Head And Neck Carcinoma Research Articles

HYPCON trial: A phase II randomized study evaluating hypofractionated versus conventional adjuvant radiation therapy in head and neck malignancies.

143 Background: Hypofractionated RT has been established as standard of care at many cancer sites but there is limited data on use of hypofractionated RT for head and neck carcinomas (HNC). The HYPCON trial (CTRI/2023/02/049804) tested to reduce 10 fractions of PORT by delivery of hypofractionated PORT. Methods: Patients of HNC after radical surgery, with intermediate risk factors, were randomized based on site, T and N stage to either standard fractionation arm A (60Gy/30 fractions/6 weeks) or hypofractionated arm B (50Gy/20 fractions/4 weeks) in a 1:2 manner. The minimum sample size for the study was estimated based on a non-inferiority trial design as 120 considering a 10% clinical effectiveness margin and 5% attrition. Treatment allocation was done based on T stage, N stage & HNC subsite. Target delineation included tumour bed with adequate margins (CTV_P) and microscopic lymph nodal (CTV_N) basin at risk. Organ delineation included all DARS. A double arc swallowing-sparing IMRT was used in both arms. The primary endpoint was locoregional control (LRC) at 1 year. Compliance, RT time (RTT), overall treatment time (OTT), progression-free survival (PFS) and overall survival (OS) were calculated in all patients. Acute & late toxicities were recorded as per RTOG scale. Results: 135 patients were enrolled, 45 in Arm A & 90 in Arm B. Majority of patients (96.9%) had oral cavity primary. Most of patients 74.8 % had early-stage disease. Compliance to PORT was 91.1% in Arm A versus 100% in Arm B. Median RTT for Arm A was 43 days (25-73 days) and 28 days (25-43 days) for Arm B (p<0.0001). Median OTT in Arm A was 91 days (70-126 days) and 77 days (57-119 days) in Arm B (p<0.0001). Median follow-up was 12.7 (2.73-23.87) months. One year, LRC was 72.9% vs 91.6% (p=0.007); PFS was 70.6% vs 90.5% (p=0.009) and OS was 88.7% vs 94.5% (p 0.02) Arm A versus Arm B respectively. Grade 3 or higher acute toxicity was seen in 39% in Arm A and 31.1% in Arm B (p=0.374). Grade 3 or higher late toxicity events were noted in 29.2% and 32.2% in arms A and B respectively (p= 0.671). Conclusions: Hypofractionated PORT reduced RTT & OTT and was associated with improved treatment compliance, treatment outcomes (LRC, PFS, OS), and similar acute and late toxicity profile. This is the first study to demonstrate the superiority of hypofractionated compared to conventional PORT delivery for HNC. Clinical trial information: CTRI/2023/02/049804 .

Glutathione S-transferase theta 1 (GSTT1) deletion polymorphism and susceptibility to head and neck carcinoma: a systematic review with five analyses

Glutathione S-transferase theta 1 (GSTT1) enzyme plays a key role in the neutralization of electrophilic compounds such as carcinogens. Herein, we aimed to evaluate GSTT1 deletion polymorphism and susceptibility to head and neck carcinoma (HNC) according to 107 articles in a systematic review with five analyses. The databases of PubMed/Medline, Web of Science, Scopus, and Cochrane Library from the beginning of each database until June 21, 2023, with no restrictions to identify pertinent articles. The RevMan 5.3 software was used to calculate the effect sizes, which were displayed as the odds ratio (OR) along with a 95% confidence interval (CI). Both the publication bias and sensitivity analyses were performed using the CMA 3.0 software. A trial sequential analysis (TSA) was conducted. Of the 1966 records retrieved from four databases, 107 articles were included in the analysis. The combined analysis revealed that the pooled OR was 1.28 (95% CI: 1.14 to 1.44; p-value < 0.0001). The pooled OR was highest in mixed ethnicity. Nasopharyngeal cancer had the highest OR (1.84), followed by oral cancer (OR = 1.20), and laryngeal cancer (OR = 1.17). Studies with less than 200 samples had a higher OR compared to those with 200 or more samples. The studies with a quality score of 7 or more had a higher OR compared to those with a score of less than 7. When both age and sex are considered, while the OR of 1.42 is significant, the high heterogeneity suggests caution in interpreting these results. There is no evidence of publication bias. TSA reported that the study does not have sufficient statistical power. This comprehensive meta-analysis revealed a significant association between the GSTT1 null genotype and an increased risk of HNC, with variations based on factors such as ethnicity, cancer type, sample size, control source, and quality score.

