Clinical outcomes of combined cervical and transthoracic surgical approaches in patients with advanced thyroid cancer.

BACKGROUND: Advanced thyroid disease involving the mediastinum may be managed surgically with a combined transcervical and transthoracic approach. Contemporary analysis of this infrequently encountered cohort will aid the multidisciplinary team in personalizing treatment approaches. METHODS: Retrospective review of patients undergoing combined transcervical and transthoracic surgery for thyroid cancer at a single high-volume institution from 1994 to 2015. RESULTS: Thirty-eight patients with median age 59 years (range 28-76) underwent surgery without perioperative mortality. Most patients had primary disease. A majority had distant metastases outside the mediastinum but had locoregionally curable disease. Common complications were temporary (39%) and permanent (18%) hypoparathyroidism, and wound infection (13%). One-year overall survival was 84%; 1-year locoregional disease-free survival was 64%. Median time to locoregional recurrence was 36 months. Only esophageal invasion was associated with worse oncologic outcomes. CONCLUSIONS: Combined transcervical and transthoracic surgery for advanced thyroid cancer can be performed without mortality and with acceptable morbidity.

Role of induction chemotherapy for oral cavity squamous cell carcinoma.

BACKGROUND: Patients with locoregionally advanced oral cavity squamous cell carcinoma (OCSCC) have a poor survival outcome. Treatment involves extensive surgery, adjuvant radiation, or chemoradiation and results in high morbidity. In this study, the authors' objective was to evaluate their experience with induction chemotherapy (IC) in the treatment of locoregionally advanced OCSCC. METHODS: A retrospective review of the medical records of all patients with locoregionally advanced (stage III and IV) OCSCC who received IC followed by definitive local therapy was conducted. Outcomes included response to IC and survival. RESULTS: In total, 120 patients were included in the study. The overall stage was stage IV in 79.2% of patients. After 2 cycles of IC, 76 patients (63.3%) achieved at least a partial response, including 13 who had a complete response. Stable disease was observed in 30 patients (25%), and 14 patients (11.7%) had progressive disease. Among responders, 16 patients received definitive chemoradiation or radiation therapy, and 60 underwent surgical resection, of whom 15 had less extensive surgery than was originally planned. Overall, organ preservation was achieved in 40.8% of patients who had a favorable response to IC. The 5-year overall and disease-specific survival rates were 51.4% and 66.9%, respectively. Patients who had at least a partial response had better 5-year overall survival (60.1%) and disease-specific survival (78.5%) compared with nonresponders (33.8% and 46.4%, respectively). CONCLUSIONS: The results demonstrate a response rate to IC in patients with advanced OCSCC similar to what has been observed in patients with cancer in other head and neck subsites. Patients who achieved at least a partial response to IC had a more favorable outcome, with ensuing organ preservation. Further studies are warranted.

Effect of Preoperative Vitamin D Deficiency on Hypocalcemia in Patients with Acute Hypoparathyroidism after Thyroidectomy.

Postoperative hypoparathyroidism is a common complication of total or completion thyroidectomy. The association between preoperative vitamin D deficiency (VDD) and the development of more severe postoperative hypocalcemia is still unclear. Objectives. To evaluate the effect of preoperative VDD on severity of hypocalcemia in patients with hypoparathyroidism following thyroidectomy. Methods. Patients who developed acute hypoparathyroidism after total or completion thyroidectomy, defined as postoperative parathyroid hormone (PTH) level <15 pg/mL and albumin-adjusted calcium level <8.6 mg/dL, were prospectively recruited. Patients were divided into two groups according to their preoperative vitamin D status (VDD group: 25-hydroxyvitamin D (25(OH)D) level <20 ng/mL; non-VDD group: 25(OH) level ≥20 ng/mL). The primary outcome was severity of hypocalcemia in postoperative hypoparathyroidism. Significant hypocalcemia was defined as calcium level ≤7.5 mg/dL. Results. Forty-three patients (21 VDD, 22 non-VDD) were enrolled. Serum total albumin-adjusted calcium level was significantly lower in the VDD group (7.71 ± 0.5 vs. 8.16 ± 0.4 mg/dL, p < 0.01), and the incidence of symptomatic hypocalcemia was significantly higher in the VDD group (43% vs. 9%, p=0.01). The median maximal daily supplementary dose of elemental calcium was significantly higher in the VDD group (2,400 vs. 1,500 mg/day, p=0.02). Length of hospital stay was nonsignificantly longer in the VDD group (p=0.06). Preoperative vitamin D level <19.6 ng/mL could predict significant and symptomatic hypocalcemia in postoperative hypoparathyroidism with sensitivity of 90% and 82% and specificity of 70% and 69%, respectively. Conclusion. VDD is an independent risk factor for both significant and symptomatic hypocalcemia in hypoparathyroidism patients after thyroid surgery.

