Lymphovascular invasion and risk of recurrence in papillary thyroid carcinoma.

BACKGROUND: Lymphovascular invasion (LVI) is an established adverse prognostic factor in many cancers, however, there are few studies assessing its significance in papillary thyroid carcinoma (PTC). We aimed to determine if LVI is an independent prognostic factor in PTC. METHODS: We conducted a single institution retrospective analysis of 610 patients with PTC treated between 1987 and 2016. LVI was defined as the presence or absence of cancer cells in blood vessels and/or lymphatics on histopathology. Multivariate Cox regression analysis was used to evaluate the association between LVI and recurrence-free survival (RFS). RESULTS: The study cohort included 481 (78.9%) females and 129 (21.1%) males, with a median age of 47.6 years and median follow-up of 3.4 years. LVI was present in 56 (9.2%) patients and was associated with nodal metastases (P < 0.001), extrathyroidal extension (P < 0.001), extranodal extension (P < 0.001), multifocality (P = 0.018) and microscopic positive margins (P < 0.001). On univariate analysis, LVI was associated with reduced RFS (hazard ratio (HR) 2.3; 95% confidence interval (CI) 1.3-4.3; P = 0.007). However, after adjusting for nodal stage (pN0, pN1a, pN1b) there was no association between LVI and RFS (HR 1.3; 95% CI 0.7-2.5; P = 0.398). Similar results were obtained in full multivariate models adjusting for additional prognostic factors (HR 1.2; 95% CI 0.6-2.4; P = 0.627). CONCLUSION: LVI is strongly associated with other adverse prognostic factors in PTC, particularly the presence and extent of nodal metastases. However, after adjusting for these, LVI is not an independent predictor of recurrence.

The extent of extrathyroidal extension is a key determinant of prognosis in T4a papillary thyroid cancer.

BACKGROUND AND OBJECTIVES: In papillary thyroid cancer (PTC), the adverse prognostic impact of extrathyroidal extension (macro-ETE) invading the subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve (T4a disease) is well established. We investigated whether the extent of macro-ETE, defined as "limited" with single structure involvement (lim-ETE) and "extensive" with multiple structures involved (ext-ETE), influences prognosis in T4a PTC. METHODS: A retrospective analysis of 610 patients with PTC identified 39 with T4a disease, including 26 with lim-ETE and 13 with ext-ETE. Univariate Cox regression was used to assess the relationship between the extent of macro-ETE and recurrence-free survival (RFS). RESULTS: Ext-ETE was associated with a five times increased risk of recurrence compared to lim-ETE (HR 5.0, P < .030), with or without adjustment for radioactive iodine administration and after adjustment for margin status (HR 4.7; P = .041). A low-risk subset of T4a disease comprising of patients aged less than 55 years with lim-ETE and clear margins accounted for one-third of the cohort and demonstrated an excellent 5-year RFS of 92%. CONCLUSIONS: The extent of macro-ETE appears to be an important determinant of prognosis in T4a PTC. A low-risk subset of T4a disease exists with an excellent prognosis.

Number of nodal metastases and prognosis in metastatic cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: Existing prognostic systems for metastatic cutaneous squamous cell carcinoma of the head and neck (cSCCHN) do not discriminate between the number of involved nodes beyond single versus multiple. This study aimed to determine if the number of metastatic lymph nodes is an independent prognostic factor in metastatic cSCCHN and whether it provides additional prognostic information to the American Joint Committee on Cancer (AJCC) staging. METHODS: We retrospectively analysed 101 patients undergoing curative intent treatment for metastatic cSCCHN to parotid and/or neck nodes by surgery +/- radiotherapy at Liverpool Hospital, Sydney, Australia. The impact of number of nodal metastases on disease-free survival (DFS) and risk of distant metastases was assessed using multivariate Cox regression. RESULTS: The mean number of nodal metastases was 2.5 (range 1-12). On multivariate analysis, increasing number of nodal metastases significantly predicted reduced DFS (hazard ratio 1.17; 95% confidence interval 1.05-1.30; P = 0.004), with a 17% increased risk of recurrence or death for each additional node. This remained significant in multivariate models adjusted for AJCC 8th edition nodal and TNM stages. Number of nodal metastases was also associated with risk of distant metastatic failure (hazard ratio 1.21; 95% confidence interval 1.05-1.39; P = 0.009). CONCLUSION: Increasing number of nodal metastases is associated with decreased DFS and increased risk of distant metastases in metastatic cSCCHN, with a cumulative risk increase with each additional node. It provides additional prognostic information to the AJCC staging, which may be improved by incorporating information on the number of nodal metastases beyond the current single versus multiple distinction.

