Definitive radiotherapy for early stage glottic cancer by 6 MV photons.

PURPOSE: To evaluate the clinical outcome of early glottic cancer (GC) treated by primary radiotherapy (RT) with 6 MV photons. METHODS AND MATERIALS: We retrospectively reviewed the medical records of 695 consecutive patients with T1N0 and T2N0 GC treated between 1983 and 2005 by RT in our institution. Clinical outcome in terms of local control (LC), overall survival (OS) and cause- specific survival (CSS) rate were evaluated. RESULTS: The median follow-up time was 10.5 years. The 10-year actuarial LC rates were as follows: T1A, 91%; T1B, 87%; T2, 77%. The 10-year OS were as follows: T1, 74.2%; T2, 70.7%. The 10-year CSS were as follows: T1, 97.7%; T2, 97.1%.Poorly differentiated histology and tumor biologically effective dose<65 Gy15 were adverse factors in both LC of T1 and T2 disease. Involvement of anterior commissure was an adverse factor in both LC and CSS of T1 disease. Subglottic extension was associated with poor LC in T2 disease whereas hemoglobin <13.0 was associated with poor LC and CSS of T2 disease. CONCLUSION: Primary RT remains an option among the various standard treatments for early GC. Clinical treatment outcome by 6MV photons is similar and comparable to historic data of Cobalt-60 and 2 MV photons.

Impact and relationship of anterior commissure and time-dose factor on the local control of T1N0 glottic cancer treated by 6 MV photons.

BACKGROUND: To evaluate prognostic factors that may influence local control (LC) of T1N0 glottic cancer treated by primary radiotherapy (RT) with 6 MV photons. METHODS: We retrospectively reviewed the medical records of 433 consecutive patients with T1N0 glottic cancer treated between 1983 and 2005 by RT in our institution. All patients were treated with 6 MV photons. One hundred and seventy seven (41%) patients received 52.5 Gy in 23 fractions with 2.5 Gy/fraction, and 256 (59%) patients received 66 Gy in 33 fractions with 2 Gy/fraction. RESULTS: The median follow-up time was 10.5 years. The 10-year LC rates were 91% and 87% for T1a and T1b respectively. Multivariate analysis showed LC rate was adversely affected by poorly differentiated histology (Hazard Ratio [HR]: 7.5, p = 0.035); involvement of anterior commissure (HR: 2.34, p = 0.011); fraction size of 2.0 Gy (HR: 2.17, p = 0.035) and tumor biologically effective dose (BED) < 65 Gy15 (HR: 3.38, p = 0.017). CONCLUSIONS: The negative impact of anterior commissure involvement could be overcome by delivering a higher tumor BED through using fraction size of > 2.0 Gy. We recommend that fraction size > 2.0 Gy should be utilized, for radiation schedules with five daily fractions each week.

Clinical features and outcome of the tall cell variant of papillary thyroid carcinoma.

OBJECTIVES: To study the clinical features and outcome of the tall cell variant (TCV) of papillary thyroid carcinoma (PTC). STUDY DESIGN AND METHODS: A single-institution retrospective analysis was performed to review patients with TCV and the usual type of PTC diagnosed from 1960 to 2000. RESULTS: Fourteen of 1,108 patients (median follow-up, 8.9 yr) diagnosed with PTC had TCV. Ten were female, and four were male, with a mean age of 53.7 (33-81) years. All were ethnic Chinese. Compared with the usual PTC cohort, TCV patients presented at an older age (mean, 53.7 vs. 45.2 yr; P = .015). They had a higher rate of extrathyroidal extension (78.6% vs. 43.4%, P = .009), tracheal invasion (28.6% vs. 9%, P = .034), and carotid vessel invasion (14.3% vs. 1.5%, P = .021). TCV patients had more frequent gross (42.9% vs. 17.2%) and microscopic (14.3% vs. 6%) postoperative locoregional residual disease (P = .008). They also had a higher percentage of stage III and IV disease (American Joint Committee on Cancer, 6th ed) (74.3% vs. 31.3%, P = .009). Ten-year local failure-free, regional failure-free, and metastasis-free survival were worse in the TCV group (78.6% vs. 88.8%. P = .017; 53.0% vs. 85.9%, P < .0001; 35.7% vs. 92.1%, P < .0001, respectively). The 10-year cause-specific survival was also lower in TCV patients (48.2% vs. 93.4%, P < .0001). CONCLUSION: TCV presents at a higher stage with more advanced local disease. It has a higher risk of locoregional and distant relapse and a worse overall survival rate. Stratification by stage reveals that TCV has significantly higher mortality compared with PTC for stage IV disease. Aggressive treatment and close follow-up of these patients is necessary.

