Role of Genetic Testing in the Management of Indeterminate Thyroid Nodules in the Indian Setting.

The increased detection of thyroid nodules in the human population has led to an increase in the number of thyroid surgeries without an improvement in survival outcomes. Though the choice for surgery is straightforward in malignant thyroid nodules, the decision is far more complex in those nodules that get categorized into indeterminate thyroid nodules (ITN) by fine needle aspiration. Therefore, there is a pressing need to develop a tool that will aid in decision-making among the ITN. In this context, the development of various molecular testing (MT) panels has helped to confirm or rule out malignancy, reducing unnecessary surgeries and potentially guiding the extent of surgery as well. Currently, such tests are widely used among the Western population but these MT panels are not used by the South Asian population because of non-availability of validated panels and the high cost involved. There is a need to develop a suitable panel which is population-specific and validate the same. In this review, we would focus on current trends in the management of ITN among the South Asian population and how to develop a novel MT panel which is cost-effective, with high diagnostic accuracy obviating the need for expensive panels that already exist.

The significance of the presence of extranodal extension in the metastatic node of differentiated thyroid cancer: a proposal for modification in the American Thyroid Association (ATA) risk stratification.

BACKGROUND: Multiple factors contribute to recurrences in differentiated thyroid cancers (DTC). Though the nodal size and number of positive nodes along with the presence of extranodal extension (ENE) have been mentioned in the present ATA risk stratification, the weightage given for ENE seems inadequate compared to the former two. METHODOLOGY: Factors predicting recurrences were analysed in this retrospective study of patients with DTC operated in a tertiary care centre. Based on our findings, we propose a modification in the present risk stratification. We have done so by comparing with existing risk stratification for fit and discrimination of this system. RESULTS: Out of 1428 patients, 859 (60.2%) patients had pathological nodal metastases (pN +) with ENE being present in 26.8% of these. The recurrence rate was 6.4% (92 patients). Recurrence rates in patients with ≤ 5 nodes without ENE, > 5 nodes without ENE, ≤ 5 nodes with ENE and > 5 nodes with ENE were 2.7%, 1.3%, 8.3% and 10.3%, respectively. Recurrence rates in patients with 0.2-3 cm without ENE, 0.2-3 cm with ENE and > 3 cm with/without ENE were 1.8%, 8.5% and 13.4%, respectively. A modified risk stratification incorporating ENE and excluding the number of metastatic nodes was proposed. The modified risk stratification had a better fit than the present system in terms of higher C index and lower AIC. CONCLUSIONS: Extranodal extension in differentiated thyroid cancer had the maximum influence on recurrence risk (recurrence-free survival) in our cohort. The prognostic impact of ENE supersedes the number of positive nodes in the risk of recurrence.

Determining the impact of COVID-19 pandemic on adjuvant therapy for oral cancer - A matched-pair analysis.

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has hard-pressed the health care systems beyond their capabilities, causing a lack of appropriate cancer treatment delivery. The aim of this study was to assess the impact of pandemic-related restrictions on adjuvant therapy delivery for oral cancer patients during these demanding times. Materials and Methods: Oral cancer patients who were operated on between February and July 2020 and scheduled to receive prescribed adjuvant therapy during the COVID-19-related restrictions (Group I) were included in the study. The data were matched for the length of hospital stay and type of prescribed adjuvant therapy, with a set of patients who were similarly managed 6 months preceding the restrictions (Group II). Demographic and treatment-specific details, including inconveniences faced in procuring prescribed treatment, were obtained. Factors associated with delay in receiving adjuvant therapy were compared using regression models. Results: A total of 116 oral cancer patients were considered for analysis, comprising 69% (n = 80) adjuvant radiotherapy alone and 31% (n = 36) concurrent chemoradiotherapy. The mean hospital stay was 13 days. In Group I, 29.3% (n = 17) of patients were not able to receive any form of their prescribed adjuvant therapy at all, which was 2.43 times higher than Group II (P = 0.038). None of the disease-related factors significantly predicted delay in receiving adjuvant therapy. Of the delay, 76.47% (n = 13) was present during the initial part of the restrictions, with the most common reason being unavailability of appointments (47.1%, n = 8), followed by inability to reach treatment centers (23.5%, n = 4) and redeem reimbursements (23.5%, n = 4). The number of patients who were delayed the start of radiotherapy beyond 8 weeks after surgery was double in Group I (n = 29) than in Group II (n = 15; P = 0.012). Conclusions: This study highlights a small part of the rippling effect the COVID-19 restrictions have on oral cancer management and pragmatic actions may be needed by policymakers to deal with such challenges.