Microscopic positive margins strongly predict reduced disease-free survival in pT4a papillary thyroid cancer.

BACKGROUND: Although microscopic positive margins appear to have no independent prognostic impact in papillary thyroid cancer (PTC), this may not be the case in pT4a tumors. METHODS: Retrospective analysis of 610 patients with PTC, 39 with pT4a tumors, to determine if microscopic positive margins impact disease-free survival (DFS) in pT4a PTC. RESULTS: On univariate analysis, microscopic positive margins were not associated with reduced DFS in patients with no extrathyroidal extension (ETE) (hazard ratio [HR], 1.7; P = 0.32), microscopic ETE (HR, 1.6; P = 0.36), or macroscopic ETE limited to strap muscles (HR, 1.2; P = 0.87). In contrast, microscopic positive margins were associated with reduced DFS in T4a disease (HR, 4.1; P = 0.04). Disease recurrence was nodal, distant, or biochemical, and did not occur directly at the site of positive margins. CONCLUSION: Although microscopic positive margins do not influence DFS in the majority of patients with PTC, they are associated with a fourfold increased risk of recurrence in pT4a disease.

A critical analysis of the prognostic performance of the 8th edition American Joint Committee on Cancer staging for metastatic cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: The 8th edition AJCC staging of cutaneous squamous cell carcinoma of the head and neck (cSCCHN) incorporated extranodal extension (ENE) for the first time. This study compared the prognostic performance of the 7th and 8th edition staging for cSCCHN with nodal metastases. METHODS: Retrospective analysis of 96 patients with metastatic cSCCHN, comparing the ability of staging systems to predict disease-specific and overall survival (OS) using the proportion of variation explained and Harrell's C-index. RESULTS: In AJCC8, the N classification was upstaged in 77% of patients due to the presence of ENE and 88% of patients were classified as TNM stage IV. AJCC8 was inferior to AJCC7 in predicting disease-specific survival for both N and TNM stages, and OS by TNM stage. CONCLUSIONS: The majority of patients with metastatic cSCCHN have ENE and are classified as TNM stage IV based on the 8th edition staging, resulting in poor prognostic performance.

The Prognostic Impact of Tumor Size in Papillary Thyroid Carcinoma is Modified by Age.

BACKGROUND: Although the importance of tumor size in papillary thyroid cancer (PTC) is well established, there is no research investigating whether age modifies the impact of tumor size, and there is conflicting evidence regarding optimal size thresholds for prognostic discrimination. We aimed to verify that tumor size is an independent prognostic factor in PTC, investigate the impact of patient age, and identify optimal size cutoffs for risk stratification using objective measures of model performance. METHODS: A retrospective analysis of 574 patients with PTC, using multivariate Cox regression models to test the impact of tumor size on recurrence-free survival (RFS). Subgroup analyses were performed in patients aged <55 and ≥55 years. Exploratory analyses to identify optimal size cutoffs for prognostic discrimination were performed using the proportion of variation explained (PVE) and Harrell's C-index. RESULTS: Tumor size predicted RFS on multivariate analysis in the overall study cohort (hazard ratio [HR] 1.16; [95% confidence interval (CI)1.01-1.34]; p = 0.038). In subgroup analysis, there was no association between tumor size and RFS in patients aged <55 years (HR 1.11; [CI 0.89-1.38]; p = 0.362). In contrast, size was an independent predictor of RFS in patients aged ≥55 years (HR 1.52; [CI 1.11-2.07]; p = 0.009). In this subgroup, an optimal size threshold of >2 cm versus ≤2 cm (HR 5.24; [CI 2.30-11.92]; p < 0.001; PVE: 36%; C-index: 0.66) provided the greatest prognostic discrimination. There was no incremental improvement in prognostic value by further stratification of size. CONCLUSION: In our PTC cohort, the impact of tumor size on RFS was limited to patients aged ≥55 years. A single size threshold of 2 cm maximized prognostic discrimination with tumors >2 cm associated with a five times higher risk of recurrence than those ≤2 cm. These findings need to be validated in independent large cohorts and the potential management and staging implications further studied.

Microscopic positive margins in papillary thyroid cancer do not impact disease recurrence.

