Well-Differentiated Thyroid Cancer: Who Should Get Postoperative Radiation?

BACKGROUND: The mainstay of treatment of well-differentiated thyroid cancer (WDTC) is surgery followed by adjuvant radioactive iodine therapy. Postoperative radiation therapy (PORT) is rarely used. OBJECTIVE: The aim of our study was to report our experience of patients with WDTC who were selected to receive PORT. MATERIALS AND METHODS: After Institutional Review Board approval, patients who received PORT were identified from a departmental database of 6259 patients with WDTC treated with primary surgery from 1986 to 2015. We carried out propensity matching to compare outcomes with a cohort of patients who did not receive PORT. The main outcome of interest was central neck recurrence-free probability (CNRFP), while secondary outcomes were lateral neck recurrence-free probability (LNRFP), disease-specific survival (DSS), and overall survival (OS). RESULTS: From 6259 patients, 32 (0.5%) patients with a median age of 65.2 years received PORT. Tall-cell variant papillary thyroid carcinoma was the most common pathology (45%). Patients who received PORT had no difference in CNRFP compared with patients treated without PORT (10-year CNRFP 88% vs. 73%; p = 0.18). Furthermore, patients who received PORT had superior LNRFP (10-year LNRFP 100% vs. 62%; p = 0.001) compared with the no-PORT cohort. Despite this, patients who received PORT had similar DSS (71% PORT vs. 75% no-PORT) and OS (65% PORT vs. 58% no-PORT group) as the no-PORT cohort. CONCLUSIONS: Our data show that select patients who received PORT had improved locoregional recurrence-free probability; however, this did not translate into improved DSS and OS. At our institution, we recommend the use of PORT only in highly selected patients with locally advanced primary tumors who are deemed to have a high risk of central neck recurrence for which salvage surgery would result in unacceptable risk to the airway.

Young non-smokers with oral cancer: What are we missing and why?

OBJECTIVES: There has been an increase in young non-smokers (YNS) who develop oral cavity squamous cell carcinomas (OSCC). Oncological outcomes in YNS are controversial and etiology has not been well-defined. We hypothesize that the etiology of cancer development in YNS and their poor outcome is related to an impaired immune system. MATERIALS AND METHODS: From a database of 2073 OSCC patients treated with primary surgery between 1985 and 2015, 9% were young patients. We categorized patients as: ≤40 years-old/non-smokers (n = 100), ≤40 years-old/smokers (n = 80), >40 years-old/non-smokers (n = 595) and >40 years-old/smokers (n = 1298). Patient and tumor variables were used to calculate propensity scores and stabilized inverse probability of treatment weights were calculated. Weighted proportional hazard models were performed. Survival and recurrence outcomes of YNS were compared to the other 3 groups. Host immune status of YNS measured by peripheral blood neutrophil-to-lymphocyte ratio (NLR) was compared to 2 control groups (YNS with thyroid cancer and YNS with benign pathologies). RESULTS: After adjusting for tumor and host factors, YNS had a higher probability of death compared to young smokers. This was driven by a higher incidence of regional and distant recurrences. Host factors showed a strong association with outcomes suggesting YNS may have an impaired immune system. Compared to the control cohorts YNS with OSCC had a higher NLR (p = .006). CONCLUSION: When adjusted by relevant covariates, YNS with OSCC have poorer survival than their young smoker counterparts. Our results suggest that an impaired immune system may be partly responsible for OSCC development and poorer outcomes in YNS.

Outcomes in surgical management of sinonasal malignancy-A single comprehensive cancer center experience.

BACKGROUND: Sinonasal malignancies are a complex and diverse group of tumors. Over the past five decades, treatment advances have changed the management paradigms for these tumors. Our aim was to analyze the outcomes of patients from a comprehensive cancer center. MATERIALS AND METHODS: We retrospectively assessed 400 patients with sinonasal malignancies treated with surgery at our center between 1973 and 2015. Multiple variables were reviewed to assess the influence on 5-year outcomes. RESULTS: The median age was 56 years (IQR 46.8-68). Two hundred and fifty-nine (65%) were males and 141 (35%) were females. Overall survival (OS) and disease-specific survival (DSS) improved in the last analyzed decade. Orbital invasion, advanced pT-classification and pN-classification, and melanoma histology were associated with poorer outcomes. CONCLUSION: Treatment outcomes for patients with sinonasal malignancy have improved over time. This is likely multifactorial with advances in surgical technique, adjuvant treatment, and patient selection. pT-classification, pN-classification, orbital invasion, and histology are predictive of survival.