Impact of Changes in Treatment Paradigms on Survival in Oral Squamous Carcinoma-a Population-Level Study.

There have been notable improvements in the treatment of oral cancers. The objective of this study was to see whether these improvements have translated into survival benefits at the population level from the SEER database. This is a retrospective study using the SEER 19 Custom database which included patients diagnosed with oral cancer between January 1, 1995, and December 31, 2015. The overall stage, age, sex, and treatment modalities were the covariates. For analysis, the patients were divided into four cohorts as per their year of diagnosis-cohort I included patients who were diagnosed between 1995 and 2000 (n = 3873), cohort II between 2001 and 2005 (n = 5881), cohort III between 2006 and 2010 (n = 6233), and cohort IV between 2011 and 2015 (n = 12567). Patients undergoing surgery with adjuvant therapy have increased significantly across cohorts and there is a significant fall in patients undergoing non-surgical treatment. Pairwise comparison by the Mantel-Cox test showed that cohort IV had significantly improved median overall survival (OS) and disease-specific survival (DSS) as compared to other cohorts and there was a significant impact of treatment modality on OS and DSS, especially in cohorts III and IV (p<0.001). Though geographical variations in the presentation and habits limit the generalization of these results, this study demonstrates that the changes and improvements in treatment paradigms incorporating level I evidence and surgical techniques have translated into improved survival outcomes at the population level. We recommend further studies on the local population to lend further credence to our observation. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01790-0.

Regression Derived Staging Model to Predict Overall and Disease Specific Survival in Patients With Major Salivary Gland Carcinomas With Independent External Validation.

PURPOSE: The current American Joint Cancer Committee (AJCC) staging system for salivary gland tumors does not include histology and grade in its classification despite their proven prognostic importance. We planned to analyze if a modified staging system integrating these two factors into the staging improves prognostic performance and then validate it externally. MATERIALS AND METHODS: From SEER database (2000-2018), patients with major salivary gland carcinoma who underwent surgical resection between 2004 and 2015 were analyzed. Histologies were recoded into two groups based on grade and type of histology into "Low Aggression" and "High aggression" groups. Cox proportional hazards model was used to identify predictor variables for overall survival and disease-specific survival and models were generated based on least absolute shrinkage and selection operator regression. Model performance was evaluated by Akaike Information Criterion, concordance index and calibration plot. The best model chosen was externally validated from our hospital database of patients who underwent surgery for salivary gland tumor between January 1, 2012 to December 31, 2019. RESULTS: Six thousand two hundred forty-six patients were analyzed with a median follow up of 58 months. Age > 65 years, male sex, metastatic disease, Histological Stratification, Grade of tumor, AJCC stage and Primary Site were the significant factors influencing overall survival and disease-specific survival. By least absolute shrinkage and selection operator regression method, Correlation analysis and Interaction testing by multiple regression, AJCC stage and Histological Risk stratification were used for generating four models, out of which the best model was selected by Akaike Information Criterion, C index and calibration plot. This model was then externally validated in our hospital database of 269 patients. CONCLUSION: We propose an externally validated modified salivary gland staging system that incorporates histology and grade of tumor for improved hazard discrimination among patient subgroups.

Incidence and impact of dysplasia at final resection margins in cancers of the oral cavity.

BACKGROUND: The literature often cites margin status as being free, close or involved by tumor but there is very sparse evidence of the relevance of dysplasia at resection margin. Aims/Objectives: To compare the impact of dysplasia at final resection margin (D-FRM) and other margin statuses on overall survival (OS) and disease free survival (DFS). METHODS: This is a retrospective review of 1700 treatment naïve oral squamous carcinoma patients who underwent surgery between January 2012 and December 2015. The study arm consisted of patients with dysplasia at final resection margin (D-FRM). Each of these patients were double propensity matched to obtain positive (P-FRM), close (C-FRM) and free final resection margins (F-FRM). RESULTS: There was no hazard discrimination in survival among the D-FRM and C-FRM (vs F-FRM; p-0.597, HR-1.207 (0.621-2.346) and p-0.075, HR-1.594 (0.947-2.684), respectively). A decreasing survival trend was observed as the grade and number of D-FRM margins increased. Although not significant, the addition of adjuvant therapy for D-FRM showed a trend towards improved survival outcomes compared to C-FRM, especially with chemotherapy. Conclusion and relevance: The presence of D-FRM, irrespective of grade, had a similar impact on survival as C-FRM and underscores the possible need for treatment intensification.