Staging systems for papillary thyroid carcinoma: a study of 2 tertiary referral centers.

OBJECTIVE: To find out the most applicable and consistent staging system for papillary thyroid carcinoma (PTC) available in the literature. BACKGROUND: The commonly used staging systems for PTC have predicted cancer-specific survival (CSS) well. However, their applicability and generalizability have not yet been evaluated in different clinical settings. METHODS: A MEDLINE search from 1965 to 2005 was carried out to identify different staging systems available in the literature and 9 systems were applicable to 1634 PTC patients within 2 tertiary-referral centers. The CSS of each staging system within individual centers were calculated using Kaplan-Meier method and the CSS of each tumor stage in one individual center was compared with that of the other by log-rank test. In addition, within each center, the predictability of each staging system relative to the others was ranked based on the proportion of variation explained (PVE) value. RESULTS: Clinicopathologic features, treatment received, and tumor stages were significantly different between the 2 centers. There were also significant differences in CSS within at least one tumor stage between the 2 centers in 8 of the 9 staging systems. The TNM was a highly predictive and consistent staging system within the 2 centers. Although the absolute PVE values differed between the 2 centers, the relative ranking of the 9 staging systems within each center correlated significantly to each other (P < 0.05). CONCLUSIONS: Despite referral, treatment, and data collection biases inherent within each center, the TNM system remained to be the most applicable and consistent staging system for PTC in 2 centers managing the same population group.

Local and regional control in patients with papillary thyroid carcinoma: specific indications of external radiotherapy and radioactive iodine according to T and N categories in AJCC 6th edition.

To identify indications for external radiotherapy (EXT) and radioactive iodine (RAI) in papillary thyroid carcinoma (PTC), we conducted a retrospective study of local and regional control in 1297 patients diagnosed with PTC in a tertiary referral center. Managed by surgery alone, patients with bilateral thyroidectomy had a lower rate of local relapse compared with lobectomy (P=0.02). EXT improved locoregional (LR) failure-free survival (FFS) (P<0.001) and survival (P=0.01) in patients with gross postoperative LR residual disease. EXT also improved local FFS in patients with pathologically confirmed positive resection margins (P<0.001) and reduced local failures in patients with T4 disease (P=0.002). In patients with lymph nodes (LN) metastasis, more extensive surgery by functional or radical neck dissection resulted in less LN relapse compared with excision alone (P<0.001). EXT improved 10-year LN FFS in patients with N1b disease (P=0.005) and patients with LN metastasis of size>2 cm (P=0.02). RAI was effective in improving local control in patients with T2 to T4 diseases and LN control in patients with N0, N1a, and N1b categories. Local or LN relapses were associated with worse survival (P<0.001 and P<0.0001). The survival of patients with PTC could be improved by reducing local or LN relapses. RAI is indicated in patients with T2 to T4 disease. EXT is indicated in patients with gross postoperative disease, positive resection margins or T4 disease, N1b, or a LN size of >2 cm. LN relapse can be reduced by RAI in N0, N1a, and N1b disease.

Health-related quality-of-life study in patients with carcinoma of the thyroid after thyroxine withdrawal for whole body scanning.