Follicular and Hurthle Cell Carcinoma: Comparison of Clinicopathological Features and Clinical Outcomes.

Background: Follicular thyroid carcinoma (FTC) and Hurthle cell carcinoma (HCC) are rare and aggressive thyroid cancers with limited published data comparing their outcomes or regarding their subtypes. The aim of this study was to describe clinicopathological features and compare clinical outcomes of patients with FTC and HCC based on the 2017 World Health Organization definition and extent of vascular invasion (VI). Methods: We retrospectively studied 190 patients with HCC and FTC primarily treated with surgery at Memorial Sloan Kettering Cancer Center between 1986 and 2015. Patients were classified as minimally invasive (MI), encapsulated angioinvasive with focal VI (EA-FVI), encapsulated angioinvasive with extensive VI (EA-EVI), and as widely invasive (WI). To compare clinical outcomes, patients were grouped as follows: group 1 = FTC-MI and FTC EA-FVI, group 2 = FTC EA-EVI and FTC-WI, group 3 = HCC-MI and HCC EA-FVI, group 4 = HCC EA-EVI and HCC-WI. Outcomes of interest were overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS), and distant recurrence-free survival (DRFS). Outcomes were determined using the Kaplan-Meier method and compared with log-rank test. Results: Patients with HCC (n = 111) were more likely to be older than 55 years old (59% vs. 27%, p < 0.001) with a tendency to present with more extensive VI (33% vs. 19%, p = 0.07) compared with FTC (n = 79). Comparing groups 1, 2, 3, and 4, group 4 patients were more likely to recur (DFS 98%, 93%, 98% vs. 73%, respectively, p = 0.0069). There was no statistically significant difference in OS, DSS LRRFS, or DRFS. Stratified by extent of VI (no, focal, and extensive VI), patients with extensive VI were more likely to recur (RFS 100%, 95%, 77%, p = 0.0025) and had poorer distant control (DRFS: 100%, 95%, 80%, p = 0.022), compared with patients absent or focal VI. Conclusions: Accurate assessment of the extent of VI and tumor phenotype (follicular vs. Hurthle) are essential in identifying patients at higher risk of recurrence.

Does macroscopic extrathyroidal extension to the strap muscles alone affect survival in papillary thyroid carcinoma?

BACKGROUND: Macroscopic extrathyroidal extension to structures adjacent to the thyroid gland is one of the most important predictors of survival in papillary thyroid carcinoma. However, the prognostic significance of macroscopic extrathyroidal extension to strap muscles alone is unknown. The aim of this study is to determine the impact on survival in patients with macroscopic extrathyroidal extension to strap muscles alone compared to those with no macroscopic extrathyroidal extension and macroscopic extrathyroidal extension involving other adjacent structures. METHODS: After institutional review board approval, adult papillary thyroid carcinoma patients were identified from an institutional database of 6,259 patients undergoing initial surgery for well-differentiated thyroid carcinoma from 1986 to 2015. Patients were classified as having no macroscopic extrathyroidal extension, macroscopic extrathyroidal extension to strap muscles alone, or macroscopic extrathyroidal extension to other adjacent structures. Disease-specific survival was calculated using the Kaplan-Meier method and groups were compared using the log-rank test. A P value < .05 was considered statistically significant and significant factors were used in a Cox proportional hazard model to predict disease-specific survival. RESULTS: There were 5,880 patients included in the analysis; 5,485 patients (93.3%) in the no macroscopic extrathyroidal extension group, 179 (3.0%) in the macroscopic extrathyroidal extension to strap muscles alone group and 216 (3.7%) in the macroscopic extrathyroidal extension involving other adjacent structures group. With a median follow-up of 64 months, the estimated 10-year disease-specific survival for patients with no macroscopic extrathyroidal extension, macroscopic extrathyroidal extension to strap muscles alone, and macroscopic extrathyroidal extension involving other adjacent structures were 98.9%, 95.7%, and 83.7%, respectively (P < .0001). In the ≥55-year-old cohort, the estimated 10-year disease-specific survival for patients with no macroscopic extrathyroidal extension, macroscopic extrathyroidal extension to strap muscles alone, and macroscopic extrathyroidal extension involving other adjacent structures were 97.6%, 89.3%, and 68.1%, respectively (P <.0001). After controlling for pathological nodal stage and distant metastasis stage, extent of extrathyroidal extension remained an independent predictor of disease-specific survival; patients with macroscopic extrathyroidal extension to strap muscles alone had a 3.3-fold increased likelihood of a disease-specific death compared to no macroscopic extrathyroidal extension patients (hazard ratio 3.294; 95% confidence interval 1.076-10.086, P < .0368). CONCLUSION: In our study, patients aged ≥55 years with papillary thyroid carcinoma and macroscopic extrathyroidal extension to strap muscles alone appear to have an increased likelihood of a disease-specific death compared to patients with no macroscopic extrathyroidal extension.

