Two by Two Factorial Design using Metformin and Curcumin for Second Primary Head and Neck Cancer Prevention Trial.

OBJECTIVE: The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without substantially increasing the required sample size. In view of the considerable preclinical evidence for Curcumin and Metformin in preventing the development and progression of head and neck squamous cell carcinoma (HNSCC), this study describes the protocol of the clinical trial towards applying the drug combination in prevention of second primary tumors. METHODS: We have applied the trial design to a large phase IIB/III double-blind, multi-centric, placebo-controlled, randomized clinical trial to determine the safety and efficacy of Metformin and Curcumin in the prevention of second primary tumours (SPT) of the aerodigestive tract following treatment of HNSCC (n=1,500) [Clinical Registry of India, CTRI/2018/03/012274]. Patients recruited in this trial will receive Metformin (with placebo), Curcumin (with placebo), Metformin, and Curcumin or placebo alone for a period of 36 months. The primary endpoint of this trial is the development of SPT, while the secondary endpoints are toxicities associated with the agents, incidence of recurrence, and identifying potential biomarkers. In this article, we discuss the 2x2 factorial design and how it applies to the head and neck cancer chemoprevention trial. CONCLUSION: 2x2 factorial design is an effective trial design for chemoprevention clinical trials where the effectiveness of multiple interventions needs to be tested parallelly.

National Cancer Grid Virtual Tumor Boards of Head and Neck Cancers: An Innovative Approach to Multidisciplinary Care.

PURPOSE: Virtual tumor board (VTB) via videoconference facility involving multiple specialists in the decision making for various tumors is well accepted, especially in high-income countries. Information on virtual tumor boards for head and neck cancers especially from low- and middle-income countries is sparse. In this study, we have audited the findings of the National Cancer Grid VTBs performed for head and neck cancers. METHODS: All patients discussed in the head and neck VTBs at our center between December 2016 and February 2022 were included in the study. Details such as the type of institute sending patients for discussion, its location, subsites within the head and neck region, histopathology, treatment setting or question for the VTB, and availability of guidelines for such patient scenarios were assessed. Also, a survey was sent to assess the usefulness of the VTBs. RESULTS: A total of 208 patients were discussed in 54 VTB sessions. The most common head and neck sites discussed in the VTBs were the oral cavity (n = 64, 30.7%) followed by skull base/nose and paranasal sinuses/eyelid-orbit tumors (n = 49, 23.5%). Nonsquamous cell carcinoma was the most common histopathology discussed; recurrent cancers/residual diseases were the most common treatment settings (n = 134, 64.4%) for which there were no existing guidelines. Survey results showed that most VTB decisions were implementable, and respondents felt that VTBs were a useful educational tool as well. CONCLUSION: Our study affirms the feasibility of VTBs in low- and middle-income countries' health care systems for managing uncommon malignancies and clinical situations, which act as an important educational platform.

Oral metronomic chemotherapy as a feasible preoperative therapy in advanced resectable oral cavity squamous cell carcinomas- a preliminary experience.

Introduction: Surgery is an important component of multimodality treatment in advanced oral cavity cancers. But in low-middle-income countries like India, with limited centres offering complex head and neck surgeries, prolonged waiting times for surgery is a major problem. An increase in waiting times for treatment has been shown to be a negative prognosticator in head and neck cancer and many patients can develop interim progression making them ineligible for radical treatment. We share our preliminary experience of using oral metronomic chemotherapy as a preoperative treatment in patients expecting delay in surgery. Methods: This was a retrospective analysis of case records of patients with resectable Stage III and Stage IV (IVA & IVB) oral cavity cancers who had received preoperative oral metronomic chemotherapy (POMT). The POMT schedule consisted of oral Methotrexate 15 mg/m2 weekly, Celecoxib 200 mg twice daily and Erlotinib 100 mg daily. Clinico-radiological assessments were done prior to surgery using standard response assessment criteria. Results: A total of 68 patients received POMT with a median age of 55 years (range: 34-73 years). Forty-eight (70%) were males, 29 (42%) had carcinoma tongue and majority (N = 52, 76%) had Stage IVA cancer. Mean duration of POMT administration was 30.45 days (standard deviation: 8.22). Thirty-seven (54%) patients had partial responses and another 23 (34%) had stable disease. Two (3%) had disease progression on POMT. Fifty-eight (85%) underwent surgery after POMT. Margin positive resection was seen in two patients. Half of the patients who received POMT did not experience any toxicity. Grade 3/4 toxicities were seen in four (6%) patients. Conclusions: POMT is a feasible strategy worth considering in cases where there are prolonged waiting times to surgery.

Validation of an Intelligibility Assessment Tool in an Indian Language for Perceptual Speech Analysis in Oral Cancer Patients.

