Role of circulating tumour cells (CTCs) in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).

Background: Liquid biopsy is emerging as a non-invasive tool, providing a personalized snapshot of a primary and metastatic tumour. It aids in detecting early metastasis, recurrence or resistance to the disease. We aimed to assess the role of circulating tumour cells (CTCs) as a predictive biomarker in recurrent/metastatic head and neck cancer (head and neck squamous cell carcinoma (HNSCC)). Methodology: Thirty-five patients receiving palliative chemotherapy underwent blood sampling [2 mL in Ethylenediaminetetraacetic acid (EDTA) vial] at baseline and at 3 months intervals. The CTCs were isolated and evaluated using anti-epithelial cell adhesion molecule antibody-based enrichment using the OncoDiscover platform. Results: CTCs isolated from 80% of patients (n = 28) showed the sensitivity of cell detection at the baseline and 3 months intervals. The median CTC count was 1/1.5 mL of blood and the concordance with clinic-radiological outcomes was 51.4%. The median CTC count (1 (range:0-4) to 0 (range:0-1)) declined at 3 months in responders, while the non-responders had an increase in levels (0 (range :0-2) to 1 (range :0-3)). Although CTCs positively correlated with progression-free survival (PFS) and overall survival (OS), the association of CTCs did not show a significant difference with these parameters (PFS: 6 months versus 4 months; hazard ratio: 0.68; 95% confidence interval (CI): 0.29-1.58, p = 0.323; OS: 10 months versus 8 months; hazard ratio: 0.54; 95% (CI):0.18-1.57 p = 0.216) between CTC positive and CTC negative patients at 3 months. Conclusion: This study highlights the utility of CTC as a disease progression-monitoring tool in recurrent HNSCC patients. Our findings suggest the potential clinical utility of CTC and the need for exploration in upfront settings of the disease as well (NCT: CTRL/2020/02/023378).

Efficacy and Safety of Percutaneous Radiological Gastrostomy (PRG) as a Rescue Measure for Enteral Feeding in Patients with Advanced Head, Neck, and Upper Digestive Malignancies.

Background Percutaneous radiologic gastrostomy is an established mode of enteral feeding for nutritional support for patients with dysphagia from upper digestive tract malignancy. Its role as a rescue measure in patients with advanced malignancy, presenting with absolute dysphagia and failure of nasogastric tube insertion has not been well established. Purpose This study was performed to assess technical success and long-term outcomes of percutaneous radiologic gastrostomy (push type) for nutritional support for patients with absolute dysphagia as a last ditch nonsurgical rescue effort for enteral access. Materials and Methods This was a prospective observational study of 31 patients who underwent push-type percutaneous radiologic gastrostomy over a period of 2 years (March 2017-March 2019). The study was a part of a larger trial approved by the institutional ethics committee. Patients were followed till the removal of tube, death, or 1 year, whichever was earlier. Gastrostomy tube-related problems and complications were documented. Descriptive summary statistics were employed to analyze the success rate and complications. Results Thirty-one patients with mean age 56 years (26-78 years) including 18 males and 13 females with head and neck squamous cell cancer and esophageal cancer presenting with absolute dysphagia or significant dysphagia with failed nasogastric or endoscopic enteral access were included. Overall technical success was 93.5% (29/31), achieved in 26/31 patients with just fluoroscopy guidance and 3/5 patients with computed tomography guidance. One major (3.3%) and two minor (6.5%) complications were encountered. Five out of 29 gastrostomy tubes had to be exchanged, after a mean of 44 days (1-128 days) after insertion. Conclusion Percutaneous radiologic gastrostomy is a safe and effective intervention even as a rescue measure in patients with absolute dysphagia from advanced upper digestive tract malignancies.

A single-arm feasibility phase II study of EMF (erlotinib + methotrexate + 5-fluorouracil) regimen in platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).