Surgical Management of Low-/Intermediate-Risk Node Negative Thyroid Cancer: A Single-Institution Study Using Propensity Matching Analysis to Compare Thyroid Lobectomy and Total Thyroidectomy.

Background: The approach for surgical treatment of patients with low-/intermediate-risk T1T2N0/Nx well-differentiated thyroid cancer (WDTC)-total thyroidectomy (TT) versus thyroid lobectomy (TL)-remains a controversial topic. Conducting a randomized controlled trial (RCT) would be the gold standard to address this issue. However, this is challenging due to excellent survival outcomes, and therefore, high number of patients and long-term follow-up would be required. As an alternative to RCT, we have used propensity score (PS) matching to determine if T1T2N0/Nx patients selected to have TL had equivalent outcomes to a similar group treated with TT. Methods: After institutional review board approval, a database of 6259 patients with WDTC treated with primary surgery at our institution between 1985 and 2016 was analyzed to identify patients with T1T2N0/Nx cancers. Of 3756 patients identified, 943 were managed by TL and 2813 by TT. To control for possible confounders and reduce potential bias, we selected age, sex, histology, 131I therapy, American Thyroid Association risk, and American Joint Committee Cancer stage as our PS matching criteria. Subsequently, 918 TL patients were successfully matched with 918 TT patients. The Pearson χ2 test or Fisher's exact test was used to compare categorical covariates, and Student's t-test was used for comparison of continuous variables between the two groups. Disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method and compared using the log-rank test. Results: After PS matching, there were no significant differences between TL and TT patients for OS (10-year OS: 92.2% vs. 91.3%, p = 0.9668), DSS (10-year DSS: 100% vs. 99.1%, p = 0.1967), or RFS (10-year RFS: 99.5% vs. 98.3%, p = 0.079). Conclusions: For low-/intermediate-risk patients with intrathyroidal thyroid cancer <4 cm, patients selected for TL have similar survival outcomes to a comparable group treated by TT.

Mucoepidermoid carcinoma: Evaluating the prognostic impact of primary tumor site.

Mucoepidermoid carcinoma (MEC) is one of the most common salivary gland malignancies. Our aim was to evaluate the prognostic impact of primary tumor site in patients with MEC. MATERIAL AND METHODS: This cohort identified 308 patients with MEC who underwent primary surgery between 1985 and 2015. Survival outcomes were determined using the Kaplan-Meier method. Hazard ratios for primary site were determined using the Cox proportional-hazards model. RESULTS: One hundred eighty (58%) patients were diagnosed with minor and 128 (42%) with major salivary gland cancer. Primary site in the minor salivary gland group included 137 (44%) oral cavity, 38 (12%) pharynx, 3 (0.9%) nasal cavity, and 2 (0.6%) trachea and larynx. The major salivary gland group included 118 (38%) parotid, 8 (3%) submandibular, and 2 (0.6%) sublingual. With a median follow-up of 73 months, 5-year overall survival and disease-specific survival were 84% and 91%, respectively. Patients with tumors located in the hard palate and retromolar trigone had the best survival, while patients with tumors located in the paranasal sinuses and submandibular gland had the poorest survival. After controlling for tumor grade and stage, MEC primary site was not predictive of survival or recurrence. On multivariate analysis, worse DSS was associated with stage III-IV tumors (HR: 7,11; 95% CI: 1.19-26.43; p = 0.0034) and high-grade tumors (HR: 19.12; 95% CI: 2.26-162.77; p = 0.0068). CONCLUSIONS: While high grade and advanced overall stage were found to be independent predictors of worse survival, primary tumor site was not predictive of poor outcome.