Weekly assessment of volumetric and dosimetric changes during volumetric modulated arc therapy of locally advanced head and neck carcinoma: Implications for adaptive radiation therapy-A prospective study.

Chemoradiation in head and neck carcinoma (HNC) shows significant anatomical resulting in erroneous dose deposition in the target or the organ at risk (OAR). Adaptive radiotherapy (ART) can overcome this. Timing of significant target and OAR changes with dosimetric impact; thus, most suitable time and frequency of ART is unclear. This dosimetric study used prospective weekly non-contrast CT scans in 12 HNC patients (78 scans). OARs and TVs were manually contoured after registration with simulation scan. Dose overlay done on each scan without reoptimization. Dosimetric and volumetric variations assessed. Commonest site was oropharynx. Gross Tumor Volume (GTV) reduced from 47.5 ± 19.2 to 17.8 ± 10.7 cc. Nodal GTV reduced from 15.7 ± 18.8 to 4.7 ± 7.1 cc. Parotid showed mean volume loss of 35%. T stage moderately correlated with GTV regression. Maximum GTV changes occurred after 3 weeks. Best time to do single fixed interval ART would be by the end of 3 weeks.

PTEN Deregulation Mechanisms in Salivary Gland Carcinomas.

Among the tumour suppressor genes that affect critically cell functions and homeostasis, phosphatase and tensin homolog deleted in chromosome 10 (PTEN- gene locus: 10q21) regulates the PI3K/Akt/mTOR signalling pathway. PTEN is deleted, mutated or epigenetically hyper-methylated in a variety of human solid malignancies. Salivary gland carcinomas (SGCs) belong to the head and neck carcinomas (HNCs) super category of solid malignancies. Histo-pathologically, they demonstrate a significant diversity due to a variety of distinct and mixed subtypes. Genetically, they are characterized by a broad spectrum of gene and chromosomal imbalances. Referring specifically to suppressor genes, PTEN deregulation plays a critical role in signaling transduction in the corresponding SGC pre- and malignant epithelia modifying the response rates to potential targeted therapeutic strategies. In the current review, we explored the role of PTEN deregulation mechanisms that are involved in the onset and progression of SGCs.

Prognostic value of diabetes and metformin use in a real-life population of head and neck cancer patients.

Head and neck carcinoma (HNC) is a disease with a poor prognosis despite currently available treatments. The management of patients with this tumor is often complicated by several comorbidities. Among these, diabetes is the second most frequent and its influence on the prognosis is not known. In this work, we collected data on progression free survival (PFS) and overall survival (OS) of one hundred twenty-three patients with HNC who received biweekly cetuximab maintenance treatment after first-line chemotherapy. We then compared the survival of nondiabetic patients versus diabetics' one. Surprisingly, both PFS (4 vs. 5 months, HR 2.297, p < 0.0001) and OS (7 vs. 10 months, HR 3.138, p < 0.0001) were in favor of diabetic patients, even after excluding other clinical confounding factors. In addition, we also studied survivals in patients taking metformin, a widely used oral antidiabetic drug that has demonstrated antitumor efficacy in some cancers. Indeed, diabetic patients taking metformin had better PFS and OS than those not taking it, 7 vs. 5 months (HR 0.56, p = 0.0187) and 11 vs. 8.5 months (HR 0.53, p = 0.017), respectively. In conclusion, real-world outcomes of biweekly cetuximab maintenance remain comparable to clinical trials. The prognostic role of diabetes and metformin was confirmed to be significant in our series, but further prospective studies are needed for a definitive evaluation.

