Advanced lung cancer inflammation index and its prognostic value in HPV-negative head and neck squamous cell carcinoma: a multicentre study.

PURPOSE: The aim of this study is to evaluate the prognostic value of pre-treatment advanced lung cancer inflammation index (ALI) in patients with HPV-negative HNSCC undergoing up-front surgical treatment. METHODS: The present multi-centre, retrospective study was performed in a consecutive cohort of patients who underwent upfront surgery with or without adjuvant (chemo)-radiotherapy for head and neck squamous cell carcinoma (HNSCC). Patients were stratified by ALI, and survival outcomes were compared between groups. In addition, the prognostic value of ALI was compared with two other indices, the prognostic nutritional index (PNI) and systemic inflammatory index (SIM). RESULTS: Two hundred twenty-three patients met the inclusion criteria (151 male and 72 female). Overall and progression-free survival were significantly predicted by ALI < 20.4 (HR 3.23, CI 1.51-6.90 for PFS and HR 3.41, CI 1.47-7.91 for OS). Similarly, PNI < 40.5 (HR = 2.43, 95% CI: 1.31-4.51 for PFS and HR = 2.40, 95% CI: 1.19-4.82 for OS) and SIM > 2.5 (HR = 2.51, 95% CI: 1.23-5.10 for PFS and HR = 2.60, 95% CI: 1.19-5.67 for OS) were found to be significant predictors. Among the three indices, ALI < 20.4 identified the patients with the worst 5-year outcomes. Moreover, patients with a combination of low PNI and low ALI resulted to be a better predictor of progression (HR = 5.26, 95% CI: 2.01-13.73) and death (HR = 5.68, 95% CI: 1.92-16.79) than low ALI and low PNI considered alone. CONCLUSIONS: Our results support the use of pre-treatment ALI, an easily measurable inflammatory/nutritional index, in daily clinical practice to improve prognostic stratification in surgically treated HPV-negative HNSCC.

Impact of the SARS-CoV-2 pandemic on the diagnostic delay of oral carcinoma: a retrospective analysis.

BACKGROUND: The aim of the present study was to investigate how the organisation of healthcare activity during the first wave of the SARS-CoV-2 pandemic affected the timing of diagnosis of oral carcinoma in the Functional Head and Neck Department of Padua (Italy). This study gives an effective temporal dimension of the diagnostic delay that occurred during the pandemic, compared with data from the literature. METHODS: A retrospective analysis of the diagnostic path of a patient affected by oral cancer during COVID-19 pandemic was performed. The time elapsed from the patient's awareness of the problem to the first curative surgical intervention was considered both during the blockage of elective care activities and in the period immediately following. The results were compared to a group of patients treated in the same period of the year 2019. RESULTS: The territorial time was 53.9% longer in the post-lockdown period than in the lockdown period (39.6 days) while the hospital time was 56.6% shorter than in the post-lockdown period (56 days). CONCLUSIONS: The response time of territorial medicine has been longer during the pandemic peak. The unintentional creation of exclusive pathways for oncological patients speeded up the diagnostic process. The organization and accessibility of operating theatres can become particularly problematic during the acute phases of a pandemic.

Multicentre study on resection margins in carcinoma of the oral cavity, oro-hypopharynx and larynx.

Objective: The prognostic significance of the resection margins is still subject of conflicting opinions. The purpose of this paper is to report the results of a study on the margins in carcinoma of the oral cavity, oro-hypopharynx and larynx. Methods: A multicentre prospective study was carried out between 2015 and 2018 with the participation of 10 Italian reference hospitals. The primary objective was to evaluate local control in patients with well-defined clinical characteristics and comprehensive histopathological information. Results: During the study period, 455 patients were enrolled; the minimum follow-up was 2 years. Previous treatment, grading and fresh specimen examination were identified as risk factors for local control in multivariate analysis. On the basis of these results, it seems possible to delineate "risk profiles" for different oncological outcomes. Discussion: The prognostic significance of the margins is reduced, and other risk factors emerge, which require diversified treatment and follow-up. Conclusions: Multidisciplinary treatment with adjuvant therapy, if indicated, reduces the prognostic importance of margins. Collaboration with a pathologist is an additional favourable prognostic factor and quality indicator.An appendix with literature review is present in the online version.

Safety of boneless reconstruction of the mandible with a CAD/CAM designed titanium device: The replica cohort study.

