Poorly differentiated thyroid cancer (PDTC) is a rare but clinically highly significant entity because it accounts for most fatalities from non-anaplastic follicular cell-derived thyroid cancer. Due ...to the relative rarity of the disease and heterogeneous diagnostic criteria, studies on PDTC have been limited. In light of the evolution of ultra-deep next-generation sequencing technologies and through correlation of clinicopathologic and genomic characteristics of PDTC, an improved understanding of the biology of PDTC has been facilitated. Here, the diagnostic criteria, clinicopathologic characteristics, management, and outcomes in PDTC, as well as genomic drivers in PDTC reported in recent next-generation sequencing studies, are reviewed. In addition, future prospects in improving the outcomes in PDTC patients are reviewed.
PDTC patients tend to present with adverse clinicopathologic characteristics: older age, male predominance, advanced locoregional disease, and distant metastases. Surgery with clearance of all gross disease can achieve satisfactory locoregional control. However, the majority of PDTC patients die of distant disease. Five-year disease-specific survival for PDTC patients has been reported at 66%. On multivariate analysis, reported predictors of poor survival in PDTC patients have been older age (>45 years), T4a pathological stage, extrathyroidal extension, high mitotic rate, tumor necrosis, and distant metastasis at presentation. BRAF
or RAS mutations (27% and 24% of cases, respectively) remain mutually exclusive main drivers in PDTC. TERT promoter mutations represent the most common alteration in PDTC (40%). Mutation in translation initiation factor EIF1AX (11%) and tumor suppressor TP53 (16%) have also been reported in PDTC. High rates of novel mutations (MED12 and RBM10) have been reported in fatal PDTC (15% and 12%, respectively). Chromosome 1q gains represent the most common arm-level alterations in PDTC, and those patients show worse survival rates. Chromosome 22q losses are also found in PDTC and show strong association with RAS mutation.
These new insights into the clinicopathologic and molecular characteristics of PDTC, together with further advancement in ultra-deep sequencing technologies, will be conducive in narrowing the focus in order to develop novel targeted therapies and improve the outcomes in PDTC patients.
Summary Oral cancer is the sixth most common cancer worldwide, with a high prevalence in South Asia. Tobacco and alcohol consumption remain the most dominant etiologic factors, however HPV has been ...recently implicated in oral cancer. Surgery is the most well established mode of initial definitive treatment for a majority of oral cancers. The factors that affect choice of treatment are related to the tumor and the patient. Primary site, location, size, proximity to bone, and depth of infiltration are factors which influence a particular surgical approach. Tumors that approach or involve the mandible require specific understanding of the mechanism of bone involvement. This facilitates the employment of mandible sparing approaches such as marginal mandibulectomy and mandibulotomy. Reconstruction of major surgical defects in the oral cavity requires use of a free flap. The radial forearm free flap provides excellent soft tissue and lining for soft tissue defects in the oral cavity. The fibula free flap remains the choice for mandibular reconstruction. Over the course of the past thirty years there has been improvement in the overall survival of patients with oral carcinoma largely due to the improved understanding of the biology of local progression, early identification and treatment of metastatic lymph nodes in the neck, and employment of adjuvant post-operative radiotherapy or chemoradiotherapy. The role of surgery in primary squamous cell carcinomas in other sites in the head and neck has evolved with integration of multidisciplinary treatment approaches employing chemotherapy and radiotherapy either sequentially or concurrently. Thus, larynx preservation with concurrent chemoradiotherapy has become the standard of care for locally advanced carcinomas of the larynx or pharynx requiring total laryngectomy. On the other hand, for early staged tumors of the larynx and pharynx, transoral laser microsurgery has become an effective means of local control of these lesions. Advances in skull base surgery have significantly improved the survivorship of patients with malignant tumors of the paranasal sinuses approaching or involving the skull base. Surgery thus remains the mainstay of management of a majority of neoplasms arising in the head and neck area. Similarly, the role of the surgeon is essential throughout the life history of a patient with a malignant neoplasm in the head and neck area, from initial diagnosis through definitive treatment, post-treatment surveillance, management of complications, rehabilitation of the sequelae of treatment, and finally for palliation of symptoms.