Image-guided permanent I-125 seed implantation for refractory head-and-neck carcinoma in China: A comprehensive review of contemporary technical and clinical aspects

Permanent I-125 seed implantation is one of the most commonly used brachytherapy (BT) forms, potentially applicable to almost any solid tumor as a standalone anti-tumor therapy or in combination with external beam radiotherapy (EBRT). The main advantage of I-125 seed implantation BT is its ability to deliver a high radiation dose within target volumes while maintaining a sharp dose drop-off profile, thereby protecting adjacent normal tissue. The clinical use of I-125 seed implantation in China has significantly increased in the past decades due to the application of an image-guided BT treatment planning system with reverse optimization capabilities and 3D printing individual template (3D-PIT) assistance. Computed tomography-guided I-125 seed implantation became a widely common modality of BT and has been used in many clinical settings for a variety of refractory cancer in China since 2002. The application has been expanded significantly not only for prostate cancer as monotherapy but also in combination with EBRT for the salvage treatment for refractory/recurrent head-and-neck carcinoma (HNC). With the assistance of 3D-PIT, since 2015, the quality control of I-125 seed implantation has been significantly adapted with high precision and real-time dose optimization. This review aims to summarize the developments and status of 3D-PIT-based I-125 seed implantation BT for the treatment of refractory HNC and standardized workflow in China.

Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment.

Cancer drug development is currently limited by a paradigm of preclinical evaluation that does not adequately recapitulate the complexity of the intact human tumor microenvironment (TME). To overcome this, we combined trackable intratumor microdosing (CIVO) with spatial biology readouts to directly assess drug effects in patient tumors in situ. In a first-of-its-kind phase 0 clinical trial, we explored the effects of an investigational stage SUMOylation-activating enzyme (SAE) inhibitor, subasumstat (TAK-981) in 12 patients with head and neck carcinoma (HNC). Patients scheduled for tumor resection received percutaneous intratumor injections of subasumstat and vehicle control 1 to 4 days before surgery, resulting in spatially localized and graded regions of drug exposure (∼1,000-2,000 μm in diameter). Drug-exposed (n = 214) and unexposed regions (n = 140) were compared by GeoMx Digital Spatial Profiler, with evaluation at single-cell resolution in a subset of these by CosMx Spatial Molecular Imager. Localized regions of subasumstat exposure revealed SUMO pathway inhibition, elevation of type I IFN response, and inhibition of cell cycle across all tumor samples. Single-cell analysis by CosMx demonstrated cell-cycle inhibition specific to the tumor epithelium, and IFN pathway induction commensurate with a TME shift from immune-suppressive to immune-permissive. Pairing CIVO with spatial profiling enabled detailed investigation of response to subasumstat across a diverse sampling of native and intact TME. We demonstrate that drug mechanism of action can be directly evaluated in a spatially precise manner in the most translationally relevant setting: an in situ human tumor.

Predictors of toxicity after curative reirradiation with intensity modulated radiotherapy or proton therapy for recurrent head and neck carcinoma: new dose constraints for pharyngeal constrictors muscles and oral cavity.

Our study aims to identify predictive factors of moderate to severe (grade ≥ 2) late toxicity after reirradiation (reRT) of recurrent head and neck carcinoma (HNC) and explore the correlations between dose organs at risk (OAR) and grade ≥ 2toxicity. Between 09/2007 and 09/2019, 55patients were re-irradiated with IMRT or proton therapy with curative intent for advanced HNC. Our study included all patients for whom data from the first and second irradiations were available. Co-variables, including interval to reRT, size of re-irradiated PTV, and dose to OAR, were analyzed as potential predictors for developing moderate to severe long-term toxicity with death as acompeting risk. Receiver-operator characteristics (ROC) analysis assessed the association between dose/volume parameters and the risk of toxicity. Twenty-three patients participated in our study. After amedian follow-up of 41months, 65% of the patients experienced grade ≥ 2late toxicity. The average dose to pharyngeal constrictor muscles (PCM) at the time of reRT showed an association with the risk of grade ≥ 2dysphagia: AUC = 0.78 (95% CI: 0.53-1), optimal cut-off value = 36.7 Gy (sensitivity 62%/specificity 100%). The average dose to the oral cavity at the time of reRT showed an association with the risk of grade ≥ 2dysgeusia: AUC = 0.96 (0.89-1), optimal cut-off value = 20.5 Gy (sensitivity 100%/specificity 88%). Our analysis depicted an association between the dose to OAR and the risk of developing moderate to severe dysphagia and dysgeusia and proposed new dose constraints for PCM (36.7 Gy) and oral cavity (20.5 Gy).