Predictors of distant metastases in sinonasal and skull base cancer patients treated with surgery.

OBJECTIVES: Sinonasal and skull base tumors comprise a heterogeneous group of malignancies with a significant rate of distant recurrence (DR). The aim of this study was to analyze tumor and host factors, including pretreatment neutrophil-to-lymphocyte ratio (NLR), that predict DR in these patients. MATERIALS AND METHODS: We retrospectively reviewed sinonasal tumors and/or tumors involving the skull base treated with surgery between 1973 and 2015 (n = 473). We stratified NLR using the top 5 percentile as cutoff. Factors predictive of outcome were determined by Cox proportional hazards model. RESULTS: Most tumors were primary (81%) and 67% had skull base resection. The most common site was the nasal cavity (37%) and the most common histology was squamous cell carcinoma (34%). Most patients presented with advanced primary tumor stage (pT3/T4; 80%) and most had no regional neck disease (pNx/N0; 93%). A total of 104 patients developed DR. The 5-year overall and disease-specific survival for patients who developed DR were 36.4% and 35.8%, compared to 69.0% and 74.9% for patients who did not. Patients with DR had a higher percentage of NLR-high patients compared patients without DR (11% vs 3%, p = .006). In a multivariable analysis, melanoma histology (HR = 5.469, 95% CI 3.171-9.433), pT3/T4 (HR = 2.686, 95% CI 1.150-6.275), pN+ (HR = 6.864, 95% CI 3.450-13.653), and NLR-high (HR = 3.489, 95% CI 1.593-7.639) were independent predictors of DR. CONCLUSION: Melanoma histology, pT, pN, and high NLR predict DR, suggesting that both tumor and host factors need to be considered. NLR may act as a surrogate marker of the host́s immune system.

Predictors of surgical complications in patients with sinonasal malignancy.

OBJECTIVES: Sinonasal and skull base tumors are rare, making it difficult to identify trends in surgical outcome. This study examines complications in a large cohort of patients undergoing surgery for sinonasal malignancy. METHODS: Following IRB approval, an institutional database was reviewed to identify patients who underwent surgery for sinonasal or skull base malignancies from 1973 to 2016 at our institution. Charlson comorbidity index score and Clavien-Dindo grade were calculated. The main study endpoint was subgroup analysis of Clavien-Dindo Grade 0, Grades 1-2, and Grades 3-5 complications. An ordinal logistic regression model was constructed to assess the association between comorbidities, demographics, tumor characteristics, and surgical complications. RESULTS: In total, 448 patients met inclusion criteria. Perioperative mortality rate at 30 days was 1.6% (n = 7). The rate of severe complications (Clavien-Dindo 3 or higher) was 13.6% (n = 61). Multivariate analysis using an ordinal logistic regression model showed no association between Charlson comorbidity index score and Clavien-Dindo grade of postoperative complication. Advanced T-stage was significantly associated with complications (p = 0.0014; odds ratio: 3.442 [95% confidence interval: 1.615, 7.338]). CONCLUSION: Surgery for sinonasal and skull base tumors is safe with a low mortality rate. Advanced T-stage is associated with postoperative complications. These findings have implications for preoperative risk stratification. Key Points Surgery for sinonasal malignancy is safe with a 30 mortality of 1.6% and rate of severe complications of 12.8%. There is no association between patient comorbidity and post operative complication. On multivariate analysis, only advanced T stage was associated with increased rate of surgical complication.

Histologic evaluation of host immune microenvironment and its prognostic significance in oral tongue squamous cell carcinoma: a comparative study on lymphocytic host response (LHR) and tumor infiltrating lymphocytes (TILs).

