusion Primary mucosal melanoma of the head and neck is a rare, but, aggressive tumor with a dismal prognosis. Surgical resection with clear margins offers the best chance of cure for early localized disease. The high incidence of locoregional as well as distant failures after surgical resection supports the use of adjuvant therapy. Deeper insights into the pathobiology of disease can help develop more specific and effective treatment strategies to improve long-term outcomes.

809 Phase 2 trial of neoadjuvant and adjuvant PD-1 checkpoint blockade in local-regionally advanced, resectable HNSCC indicates pathological response is associated with high disease-free survival

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A859-A860
Author(s):  
Trisha Wise-Draper ◽  
Shuchi Gulati ◽  
Vinita Takiar ◽  
Sarah Palackdharry ◽  
Francis Worden ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Pathological Response ◽  
Intermediate Risk ◽  
Free Survival ◽  
Disease Free

BackgroundPatients with newly diagnosed, resected, head and neck squamous cell carcinoma (HNSCC) with high-risk (positive margins, extracapsular spread [ECE]) or intermediate-risk pathological features have an estimated 1-year disease free survival (DFS) of 65% and 69%, respectively.1 PD-1/PD-L1 immune checkpoint blockade has improved survival of patients with recurrent/metastatic HNSCC, and preclinical models indicate radiation upregulates PD-L1.2 Therefore, we hypothesized that pre and post-operative administration of the PD-1 inhibitor pembrolizumab would improve 1-year DFS for patients with resectable, loco-regionally advanced (clinical T3/4 and/or ≥2 nodal metastases) HNSCC (NCT02641093).MethodsEligible patients received pembrolizumab (200 mg I.V. x 1) 1-3 weeks before resection. Adjuvant pembrolizumab (q3 wks x 6 doses) was administered with weekly cisplatin (40mg/m2 X 6) and radiation (60-66Gy) for those with high-risk features and radiation alone for patients with intermediate-risk features. The primary endpoint was DFS, which was compared by log-rank test to historical controls (RTOG 9501). Evidence of pathological response to neoadjuvant pembrolizumab was evaluated by comparing pre- and post-surgical tumor specimens for treatment effect (TE) defined as tumor necrosis and/or histiocytic inflammation and giant cell reaction to keratinaceous debris. Response was classified as none (NPR, <20%), partial (PPR, ≥20% and <90%) and major (MPR, ≥90%) pathological response. Gene expression analysis in paired tumor specimens was evaluated by Nanostring.ResultsSixty-six of 84 enrolled patients had received adjuvant pembrolizumab and therefore were evaluable for DFS at the time of interim analysis. Patient characteristics included: median age 59 (range of 27 – 76) years; 30% female; 85% oral cavity, 11% larynx, and 2% human papillomavirus negative oropharynx; 85% clinical T3/4 and 68% ≥2N; 41(51%) high-risk (positive margins, 49%; ECE, 80%). At a median follow-up of 16 months, 1-year DFS was 66% (95%CI 0.48-0.84) in the high-risk group (p=1) and 91% (95%CI 0.79-1) in the intermediate-risk group (versus 69% in RTOG 9501, p=0.05) (figure 1). Among 70 patients evaluable for pathological response, TE was scored as NPR in 40, PPR in 27, and MPR in 3 patients. Patients with pathological response that were also evaluable for DFS (PPR + MPR) had significantly improved 1-year DFS when compared with those with NPR (100% versus 57%, p=0.0033; HR = 0.18 [95%CI 0.05-0.64]) (figure 2). PPR/MPR was associated with robust macrophage infiltration via Nanostring.Abstract 809 Figure 1Disease Free Survival by Pathological RiskPatients were stratified by pathological risk and DFS was measuredAbstract 809 Figure 2Disease Free Survival by Pathological ResponsePaired patient tissue was assessed for treatment effect (TE) and patients with greater than or equal to 20% TE were considered to have developed pathological response. Patients were stratified into responders and non-responders and DFS was determined.ConclusionsNeoadjuvant and adjuvant pembrolizumab led to high DFS in intermediate-risk, but not high-risk, resected HNSCC patients. Pathological response to neoadjuvant pembrolizumab was associated with high 1-year DFS.AcknowledgementsWe’d like to acknowledge the UCCC clinical trials office for their hard work on this study as well as our patients. We’d also like to acknowledge Merck & Co, Inc as they partially funded the clinical trial.Trial RegistrationNCT02641093Ethics ApprovalThis study was approved by the University of Cincinnati IRB with approval number 2015-6798ReferencesCooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350(19):1937-1944. doi:10.1056/NEJMoa032646Oweida A, Lennon S, Calame D, et al. Ionizing radiation sensitizes tumors to PD-L1 immune checkpoint blockade in orthotopic murine head and neck squamous cell carcinoma. Oncoimmunology2017;6(10):e1356153. Published 2017 Aug 3. doi:10.1080/2162402X.2017.1356153

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