Carotid Sheath Dissection and Histopathology During Neck Dissection in Head and Neck Carcinomas.

To investigate the carotid sheath in neck dissection (ND) specimens histopathologically in patients with head and neck carcinomas who had no evidence of previous neck surgery or direct involvement of the carotid sheath in their pre- or intra-operative evaluations. In this study, carotid sheath (CS) specimens of 40 patients with head and neck carcinomas (HNCA) who, depending on the condition of the primary tumor, required unilateral or bilateral elective or therapeutic selective neck dissection were histopathologically investigated by an expert head and neck pathologist to find any lymphoid or thyroid like tissue or tumor cells infiltration. A total of 50 carotid sheath (CS) specimens were investigated. None of the samples showed any evidence of tumor infiltration or accumulation of lymphatic tissue. We conclude that in patients with no histopathologic involvement of the carotid sheath in pre-operative or intra-operative tumor invasion, it is not necessary to remove CS in routine neck dissection.

PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications.

High-risk human papillomaviruses (HR-HPVs) are the causal agents of cervical, anogenital and a subset of head and neck carcinomas (HNCs). Indeed, oropharyngeal cancers are a type of HNC highly associated with HR-HPV infections and constitute a specific clinical entity. The oncogenic mechanism of HR-HPV involves E6/E7 oncoprotein overexpression for promoting cell immortalization and transformation, through the downregulation of p53 and pRB tumor suppressor proteins, among other cellular targets. Additionally, E6/E7 proteins are involved in promoting PI3K/AKT/mTOR signaling pathway alterations. In this review, we address the relationship between HR-HPV and PI3K/AKT/mTOR signaling pathway activation in HNC with an emphasis on its therapeutic importance.

Assessment of quality of life after soft tissue resection of head and neck carcinoma and reconstruction with double-paddle peroneal artery perforator free flap

We aimed to assess the quality of life for head and neck carcinoma (HNC) patients who underwent soft tissue resection and reconstruction with double-paddle peroneal artery perforator (DPAP) free flap. The quality of life was assessed by means of the University of Washington quality of life (UW-QOL) and the 14-item Oral Health Impact Profile (OHIP-14) questionnaires at 12 months postoperatively. Data from 57 patients were retrospectively analysed. Out of these, 51 patients were at TNM stage III or IV. Finally, 48 patients finished and returned the two questionnaires. In the UW-QOL questionnaire, the mean (SD) higher scores were pain 76.5 (6.4), shoulder 74.3 (9.6), and activity 71.6 (6.1), whereas the lower scores were chewing 49.7 (5.2), taste 51.1 (7.7), and saliva (56.7 (7.4). In the OHIP-14 questionnaire, the higher-scoring domains were psychological discomfort (69.3 (9.6) and psychological disability 65.2 (5.8), whereas the lower-scoring domains were handicap 28.7 (4.3) and physical pain 30.4 (8.1). The DPAP free flap significantly improved appearance, activity, shoulder, mood, psychological discomfort, and handicap compared with pedicled pectoralis major myocutaneous flap reconstruction. In conclusion, DPAP free flap for reconstruction of tissue defects after soft tissue resection of HNC significantly improved the patients' QOL compared to pedicled pectoralis major myocutaneous flap reconstruction.

Radiotherapy Increases aMMP-8-Levels and Neutrophil/Lymphocyte Ratio Rapidly in Head and Neck Cancer Patients: A Pilot Study.

