Revisiting the Relationship between Tumor Size and Risk in Well-Differentiated Thyroid Cancer.

INTRODUCTION: Large tumor size is associated with poorer outcomes in well-differentiated thyroid cancer (WDTC), yet it remains unclear whether size >4 cm alone confers increased risk, independent of other markers of aggressive disease. The goal of this study was to assess the relationship between tumor size, other high-risk histopathologic features, and survival in WDTC, and to evaluate the significance of 4 cm as a cutoff for management decisions. METHODS: Patients with WDTC were identified from the National Cancer Database (2010-2015) and categorized by tumor size [i.e., small (≤4 cm) or large (>4 cm)] and presence of high-risk histopathologic features (e.g., extrathyroidal extension). First, propensity score matching was used to identify patients who were similar across all other observed characteristics except for small vs. large tumor size, and a multivariable Cox proportional hazards model was used to estimate the relationship between tumor size and survival. Second, we assessed whether the presence of high-risk features demonstrate conditional effects on survival based on the presence of tumor size >4 cm using an interaction term. Finally, additional models assessed the relationship between incremental 1 cm increases in tumor size and survival. Analyses were repeated using a validation cohort from the Surveillance, Epidemiology, and End Results Program (2008-2013). RESULTS: Of 193,133 patients in the primary cohort, 7.9% had tumors >4 cm, and 30% had at least one high-risk feature. After matching, tumor size >4 cm was independently associated with worse survival (HR 1.63, p<0.001). However, tumor size >4 cm and one or more other high-risk features together yielded worse survival than either size >4 cm alone (MMD: 0.70, p<0.001) or other high-risk features alone (MMD: 0.49, p<0.001). When assessed in 1 cm increments, the largest increases in hazard of death occurred at 2 cm and 5 cm, not 4 cm. Results from the validation cohort were largely consistent with our primary findings. CONCLUSIONS: Concomitant high-risk features confer worse survival than large tumor size alone, and a 4 cm cutoff is not associated with the greatest increase in risk. These findings support a more nuanced approach to tumor size in the management of WDTC.

Surgical Management of Metastatic Adrenocortical Carcinoma.

Introduction: Adrenocortical carcinoma (ACC) is a notoriously aggressive cancer with a dismal prognosis, especially for patients with metastatic disease. Metastatic ACC is classically a contraindication to operative management. Here, we evaluate the impact of primary tumor resection and metastasectomy on survival in metastatic ACC. Methods: We performed a retrospective cohort study of patients with metastatic ACC (2010-2019) utilizing the National Cancer Database. The primary outcome was overall survival (OS). Cox proportional hazards models were developed to evaluate the associations between surgical management and survival. Propensity score matching (PSM) was utilized to account for selection bias in receipt of surgery. Results: Of 976 subjects with metastatic ACC, 38% underwent surgical management. Median OS across all patients was 7.6 months. On multivariable Cox proportional hazards regression, primary tumor resection alone (HR: 0.523; p<0.001) and primary resection with metastasectomy (HR: 0.372; p<0.001) were significantly associated with improved OS. Metastasectomy alone had no association with OS (HR: 0.909; p=0.740). Primary resection with metastasectomy was associated with improved OS over resection of the primary tumor alone (HR: 0.636; p=0.018). After PSM, resection of the primary tumor alone remained associated with improved OS (HR 0.593; p<0.001), and metastasectomy alone had no survival benefit (HR 0.709; p=0.196) compared with non-operative management; combined resection was associated with improved OS over primary tumor resection alone (HR 0.575, p=0.008). Conclusion: In metastatic ACC, patients may benefit from primary tumor resection alone or in combination with metastasectomy, however further research is required to facilitate appropriate patient selection.