Survival in Differentiated Thyroid Cancer: Comparing the AJCC Cancer Staging Seventh and Eighth Editions.

BACKGROUND: The American Joint Committee on Cancer Cancer Staging System for differentiated thyroid cancer has been recently revised. The purpose of this study was to compare survival prognostication between the seventh and eighth editions. MATERIALS AND METHODS: We retrospectively reviewed 2579 differentiated thyroid cancer patients who underwent surgery at MD Anderson Cancer Center between 2000 and 2015. Disease-specific survival (DSS) and overall survival were estimated using the Kaplan-Meier method and compared using log rank test. The effect of potential predictor was estimated using Cox proportional hazards model. Power of survival prediction was estimated using Harrell's C concordance index (C-index), and predictive capacities for DSS were estimated using proportion of variance explained (PVE). RESULTS: Revision of tumor-node-metastasis (TNM) categories, age cutoff, and stage reassignment in the 8th edition caused reclassification of overall stage compared with the seventh edition. The proportion of patients in stage I and II increased from 62% to 83% and 5% to 12%, respectively, while the proportion of patients in stage III and IV decreased from 20% to 2% and 14% to 3%, respectively. Ten-year DSS for stages I-IV based on the seventh edition were 100%, 97.5%, 98.3%, and 82.6%, respectively, while 10-year DSS for the corresponding stage in the eighth edition were 99.8%, 88.3%, 72.4%, and 71.9%, respectively. In multivariate analysis for both seventh edition (C-index 0.94, PVE 4.6%) and eighth edition (C-index 0.94, PVE 4.8%), the factors predictive of worse outcome for DSS were older age, advanced tumor size category, and distant metastasis while cervical lymph node metastases did not predict worse survival. For the eighth edition, patients <55 years of age with stage II disease had significantly worse DSS (p < 0.001) than patients ≥55 years with stage II disease but appeared to be similar to patients ≥55 years with stage III (p = 0.742) and IV disease (p = 0.566). Patients ≥55 years old with T3a and T3b disease had 10-year DSS of 67% and 92%, respectively (p = 0.390). CONCLUSION: The AJCC eighth edition is similar to the seventh edition in disease-specific survival prediction. Potential modifications that may improve disease-specific survival prediction in future renditions include reconsideration of T3b tumor category and upstaging classification of patients <55 years of age with distant metastases.

Extrathyroidal Extension: Does Strap Muscle Invasion Alone Influence Recurrence and Survival in Patients with Differentiated Thyroid Cancer?

BACKGROUND: According to the 8th edition American Joint Committee on Cancer staging system, extrathyroidal extension (ETE) and primary tumor size remain the principle determinants of T stage. However, impact of gross ETE into strap muscles on survival remains controversial. PATIENTS AND METHODS: A retrospective review of 2084 patients with ≤ 4 cm nonmetastatic differentiated thyroid cancer who underwent surgery between 2000 and 2015 was conducted. Patients were divided into three groups according to degree of ETE: no ETE (group 1), ETE into perithyroidal soft tissue (group 2), and gross ETE into strap muscle (group 3). Survivals were analyzed using Kaplan-Meier method and compared using log-rank test. Factors predictive of survival were analyzed using Cox proportional hazard model. RESULTS: Ten-year disease-free survival (DFS) of patients in groups 1-3 was 90, 82, and 83%, respectively (p = 0.003). On multivariate analysis, age ≥ 55 years, male sex, and pathologic N1b category predicted significantly worse DFS, while ETE into perithyroidal soft tissue or gross strap muscle invasion did not predict worse DFS. Overall survival (p = 0.957) and disease-specific survival (p =0.910) were not significantly different between the three groups. There was a statistically significant difference in locoregional recurrence-free survival between groups 1 and 2 [HR 2.02, 95% CI 1.06-3.94]. CONCLUSION: Gross strap muscle invasion may not be an important survival prognostic factor for staging purposes. Although both gross strap muscle invasion and perithyroidal soft tissue extension may be predictive for locoregional recurrence, the distinction between them may not be as important for postoperative risk stratification.

Effect of Tumor Size and Minimal Extrathyroidal Extension in Patients with Differentiated Thyroid Cancer.