BACKGROUND: Host immune microenvironment is a key component of anti-tumoral immune response, influencing tumor progression, regression, and treatment responses. There is a need for simple and reliable histologic measurements of host immune response in routine histopathologic diagnosis. METHODS: The prognostic value of lymphocytic host response (LHR), a qualitative histologic grading scheme, was compared to stromal/intratumoral TIL (sTIL/iTIL) percentage, a quantitative measurement in a retrospective study of 329 patients with oral tongue squamous cell carcinoma (OTSCC) of 4 cm or less in size. RESULTS: High sTIL predicted improved distant recurrence free survival on univariate survival analysis and was an independent prognostic factor for better overall survival on multivariate analysis. LHR and iTIL were not associated with the risk of nodal metastasis or outcome. CONCLUSIONS: sTIL appears to be a superior quantitative histologic measurement for the host immune microenvironment compared with the qualitative LHR grading scheme. sTIL is an independent prognostic factor for overall survival in OTSCC.

Margin status, local control, and disease-specific survival in surgically resected parotid carcinomas with parapharyngeal extension.

BACKGROUND: Resection of parotid carcinomas involving the parapharyngeal space is challenging. How this affects tumor margin control, recurrence, and survival is unclear. METHODS: Patients who underwent resection of parotid carcinomas between 1985 and 2015 at Memorial Sloan Kettering Cancer Center were evaluated for the impact of parapharyngeal extension (PPE) on margin status, local recurrence-free probability (LRFP), and disease-specific survival (DSS). RESULTS: Out of 214 patients in whom preoperative imaging was available for review, 22 (10.3%) had PPE. Matched by histotypes, carcinomas with PPE had comparable margin positivity (p = 0.479), T classification (p = 0.316), pathologic risk (p = 0.936), and adjuvant therapy (p = 0.617) to those without PPE. The 3-year LRFP was 88.9% versus 95.4% (hazard ratio [HR] 2.23 after adjusting for pT classification, p = 0.342) and the 5-year DSS was 74.2% versus 69.5% (adjusted HR 0.45, p = 0.232) in patients with and without PPE. CONCLUSION: PPE does not appear to worsen oncologic outcomes in the resection of parotid carcinomas.

The prognostic role of histologic grade, worst pattern of invasion, and tumor budding in early oral tongue squamous cell carcinoma: a comparative study.

Major pathology guidelines often mandate stating the histologic grade as a component of the pathology report for various types of cancer. However, the prognostic value of histologic grade in head and neck squamous cell carcinoma (HNSCC) is controversial at best, and there is a need for more reliable prognostic histologic factors to better stratify and manage patients with HNSCC. In this study, we compared three relevant histopathologic features (histologic grade, worst pattern of invasion (WPOI), and tumor budding) in a large single-center retrospective cohort of early oral tongue squamous cell carcinoma (OTSCC) with tumor greatest dimension ≤ 4 cm. Only histologic grade predicted distant metastasis free survival (DMFS) on univariate analysis. Tumor budding was associated with nodal metastasis, overall survival (OS), regional recurrence-free survival (RRFS), and DMFS and was a significant predictor for nodal metastasis on the multivariable logistic regression model. WPOI 5 was associated with high frequency of nodal metastasis and shortened OS and was an independent adverse prognostic factor for OS on multivariate analysis using the Cox proportional hazards model. WPOI and tumor budding were prognostically more relevant than histologic grade. Consideration should be given to include WPOI and tumor budding in the pathology reporting of OTSCC.

Depth of invasion versus tumour thickness in early oral tongue squamous cell carcinoma: which measurement is the most practical and predictive of outcome?

AIMS: The 8th edition of the American Joint Committee on Cancer (AJCC) Staging introduced depth of invasion (DOI) into the pT category of oral cavity squamous cell carcinoma. However, we noted multiple practical obstacles in accurately measuring DOI histologically in our daily practice. METHODS AND RESULTS: To compare the prognostic effects of DOI and tumour thickness (TT), a meticulous pathology review was conducted in a retrospective cohort of 293 patients with AJCC 7th edition pT1/T2 oral tongue squamous cell carcinoma. Overall survival (OS) and nodal metastasis rate at initial resection were the primary and secondary outcomes, respectively. We found that TT and DOI were highly correlated with a correlation coefficient of 0.984. The upstage rate was only 6% (18 of 293 patients) when using TT in the pT stage compared with using DOI. More importantly, DOI and TT, as well as pT stage using DOI and pT stage using TT, performed identically in predicting risk of nodal metastasis and OS. CONCLUSIONS: We therefore propose to replace DOI, a complicated measurement with many challenges, with TT in the pT staging system.