Radiotherapy for head and neck carcinoma (HNC) has both curative and palliative purposes. This study investigated mouthrinse aMMP-8 levels, molecular forms of MMP-8, blood neutrophil counts and neurophil/lymphocyte ratios before and 3 weeks after HNC radiotherapy started. Thirteen HNC patients undergoing radiotherapy were included. Mouthrinse samples (before and 3 weeks after HNC radiotherapy had started) were assayed quantitatively by aMMP-8 point-of-care-kit (PerioSafe®/ORALyzer®) and by western immunoblot. Total neutrophil counts and neutrophil/lymphocyte ratios were evaluated in the hemogram results. Three weeks after HNC radiotherapy started, significant increases in aMMP-8 levels and neutrophil/lymphocyte ratios were observed. No significant difference was found in total neutrophil counts. Elevations of the activated and fragmented MMP-8 levels after HNC radiotherapy application were observed on western immunoblot analysis. The increase in the aMMP-8 levels and neutrophil/lymphocyte ratios indicate inflammation both locally and systemically suggesting increased risk for periodontitis due to the HNC radiotherapy.

The relationship of serum gastrin-17 and oral mucositis in head and neck carcinoma patients receiving radiotherapy

ObjectiveThe aim of this study was to analyze the relationship of serum gastrin-17 (G-17) and oral mucositis in head and neck carcinoma (HNC) patients receiving radiotherapy.MethodsSerum G-17 were detected in patients before and after radiotherapy. Patients were divided into high G-17 group (baseline serum G-17 ≥ 5pmol/L) and low G-17 group (baseline serum G-17 < 5pmol/L). The severity of oral mucositis was analyzed between the two groups. Other complications such as dysphagia, salivary gland, mandible, thyroid function, larynx, pain, and weight loss were also investigated.ResultsForty-two patients were analyzed in this study. The level of serum G-17 had a significant decrease after radiotherapy (7.29 ± 5.70pmol/L versus 4.93 ± 4.46pmol/L, P = 0.038). In low serum G-17 group, the incidences of grade 0, 1–2 and 3–4 of oral mucositis were 0%, 30.4%, and 69.6%, respectively. In high serum G-17 group, the incidences of grade 0, 1–2 and 3–4 of oral mucositis were 0%, 63.2%, and 36.8%, respectively. Pearson correlation analysis showed that serum G-17 was negatively correlated with oral mucositis (r=-0.595, P < 0.01). Weight loss of low G-17 group was more serious than that of high G-17 group.ConclusionSerum G-17 has a close relationship with oral mucositis. Baseline serum G-17 may be a potential predictor for the severity of oral mucositis in HNC patients receiving radiotherapy.

Concordance of p16INK4a and E6*I mRNA among HPV-DNA-Positive Oropharyngeal, Laryngeal, and Oral Cavity Carcinomas from the ICO International Study.

