Site of distant metastasis affects the prognosis with recurrent/metastatic head and neck squamous cell carcinoma patients treated with Nivolumab.

BACKGROUND: Nivolumab is approved for the treatment of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, the influence of the site of distant metastasis on the efficacy of immune checkpoint inhibitor in R/M HNSCC remains unclear. We investigated the prognosis of R/M HNSCC patients treated with nivolumab, focusing on the site of distant metastasis. METHODS: We reviewed the data of R/M HNSCC patients treated with nivolumab between April 2017 and June 2020 at Saitama Prefectural Cancer Center. The differences in the prognosis were evaluated according to the site of distant metastasis. RESULTS: Of the 41 patients enrolled, 26 (63.4%) had lung metastasis, 7 (17.1%) had bone metastasis, and 4 (9.8%) had liver metastasis. Ten patients (24.4%) had single-organ distant metastasis (lung metastasis in all cases). Univariate analysis identified lung metastasis alone (single-organ distant metastasis) was associated with a significantly better prognosis [HR0.37 (95% CI) 0.14-0.97 p = 0.04], while liver metastasis was associated with a significantly worse prognosis [HR3.86 (95% CI) 1.26-11.8 p = 0.02]. Multivariate analysis identified lung metastasis alone and liver metastasis as independent prognostic factors. While 7 patients (70%) with lung metastasis alone could be continued on nivolumab treatment or received subsequent chemotherapy, only 1 patient (25%) with liver metastasis received subsequent chemotherapy. CONCLUSION: The site of distant metastasis affects the prognosis of R/M HNSCC patients treated with nivolumab. Lung metastasis alone appears to be associated with a better prognosis, in that it allows easier transition to subsequent chemotherapy, while liver metastasis associates with a worse prognosis.

Stiffness as measured with strain elastography is a prognostic factor for pT1/T2 tongue squamous cell carcinoma with muscle-layer invasion.

OBJECTIVE: The objective was to evaluate stiffness as a prognostic factor for tongue squamous cell carcinoma (TSCC). STUDY DESIGN: This retrospective study included 55 patients with pathologic stage pT1 or T2 TSCC with muscle-layer invasion who underwent preoperative strain elastography of the tongue, followed by surgery, as the primary treatment modality at our cancer center. The stiffness of TSCC was semi-quantified as the ratio of the strain value of a non-tumor site to the strain value of the tumor site (strain ratio [SR]) using ultrasound strain elastography findings. RESULTS: SR cutoff values that maximized the significance of the difference for prognosis of delayed cervical lymph node metastasis (DCLNM) and overall survival (OS) were 7.10 and 7.49, respectively. In univariate analysis, SR, age, depth of invasion, pT stage, and perineural invasion were significant risk factors for DCLNM, whereas SR, sex, and DCLNM were identified as having an association with OS. In multivariate analysis, SR was a significant risk factor for DCLNM (hazard ratio [HR] = 3.102; P = .021) and a non-significant but relevant risk factor for OS (HR = 8.774; P = .073). Age also had an association with OS (HR = 0.382; 95% CI 0.127-1.152; P = .088). CONCLUSION: Tongue stiffness is a prognostic factor in patients with pT1/T2 TSCC with muscle-layer invasion. SR values >7.10 indicate a poor prognosis, thereby warranting a strict follow-up regimen in these cases.

Multicenter retrospective study of nivolumab for recurrent/metastatic oral squamous cell carcinoma.

