Koon-Yat Wan

Concurrent and Adjuvant Chemotherapy for Nasopharyngeal Carcinoma: A Factorial Study

PURPOSE To study the efficacy of concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS Patients with Hos stage T3 or N2/N3 NPC or neck node > or = 4 cm were eligible. Patients were randomly assigned to have radiotherapy (RT) or CRT with uracil and tegafur and to have AC or no AC after RT/CRT. AC comprised alternating cisplatin, fluorouracil, vincristine, bleomycin, and methotrexate for six cycles. There were four treatment groups: A, RT; B, CRT; C, RT and AC; D, CRT and AC. For CRT versus RT, groups B and D were compared with groups A and C. For AC versus no AC, groups C and D were compared with groups A and B. RESULTS Three-year failure-free survival (FFS) and overall survival (OS) for CRT versus RT were 69.3% versus 57.8% and 86.5% versus 76.8%, respectively (P =.14 and.06; n = 110 v 109). Distant metastases rate (DMR) was significantly reduced with CRT (14.8% v 29.4%; P =.026). Locoregional failure rates (LRFR) were similar (20% v 27.6%; P =.39). Three-year FFS and OS for AC versus no AC were 62.5% versus 65% and 80.4% versus 83.1%, respectively (P =.83 and.69; n = 111 v 108). DMR and LRFR were not reduced with AC (P =.34 and.15, respectively). Cox model showed CRT to be a favorable prognostic factor for OS (hazard ratio, 0.42; P =.009). CONCLUSION An improvement in OS with CRT was observed but did not achieve statistical significance. The improvement seemed to be associated with a significant reduction in DMR. AC did not improve outcome.

Anaplastic carcinoma of the thyroid

BACKGROUND Anaplastic thyroid carcinoma, albeit rare, is one of the most aggressive human tumors, with a dismal prognosis. METHODS Twenty-eight patients with anaplastic thyroid carcinoma were identified during the past 30 years to evaluate its clinicopathologic features and to document our experience in management. Potential risk factors for survival time were analyzed. RESULTS The usual presentation was that of a rapidly enlarging neck mass. Distant metastases were present in 50% of patients on presentation. Palliative resection was performed in 16 patients. The median survival was 38 days, and the 2-year survival rate was 4%. Among factors analyzed, patients selected for surgical resection, absence of distant metastases at presentation, young age, and tumor size <6 cm were associated with an increased survival time. Concomitant well-differentiated thyroid carcinoma and p53 overexpression were present in 12 of the 22 and 13 of the 19 specimens, respectively. CONCLUSIONS Patients with anaplastic carcinoma of thyroid have a dismal prognosis heralding imminent death. Surgical ablation followed by adjuvant therapy can provide palliation for selected patients only.

Staging Systems for Papillary Thyroid Carcinoma : a review and comparison

Objective:To find out the most predictive staging system for papillary thyroid carcinoma (PTC) currently available in the literature. Background:Various staging systems or risk group stratifications have been used extensively in the clinical management of patients with PTC, but the most predictive system for cancer-specific survival (CSS) based on distinct histologic types remains unclear. Methods:Through a comprehensive MEDLINE search from 1965 to 2005, a total of 17 staging systems were found in the literature and 14 systems were applied to the 589 PTC patients managed at our institution from 1961 to 2001. CSS were calculated by Kaplan-Meier method and were compared by log-rank test. Using Cox proportional hazards analysis, the relative importance of each staging system in determining CSS was calculated by the proportion of variation (PVE). Results:All 14 staging systems significantly predicted CSS (P < 0.001). The 3 highest ranked staging systems by PVE were the Metastases, Age, Completeness of Resection, Invasion, Size (MACIS) (18.7) followed by the new AJCC/UICC 6th edition tumor, node, metastases (TNM) (17.9), and the European Organization for Research and Treatment of Cancer (EORTC) (16.6). Conclusions:All of the currently available staging systems predicted CSS well in patients with PTC regardless of which histologic type from which they were derived. When predictability was measured by PVE, the MACIS system was the most predictive staging system and so should be the staging system of choice for PTC in the future.