Background: Head and neck squamous cell carcinoma (HNSCC) is a huge burden in India with the majority of patients presenting in advanced unresectable stages. Innovative, low-cost but efficacious regimens that can be easily administered in the outpatient setting are the need of the hour. We envisaged assessing whether a readily available triplet therapy of erlotinib + methotrexate + 5-fluorouracil (EMF) is efficacious in terms of extending life and maintaining the quality of life in such patients. Patients and methods: This was a single-arm, phase II, investigator-initiated interventional study. Thirty-five platinum-resistant/refractory patients of HNSCC were treated with a combination of erlotinib 150 mg, methotrexate 40 mg/m2 (d1, d8) and 5-fluorouracil 500 mg/m2 (d1, d8) every 28 days till progression or unacceptable toxicities. The primary endpoint was overall response rates (ORRs) at 3 months; additional endpoints were disease control rate (DCR) at 3 months, overall survival (OS) and progression-free survival (PFS), safety and patient-reported quality of life. Results: The ORR and DCR at 3 months were 45.7% and 68.5%, respectively. The PFS was 5 months (95% confidence interval (95% CI): 3.9-6 months) and the OS was 9 months (95% CI: 7.4-10.5 months). The 3- and 6-month PFS rates were 86% ± 6% and 45% ± 9%, respectively, while the OS rates at 3 and 6 months were 91% ± 5% and 68% ± 8%, respectively. Rash, mucositis and fatigue were common adverse events occurring in 23 (65%), 14 (40%) and 9 (25.7%), respectively. The most common grade 3 events seen were rash in 5 (14.2%) and diarrhoea in 2 (5.7%). Clinically significant improvement from baseline was seen in many domains of Quality of Life Core Questionnaire and Quality of Life Head and Neck Module. Conclusions: The triplet regimen of EMF is a feasible and safe therapeutic option in patients with platinum-resistant/refractory HNSCC. It has demonstrated favourable response rates and improvement in quality of life; however, a randomised phase III study would add more robust value (NCT: CTRI/2020/02/023378).

Oral Cancer in the Indian Subcontinent-Survival Outcomes and Risk Factors with Primary Surgery.

OBJECTIVE: To assess the oncological outcome and prognostic factors for primary Oral Squamous Cell Cancer (OSCC) staged as per AJCC 8th pTNM, and treated by the contemporary standard of primary surgery and pathology directed adjuvant radiation-chemoradiation. METHODS: A single institution cohort from a tertiary care academic institution in North India. Case inclusion 2013 to 2016; n = 218, median follow-up 35 months. All patients were restaged as per the AJCC 8th pTNM classification. Analysis for Overall Survival (OS), Disease-free Survival(DFS), and factors impacting outcome (Cox proportionate model Multivariate analysis). RESULTS: AJCC pTNM 7th to 8th edition conversion led to upstaging in 16.5%. Stage-II demonstrated greatest stage migration and apparent improvement in OS and DFS (P < .09). Discordance was noted between the presurgical (clinico-radiologic) and postsurgical (pathological) nodal status in 40.3% (88/218; 54 pathologically upstaged;34 downstaged). Pathological downstaging was particularly significant with advanced stage Gingivo-Buccal Cancers (25/73-34.7%). Stage-I-II early cancers had 3 years. OS-86.7% and DFS-78.8%; Stage-III-IV advanced cancers had 3 years. OS-56.7% and DFS-46.6%. Multivariate analysis identified poorer OS and DFS for age < 40 years (HR-1.8; 2.0), skin involvement (HR-2.1; 2.6) and pN+ status (HR-2.4; 3.5). Bone involvement did not compromise survival in this surgically treated set of patients. CONCLUSION: Age < 45 is newly identified as significantly compromising DFS and OS in Oral Cancer. Established factors of skin involvement and pN+ are confirmed as impacting DFS-OS. An apparent improvement in survival in Stage II Cancers is noted as consequent to adoption of AJCC 8th edition staging. LEVEL OF EVIDENCE: 2 (OCEBM 2011-Inception Cohort Study for Prognosis) Laryngoscope, 131:2254-2261, 2021.

Diagnostic Significance of p38 Isoforms (p38α, p38ß, p38γ, p38δ) in Head and Neck Squamous Cell Carcinoma: Comparative Serum Level Evaluation and Design of Novel Peptide Inhibitor Targeting the Same.