OBJECTIVES: Immunotherapy with nivolumab for patients with recurrent/metastatic oral squamous cell carcinoma has not been evaluated. Here, we aimed to examine the efficacy, safety, and prognostic factors of nivolumab in these patients. MATERIALS AND METHODS: This multicenter retrospective observational study involved patients who received nivolumab between April 2017 and June 2019. The patient characteristics were evaluated for association with progression-free and overall survival. Progression-free and overall survival rates were calculated; parameters that were significant in the univariate analysis were used as explanatory variables. Independent factors for progression-free and overall survival were identified using multivariate analysis. RESULTS: Totally, 143 patients were included. The overall response and disease control rates were 27.3% and 46.2%, respectively. The median, 1- and 2-year progression-free survival rates were 2.7 months, 25.4%, and 19.2%, respectively; those for overall survival were 11.2 months, 47.3%, and 33.6%, respectively. The independent factors affecting progression-free survival were performance status and immune-related adverse event occurrence, whereas those affecting overall survival were performance status, target disease, and number of previous lines of systemic cancer therapy. Eight patients reported grade ≥3 immune-related adverse events. CONCLUSION: Nivolumab was effective for recurrent/metastatic oral squamous cell carcinoma treatment and was well tolerated by patients.

Protocol for a multicentre, prospective observational study of elective neck dissection for clinically node-negative oral tongue squamous cell carcinoma (END-TC study).

INTRODUCTION: In early-stage oral tongue squamous cell carcinoma (OTSCC), elective neck dissection (END) is recommended when occult lymph node metastasis is suspected; however, there is no unanimous consensus on the risks and benefits of END in such cases. The management of clinically node-negative (cN0) OTSCC remains controversial. This study, therefore, aimed to evaluate the efficacy of END and its impact on the quality of life (QoL) of patients with cN0 OTSCC. METHODS AND ANALYSIS: This is a prospective, multicentre, nonrandomised observational study. The choice of whether to perform END at the same time as resection of the primary tumour is based on institutional policy and patient preference. The primary endpoint of this study is 3-year overall survival. The secondary endpoints are 3-year disease-specific survival, 3-year relapse-free survival and the impact on patient QoL. Propensity score-matching analysis will be performed to reduce selection bias. ETHICS AND DISSEMINATION: This study was approved by the Clinical Research Review Board of the Nagasaki University. The protocol of this study was registered at the University Hospital Medical Information Network Clinical Trials Registry. The datasets generated during the current study will be available from the corresponding author on reasonable request. The results will be disseminated internationally, through scientific and professional conferences and in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: UMIN000027875.

Stiffness of tongue squamous cell carcinoma measured using strain elastography correlates with the amount of collagen fibers in the tumor.

OBJECTIVES: To evaluate the stiffness of tongue squamous cell carcinoma (TSCC) using ultrasound strain elastography, a relatively new sonographic imaging technique, and to identify the factors that affect this stiffness. METHODS: We treated 62 patients diagnosed with muscle invasive TSCC, who were treated at the department of oral surgery of our institution. Each patient's tumor stiffness was semi-quantified according to the ratio of cancer to tongue muscle strain measured using ultrasound strain elastography (the strain ratio). Histopathological diagnosis was made on the same section as the ultrasound strain elastography. We set the following histopathological parameters: cancer cell content in the tumor area (%CCC), collagen fiber content in the tumor area (%CFC), and tumor-infiltrating inflammatory cell content in the stromal compartment (%TIIC). Spearman's rank correlation (rs) was used to assess correlations, and P values < 0.05 were considered significant. RESULTS: The mean strain ratio was 9.7 ± 9.8. The mean %CCC was 38.4 ± 11.3%, and % CFC was 31.1 ± 7.8%, % TIICs was 19.9 ± 8.9%. Log (strain ratio) by ultrasound strain elastography was positively correlated with %CFC (rs = 0.379, P = 0.024). %CFC was negatively correlated with %TIICs (rs = - 0.318, P = 0.012). No correlations were observed between other clinico-histopathological factors and either strain ratio, or %CFC. CONCLUSION: The strain ratio of the cancer to the strain of the tongue muscle measured through ultrasound strain elastography positively correlates with the collagen fiber content of the tumor area.

General rules for clinical and pathological studies on oral cancer (2nd edition): a synopsis.