Follicular Thyroid Carcinoma: The Role of Histology and Staging Systems in Predicting Survival

Objective:To evaluate the risk factors including tumor histomorphology for survival specific to follicular thyroid carcinoma (FTC) and to apply commonly employed staging systems in predicting survival for patients with FTC. Summary Background Data:FTC is usually analyzed collectively with papillary thyroid carcinoma (PTC) in risk group analysis. Risk factors and risk group analysis are important in the management of patients with FTC, although current published therapeutic guidelines call for total thyroidectomy followed by radioactive iodine (I131) ablation for all FTC patients. Methods:Over a 40-year period, 156 patients surgically treated for FTC with an average follow-up of 14.4 years were retrospectively studied after histologic reclassification according to the type and degree of invasiveness of the tumor. Potential risk factors for survival were calculated using multivariate analysis, and the prognostic accuracy of AMES risk group stratification, UICC/AJCC pTNM staging, Degroot classification, and MACIS scoring schemes in predicting survival was compared. Results:Seventeen (11%) patients had distant metastases at presentation, and bilateral thyroid resection was performed for 131 (84%) patients. Seventeen (11%) patients died of recurrent or metastatic disease. The overall and cancer-specific survival (CSS) rates at 10 years were 79% and 88%, respectively. None of the patients with minimally invasive (n = 49) or angioinvasive (n = 23) carcinomas died compared with 17 of 84 patients with widely invasive carcinomas (P = 0.0007). Using the Cox proportional hazards model, old age, the presence of distant metastases, and incomplete tumor excision were independent prognostic factors for survival. For patients who underwent curative treatment, old age and widely invasive carcinoma were risk factors for poor survival. All staging systems studied accurately predicted CSS, and the pTNM UICC/AJCC staging system yielded the best prognostic information. Conclusions:Commonly adopted staging systems can be applied specifically to patients with FTC. The distinction of FTC in minimally invasive and widely invasive carcinoma based on the extent of invasiveness rather than vascular invasion is important in identifying low-risk FTC patients for a more conservative management.

Insular and Anaplastic Carcinoma of the Thyroid: A 45-year Comparative Study at a Single Institution and a Review of the Significance of p53 and p21

OBJECTIVE To analyze the clinicopathologic features of a large cohort of patients with insular or anaplastic carcinomas treated at a single institution. SUMMARY BACKGROUND DATA Insular and anaplastic carcinomas of the thyroid, although uncommon, have more aggressive clinical behavior than well-differentiated carcinomas of the thyroid. In the literature, the incidence and features of these carcinomas have not been fully characterized. METHODS The authors reclassified 740 primary thyroid carcinomas diagnosed and treated between January 1, 1954, and December 30, 1998, to select those with features that met the histologic criteria of insular or anaplastic carcinoma. The clinicopathologic features of these carcinomas were studied and compared. The expression of p53 and p21 in these tumors was analyzed by immunohistochemistry. RESULTS Twenty-two patients (5 men, 17 women) with insular carcinoma and 38 patients (7 men, 31 women) with anaplastic carcinoma were found. Patients with insular carcinomas were younger (mean age 45 vs. 70 years) and had smaller tumors than those with anaplastic carcinomas (mean diameter 5 vs. 8 cm). Insular carcinomas were commonly mislabeled as other histologic subtypes, whereas anaplastic carcinomas might be overdiagnosed on pathologic examination. A history of longstanding goiter (>10 years) was noted in 27% of patients with insular carcinoma and 24% of patients with anaplastic carcinomas. Concomitant well-differentiated carcinomas of the thyroid were noted in 59% of patients with insular carcinoma and 39% of patients with anaplastic carcinoma. In anaplastic carcinomas, 13% of patients had concomitant insular carcinoma. Calcification or bone was noted in the stroma of 23% of patients with insular carcinomas and 47% of those with anaplastic carcinomas. The 10-year survival rates for patients with insular carcinoma and anaplastic carcinoma were 42% and 3%, respectively. Distant metastases were seen in 32% of patients with insular carcinoma and in 47% of patients with anaplastic carcinomas. In both types of carcinomas, metastatic tumors were often seen in bone and lung. Distant metastases were noted in a variety of organs in anaplastic carcinomas. In insular carcinoma, neither p53 nor p21 expression was present. In anaplastic carcinoma, p53 and p21 expression was identified in 69% and 3%, respectively. Concomitant expression of p53 and p21 was noted in one tumor. CONCLUSIONS Insular carcinoma and anaplastic carcinoma had distinctive clinicopathologic features, and recognition of these histologic variants is important for better management of these tumors in the future. p53 overexpression might have a role in dedifferentiation from insular carcinoma to anaplastic carcinoma.

