Lymph node level ratio: Are we relying too much on numbers?

The lymph node level ratio appears to be a continuation of nodal yield and nodal density, two prognostic metrics already in use. A retrospective analysis conducted in the current study showed that a value of fewer than 4 lymph nodes/level is linked to a lower overall and disease-specific survival. This letter aims to review the reasoning behind the use of node level ratios and nodal yields as quality and prognostic indicators, and to explore possible factors that could affect these.

The Impact and Prognostic Significance of Extra-Nodal Extension in Clinically N0 Oral Cancer: A Prospective Clinical Study.

Oral cavity squamous cell carcinoma (OCSCC) demonstrates a high propensity to metastasize to regional lymph nodes. Despite technological and scientific advances, identification of pathological adverse features preoperatively remains elusive. This study intended to identify the true occurrence of extra-nodal extension (ENE) in clinically and radiologically N0 OCSCC patients and to investigate its impact and prognostic significance. A prospective, single-centre, non-randomized study was conducted at a tertiary cancer centre in South India to include all untreated operable patients of OCSCC without clinical, radiological, or cytological evidence of nodal metastasis (cN0). All the patients underwent tumor resection surgery with neck dissection and received adjuvant therapy when indicated. Patients were followed up and neck dissection specimens were histopathologically analyzed. The primary outcome was to assess the presence of ENE in cN0 OCSCC patients and its extent. The secondary outcomes were 2-year disease-free survival (DFS) and tumor characteristics. A total of 237 patients with operable OCSCC were evaluated. Out of these, 80 patients who were clinically and radiologically N0 were included in the study and they underwent tumor resection surgery and neck dissection. The final histopathological evaluation revealed that 21.25% of patients (n = 17) had metastatic neck disease and 7.5% of patients (n = 6) had ENE, and all were reported as microscopic ENE. Within the node-positive group, the 2-year DFS for patients with and without ENE were 50% and 90.9%, respectively (p = 0.0362). The results suggest that ENE remains a strong predictor of adverse outcomes, recurrence, and survival in oral cancer patients.

Upper oral cavity tumors: Is the risk of nodal metastasis different?

The state of the clinically evident cervical lymph nodes at the time of diagnosis is one of the most important factors impacting long-term survival. While squamous cell carcinomas (SCC) of the hard palate and maxillary alveolus are uncommon in comparison to other primary sites, there is a scarcity of published data on the effective management of the neck nodes for malignancies of these specific subsites. In such circumstances, an intraoperative frozen section or Sentinel node biopsy would aid in the optimal therapy of the neck.

Decoding the influence of the immune system and immunotherapy targets on carcinomas: A hidden prism in oral cancer therapy.

In recent decades, understanding tumorigenesis and the complex interaction between the host and the immune system has been the pillar for significant advances in anticancer therapy. Conventional anticancer therapy (e.g., cut, burn, and cytotoxic drugs) involves multiple targeting of tumor cells. However, the tumor tissue microenvironment can present a dysregulated, stimulating, or subverted immune response which, in turn, reveals pro-tumor activities favoring tumor expansion and progression. Recently, new potential targets have been identified based on immunomodulatory therapies, which are crafted to re-establish the host anti-tumoral immune response. Clinicians should fully understand the intricate interactions between carcinogens, the tumor milieu, the immune system, and traditional anticancer therapies in order to progress and to overcome the refractory/recurrent challenges and morbidity of the disease. Thus, in this article, we highlight the complex milieu of the oral cancer immune response, pointing out potential therapeutic immunotargets for oral squamous cell carcinomas. The impact of traditional anticancer therapy on the immune system is also outlined.

Swallowing: A delayed milestone post-surgery in tongue cancers.