Simple SummaryThe utility of a diagnostic algorithm for the detection of HPV-driven oral cavity (OCC), oropharyngeal (OPC), and laryngeal (LC) carcinomas using HPV-DNA testing followed by p16INK4a immunohistochemistry, taking E6*I mRNA detection as the reference standard, was assessed in HPV-DNA-positive formalin-fixed paraffin-embedded samples from 29 countries. The concordance of p16INK4a and E6*I mRNA among 78, 257, and 51 HPV-DNA-positive OCC, OPC, and LC, respectively, was moderate to substantial in OCC and OPC but only fair in LC. A different p16INK4a expression pattern was observed in those cases HPV-DNA-positive for types other than HPV16, as compared to HPV16-positive cases. We concluded that the diagnostic algorithm of HPV-DNA testing followed by p16INK4a immunohistochemistry might be helpful in the diagnosis of HPV-driven OCC and OPC, but not LC. Our study provides new insights into the use HPV-DNA, p16INK4a, and HPV-E6*I mRNA for diagnosing an HPV-driven head and neck carcinoma.Background: Tests or test algorithms for diagnosing HPV-driven oral cavity and laryngeal head and neck carcinomas (HNC) have not been yet validated, and the differences among oral cavity and laryngeal sites have not been comprehensively evaluated. We aimed to assess the utility of a diagnostic algorithm for the detection of HPV-driven oral cavity (OCC), oropharyngeal (OPC) and laryngeal (LC) carcinomas using HPV-DNA testing followed by p16INK4a immunohistochemistry, taking E6*I mRNA detection as the reference standard. Methods: Formalin-fixed paraffin-embedded OCC, OPC, and LC carcinomas were collected from pathology archives in 29 countries. All samples were subjected to histopathological evaluation, DNA quality control, and HPV-DNA detection. All HPV-DNA-positive samples (including 78 OCC, 257 OPC, and 51 LC out of 3680 HNC with valid HPV-DNA results) were also tested for p16INK4a immunohistochemistry and E6*I mRNA. Three different cutoffs of nuclear and cytoplasmic staining were evaluated for p16INK4a: (a) >25%, (b) >50%, and (c) ≥70%. The concordance of p16INK4a and E6*I mRNA among HPV-DNA-positive OCC, OPC, and LC cases was assessed. Results: A total of 78 OCC, 257 OPC, and 51 LC were HPV-DNA-positive and further tested for p16INK4a and E6*I mRNA. The percentage of concordance between p16INK4a (cutoff ≥ 70%) and E6*I mRNA among HPV-DNA-positive OCC, OPC, and LC cases was 79.5% (95% CI 69.9–89.1%), 82.1% (95% CI 77.2–87.0%), and 56.9% (95% CI 42.3–71.4%), respectively. A p16INK4a cutoff of >50% improved the concordance although the improvement was not statistically significant. For most anatomical locations and p16INK4a cutoffs, the percentage of discordant cases was higher for HPV16- than HPV-non16-positive cases. Conclusions: The diagnostic algorithm of HPV-DNA testing followed by p16INK4a immunohistochemistry might be helpful in the diagnosis of HPV-driven OCC and OPC, but not LC. A different p16INK4a expression pattern was observed in those cases HPV-DNA-positive for types other than HPV16, as compared to HPV16-positive cases. Our study provides new insights into the use HPV-DNA, p16INK4a, and HPV-E6*I mRNA for diagnosing an HPV-driven HNC, including the optimal HPV test or p16INK4a cutoffs to be used. More studies are warranted to clarify the role of p16INK4a and HPV status in both OPC and non-OPC HNC.

SPP1 as a key gene in the lymph node metastasis and a potential predictor of poor prognosis in head and neck carcinoma.

Lymph node metastasis (LNM) is an important cause leading to recurrence and development of head and neck carcinoma (HNC), with the precise mechanisms unclear. Thus, we aimed to identify the key genes involved in LNM and further evaluate their expressions and roles. A cohort of HNC in the TCGA was analyzed. The study involved three phases (one screening and two validation phases). First, the differentially expressed genes regarding LNM were screened, from which a key gene was identified by a series of data mining approaches. Then, the expressions and roles of the key gene were validated in HNC through bioinformatics. Afterward, the expression of the key gene was detected by qPCR, western blot, and Immunohistochemistry based on a cell model and a tissue microarray. Further, colony formation and transwell migration and invasion assays were used to evaluate the roles of the key gene. SPP1 was overexpressed in HNC tissues and was identified as the key gene. Overexpression of SPP1 in HNC was correlated with advanced pathological stages and T-stage, as well as the presence of LNM, which predicted poor prognosis. The expression of SPP1 was closely associated with the infiltration of immune cells in HNC, especially M2 macrophages. Lab experiments confirmed that SPP1 silence in HNC cells resulted in weakened invasive and metastatic abilities. This study reveals that SPP1 may be a key gene associated with LNM in HNC, raising the possibility of SPP1 as a target for HNC prevention and treatment.

Frequency and Consequences of Cervical Lymph Node Overstaging in Head and Neck Carcinoma.

