Effect of age and gender in non-smokers with oral squamous cell carcinoma: Multi-institutional study.

BACKGROUND: In developing countries, oral squamous cell carcinoma (OSCC) is predominantly a cancer affecting older males who smoke tobacco. In countries with effective public health strategies, smoking rates are declining rapidly. It is not clear if patients who develop OSCC without these traditional risk factors represent a clinically distinct cohort with different prognosis. A recent analysis found that elderly non-smoking females with OSCC had significantly worse prognosis, concluding that this was a distinct patient population with poorer survival. The primary aim of this study was to determine the effect of gender and age on prognosis in OSCC, and the interaction between these two variables. METHODS: Multinational multi-institutional data were collected from six sites. The primary outcome of interest was disease specific survival (DSS). Time to local, regional, and distant recurrence were investigated as secondary outcomes. RESULTS: 3379 patients with OSCC were included. Males had significantly worse DSS compared to females (HR 1.24, 95% CI 1.08-1.43, p = 0.003). Females <70 years of age had significantly better DSS compared to females ≥70 years of age (HR 0.69, 95% CI 0.51-0.94, p < 0.001) but elderly females had similar DSS to males, regardless of age. When age was divided into three groups, the middle-aged group (45-69 years) had a significantly better DSS compared to elderly patients (HR 0.87, 95%CI 0.78-0.96, p < 0.001), however younger patients had similar DSS to elderly patients. When the effect of age (young v middle v elderly) was compared in each gender, young and middle-aged females had the most favourable DSS (log-rank p < 0.001). Middle-aged females who smoked had a 10% survival advantage compared to middle-aged males that smoked at five years. CONCLUSIONS: Age, gender, tumour subsite, and smoking status are important drivers of survival in OSCC. However, gender appears to be the most important predictor with young and middle-aged females having the most favourable prognosis.

Young age is not a predictor of disease specific survival in oral cancer: A multi-institutional study.

BACKGROUND: Over the last few decades evidence has accumulated for increasing incidence of oral cavity squamous cell carcinoma (OSCC) in a younger cohort. Prior studies examining the effect of age at diagnosis on prognosis have produced conflicting data. METHODS: A multi-institutional cohort study was performed across 6 different sites in Australia, Canada, India and Singapore. Disease-free (DFS), overall (OS) and disease-specific (DSS) survival were analysed. The association of the number of adverse features with survival outcomes was investigated. RESULTS: From 3179 patients, age was a significant predictor of OS with patients older than 45 years having a 66% increased risk of death (HR 1.66, 95%CI 1.33 - 2.07, p < 0.001). The number of adverse features was a significant predictor of OS with 3 or more adverse features having a 199% increased risk (HR 2.99, 95%CI 2.61-3.43. p < 0.001). The estimate effect was greater in patients ≤ 45 years (HR 3.49 vs HR 2.81). Age was not a significant predictor of DSS with similar rates of death from OSCC in multivariable models. The number of adverse features was a significant predictor of DFS with ≥ 3 adverse features having a 140% increased risk of death. The number of adverse features was a significant predictor of DSS with ≥ 3 adverse features having a 230% increased risk of disease specific death. CONCLUSIONS: Age is not an independent predictor of disease specific mortality in OSCC. Differences in outcomes are due to the confounding effect of adverse clinicopathological features and the ability to tolerate surgery and adjuvant therapy.

Phenotype-driven precision oncology as a guide for clinical decisions one patient at a time.

Genomics-driven cancer therapeutics has gained prominence in personalized cancer treatment. However, its utility in indications lacking biomarker-driven treatment strategies remains limited. Here we present a "phenotype-driven precision-oncology" approach, based on the notion that biological response to perturbations, chemical or genetic, in ex vivo patient-individualized models can serve as predictive biomarkers for therapeutic response in the clinic. We generated a library of "screenable" patient-derived primary cultures (PDCs) for head and neck squamous cell carcinomas that reproducibly predicted treatment response in matched patient-derived-xenograft models. Importantly, PDCs could guide clinical practice and predict tumour progression in two n = 1 co-clinical trials. Comprehensive "-omics" interrogation of PDCs derived from one of these models revealed YAP1 as a putative biomarker for treatment response and survival in ~24% of oral squamous cell carcinoma. We envision that scaling of the proposed PDC approach could uncover biomarkers for therapeutic stratification and guide real-time therapeutic decisions in the future.Treatment response in patient-derived models may serve as a biomarker for response in the clinic. Here, the authors use paired patient-derived mouse xenografts and patient-derived primary culture models from head and neck squamous cell carcinomas, including metastasis, as models for high-throughput screening of anti-cancer drugs.

Complications of thyroid surgery: prevention and management.

The essentials of thyroid surgery include intimate knowledge of thyroid gland anatomy, sound understanding of thyroid pathology and meticulous technique. While mortality due to thyroid surgery is rare, complications can result in debilitating sequelae. Thyroid surgeons need to understand and anticipate situations when these may occur, and actively take steps to prevent them, as treatment of these complications is often difficult and frustrating. Surgeons also need to maintain an audit of their own complication rates and convey these to patients instead of quoting data from published literature, which is biased towards high-volume specialized units rather than "real world data". This review addresses the common complications that occur during thyroid surgery and the issues therein.

Current concepts in the management of primary hyperparathyroidism.

Primary hyperparathyroidism is the commonest cause of hypercalcemia in the ambulatory setting. Widespread use of routine laboratory screening has resulted in a large number of patients presenting with subclinical disease. In truly asymptomatic patients, consensus guidelines have been developed to determine which patients need definitive treatment. The most common pathologic finding is parathyroid adenoma, followed by hyperplasia, double adenomas and parathyroid carcinoma. The mainstay of treatment is surgery. While there is still an important role for four gland exploration and evaluation, there is now considerable interest in a more focused surgical approach. This paradigm shift is based on localizing studies that combine sestamibi scanning with anatomic imaging, most commonly ultrasound scanning. A range of minimally invasive approaches have been developed to treat parathyroid adenomas, including unilateral and single gland explorations as well as a number of different endoscopic techniques. Intra-operative rapid parathormone assay has replaced histologic examination as a more effective method to confirm the adequacy of surgery in most cases. Functional localization and exploration using a gamma probe has also been described. The management of patients with persistent or recurrent hyperparathyroidism is difficult and requires a multidisciplinary approach.