Functional rehabilitation remains an important factor in the post-operative period following tongue cancer surgeries. Patients undergoing surgery for tongue cancers require intense rehabilitation in order to restore their swallowing function, and improve their nutritional status and quality of life. Various swallowing scales like the Functional Oral Intake Scale (FOIS), Performance status scale in head and neck cancer (PSSHNC) and 100 ml water swallow test are used to assess functionality in these patients. These aid in timely assessment and early intervention for better rehabilitation, in turn improving quality of life. Nasogastric tube (NG) or percutaneous endoscopic gastrostomy (PEG) aids in providing adequate nutrition in the immediate post-operative period and during adjuvant therapy to overcome radiation-induced dysphagia.

The spiral ladder technique of facial nerve trunk identification during parotidectomy: A convenient roadmap for the beginners.

The intricate relationship between the facial nerve and the parotid gland makes the surgeries involving the gland challenging. Though several landmarks have been described to locate the nerve trunk, variations do exist due to the physical and racial characteristics of an individual. The spiral ladder technique described here uses multiple landmarks that appear in a stepwise manner as a beginner proceeds through the surgery as a road map to the nerve trunk. This simple adoption of a cluster of existing landmarks increases the certainty factor. This method may help beginners and in turn, reduce the chances of iatrogenic facial nerve injuries.

Oral cancer in India, a growing problem: Is limiting the exposure to avoidable risk factors the only way to reduce the disease burden?

Cancer represents an uncontrolled growth of cells that invade and cause damage to the adjacent tissues. Globally oral cancer ranks as the sixth most common type of cancer. As compared to the west, the problem of oral cancer is significantly higher in India. The spectrum of oral diseases is formed with oral cancer at one extreme and potentially malignant disorders (PMDs) at the other extreme. Screening programs for the early detection and prevention of oral cancer indicate that visual examination as a part of a population-based screening program reduces the mortality rate of oral cancer in high-risk individuals. Tobacco and alcohol consumption remains the main factors for oral cancer and education of the population about the ill effects of tobacco and alcohol consumption is necessary at a broader scale.

Multidimensional Mutational Profiling of the Indian HNSCC Sub-Population Provides IRAK1, a Novel Driver Gene and Potential Druggable Target.

Head and neck squamous cell carcinomas (HNSCC) include heterogeneous group of tumors, classified according to their anatomical site. It is the sixth most prevalent cancer globally. Among South Asian countries, India accounts for 40% of HNC malignancies with significant morbidity and mortality. In the present study, we have performed exome sequencing and analysis of 51 Head and Neck squamous cell carcinoma samples. Besides known mutations in the oncogenes and tumour suppressors, we have identified novel gene signatures differentiating buccal, alveolar, and tongue cancers. Around 50% of the patients showed mutation in tumour suppressor genes TP53 and TP63. Apart from the known mutations, we report novel mutations in the genes AKT1, SPECC1, and LRP1B, which are linked with tumour progression and patient survival. A highly curated process was developed to identify survival signatures. 36 survival-related genes were identified based on the correlation of functional impact of variants identified using exome-seq with gene expression from transcriptome data (GEPIA database) and survival. An independent LASSO regression analysis was also performed. Survival signatures common to both the methods led to identification of 4 dead and 3 alive gene signatures, the accuracy of which was confirmed by performing a ROC analysis (AUC=0.79 and 0.91, respectively). Also, machine learning-based driver gene prediction tool resulted in the identification of IRAK1 as the driver (p-value = 9.7 e-08) and also as an actionable mutation. Modelling of the IRAK1 mutation showed a decrease in its binding to known IRAK1 inhibitors.

Does SLNB substitute END in the future with the sole advantage of preventing shoulder morbidity?

SLNB has emerged as a rational proposition in the management of early-stage oral cancer and has mixed responses within the oncological community. It is high time for the clinicians to look into the fact that, when a patient post-surgery has a regional recurrence within 6 months, it could be reasonable to believe that a tumor seed which was earlier an isolated tumor cell (ITC) or in the form of a micro-metastasis (MM) would have led to this. SLNB has the potential to become a standard of care in the future owing to the development and utility of better evaluation tools to pick nodal metastasis. It is not an overemphasizing statement to say that SLNB could become a standard recommendation in the near future, however, it still looks like a distant dream considering its logistical and technological limitations.