OBJECTIVES/HYPOTHESIS: The authors studied the change of health-related quality of life (HR-QOL) in patients with differentiated thyroid carcinoma (DTC) with thyroxine (T4) withdrawal in preparation for whole body radioactive iodine scanning. STUDY DESIGN: Seventy-eight patients with DTC and history of radioactive iodine (RAI) ablation were prospectively recruited. They completed the Functional Assessment of Cancer Treatment-General (FACT-G) questionnaire on weeks 0, 2, and 4 after T4 withdrawal with corresponding checking of serum thyroid-stimulating hormone (TSH). RESULTS: Overall, 74.5% (58 of 78) of patients completed all FACT-G. Comparing FACT-G scores at weeks 0 and 4, "physical" (P < .001), "social" (P = .04), and "emotional" (P = .047) aspects were lowered as well as "total" HR-QOL (P = .001). However, the "functional" domain of HR-QOL was not affected (P = .14). Comparing FACT-G scores at week 0 and 2, we found that "physical" (P = .049) and "total" (P = .05) HR-QOL were affected early (in the first 2 weeks) in T4 withdrawal. Comparison of week 2 and 4 showed that in the later half of the withdrawal period, "physical" (P = .001), "emotional" (P = .02), and "total" FACT-G scores (P = .002) were affected. Mean TSH level (in mIU/L) increased gradually: 2.8 (week 0), 42.8 (week 2), 97 (week 3), and 153 (week 4). The percentage of patients attaining TSH level of >30 mIU/L were 55% (week 2), 96.2% (week 3), and 100% (week 4). CONCLUSIONS: HR-QOL declines with time of T4 withdrawal. The impact is more severe in the later period of T4 withdrawal. In 3 weeks, 96.2% of our patients attained TSH level of 30 mIU/L. To minimize the impact on HR-QOL, duration of T4 withdrawal can be decreased to 3 weeks.

Pregnancy outcome after diagnosis of differentiated thyroid carcinoma: no deleterious effect after radioactive iodine treatment.

PURPOSE: Thyroid carcinoma is the second most common malignancy in young women, after breast cancer, aged 15-34 years in Hong Kong. Radioiodine or (131)I (RAI) has been confirmed as a useful treatment in the management of differentiated thyroid carcinoma (DTC). Serious concerns have been raised of the potential risks on subsequent pregnancies. METHODS AND MATERIALS: We conducted a single-institute, retrospective analysis of the gestational history of 104 patients who became pregnant after the diagnosis of DTC. The patients were interviewed for pregnancy outcome, and the data were supplemented by a review of the medical records in the Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong. RESULTS: Of 263 pregnancies observed, the prior RAI administration in 153 (scanning dose or ablative dose) did not adversely affect the pregnancy outcome as determined by the rate of successful delivery, mode of delivery, live birth demographics (e.g., birth weight, gender distribution). In all live births, neither congenital malformations nor first year neonatal mortality was observed. Of 116 pregnancies in 68 patients who received an ablative dose (mean, 96.6 mCi) of RAI, 78 live births were reported. The updated information on these children at age 1 month to 30.8 years (mean, 7.9 years; SD 7.3) showed that they had no abnormal development. The incidence of miscarriages was not different in those with prior RAI administration. However, the incidence of preterm delivery was greater in those with a history of RAI (p = 0.03). A higher ablative dose (>80 mCi) and shorter interval between RAI and conception (<1 year) did not significantly alter the pregnancy outcome. Two patients were inadvertently given an RAI scanning dose during pregnancy. One decided to continue the pregnancy; a healthy 6-year-old boy was reported at the last update. Fifteen patients had DTC diagnosed during pregnancy; 2 terminated the pregnancy and 13 decided to continue their pregnancy. All children were born in good health. For DTC diagnosed during the first trimester of pregnancy, the deferral of thyroid surgery to the second trimester is a good compromise for earlier treatment of the malignancy while continuing the pregnancy. CONCLUSION: Radioiodine in young women with DTC did not have deleterious effects on subsequent pregnancies. Proper education and instruction for avoiding conception within 1 year after RAI is a prudent recommendation, allowing for RAI clearance and hormonal stabilization.

Differentiated thyroid carcinoma in childhood and adolescence-clinical course and role of radioiodine.