Prognostic Factors in Papillary and Follicular Thyroid Carcinoma: Their Implications for Cancer Staging

Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are two distinct histological types of thyroid carcinoma but have often been studied and staged as a collective group, known as differentiated thyroid carcinoma (DTC). However, this may not be an optimal approach to cancer staging. A total of 760 patients with DTC, comprising 589 (77.5%) with PTC and 171 with (22.5%) FTC, being managed at our institution from 1961 to 2001 were retrospectively reviewed. Their clinicopathological features, treatment modalities received, and postoperative outcome were analyzed. Both univariate and multivariate analyses were performed to identify prognostic factors related to cancer-specific survival (CSS) for PTC and FTC. There were statistically significant differences between PTC and FTC in terms of age ≥50 years at diagnosis (P = .040), tumor size (P < .001), lymph node metastases (P < .001), distant metastases (P < .001), extrathyroidal extension (P < .001), multifocality (P = .002), capsular invasion (P < .001), extent of thyroid resection (P < .001), radioiodine ablation (P < .001), and external-beam irradiation (P = .003). Although PTC and FTC had similar 10-year and 15-year CSS (P = .846), each possessed its own set of independent prognostic factors for CSS. Age at diagnosis and completeness of resection were independent prognostic factors in both PTC and FTC. There were marked differences in clinicopathologic features, treatment, and prognostic factors between the two histologic types of DTC. Different staging systems should be evaluated and validated for PTC and FTC individually in the future.

Classical and follicular variant of papillary thyroid carcinoma: a comparative study on clinicopathologic features and long-term outcome.

IntroductionThe follicular variant of papillary thyroid carcinoma (FVPTC) is the most common histologic subtype of papillary thyroid carcinoma (PTC). However, it is still controversial whether FVPTC should behave differently from classical PTC (CPTC). The present study aimed at evaluating any potential difference in clinicopathologic features and long-term outcome of FVPTC as compared with CPTC.Patients and MethodsOf 568 patients with PTC managed from 1973 to 2004, 308 were shown to have CPTC (54.2%) and 67 (11.8%) FVPTC after histologic review. The mean (± SD) follow-up period was 11.3 (± 8.9) years. The two groups were compared in terms of clinicopathological features, treatment received, and outcome regarding recurrence and disease-specific survival.ResultsThere was no difference in age and gender ratio between the CPTC and FVPTC patients. Both groups had similar tumor characteristics in terms of tumor size, presence of multifocality, capsular invasion, lymphovascular permeation, and perineural infiltration. However, FVPTC patients had significantly fewer histologically confirmed cervical lymph node metastases (P = 0.027) and extrathyroidal involvement (P = 0.005). The proportion of bilateral resection, adjuvant radioactive iodine, and lymph node dissection did not differ significantly between the two groups. The FVPTC patients had a more favorable tumor risk by DeGroot classification (P = 0.003) and MACIS (Metastasis, Age, Completeness of excision, Invasiveness, and Size) score (P = 0.026). The 10- and 15-year actuarial disease-specific survivals did not differ significantly between FVPTC and CPTC patients (96.2% versus 90.7% and 96.2% versus 89.1%, respectively).ConclusionsAlthough patients with FVPTC had more favorable clinicopathologic features and a better tumor risk group profile, their long-term outcome was similar to that of CPTC patients.