BACKGROUND: The prognostic significance of microscopic positive margins in papillary thyroid carcinoma (PTC) remains unclear. The aim of this study was to determine if microscopic positive margins are associated with increased risk of disease recurrence. METHODS: This is a retrospective analysis of 610 patients with PTC using multivariate Cox regression to evaluate the association between microscopic positive margins and disease-free survival. RESULTS: Microscopic positive margins were found in 67 (11%) patients and associated with extrathyroidal extension (P < 0.001), multifocality (P < 0.001), nodal metastases (P < 0.001), lymphovascular invasion (P < 0.001), age ≥55 years (P = 0.048), administration of radioactive iodine (RAI) therapy (P = 0.001) and a trend towards larger tumour size (18 versus 15 mm; P = 0.074). After a median follow-up of 3.4 years, there were 83 recurrences. Although involved margins were associated with increased risk of recurrence on univariate analysis (hazard ratio 2.6, 95% confidence interval 1.5-4.6; P = 0.001), there was no association after adjusting for age, nodal metastases, tumour size and extrathyroidal extension on multivariate analysis (hazard ratio 1.5, 95% confidence interval 0.8-2.9; P = 0.242). Similar results were obtained after adjusting for RAI and if margins were analysed as focal versus widely positive. In our study cohort, patients with involved margins generally had other indications for RAI. However, in the nine patients who did not receive RAI, there was no recurrence in the thyroid bed. CONCLUSION: Despite a strong association between microscopic positive margins and other adverse prognostic factors in PTC, there is no independent association with disease recurrence on multivariate analysis. Microscopic positive margins are rare (1.1%) in the absence of other indications for RAI.

An Analysis of The American Joint Committee on Cancer 8th Edition T Staging System for Papillary Thyroid Carcinoma.

Background: The American Joint Committee on Cancer (AJCC) removed microscopic extrathyroidal extension (ETE) from the 8th edition T staging for papillary thyroid cancer (PTC) based on increasing evidence that it is not an independent prognostic factor. Objectives: We compared the prognostic performance of AJCC 7th (pT7) and 8th (pT8) edition T stage systems, particularly in patients ≥55 years old without macroscopic ETE or distant metastases in whom T classification affects AJCC Tumor Node Metastasis (TNM) stage. Method: A retrospective analysis of disease-free survival (DFS) in 577 patients with PTC comparing pT8 vs pT7 using the Akaike information criterion (AIC), Harrell's C-index, and Proportion of Variation Explained (PVE). Results: Of 105 patients with AJCC7 T3 disease, 74 were down-staged. Overall, the prognostic performance of pT7 and pT8 was similar. However, in patients ≥55 years old without macroscopic ETE or distant metastases, pT8 was inferior to pT7 on the basis of higher AIC, lower C-index (0.67 vs 0.76), and lower PVE (30% vs 45%). In this subset, microscopic ETE was associated with multiple other adverse prognostic features and reduced DFS (hazard ratio, 2.8; 95% confidence interval, 1.5 to 5.2; P = 0.002), irrespective of tumor size. Discussion: In our cohort, pT8 was inferior to pT7 in patients ≥55 years old without macroscopic ETE or distant metastases in whom T classification affects TNM stage. Microscopic ETE was strongly associated with other adverse prognostic factors and reduced DFS in this patient subgroup and may be an effective surrogate for disease biology in PTC, irrespective of whether it is an independent prognostic factor.

Education and support needs in patients with head and neck cancer: A multi-institutional survey.

BACKGROUND: Head and neck cancer (HNC) encompasses a diverse group of tumors, and thus providing appropriate and tailored information to patients before, during, and after treatment is a challenge. The objective of the current study was to characterize the experience and unmet needs of patients with HNC with regard to information and support provision. METHODS: A 28-question, cross-sectional survey was completed by patients treated for HNC at 1 of 4 institutions in New South Wales, Australia (Chris O'Brien Lifehouse and Liverpool, Westmead, and Wollongong hospitals). It consisted of the adapted Kessler Psychological Distress Scale and questions assessing information quality, quantity, and format. RESULTS: A total of 597 patients responded. The mean age of the patients was 58 years (range, 21-94 years) with 284 men and 313 women (1:1.1). The majority of patients reported information concerning the disease process (76%), prognosis (67%), and treatment (77%) was sufficient, and approximately 50% reporting having received little or no information regarding coping with stress and anxiety. A substantial percentage of patients reported receiving minimal information concerning psychosexual health (56%) or the availability of patient support groups (56%). The majority of patients preferred access to multiple modes of information delivery (72%), with the preferred modality being one-on-one meetings with a health educator (37%) followed by internet-based written information (19%). CONCLUSIONS: Patients with HNC are a diverse group, with complex educational and support needs. Patients appear to be given information regarding survivorship topics such as psychological well-being, patient support groups, and psychosexual health less frequently than information concerning disease and treatment. Verbal communication needs to be reinforced by accessible, well-constructed, written and multimedia resources appropriate to the patient's educational level. Cancer 2017;123:1949-1957. © 2017 American Cancer Society.