Pathogenetic, Diagnostic and Therapeutic Perspectives in Head and Neck Cancer

Background and purpose: Muscle loss is a significant indicator of cancer cachexia and is associated with a poor prognosis in cancer patients. Given the absence of comparable studies, the current retrospective study sought to examine the correlation between the total masseter muscle volume (TMMV) before treatment and the survival outcomes in locally advanced nasopharyngeal cancer (LA-NPC) patients who received definitive concurrent chemoradiotherapy (CCRT). Methods: A three-dimensional segmentation model was used to determine the TMMV for each patient by analyzing pre-CCRT magnetic resonance imaging. The optimal TMMV cutoff values were searched using receiver operating characteristic (ROC) curve analyses. The primary and secondary endpoints were the relationship between the pre-CCRT TMMV measures and overall survival (OS) and progression-free survival (PFS), respectively. Results: Ninety-seven patients were included in this study. ROC curve analyses revealed 38.0 cc as the optimal TMMV cutoff: ≤38.00 cc (n = 42) and >38.0 cc (n = 55). Comparisons between the two groups showed that the TMMV>38.0 cc group had significantly longer PFS [Not reached (NR) vs. 28; p < 0.01] and OS (NR vs. 71; p < 0.01) times, respectively. The results of the multivariate analysis demonstrated that the T-stage, N-stage, number of concurrent chemotherapy cycles, and TMMV were independent associates of PFS (p < 0.05 for each) and OS (p < 0.05 for each) outcomes, respectively. Conclusion: The findings of the current retrospective research suggest that pretreatment TMMV is a promising indicator for predicting survival outcomes in LA-NPC patients receiving definitive CCRT. Full article

Background: maxillary bone invasion (MBI) is not uncommon in hard palate or upper alveolus (HP/UA) cancer; however, there have been relatively few reports about the MBI of HP/UA cancer. Patients and Methods: this was a multi-center retrospective study, enrolling 144 cases of HP/UA cancer. MBI was defined by surgical pathology or radiology follow-up. The multiple prediction models for MBI were developed in total cases and in cases having primary bone resection, using clinical and radiological variables. Results: computerized tomography (CT) alone predicted MBI, with an area under receiver operating curve (AUC) of 0.779 (95% confidence interval (CI) = 0.712–0.847). The AUC was increased in a model that combined tumor dimensions and clinical factors (male sex and nodal metastasis) (0.854 (95%CI = 0.790–0.918)). In patients who underwent ¹⁸fluorodeoxyglucose positron emission tomography/CT (PET/CT), the discrimination performance of a model including the maximal standardized uptake value (SUVmax) had an AUC of 0.911 (95%CI = 0.847–0.975). The scoring system using CT finding, tumor dimension, and clinical factors, with/without PET/CT SUVmax clearly distinguished low-, intermediate-, and high-risk groups for MBI. Conclusion: using information from CT, tumor dimension, clinical factors, and the SUVmax value, the MBI of HP/UA cancer can be predicted with a relatively high discrimination performance. Full article

Aims: Oral squamous cell carcinoma (OSCC) frequently invades the jaw. The exact mechanism of bone invasion remains unclear. This study investigates (premature) osteoclasts and the expression of its differentiation regulating proteins RANKL, OPG and RANK in patients with OSCC. Methods: Resection specimens from OSCC patients were divided into NI group (No Invasion), E group (Erosion) or I group (bone Invasion). Tissue sections were stained with Cathepsin K (osteoclast-counting), RANKL, OPG and RANK. The staining intensity was scored on different regions of the tumor: front, center, back and normal mucosa. Immunohistochemistry and qPCR for RANKL/OPG/RANK were performed on five head and neck squamous cell carcinoma (HNSCC) organoids. Results: The mean number of osteoclasts (I group) and premature osteoclasts (E group) was significantly higher compared to the NI group (p = 0.003, p = 0.036). RANKL expression was significantly higher in the tumor front and tumor center compared to normal mucosa (all groups). In the I group, RANKL and RANK expression was significantly higher in the tumor front compared to the tumor back and there was a trend of higher RANKL expression in the tumor front compared to the E group and NI group. qPCR showed a 20–43 times higher RANKL mRNA expression in three out of five tumor organoids compared to a normal squamous cell organoid line. There was no correlation between protein and mRNA expression in the HNSCC organoids. Conclusions: These findings suggest that OSCCs induce bone invasion by stimulating osteoclast activation by regulating the production of RANKL and RANK proteins. Full article