Papillary Microcarcinoma: Is There Any Difference between Clinically Overt and Occult Tumors?

Papillary microcarcinoma (PMC) is a subtype of papillary thyroid carcinoma (PTC) associated with excellent prognosis. However, clinical and biologic behaviors of PMC may vary considerably between tumors that are clinically overt and those that are occult. From 1964 to 2003, 185 of 628 patients with PTC were identified as having PMC, based on tumor size ≤1 cm. There were 110 overt and 75 occult PMCs detected based on clinical presentation. The clinicopathologic features, treatment, and long-term outcome of PMCs were evaluated and compared between the two groups. There were 37 men and 148 women with a median age of 45 years (range: 11–84 years). The median tumor size was 6.2 mm. Thirty-eight (21%) patients presented with cervical nodal metastases. Three (1.6%) had distant metastases and 5 (2.7%) underwent incomplete resection. Bilateral procedures were performed for 129 patients (70%) and 53 (29%) received postoperative I131treatment. During a mean follow-up of 8.2 years, 4 patients died of the disease and 13 developed recurrence. Clinically overt PMCs were significantly larger, were more likely to be multifocal, and more likely to lead to bilateral thyroidectomy. Extrathyroidal or lymphovascular invasion, nodal metastases, I131ablation, high-risk tumors, and postoperative recurrence occurred in overt PMC only. Patients with nodal metastases had a decreased survival and an increase in locoregional recurrence. Despite a relatively good prognosis in PMC, a distinction should be made between clinically overt and occult PMCs in which clinically overt PMC should be managed according to tumor risk profile and clinical presentation.

The time course of histologic remission after treatment of patients with nasopharyngeal carcinoma

The objective of this study was to define the time course of histologic remission and to evaluate the prognostic significance of delayed histologic remission of patients with nasopharyngeal carcinoma (NPC).

Risk of second primary malignancy in differentiated thyroid carcinoma treated with radioactive iodine therapy.

BACKGROUND Differentiated thyroid cancer survivors are at increased risk of nonsynchronous second primary malignancy, but the cause remains unclear. This study aimed to evaluate the association between radioiodine therapy and risk of nonsynchronous second primary malignancy and to examine whether the risk of nonsynchronous second primary malignancy in differentiated thyroid cancer survivors treated with radioiodine therapy is increased relative to the general population. METHODS Among 895 radiation-naïve patients with differentiated thyroid cancer, 643 (71.8%) received ≥1 course of radioiodine therapy (radioiodine therapy-positive group) and 252 (28.2%) received no radioiodine therapy (radioiodine therapy-negative group). After a median follow-up of 93.5 months (range, 23.4-570.8), 64 (7.2%) patients developed ≥1 nonsynchronous second primary malignancy. Potential risk factors for nonsynchronous second primary malignancy were entered into a multivariable regression model and cancer incidence in the radioiodine therapy-positive and -negative groups were compared to that of the general population by estimating the standardized incidence ratios. RESULTS The 20-year cumulative nonsynchronous second primary malignancy risk in radioiodine therapy-positive group was significantly higher than radioiodine therapy-negative group (13.5% vs 3.1%; P = .015). Cumulative radioiodine therapy activity of 3.0 to 8.9 GBq (relative risk, 2.77; 95% CI, 1.079-7.154; P = .034) was the only independent risk factor for nonsynchronous second primary malignancy after adjusting for age, sex, period of differentiated thyroid cancer diagnosis, and stage of differentiated thyroid cancer. For females, the standardized incidence ratio in the radioiodine therapy-positive group was 1.54 (95% CI, 1.11-2.08) and in the radioiodine therapy-negative group it was 0.92 (95% CI, 0.37-1.90). CONCLUSION Differentiated thyroid cancer female survivors treated by radioiodine therapy appeared to be at elevated risk of nonsynchronous second primary malignancy when compared to the general population and this risk was not apparent in those not previously treated by radioiodine therapy.