This study aimed to develop a speech intelligibility tool in Malayalam, an Indian language, based on the perceptual analysis. The tool had components of vowel, consonant, word, passage, and overall intelligibility. After face and content validation, a sample of 30 consecutive oral cancer patients underwent preliminary testing for internal consistency, inter- and intra-rater reliability, concurrent, and known-group validity. Subsequent validation was done in 80 T1-T4 patients from two centers. The scale had a high level of internal consistency; the Cronbach's alpha was 0.847 and good intra-rater and inter-rater agreement amongst all raters. There was a strong correlation between the Malayalam and the English passage. Pearson correlation coefficient of 0.646 proved concurrent validity. On known-group and subsequent validation, the tool showed expected differences between the treatment groups. The speech tool proved to be reliable and valid for perceptual evaluation of speech intelligibility in oral cancer patients.

Expression of p16INK4a in oropharyngeal squamous cell carcinoma from a tertiary cancer centre of South India: A preliminary study.

Background & objectives: Human papillomavirus (HPV) and oropharyngeal squamous cell carcinoma (OPSCC) are found to be strongly associated with each other with an increase in incidence has been noted globally over the years. A literature search for data depicting the role of HPV in oropharyngeal carcinoma in South India, however, has resulted in little information, thus, the present study was aimed to assess a possible association between the two among OPSCC patients from a tertiary care cancer centre in South India. Methods: One hundred and fourty three OPSCC cases were included in the study and analyzed for age, gender, marital status, habits, clinical TNM staging, site, laterality, symptoms, histological type (keratinizing and non-keratinizing), primary treatment and follow up period. All the cases were subjected to p16INK4a immunostaining. Statistical analysis was done using SPSS software. Results: Of the 143 cases 12 were found to be p16 positive with no significant difference between the study variables among p16 positive and negative cases. Base of the tongue was the most commonly involved site for the p16 positive cases. The p16 positive cases presented at an elderly age, early stage and were mainly the keratinizing type. Interpretation & conclusions: The p16 positive OPSCC cases constituted a small proportion in the present study and behaved similar to p16 negative cases. Usage of tobacco and alcohol appear to be the susceptible factors even in p16 positive cases. More studies from other States would be helpful to determine if HPV-related SCC in the Indian subcontinent behave differently or similarly to cases from Western countries.

Incipient Warthin tumor of intraparotid lymph node in a patient with squamous cell carcinoma of the external auditory canal: An incidental finding.

The occurrence of intranodal salivary gland neoplasm is uncommon; squamous cell carcinoma (SCC) of the external auditory canal (EAC) is another rare occurrence. Clinically, SCC of EAC presents with symptoms similar to other benign otologic conditions. A case of Stage I SCC in EAC region is presented here in a 60-year-old male patient with incidental intranodal Warthin tumor along with the histological differential diagnosis. The patient is being followed up. There is no evidence of recurrence 1 year and 11 months after surgery.

Prognostic efficiency of clinicopathologic scoring to predict cervical lymph node metastasis in oral squamous cell carcinoma.

BACKGROUND: The extent of involvement of cervical lymph nodes is known to be the most important prognosticator in oral squamous cell carcinoma (SCC) that significantly affects the survival rate of patients. The clinical, radiological and pathological factors that can predict cervical lymph node metastasis are yet to be ascertained clearly, which poses a challenge for the surgeon to determine the extent of neck dissection. AIM: This study aims to identify the clinical and histopathologic predictors of lymph node metastasis among patients with oral SCC and to devise a scoring system based on those predictors to aid in better clinical decision-making regarding the extent of neck dissection. SETTING: Malabar Cancer Centre, a specialized tertiary cancer care center in Kerala, India. METHODS: A retrospective review of 160 patient records and biopsy slides collected and preserved between June 2014 and May 2016. CONCLUSION: The clinicopathologic parameters such as site of cancer (P = 0.03), histologic differentiation (P = 0.03), shape of rete pegs (P = 0.002), pattern of invasion (P = 0.0001) and depth of invasion >3 mm (P = 0.016) were significantly associated with the risk of lymph node metastasis. The risk score devised based on these predictors serves as an efficient tool in aiding clinical decision-making regarding the extent of neck dissection.

Laryngeal Basaloid Squamous Cell Carcinoma with a Substantial Spindle Cell Component: Case Presentation and Updated Review of Literature.

Basaloid squamous cell carcinoma with spindle cell component is an uncommon aggressive variety of squamous cell carcinoma with only a few reported cases in literature. Histologically a combination of basaloid squamous cell carcinoma and spindle cell squamous cell carcinoma is appreciated and immunohistochemistry serves a role in differentiation from malignant neoplasms of salivary gland or neuro-endocrine origin. Prime treatment modality is combination of surgery and external beam radiotherapy. A case of basaloid squamous cell carcinoma with proliferation of bizarre mesenchymal component is being reported here with an updated literature review.

A rare presentation of pulmonary lymphangitic carcinomatosis in cancer of lip: case report.

Squamous cell carcinoma of lip is a common malignancy in Indian subcontinent. Metastatic spread is infrequent. Although advanced tumours spread to lymph nodes in the neck, it does not typically present with lung metastasis or with lymphangitic carcinomatosis. We describe a patient who developed cough and increasing dyspnoea while on treatment for carcinoma of lip. Chest x-ray and computed tomography were consistent with lymphangitic carcinomatosis. Lymphangitic carcinomatosis occurs with many different primary tumours and can rarely occur in oral cancers. This is the first report from carcinoma of lip.