For doctors and other medical staff treating oral cancer, it is necessary to standardize the basic concepts and rules for oral cancer to achieve progress in its treatment, research, and diagnosis. Oral cancer is an integral part of head and neck cancer and is treated in accordance with the general rules for head and neck cancer. However, detailed rules based on the specific characteristics of oral cancer are essential. The objective of this article was to contribute to the development of the diagnosis, treatment, and research of oral cancer, based on the correct and useful medical information of clinical, surgical, pathological, and imaging findings accumulated from individual patients at various institutions. Our general rules were revised as the UICC was revised for the 8th edition and were published as the Japanese second edition in 2019. In this paper, the English edition of the "Rules" section is primarily presented.

Identification of highly sensitive biomarkers that can aid the early detection of pancreatic cancer using GC/MS/MS-based targeted metabolomics.

BACKGROUND: To improve prognosis of pancreatic cancer (PC) patients, the discovery of more reliable biomarkers for the early detection is desired. METHODS: Blood samples were collected by 2 independent groups. The 1st set was included 55 early PC and 58 healthy volunteers (HV), and the 2nd set was included 16 PC and 16HV. The 16 targeted metabolites were quantitatively analyzed by gas chromatography/tandem mass spectrometry together with their corresponding stable isotopes. In the 1st set, the levels of these metabolites were evaluated, and diagnostic models were constructed via multivariate logistic regression analysis, leading to validation using the 2nd set. RESULTS: In the 1st set, model X consisting of 4 candidates based on our previous report possessed higher sensitivity (74.1%) than carbohydrate antigen 19-9 (CA19-9). Model Y, consisting of 2 metabolites newly selected from 16 metabolites via stepwise method possessed higher sensitivity (70.4%) than CA19-9. Furthermore, combining model Y with CA19-9 increased its sensitivity (90.7%) and specificity (89.5%). In the 2nd set, combining model Y with CA19-9 displayed high sensitivity (81.3%) and specificity (93.8%). In particular, it displayed very high sensitivity (100%) for resectable PC. CONCLUSIONS: Quantitative analysis confirmed that metabolomics-based diagnostic methods are useful for detecting PC early.

Identification of IGFBP2 and IGFBP3 As Compensatory Biomarkers for CA19-9 in Early-Stage Pancreatic Cancer Using a Combination of Antibody-Based and LC-MS/MS-Based Proteomics.

Pancreatic cancer is one of the most lethal tumors, and reliable detection of early-stage pancreatic cancer and risk diseases for pancreatic cancer is essential to improve the prognosis. As 260 genes were previously reported to be upregulated in invasive ductal adenocarcinoma of pancreas (IDACP) cells, quantification of the corresponding proteins in plasma might be useful for IDACP diagnosis. Therefore, the purpose of the present study was to identify plasma biomarkers for early detection of IDACP by using two proteomics strategies: antibody-based proteomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics. Among the 260 genes, we focused on 130 encoded proteins with known function for which antibodies were available. Twenty-three proteins showed values of the area under the curve (AUC) of more than 0.8 in receiver operating characteristic (ROC) analysis of reverse-phase protein array (RPPA) data of IDACP patients compared with healthy controls, and these proteins were selected as biomarker candidates. We then used our high-throughput selected reaction monitoring or multiple reaction monitoring (SRM/MRM) methodology, together with an automated sample preparation system, micro LC and auto analysis system, to quantify these candidate proteins in plasma from healthy controls and IDACP patients on a large scale. The results revealed that insulin-like growth factor-binding protein (IGFBP)2 and IGFBP3 have the ability to discriminate IDACP patients at an early stage from healthy controls, and IGFBP2 appeared to be increased in risk diseases of pancreatic malignancy, such as intraductal papillary mucinous neoplasms (IPMNs). Furthermore, diagnosis of IDACP using the combination of carbohydrate antigen 19-9 (CA19-9), IGFBP2 and IGFBP3 is significantly more effective than CA19-9 alone. This suggests that IGFBP2 and IGFBP3 may serve as compensatory biomarkers for CA19-9. Early diagnosis with this marker combination may improve the prognosis of IDACP patients.