Defining Optimal Management of Non-metastatic Adrenocortical Carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive, deadly malignancy. Resection remains the primary treatment; however, there is conflicting evidence regarding the optimal approach to and extent of surgery and the role of adjuvant therapy. We evaluated the impact of surgical technique and adjuvant therapies on survival in non-metastatic ACC. METHODS: We performed a retrospective cohort study of subjects who underwent surgery for non-metastatic ACC between 2010 and 2019 utilizing the National Cancer Database. The primary outcome was overall survival. Cox proportional hazards models were developed to identify associations between clinical and treatment characteristics and survival. RESULTS: Overall, 1175 subjects were included. Their mean age was 54 ± 15 years, and 62% of patients were female. 67% of procedures were performed via the open approach, 22% involved multi-organ resection, and 26% included lymphadenectomy. Median survival was 77.1 months. Age (hazard ratio [HR] 1.019; p < 0.001), advanced stage (stage III HR 2.421; p < 0.001), laparoscopic approach (HR 1.329; p = 0.010), and positive margins (HR 1.587; p < 0.001) were negatively associated with survival, while extent of resection (HR 1.189; p = 0.140) and lymphadenectomy (HR 1.039; p = 0.759) had no association. Stratified by stage, laparoscopic resection was only associated with worse survival in stage III disease (HR 1.548; p = 0.007). Chemoradiation was only associated with improved survival in patients with positive resection margins (HR 0.475; p = 0.004). CONCLUSION: Tumor biology and surgical margins are the primary determinants of survival in non-metastatic ACC. Surgical extent and lymphadenectomy are not associated with overall survival. In advanced disease, the open approach is associated with improved survival.

Tricks of the trade: Techniques for preoperative localization in reoperative parathyroidectomy.

BACKGROUND: Reoperative parathyroidectomy for recurrent/persistent primary hyperparathyroidism (PHPT) has high rates of failure. The goal of this study was to analyze our experience with imaging and parathyroid vein sampling (PAVS) for recurrent/persistent PHPT. METHODS: We performed a retrospective cohort study (2002-2018) of patients with recurrent/persistent PHPT undergoing reoperative parathyroidectomy. RESULTS: Among 181 patients, the most common imaging study was sestamibi (89.5%), followed by ultrasound (75.7%). CT had the highest rate of localization (70.8%) compared to sestamibi (58.0%) and ultrasound (47.4%). PAVS was performed in 25 patients, and localized in 96%. Ultrasound and sestamibi both demonstrated 62% PPV for operative pathology, compared to 41% in CT. PAVS was 95% sensitive with 95% PPV for predicting the correct side of abnormal parathyroid tissue. CONCLUSIONS: We recommend a sequential imaging evaluation for reoperative parathyroidectomy, with sestamibi and/or ultrasound followed by CT. PAVS should be considered if non-invasive imaging fails to localize.

External beam radiotherapy for thyroid cancer: Patients, complications, and survival.

BACKGROUND: Patterns of utilization of external beam radiation therapy (EBRT) in thyroid cancer are incompletely described. We characterize therapeutic intent, complications, and survival in thyroid cancer treated with EBRT. METHODS: In this retrospective study of 105 thyroid cancer patients treated with EBRT at one institution (2008-2018), the primary outcome was overall survival. Secondary outcomes included incomplete treatment, emergency department (ED) visits, weight change, and gastrostomy placement. RESULTS: Dominant histopathology was differentiated (44%), anaplastic (45%) and poorly-differentiated (11%) disease. EBRT was mainly utilized for locoregional control (differentiated 87%, poorly-differentiated 75%, anaplastic 92%). Palliative EBRT was more common in poorly-differentiated disease (42%). Weight loss was greater in aggressive/advanced disease (differentiated 10 lb, poorly-differentiated 27 lb, anaplastic 18 lb). Anaplastic cancer had higher rates of gastrostomy (34%) and lowest rates of treatment completion (83%). ED encounters were common (differentiated 44%, poorly-differentiated 50%, anaplastic 45%). Gastrostomy was associated with mortality on multivariable analysis in non-anaplastic malignancy. CONCLUSIONS: EBRT was most frequently administered for locoregional control in thyroid cancer. Despite complications, the majority of patients completed EBRT therapy.