Clinical lymph node staging in head and neck carcinoma (HNC) is fraught with uncertainties. Established clinical algorithms are available for the problem of occult cervical metastases. Much less is known about clinical lymph node overstaging. We identified HNC patients clinically classified as lymph node positive (cN+), in whom surgical neck dissection (ND) specimens were histopathologically negative (pN0) and in addition the subgroup, in whom an originally planned postoperative radiotherapy (PORT) was omitted. We compared these patients with surgically treated patients with clinically and histopathologically negative neck (cN0/pN0), who had received selective ND. Using a fuzzy matching algorithm, we identified patients with closely similar patient and disease characteristics, who had received primary definitive radiotherapy (RT) with or without systemic therapy (RT ± ST). Of the 980 patients with HNC, 292 received a ND as part of primary treatment. In 128/292 patients with cN0 neck, ND was elective, and in 164 patients with clinically positive neck (cN+), ND was therapeutic. In 43/164 cN+ patients, ND was histopathologically negative (cN+/pN−). In 24 of these, initially planned PORT was omitted. Overall, survival did not differ from the cN0/pN0 and primary RT ± ST control groups. However, more RT ± ST patients had functional problems with nutrition (p = 0.002). Based on these data, it can be estimated that lymph node overstaging is 26% (95% CI: 20% to 34%). In 15% (95% CI: 10% to 21%) of surgically treated cN+ HNC patients, treatment can be de-escalated without the affection of survival.

MMP-2 and MMP-9 gene polymorphisms and risk of head and neck carcinomas

Abstract Background: Head and neck carcinomas (HNC) account for a majority of ear, nose and throat tumours. They account for 6.3% of all incident malignancies and 6.2 % of all deaths from cancer in Romania in 2020, the fifth most common cancer in this Eastern Europe country. Aim of the study: The aim of our study was to investigate the association between two MMP-2 and MMP-9 promoter gene polymorphisms and head and neck cancer. Methods. We enrolled 142 subjects, 65 cancer patients, and 77 control subjects and tested them for MMP-2 -735 C/T and MMP-9 -1562 C/T polymorphisms by PCR-RFLP. Results. Comparison between cancer patients and controls demonstrated the presence of MMP-2 -735 C/T and MMP-9 -1562 C/T in head and neck malignant tumours, with OR = 2.206 (95% CI 1.058-4.599, P = 0.03) for MMP-2 and OR = 2.748 (95% C.I. 1.262-5.981, P=0.009) for MMP-9 gene polymorphism. This means that the presence of T allele could be a risk factor for head and neck cancer development. The analysis included a stratification of studied groups by age and gender. Conclusions. Both genotypes were associated with a significant risk for head and neck carcinomas in case of the presence of the T allele. MMP-2 -735 C/T (rs2285053) and MMP-9 -1562 C/T (rs3918242) gene polymorphism could be an important genetic marker for head and neck cancer susceptibility. This finding could be useful for genetic screening in head and neck carcinomas.

Abstract No. : ABS2276: Modulation of mRNA expression of mTORC1 and IL-6 and comparison of the efficacy and safety of transdermal fentanyl versus transdermal buprenorphine for prevention of chronic persistent post surgical pain in head and neck cancer patients: A randomised, pilot study

Background and Aims:This study compared the efficacy and safety of transdermal buprenorphine (TDB) and transdermal fentanyl (TDF) in prevention of chronic persistent post-surgical pain (CPPP) and modulation of mRNA expression of interlukin (IL-6) and mTORC1 genes in patients of head and neck carcinoma (HNC).Methods:Patients aged >18 years who were operated for HNC with numerical rating scale(NRS)pain scores≥4/10 on post-operative day-6 were enroled. A baseline assessment was done and written informed consent was obtained. The pain intensity and severity were evaluated byNRS-pain, PDQ scores (pain detect questionnaire), and neuropathic pain symptom inventory (NPSI) scores and quality of life was evaluated by utilizing Short Form-12 (SF-12). Gene expression analysis was carried out at baseline and after treatment completion. On post-operative day 6, patients of group F (n=20) received TDF (50 µg/hour) and group B (n=20) received TDB (10 µg/hour).Results:the A total of 40 patients with 20 in each group were included in this study. Following 12 weeks of treatment, gene studiesdemonstrated downregulation of the mRNA expression of IL-6 and mTORC1, which was statistically significant in both groups. A statistically significant decline in NRS-Pain, PDQ scores and NPSI scores and a statistically significant improvement in the physical and mental component scores of SF-12 was also observed in both groups (table 1).NRS Pain ScoreGroup-B Mean±SDIntra group comparison with Baseline line (P)Group-F Mean±SDIntra group comparison with Baseline line (P)Inter group comparison PBaseline7.45±1.23____7.5±7.48____1.00End of week 16.1±1.25<0.0015.15±5.63<0.0010.108End of week 25.05±1.15<0.0014.25±4.65<0.0010.252End of week 43.2±1.11<0.0013.4±3.3<0.0011.00End of week 81.8±1.11<0.0012.5±2.15<0.0010.402End of week 120.6±0.68<0.0011.29±0.93<0.0010.049SD- standard deviation, NRS -numerical rating scaleConclusion:Significant downregulation in mRNA expression of IL-6 and mTORC1 was observed after both transdermal fentanyl and transdermal buprenorphine and both were equally efficacious for prevention of CPPP and improving quality of life following HNC surgery.