INTRODUCTION: Risk-stratified treatment strategies have become a focus in the treatment of differentiated thyroid cancer (DTC). In the 2015 American Thyroid Association treatment guidelines, adjuvant treatment with radioactive iodine (RAI) is considered in the presence of minimal extrathyroidal extension (mETE). This study aimed to investigate the prognostic significance of mETE and tumor size in patients with DTC. METHODS: A retrospective review was undertaken of 2323 consecutive patients treated surgically for T1-T3 (defined per seventh edition of the American Joint Committee on Cancer staging criteria) and M0 DTC from 2000 to 2015 at The University of Texas MD Anderson Cancer Center. Patients were divided into four groups according to the size of the tumor (≤4 cm vs. >4 cm) and the presence of mETE. Predictors of disease-free survival (DFS), disease-specific survival, locoregional failure (LRF), and distant metastatic failure (DMF) were compared using the log-rank test and Cox's proportional hazards models. RESULTS: There were only seven DTC-related deaths, limiting the clinical significance of the analysis, especially of overall and disease-specific survival. Following multivariate analysis, patients with tumors >4 cm did worse than patients with tumors ≤4 cm with respect to DFS (group 3 [>4 cm without mETE] adjusted hazard ratio (HRadj) = 2.1 [confidence interval (CI) 1.1-3.8]; group 4 [>4 cm with mETE] HRadj = 2.9 [CI 1.6-5.1]). However, patients did not differ according to DFS, regardless of the presence of mETE within each size category (group 2 [≤4 cm with mETE] vs. group 1 [≤4 cm without mETE] HRadj = 1.3 [CI 0.9-1.8]; group 4 [>4 cm without mETE] vs. group 3 [>4 cm with mETE] HRadj = 1.0 [CI 0.5-2.3]). For LRF and DMF, size but not mETE was also an independent risk factor. CONCLUSION: Tumor size, but not the presence of mETE, was an independent predictor of DFS, LRF, and DMF in DTC.

Association of Lymph Node Density With Survival of Patients With Papillary Thyroid Cancer.

Importance: Lymph node metastases are common in papillary thyroid cancer (PTC), yet the impact of nodal metastases on survival remains unclear. Lymph node density (LND) is the ratio between the number of positive lymph nodes excised and the total number of excised lymph nodes. Lymph node density has been suggested as a prognostic factor in many types of cancer. Objective: To evaluate the prognostic role of LND in PTC. Design, Setting, and Participants: This cohort study reviewed medical records of patients with PTC who were treated at the University of Texas MD Anderson Cancer Center between January 1, 2000, and December 31, 2015. Survival and recurrence outcomes were calculated by using the Kaplan-Meier method. Significant variables on univariate analysis were subjected to a Cox proportional hazards regression multivariate model. Main Outcomes and Measures: Primary study outcome was disease-specific survival (DSS); other measurements included overall survival (OS). Results: The study cohort included data for 2542 patients (1801 [71%] male; median age, 48 years [range, 18-97 years]) with a median follow-up of 55 months (range, 4-192 months). The 10-year disease-specific survival rate was 98% for patients with LND of 0.19 or less, compared with 90% for those with LND greater than 0.19 (effect size, 8%; 95% CI, 4%-15%). The 10-year overall survival was 87% for patients with LND of 0.19 or less, compared with 79% for patients with LND greater than 0.19 (effect size, 8%; 95% CI, 3%-15%). Multivariable analysis revealed that LND greater than 0.19 was independently associated with an adverse DSS (hazard ratio [HR], 4.11; 95% CI, 2.11-8.97) and OS (HR, 1.96; 95% CI, 1.24-4.11). Subgroup analysis of patients with 18 or more lymph nodes analyzed revealed that LND greater than 0.19 remained a significant marker for DSS (HR, 2.94; 95% CI, 1.36-9.81) and OS (HR, 2.26; 95% CI, 1.12-5.34). Incorporating LND into the current American Joint Committee on Cancer staging system successfully stratified risk groups compared with the traditional TNM staging system. Conclusions and Relevance: This single-institute study demonstrates the reproducibility of LND as a predictor of outcomes in PTC. Lymph node density can potentially assist in identifying patients with poorer survival who may benefit from more aggressive adjuvant therapy.

Vascular endothelial growth factor ­634G/C polymorphism is associated with increased breast cancer risk and aggressiveness.

Polymorphisms in the promoter and 5' untranslated region of vascular endothelial growth factor (VEGF) have been associated with VEGF levels. To investigate the role of VEGF polymorphisms in breast cancer, the VEGF ­2578C/A, ­1498C/T, ­1154G/A and ­634G/C polymorphisms were genotyped in 483 breast cancer patients and 524 healthy controls. VEGF mRNA levels in breast cancer tissue were determined using semi­quantitative RT­PCR. The genotypes, ­634G/C and ­634C/C, were associated with an increased risk for breast cancer when compared with the ­634G/G genotype. The VEGF ­634G/C genotype was associated with tumor size >20 mm, perineural invasion and stage II­IV. Individuals with ­634C/C had lower disease­free survival. Patients with the VEGF ­634C/C genotype exhibited the highest VEGF mRNA levels. High VEGF mRNA expression correlated with tumor size >20 mm, presence of lymphovascular invasion and axillary nodal metastasis. These observations suggested that VEGF ­634G/C polymorphisms have a significant role in breast cancer susceptibility and aggressiveness.