Purpose of Review
The objectives of this article are to review the major changes in the staging of head and neck cancers and the rationale for the modifications.
Recent Findings
Information gathered ...from various institutional reports lead to a better understanding of the clinical and biological behavior of head and neck tumors, resulting in distinct outcomes, which were used to update the staging system.
Summary
This article reviews the changes in the staging of head and neck cancers published in the 8th edition of the AJCC/UICC TNM staging system.
•2082 patients with OSCC operated at a tertiary cancer care center from 1985 to 2015 were studied.•Age, comorbidity, margin, vascular and perineural invasion, T, N were independent predictors of ...OS.•Alcohol use, margin, vascular and perineural invasion, T, and N were independent predictors of DSS.•pN was the single most powerful and consistent predictor of outcome in patients with OSCC.
To present treatment results of oral squamous cell carcinoma (OSCC) at a tertiary cancer care center from 1985 to 2015.
A total of 2082 patients were eligible for this study. Main outcomes measured were overall survival (OS) and disease specific survival (DSS). Prognostic variables were identified with bivariate analyses using Kaplan-Meier curves and log-rank testing for comparison. A p-value < 0.05 was considered statistically significant and significant factors were entered into multivariate analysis. Median age was 62 years (16–100), 56% were men, 66% reported a history of tobacco use and 71% of alcohol consumption. The most common subsite was tongue (51%). Seventy-three percent of patients had cT1-2 and 71% had clinically negative necks (cN0). Surgery alone was performed in 1348 patients (65%), adjuvant postoperative radiotherapy in 608 patients (29%) and postoperative chemoradiation in 126 patients (6%). Neck dissection was performed in 920 patients with cN0, and in 585 patients with a clinically involved neck. The median follow-up was 37.6 months (range 1–382).
The 5-year OS and DSS were 64.4% and 79.3%, respectively. Age, comorbidities, margin status, vascular invasion, perineural invasion, AJCC 8th edition pT, and pN were independent prognostic factors of OS (p < 0.05). History of alcohol consumption, margin status, vascular invasion, perineural invasion, pT, and pN were independent prognostic factors of DSS (p < 0.05).
pN stage is the most powerful and consistent predictor of outcome in patients with OSCC treated with primary surgery and appropriate adjuvant therapy.
Health care equality is an idealistic goal that is difficult to achieve. However, uplifting the quality of care in surgery for cancer is achievable through several means, the most important of which ...is training of surgeons through properly structured training programs. However, such programs vary greatly, and no uniformity of curriculum exists throughout the world. On the other hand, several avenues are available for uplifting the quality of care through education and dissemination of knowledge at an individual level, an institutional level, a national level, and an international level. Efforts to uplift the quality of surgical care at an individual level can be by direct delivery of care or by dissemination of knowledge and experiences through personal interactions, lectures, and published works. Conferences, webinars, and travel grants are effective means offered by several institutions and national professional organizations. At an international level, however, much more can be done. For example, in the specialty of head and neck surgery, the International Federation of Head and Neck Oncologic Societies (IFHNOS) has done extraordinary work through world congresses, world tour programs, master courses on operative techniques, and its most impactful program, the Global On Line Fellowship in head and neck surgery and oncology. The programs offered by IFHNOS have had a huge impact on the quality of surgical care for head and neck cancer worldwide. This prototype can be used in many other specialties of surgical oncology to uplift the quality of care globally.
Background
We aimed to review our experience and the changing trends in the management of head and neck paragangliomas (HNPG) over the last three decades.
Methods
We retrospectively reviewed 103 ...patients with HNPG treated at our center (1986‐2017). We included patients treated with surgery, radiotherapy, and patients maintained under active surveillance.