Predicting Cervical Lymph Node Metastasis Following Endoscopic Surgery in Superficial Head and Neck Carcinoma.

BackgroundEarly detection of head and neck carcinoma (HNC) as superficial HNC (SHNC) identified using recently developed optical techniques, such as magnifying endoscopy and narrow-band imaging (NBI), in combination with endoscopic surgeries enables minimally invasive treatment with favorable outcomes for HNC. This study aimed to identify the predictive factors for the rare but important clinical issue of SHNC, namely cervical lymph node metastasis (CLNM), following endoscopic resection.MethodsSixty-nine patients with SHNC who underwent endoscopic resection were enrolled in the study. Clinical data, preoperative endoscopic findings, pathological findings, and treatment outcomes were retrospectively reviewed. Because the pharyngeal mucosa lacks the muscularis mucosa, we measured tumor thickness in permanent pathology as an alternative to the depth of invasion. Correlations with the occurrence of CLNM were statistically examined.ResultsThe 5-year disease-specific survival rate was 100%. Of 69 patients, 3 (4.3%) developed CLNM. All had subepithelial but not epithelial tumors. The 0-IIa type in the macroscopic findings, type B2/B3 vessels in narrow-band imaging, tumors ≥ pathological stage T2, lymphatic invasion, positive surgical margins, and tumor thickness >1,000 μm showed significant correlations with CLNM following endoscopic resection. Furthermore, the classification of type B vessels was significantly associated with tumor thickness.ConclusionThe treatment outcomes following endoscopic resection for SHNC were favorable. The risk of CLNM following endoscopic resection in SHNC can be predicted by several preoperative endoscopic and postoperative pathological findings. Among them, the classification of type B vessels, which correlated with both tumor thickness and CLNM, might be a useful predictive factor.

El-Ganzouri multivariate risk index based airway management in head and neck cancer patients: A retrospective analysis of 1000 patients in a tertiary care center.

Background and Aims:Intubation in head and neck carcinoma (HNC) is difficult due to many reasons. Various guidelines recommend strategies for airway management in such anticipated difficult airway cases. However, literature is limited on airway management planning as per the level of difficulty based on airway assessment in these patients. EL-Ganzouri risk index (EGRI) has been proposed to aid in making airway management plan in HNC cases by some authors. This retrospective study was conducted to look at the data related to the pre-anesthetic airway assessment and the airway management plan executed by the anesthesiologists in 1000 patients of HNC in the previous nearly four years in order to determine how the choices made conformed to EGRI scores.Material and Methods:Records of all the patients with oral cancer posted for surgery over four years from January 2014 to December 2017 were retrospectively analyzed for preoperative airway assessment using El Ganzouri risk index assessment (EGRI), the intraoperative technique for nasotracheal intubation, airway management plan, and any intraoperative complications.Results:The risk of predicted airway difficulty was low (EGRI <4) in 38 patients and was high in the rest. The EGRI score was higher in the FOB group [4-9] as compared to DL [2-3] and VL [1-6]. The patients with EGRI >7 were intubated awake and those with EGRI <7 were intubated under general anesthesia (79.8%). Overall, the technique of choice for intubation was fibreoptic bronchoscopy (54%) followed by video laryngoscopy (42.6%).Conclusion:The airway management plan used in a tertiary care cancer center conformed to the approach suggested by the multivariate El Ganzouri risk index (EGRI). EGRI appears to be a useful means to ascertain the appropriate strategies for intubation in head and neck cancer patients.