PURPOSE: The p38 mitogen-activated protein kinase (MAPKs) play a crucial role in the production of pro-inflammatory cytokines and over-expression of it increase cytokines which promote cancer. Among four isoforms, p38α has been well studied in head and neck squamous cell carcinoma (HNSCC) and other cancers as a therapeutic target. p38δ has recently emerged as a potential disease-specific drug target. Elevated serum p38α level in HNSCC was reported earlier from our lab. This study aims to estimate the levels of p38 MAPK-isoforms in the serum of HNSCC and design peptide inhibitor targeting the same. MATERIALS AND METHODS: Levels of p38 MAPK isoforms in the serum of HNSCC and healthy controls were quantified by surface plasmon resonance technology. The peptide inhibitor for p38 MAPK was designed by molecular modeling using Grid-based Ligand Docking with Energetics tools and compared with known specific inhibitors. RESULTS: We have observed highly elevated levels of all four isoforms of p38 MAPK in serum of HNSCC patients compared to the control group. Further, serum p38α, p38ß, and p38δ levels were down regulated after therapy in follow-up patients, while p38γ showed no response to the therapy. Present study screened designed peptide WFYH as a specific inhibitor against p38δ. The specific inhibitor of p38δ was found to have no effect on p38α due to great structural difference at ATP binding pocket. CONCLUSION: In this study, first time estimated the levels of p38 MAPK isoforms in the serum of HNSCC. It can be concluded that p38 MAPK isoforms can be a diagnostic and prognostic marker for HNSCC and p38δ as a therapeutic target.

Operable Oral Tongue Squamous Cell Cancer: 15 Years Experience at a Tertiary Care Center in North India.

The aim of the present study was to provide insight into various demographic, clinical, and management profile of Indian patients with oral tongue squamous cell cancer (OTSCC). All the OTSCC patients who had undergone surgical treatment during 1995 to 2010 at a tertiary care center in North India were considered for the present study. The details of the patients were retrieved from a prospectively maintained computerized database. A total of 124 patients were included in the present study. Mean age of the patients was 50.4 ± 12.0 years. Lateral border of the tongue was the most common sub-site involved in 110 (88.7%) patients. Neck nodes were clinically palpable in 56.4% patients. Hemiglossectomy and anterior partial glossectomy were common surgical procedure undertaken in 57.2 and 25.8% patients. Negative resection margin was achieved in 97.5% patients. Pathological neck metastasis was seen in 40.3% patients. Occult neck metastasis was present in 25.9% patients among clinical N0 neck. At a mean follow-up of 29.8 months (SD 3.1), 20.1% developed disease relapse and 4.0% patients developed second primaries. Kaplan-Meier analysis estimated a 5-year disease-free survival of 81.5% and a 5 years overall survival of 78.6%. Cox proportional regression analysis predicted tumor size and number of positive nodes to be independent predictive variables for disease recurrence. Quality controlled surgery, coupled with adjuvant treatment when required, provides a safe and effective treatment of OTSCC with a good disease-free survival and loco-regional control.

Effects of Tobacco Habits on the Polymorphism of NFKB1 and NFKB1A Gene of Head and Neck Squamous Cell Carcinoma in Indian Population

Background: Polymorphism of NFKB1 and NFKB1A are highly associated with cancer. We have assessed polymorphism in the promoter region of NFKB1 -94 del/ins ATTG (rs28362491) and NFKB1A -826 C/T (rs2233406) with the risk of HNSCC in Indian population. Methods: Polymerase chain reaction­restriction fragment length polymorphism (PCR-RFLP) method was used for the genotyping NFKB1 -94 del/ins ATTG and NFKB1A -826 C/T. Sequencing was done to validate the results of PCR-RFLP. Statistical analysis of data was done by Stata/SE-14.0 software. Results: ins/ins genotype was observed to be a risk factor of HNSCC as compared del/del genotype of NFKB1 -94 ATTG. Interactive effects of smoking and chewing on ins/ins genotype showed 13.96 and 10.92 fold increased risk of HNSCC. NFKB1A -826 C/T polymorphism, TT genotype showed no association with the risk of HNSCC as compared to wild type CC genotype. Conclusion: Our results showed NFKB1 -94 del/ins ATTG with smoking and tobacco chewing may increase the risk of HNSCC while NFKB1A -826 C/T plays a protective role in Indian population.