Results
Of the surgically treated patients (n = 79), 20% (12/59) of the carotid body tumors (CBT) had a cranial nerve deficit as sequela compared to 95% (19/20) of the non‐CBT. Radiotherapy controlled growth in all tumors treated with this modality (n = 10). Of the initially observed patients, 70% (14/20) remained stable and did not require additional treatment. Stratifying by decades, there was a progressive increase in patients initially attempted to be observed and a decrease in upfront surgery. No deaths attributable to the HNPG were encountered.
Conclusions
Surgery is an effective treatment for CBT. Nonsurgical treatment should be considered for non‐CBT.
Background: Complete hepatic venous isolation and extracorporeal charcoal hemoperfusion (HVI·CHP) can limit systemic exposure to high-dose chemotherapeutic agents when given by hepatic arterial ...infusion (HAI). The purpose of this study was to determine if the concomitant use of sodium thiosulfate (STS) could further expand the advantages of pharmacologic delivery of HVI·CHP for cisplatin (CDDP) during HAI chemotherapy. Methods: CDDP (4mg/kg) was administered over 20 minutes via HAI under conditions of HVI·CHP in 14 mongrel dogs. HVI·CHP was performed for 30 minutes after initiation of HAI. During CDDP infusion, 7 dogs each received 400 mg/kg STS (a 100-fold molar ratio to CDDP) over 20 minutes via the prefilter (STS group) circuit line, while the remaining 7 dogs (controls) received no STS. Blood samples were taken serially from the prefilter circuit line (hepatic venous blood), postfilter line, and the left carotid artery (systemic blood). The free and total CDDP concentrations in these samples were determined by flameless atomic absorption spectrophotometry. Results:During 20 minutes HAI of CDDP, the mean CDDP extraction ratios (ER) by CHP filter were always higher in the STS group than in the control group, regardless of the form (free or total) of CDDP. The differences between the STS and control groups in the extraction ratios of free and total CDDP were significant at all time points measured (P < .05). Consequently, systemic exposure to CDDP, as assessed by area under the time-concentration curve of total CDDP, was significantly lower in the STS group than in the control group (P < .05). Conclusions: These results indicated that concomitant STS infusion could further increase the effect of HVI·CHP on CDDP removal after HAI.
Active surveillance of low-risk papillary thyroid cancer (PTC) is now an accepted alternative to immediate surgery, but experience with this approach outside of Japan is limited. The kinetics ...(probability, rate, and magnitude) of PTC tumor growth under active surveillance have not been well defined.
To describe the kinetics of PTC tumor growth during active surveillance.
Cohort study of 291 patients undergoing active surveillance for low-risk PTC (intrathyroidal tumors ≤1.5 cm) with serial tumor measurements via ultrasonography at a tertiary referral center in the United States.
Active surveillance.
The cumulative incidence, rate, and magnitude of the change in tumor diameter or volume, as well as associations with patient and tumor characteristics.
Of the 291 patients, 219 (75.3%) were women; mean (SD) age was 52 (15) years. During a median (range) active surveillance of 25 (6-166) months, growth in tumor diameter of 3 mm or more was observed in 11 of 291 (3.8%) patients, with a cumulative incidence of 2.5% (2 years) and 12.1% (5 years). No regional or distant metastases developed during active surveillance. In all cases, 3-dimensional measurements of tumor volume allowed for earlier identification of growth (median, 8.2 months; range, 3-46 months before increase in tumor diameter). In multivariable analysis, both younger age at diagnosis (hazard ratio per year, 0.92; 95% CI, 0.87-0.98; P = .006) and risk category at presentation (hazard ratio for inappropriate, 55.17; 95% CI, 9.4-323.19; P < .001) were independently associated with the likelihood of tumor growth. Of the tumors experiencing volume growth, kinetics demonstrated a classic exponential growth pattern, with a median doubling time of 2.2 years (range, 0.5-4.8 years; median r2 = 0.75; range, 0.42-0.99).
The rates of tumor growth during active surveillance in a US cohort with PTCs measuring 1.5 cm or less were low. Serial measurement of tumor volumes may facilitate early identification of tumors that will continue to grow and thereby inform the timing of surveillance imaging and therapeutic interventions.
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