Horizontal glottectomy (HG) is a particular type of partial laryngectomy indicated for exclusive glottic tumor with anterior commissure involvement. The purpose of this study is to systematically review the literature about functional and oncological outcome of HG. This systematic review adhered to the recommendations of the PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-analysis) 2009 guidelines. Articles mentioning patients undergoing HG for laryngeal squamous cell carcinoma were included. A total of 14 articles were selected and reviewed from 19 identified. The whole study population consisted of 420 patients who underwent HG. Three hundred and thirty-nine patients out of 359 were staged as T1. The range of post-operative follow-up was 5 months to 10 years. Fifty-five recurrences were experienced, being local, regional and distant in 35, 12 and 8 patients, respectively. Laryngeal preservation rate was 93.6%. Nasogastrict tube was removed on average after 10.1 days. The tracheostomy was maintained for 11.3 days. Mean hospitalization lasted for 11.7 days. According to the results of this systematic review, HG is an oncologically safe surgical option for T1a–T1b glottic tumors with oncological outcomes comparable to other treatment. HG could be a good therapeutical choice whenever poor laryngeal exposure and/or patient’s refusal of radiotherapy are encountered, or when patient’s medical history represents a contraindication for radiation therapy. Full article

Background: Cisplatin (CDDP) is a major ototoxic chemotherapy agent for head and neck squamous cell carcinoma (HNSCC) treatment. Clinicopathological features and genotypes encode different stages of CDDP metabolism, as their coexistence may influence the prevalence and severity of hearing loss. Methods: HNSCC patients under CDDP chemoradiation were prospectively provided with baseline and post-treatment audiometry. Clinicopathological features and genetic variants encoding glutathione S-transferases (GSTT1, GSTM1, GSTP1), nucleotide excision repair (XPC, XPD, XPF, ERCC1), mismatch repair (MLH1, MSH2, MSH3, EXO1), and apoptosis (P53, CASP8, CASP9, CASP3, FAS, FASL)-related proteins were analyzed regarding ototoxicity. Results: Eighty-nine patients were included, with a cumulative CDDP dose of 260 mg/m². Moderate/severe ototoxicity occurred in 26 (29%) patients, particularly related to hearing loss at frequencies over 3000 Hertz. Race, body-mass index, and cumulative CDDP were independent risk factors. Patients with specific isolated and combined genotypes of GSTM1, GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A, EXO1 c.1762G>A, MSH3 c.3133A>G, FASL c.-844A>T, and P53 c.215G>C SNVs had up to 32.22 higher odds of presenting moderate/severe ototoxicity. Conclusions: Our data present, for the first time, the association of combined inherited nucleotide variants involved in CDDP efflux, DNA repair, and apoptosis with ototoxicity, which could be potential predictors in future clinical and genomic models. Full article

Cancer metastasis is a main cause of failure in treating subjects with nasopharyngeal carcinoma (NPC) and is frequently linked to high death rates. EF-24, an analog of curcumin, has exhibited many anti-cancer properties and enhanced bioavailability over curcumin. Nevertheless, the effects of EF-24 on the invasiveness of NPC are poorly understood. In this study, we demonstrated that EF-24 effectively inhibited TPA-induced motility and invasion responses of human NPC cells but elicited very limited cytotoxicity. In addition, the TPA-induced activity and expression of matrix metalloproteinase-9 (MMP-9), a crucial mediator of cancer dissemination, were found to be reduced in EF-24-treated cells. Our reporter assays revealed that such a reduction in MMP-9 expression by EF-24 was transcriptionally mediated by NF-κB via impeding its nuclear translocation. Further chromatin immunoprecipitation assays displayed that the EF-24 treatment decreased the TPA-induced interaction of NF-κB with the MMP-9 promoter in NPC cells. Moreover, EF-24 inhibited the activation of JNK in TPA-treated NPC cells, and the treatment of EF-24 together with a JNK inhibitor showed a synergistic effect on suppressing TPA-induced invasion responses and MMP-9 activities in NPC cells. Taken together, our data demonstrated that EF-24 restrained the invasiveness of NPC cells through the transcriptional suppression of MMP-9 gene expression, implicating the usefulness of curcumin or its analogs in controlling the spread of NPC. Full article