Tumor-stroma ratio in preoperative biopsies and matched surgical specimens in oral squamous cell carcinoma: Concordance and impact on recurrence-free and overall survival.

Stroma-richness is commonly associated with decreased survival times as well as advanced tumor stages in various malignant tumors. A previous study on laryngeal squamous cell carcinomas showed very good agreement for tumor-stroma ratio assessment between pre-treatment biopsies and resection specimens. We therefore aimed to determine whether similar results could be shown for oral squamous cell carcinomas. 107 preoperative biopsies and matched surgical specimens were obtained from the histological archive, dating from 2011-2022. Tumor-stroma ratio was determined on all samples and cases were divided into stroma-rich (≥50% stroma) and stroma-poor (<50% stroma). Results were then correlated with recurrence-free and overall survival. Tumor-stroma ratio showed substantial agreement between preoperative biopsies and surgical specimens with a kappa correlation coefficient of 0.643. Concerning preoperative biopsies, 28 cases were stroma-rich (26.2%), in the group of tumor resections, 32 cases were stroma-rich (29.9%). No association with either recurrence-free or overall survival could be shown for both groups (p-values 0.158-0.495). Concordance between pre-treatment biopsies and resections was substantial in our study, however, as no association with survival times could be demonstrated, the prognostic significance in our cohort remains unclear. This might be attributable to the fact that almost 75% of our patients presented with early-stage tumors, which sometimes seem to show a less pronounced prognostic effect of the tumor-stroma ratio.

Phase III study of nivolumab alone or combined with ipilimumab as immunotherapy versus standard of care in resectable head and neck squamous cell carcinoma.

Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) often requires postoperative chemoradiation with high risk of toxicity. Disease-free survival (DFS) after 2 years is approximately 70%. Combining nivolumab (N), a PD-1-inhibitor and ipilimumab (I), a CTLA4- inhibitor, may improve DFS due to antitumor effects of immunotherapy. The IMSTAR-HN study compares neoadjuvant N and N ± I 6 months after adjuvant therapy versus standard therapy as first-line treatment for LA-HNSCC. Eligible patients have treatment-naive LA-HNSCC, Eastern cooperative oncology group performance score (PS) ≤1 and no distant metastasis. 276 patients will be randomized into two arms. Primary endpoint is DFS and secondary endpoint includes locoregional control (LRC) and overall survival (OS). This study is one of the first in HNSCCs implementing immunotherapy in first-line treatment in a curative setting. Clinical Trial Registration: NCT03700905 (ClinicalTrials.gov).

Prognostic implications of the 8th edition American Joint Committee on Cancer (AJCC) staging system in oral cavity squamous cell carcinoma.

BACKGROUND: The American Joint Committee on Cancer (AJCC) has changed the staging system of oral squamous cell carcinoma (OSCC) in the 8th edition of its staging manual to include depth of invasion (DOI) of the primary tumor as a modifier to the T category and extranodal extension (ENE) to upstage node positive OSCC. This study aims to evaluate the performance of the AJCC 8 pathologic staging system in OSCC and compare it to its predecessor (AJCC 7). METHODS: Analysis of 663 patients with OSCC from a prospective database was performed using the Cox proportional hazards competing risk model. The prognostic performance of the pathologic staging system was assessed using the Akaike Information Criterion (AIC) and Harrell's concordance index (C-index). RESULTS: AJCC 8 led to upstaging of 35.6% (N = 235) of patients in this cohort. Both AJCC 7 and 8 show limited monotonicity and poor stratification between stage groups I to III. The estimates for model performance reveal that AJCC 8 has modest predictive capacity for overall survival (OS) and disease specific survival (DSS) (Harrell's C of 0.70 and 0.74, respectively) but is superior to AJCC 7 (Harrell's C of 0.65 and 0.69, respectively). CONCLUSIONS: The AJCC 8 staging system is more complex than its former version due to the inclusion of DOI and ENE. Compared with AJCC 7, it performs better in stratifying survival of OSCC patients by stage.

Analysis and Comparison of the 8th Edition American Joint Committee on Cancer (AJCC) Nodal Staging System in Cutaneous and Oral Squamous Cell Cancer of the Head and Neck.

BACKGROUND: The American Joint Committee on Cancer (AJCC) uses the same nodal staging system for cutaneous and mucosal squamous cell carcinoma of the head and neck in its 8th edition (AJCC 8) despite differences in the etiology, risk factors, and clinical behavior of the two diseases. This study aims to evaluate the performance of the AJCC 8 nodal staging system by direct comparison of cutaneous (cSCC) versus oral squamous cell carcinoma (oSCC) patients. METHODS: Patients with metastatic cSCC (N = 382) and oSCC (N = 325) were identified from a prospective database (years 1987-2016). Multivariable analysis was performed using Cox proportional hazards competing risk model. To assess staging system performance, an explained variation measure (proportion of variation explained, PVE) as well as a discrimination measure (Harrell's concordance index, C-index) were used. RESULTS: Inclusion of extranodal extension (ENE) in AJCC 8 increased the proportion of patients in N3b category (48.7% in cSCC, 40.3% in oSCC). AJCC 8 stratified poorly with regards to risk of death from cSCC and oSCC and showed limited monotonicity of the nodal categories. Estimates of model performance revealed modest predictive capacity for overall survival (OS) and disease-specific survival (DSS) in oSCC (Harrell's C of 0.66 in both) and weak predictive capacity in cSCC (Harrell's C of 0.58 and 0.61, respectively). CONCLUSIONS: The AJCC 8 nodal staging system performs poorly in terms of stratifying survival by N category, especially in cSCC. The data indicate that cSCC merits an independent nodal staging system from that for mucosal SCC.

Tumor thickness versus depth of invasion - Analysis of the 8th edition American Joint Committee on Cancer Staging for oral cancer.

OBJECTIVES: The primary aim of this study is to compare the effect of using tumor thickness versus depth of invasion (DOI) to determine the 8th edition AJCC T-category on survival in a large cohort of OSCC. MATERIALS AND METHODS: A retrospective cohort study of patients whose clinicopathologic information had been collected prospectively into a dedicated head and neck database. 927 patients with oral SCC were identified in this cohort, with the final study population including 456 patients with complete information on DOI, tumor thickness, T and N staging and follow-up. RESULTS: 26 (5.7%) patients had a different AJCC 8 T category when using thickness instead of depth. 15 were upstaged from T1 to T2, 10 upstaged from T2 to T3 and 1 down staged from T2 to T1. Additionally, similar stratification of disease-specific and overall survival curves were found for T category based on DOI and thickness. CONCLUSION: The T category and TNM stage prognostic performance of 8th edition AJCC staging of oral cancer is similar regardless of whether DOI or thickness is used as the T-category modifier. In centers without complete DOI data it is reasonable to impute thickness for retrospective survival analyses using the 8th edition of the AJCC staging system.