OBJECTIVE: We evaluated the safety of REPLICA, a CAD/CAM-designed patient-specific titanium mandible, in patients with mandibular defects not suitable for reconstruction with traditional techniques. PATIENTS AND METHODS: We performed a cohort study with a composite primary outcome assigned at the end of a 1-year follow-up. The outcome was assigned in the presence of all the following: 1) absence of intraoral or skin extrusion of REPLICA; 2) decrease or cessation of oral pain; 3) stability or increase in mouth opening; 4) resumption of oral feeding without the need of nasogastric tube; 5) absence of fracture at multidetector computer tomography (MDCT); 6) absence of displacement (MDCT); 7) absence of screw loosening (MDCT). The secondary outcome was the patient-reported QOL at 6 months of follow-up as detected by the EORTC QLQ-C30 and QLQ-H&N35 questionnaires. RESULTS: Between March 2012 and June 2017, 18 consecutive patients, with a median (IQR) age of 67 (65;74) underwent reconstruction of mandibular defects with REPLICA at our Unit. The primary outcome was reached by 14 of the 18 patients. QOL data were available for 15 patients at the 6-month follow-up, showing a good profile of general and disease-specific QOL. CONCLUSION: REPLICA offered a safe solution at 1-year for the treatment of mandibular defects not suitable for reconstruction with traditional techniques, and was associated with subjective well-being and satisfaction. Further studies are needed to assess the full range of indications of REPLICA.

[18F]FDG PET/MRI versus contrast-enhanced MRI in detecting regional HNSCC metastases.

OBJECTIVE: To compare the accuracy of contrast-enhanced MRI using established dimensional and morphological criteria versus integrated [18F]FDG PET/MRI in identifying regional lymph node metastases in patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC). For this purpose, we compare MRI and PET/MRI using the histopathological findings in dissected lymph nodes as the gold standard. METHODS: We retrospectively reviewed 26 patients with histologically proven HNSCC who underwent gadolinium-enhanced [18F]FDG PET/MRI as part of their staging. All neck lymph nodes were classified on MRI using dimensional and/or morphological criteria. Then, they were jointly assessed by a nuclear medicine physician and a radiologist using integrated [18F]PET/MR images. ROC curves were obtained to compare the techniques. Lymph node histopathology was considered as the reference standard. RESULTS: Out of 865 lymph nodes, 35 were malignant at histopathology (3 with micro-metastases). Sensitivity and specificity were 48.6% and 99.5% for MRI using dimensional criteria; 60.0% and 99.6% for MRI using morphological criteria; 60.0% and 99.4% for MRI using both; and 74.3% and 97.6% for PET using MR as anatomic localization. The area under the ROC curve was higher for PET and MRI localization (0.859) than for MRI using dimensional (0.740; p < 0.05), or morphological (0.798; p < 0.05), or both criteria (0.797; p < 0.05). PET/MR using a PET SUVmax cutoff of 5.7 combined with MRI using dimensional and/or morphological criteria reached high values for accuracy (98.2%), NPV (98.2%), and PPV (95.2%). CONCLUSIONS: Compared with traditional contrast-enhanced MRI or PET alone, integrated PET/MRI could improve diagnostic accuracy in detecting metastatic lymph nodes in patients with HNSCC.

TERT Promoter Mutations and rs2853669 Polymorphism: Useful Markers for Clinical Outcome Stratification of Patients With Oral Cavity Squamous Cell Carcinoma.

OBJECTIVE: To date, no useful prognostic biomarker exists for patients with oral squamous cell carcinoma (OCSCC), a tumour with uncertain biological behaviour and subsequent unpredictable clinical course. We aim to investigate the prognostic significance of two recurrent somatic mutations (-124 C>T and -146 C>T) within the promoter of telomerase reverse transcriptase (TERT) gene and the impact of TERT single nucleotide polymorphism (SNP) rs2853669 in patients surgically treated for OCSCC. METHODS: The genetic frequencies of rs2853669, -124 C>T and -146 C>T as well as the telomere length were investigated in 144 tumours and 57 normal adjacent mucosal (AM) specimens from OCSCC patients. RESULTS: Forty-five tumours harboured TERT promoter mutations (31.3%), with -124 C>T and -146 C>T accounting for 64.4% and 35.6% of the alterations respectively. Patients with -124 C>T TERT promoter mutated tumours had the shortest telomeres in the AM (p=0.016) and showed higher risk of local recurrence (hazard ratio [HR]:2.75, p=0.0143), death (HR:2.71, p=0.0079) and disease progression (HR:2.71, p=0.0024) with the effect being potentiated by the co-occurrence of T/T genotype of rs2853669. CONCLUSION: -124 C>T TERT promoter mutation as well as the T/T genotype of the rs2853669 SNP are attractive independent prognostic biomarkers in patients surgically treated for OCSCC, with the coexistence of these genetic variants showing a synergistic impact on the aggressiveness of the disease.

Postoperative radiotherapy for laryngeal cancer. The prognostic role of programmed death-ligand 1: An immune microenvironment-based cluster analysis.