Factorial structure of a scale: Strategies Used by People to Promote Health--Chinese version.

BACKGROUND: The Strategies Used by People to Promote Health (SUPPH) is an instrument used to measure self-reported self-efficacy in patient populations. Self-efficacy has a major impact on quality of life and psychological well-being. Previous findings of dimensionality of the SUPPH vary, and cultural differences exist suggesting the need for further investigation and psychometric testing to establish construct validity of the SUPPH in different cultures. OBJECTIVE: The purpose of this study was to examine the factorial structure of the Chinese version of the SUPPH (C-SUPPH). METHODS: Using reports from 764 oncology patients in China, the factorial structure of the C-SUPPH was assessed via 2 analytical strategies. First-order confirmatory factor analysis (CFA) models were used to examine the dimensionality of the C-SUPPH; a second-order CFA was used to determine the existence of a factorial structure hierarchy of the C-SUPPH. RESULTS: Compared with the 2- and 4-factor solutions, the 3-factor CFA of the C-SUPPH had a better fit with the data (comparative fit index = 0.94, Tucker-Lewis index = 0.94, root-mean-square error of approximation = 0.05, the close-fit test P = .565, and standardized root-mean-square residual = 0.04). Our findings confirmed the 3-scale structure: Positive Attitude, Stress Reduction, and Making Decisions; together, the 3 factors represent an underlying higher-order factor, that of general self-care self-efficacy. CONCLUSIONS: The C-SUPPH has a valid factorial structure and can be readily applied to studying self-efficacy in Chinese patients who are diagnosed with cancers. IMPLICATIONS FOR PRACTICE: Our findings provide support for a culturally sensitive, reliable, and valid self-efficacy measure (the C-SUPPH) of Chinese adult cancer patients' self-care self-efficacy.

Testing measurement invariance of the Chinese version of the Strategies Used by Patients to Promote Health among patients with cancer.

BACKGROUND AND PURPOSE: The Chinese version of the Strategies Used by Patients to Promote Health (C-SUPPH) is a self-report instrument used to measure self-efficacy among patients with cancer. The purpose of this article is to examine measurement invariance of C-SUPPH using data of 764 cancer patients recruited in China. METHODS: Multigroup confirmatory factor analysis (CFA) models were applied across the selected sociodemographic groups of gender, age, education, and monthly income levels. RESULTS: The factorial structure and factor loadings (relationships between items and their underlying factors) of C-SUPPH were invariant across all sociodemographic groups. CONCLUSIONS: The findings showed that the C-SUPPH measures the same latent constructs/factors in the same way when administered to different sociodemographic groups and thus can be readily applied to studying self-efficacy of cancer patients in China.

Smartphone interventions for long-term health management of chronic diseases: an integrative review.

INTRODUCTION: Long-term health management is challenging for the rapidly growing number of patients with chronic diseases. Smartphone interventions offer promising solutions. This article presents features of smartphone interventions for long-term chronic condition management, illustrating how these applications benefit patients with chronic diseases. MATERIALS AND METHODS: Systematic searches for smartphone health interventions were conducted in five publication databases. Articles were included only if (1) the smartphone application (app) was exclusively developed for patients with chronic diseases and (2) the article incorporated a defined outcome measurement to evaluate the effects of the implemented intervention. Sixteen articles were included in the final review, including studies in diabetes, mental health problems, overweight, cancer, and chronic obstructive pulmonary disease. RESULTS: These studies found that the smartphone intervention was a completely or at least partially effective tool to assist in managing some chronic diseases. With the help of health-related smartphone apps, patients with chronic conditions (1) felt secure in the knowledge that their illnesses were closely monitored, (2) participated in their own health management more effectively, and (3) felt that they had not been forgotten by their doctors and were taken good care of even outside the hospital/clinic. CONCLUSIONS: However, there are limited smartphone apps for the long-term health management of chronic diseases. More smartphone apps need to be developed to help people manage chronic diseases.