BACKGROUND: The prognostic role of programmed death-ligand 1 (PD-L1) expression and the tumor's immune microenvironment has yet to be investigated in the specific setting of adjuvant postoperative radiotherapy (PORT) for laryngeal carcinoma (LSCC). The main aim of this exploratory study was to investigate, also by cluster analysis, whether PD-L1 expression (in terms of combined positive score [CPS]), tumor-infiltrating lymphocytes (TIL), and tertiary lymphoid structures (TLS) correlated prognostically with response to PORT in a cohort of consecutive LSCC patients. METHODS: PD-L1, TIL and TLS were assessed in 24 consecutive patients with LSCC who underwent PORT. Cluster analysis was used to classify cases on the strength of these parameters. RESULTS: A CPS ≥ 1 was associated with a significantly lower recurrence rate (p = 0.033), and longer disease-free survival (DFS) (p = 0.012) than a CPS < 1. Two clusters of prognostic relevance emerged from our analysis. Cluster 1 was characterized by a mean CPS of 23.0 ± 37.9, a mean TIL count of 68.0 ± 16.4, and the presence of TLS in all cases. Cluster 2 featured a mean CPS of 3.1 ± 7.3, a mean TIL count of 23.9 ± 16.5, and no cases with TLS. Cluster 1 showed a trend towards a lower recurrence rate (p = 0.071) and longer DFS (p = 0.054) than cluster 2. CONCLUSIONS: Judging from this preliminary investigation, assessing PD-L1 and immune microenvironment markers seems a promising approach for identifying patients at higher risk of LSCC recurrence after PORT, who might reasonably benefit from adjuvant postoperative chemo-RT, or immunotherapy.

ß-Arrestin-1 expression and epithelial-to-mesenchymal transition in laryngeal carcinoma.

AIM: The novel primary end-point of the present study was to ascertain ß-arrestin-1 expression in a cohort of consecutive patients with laryngeal squamous cell carcinoma (LSCC) with information available on their cigarette-smoking habits. A secondary end-point was to conduct a preliminary clinical and pathological investigation into the possible role of ß-arrestin-1 in the epithelial-to-mesenchymal transition (EMT), identified by testing for E-cadherin, Zeb1, and Zeb2 expression, in the setting of LSCC. METHODS: The expression of ß-arrestin-1, E-cadherin, zeb1, and zeb2 was ascertained in 20 consecutive LSCCs. RESULTS: Statistical analysis showed no significant associations between ß-arrestin-1 and EMT (based on the expression of E-cadherin, Zeb1, and Zeb2). The combined effect of nicotine and ß-arrestin-1 was significantly associated with a shorter disease-free survival ( P=0.01) in our series of LSCC. This latter result was also confirmed in an independent, publicly available LSCC cohort ( P=0.047). CONCLUSIONS: Further investigations on larger series (ideally in prospective settings) are needed before we can consider closer follow-up protocols and/or more aggressive treatments for patients with LSCC and a combination of nicotine exposure and ß-arrestin-1 positivity in tumor cells at the time of their diagnosis. Further studies on how ß-arrestin functions in cancer via different signaling pathways might reveal potential targets for the treatment of even advanced laryngeal malignancies.

Relaxin-2 expression in oral squamous cell carcinoma.

BACKGROUND: When advanced, oral squamous cell carcinoma (OSCC) may involve adjacent non-epithelial structures, and the prognosis is worse for bone invasion. Human relaxin-2 is a peptide hormone that has recently been associated with cancer. It can induce human osteoclast differentiation and activation, suggesting a role in tumor-driven osteolysis. This study was a preliminary assessment of the prognostic role of relaxin-2 in surgical specimens of OSCC tissue and adjacent but uninvolved mandibular/maxillary bone. METHODS: Relaxin-2 immunohistochemical expression and reaction intensity were assessed in tumor and uninvolved adjacent mandibular/maxillary bone specimens from 23 operated OSCC patients. RESULTS: All OSCC specimens were positive for relaxin-2. The intensity of its reaction in OSCC correlated significantly with the pattern of the tumor's invasion front (p = 0.02), being higher with the infiltrative pattern. Mean relaxin-2 immunohistochemical expression was higher in patients whose OSCC recurred after treatment than those experiencing no recurrence (81.3% ± 22.6% vs. 59.5% ± 29.7%, respectively). A significant direct association emerged between relaxin-2 expression in OSCC specimens and recurrence rate (p = 0.049). CONCLUSIONS: Relaxin-2 expression in OSCC should be further investigated as a potentially useful marker for identifying patients at higher risk of recurrence, who might benefit from closer follow-up and more aggressive adjuvant therapy. In other oncological settings, increasing evidence of relaxin being produced by cancer cells is prompting efforts to synthesize human relaxin-2 analogs capable of acting as antagonists and limiting tumor growth.

Parotid localized Castleman's disease and HHV-8 infection: a case report.

Castleman's disease (CD) is an unusual massive proliferation of lymphoid tissue distinct in two clinical forms, localized and multicentric. The multicentric form has been related to human herpesvirus 8 (HHV-8), especially in HIV-infected patients, whereas the localized form of CD is still unrelated to viral pathogens. We report a case of a HIV-negative 16-year-old male referred to our hospital with a 12-month history of a painless swelling in his right parotid region. A parotidectomy was performed, and histological analysis evidenced a localized CD. The search for HHV-8 revealed an active virus infection. The patient was commenced on corticosteroid therapy and a follow-up was performed every 6 months. The patient was commenced on corticosteroid therapy and there has been no recurrence after 24 months. The authors report a case of localized parotid CD in a patient with evidence of an active HHV-8 infection. The results of this study does for the first time suggest an association between HHV-8 and localized CD in HIV-negative subjects.