BACKGROUND: Differentiated thyroid carcinoma (DTC) in childhood has a good prognosis despite a high incidence of relapse. The use of radioactive iodine (RAI) has not been well established. PROCEDURE: This is a review of 60 patients less than 21 years of age; mean follow-up was 14 years. RESULTS: Patients had a higher relapse rate with papillary thyroid carcinoma (PTC) than with follicular thyroid carcinoma (FTC): 24.5 vs. 9.1%. Compared with 997 patients with age > or = 21, patients <21 years of age had a higher female to male ratio (7.6 vs. 3.9), higher incidence of nodal metastasis (45 vs. 28%), and lung metastasis (15 vs. 7.8%), and improved 10-year cause-specific survival (CSS) (98.3 vs. 89.5%). The 10-year rates of CSS, local-regional failure-free survival (LRFFS), and distant metastasis failure-free survival (DMFFS) for the young patients were 98.3, 79.3, and 90.7%, respectively. In patients with no distant metastasis at presentation, RAI improved 10-year LRFFS (71.9 vs. 86.5%; P = 0.04). At last follow-up, 10 of 12 patients (80%) with local-regional (LR) relapse and five of nine patients (55.6%) with distant metastasis were rendered disease-free. No patient has experienced a second malignancy. CONCLUSIONS: Prognosis of DTC in young patients was good. Patients with LR relapse and distant metastasis had a high rate of remission after treatment. RAI treatment can reduce the rate of LR relapse in patients with no distant metastasis and result in complete remission in half of those with distant metastasis. No patient experienced a second malignancy.

Papillary microcarcinoma of the thyroid-Prognostic significance of lymph node metastasis and multifocality.

BACKGROUND: It is known that patients with papillary microcarcinoma (PMC) of the thyroid gland have a very favorable prognosis. The rising incidence of PMC among papillary thyroid carcinoma (PTC) necessitates the identification of prognostic factors and the formulation of treatment protocols. METHODS: The authors conducted a retrospective analysis of 203 patients with PMC who were diagnosed on or before 1999 and were treated at the Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong. RESULTS: The cause specific survival, locoregional (LR) failure free survival, and distant metastases failure free survival rates at 10 years were 100%, 92.1%, and 97.1%, respectively. Five patients had lung metastases; 2 patients died of their metastases 12.9 years and 14.8 years after diagnosis, and 3 patients achieved clinical remission after radioiodine (RAI) treatment. Twelve patients had LR recurrences. Patients with LR recurrence were highly salvageable with a combination of surgery, RAI treatment, and external radiotherapy; all but one (who refused treatment) were alive without disease at last follow-up. Multivariate analyses did not reveal any independent prognostic factor for survival. The risk of cervical lymph node (LN) recurrence increased 6.2-fold (P = 0.01) and 5.6-fold (P = 0.02) when LN metastases and multifocal disease were present at diagnosis. RAI ablation reduced the LN recurrence rate to 0.27 (P = 0.04). The presence of LN metastasis increased the rate of distant metastasis 11.2-fold (P = 0.03). Age was not a significant factor in predicting disease recurrence or survival. Subdivision by tumor sizes 5 mm did not affect the outcome, but no patient with tumors

Follicular thyroid carcinoma: prognostic factors and the role of radioiodine.

BACKGROUND: The objective of this study was to investigate the patterns of recurrence, various prognostic factors, and the role of radioiodine in the treatment of patients with follicular thyroid carcinoma (FTC). METHODS: The clinical outcomes of 215 patients with FTC who were treated at a single institution were analyzed retrospectively. The mean follow-up was 10.8 years. RESULTS: The actuarial rates of cause specific survival (CSS), locoregional (LR) control, and freedom from distant metastasis (DM) at 10 years were 81%, 83%, and 72.3%, respectively. The independent prognostic factors for survival were metastasis at presentation (relative risk [RR], 47.7), radioiodine (RAI) treatment (RR, 0.25), extrathyroidal extension (RR, 3.8), and the postoperative absence of macroscopic disease in the neck region (RR, 0.06). In patients who were treated with RAI, both the LR failure rate (RR, 0.24) and the mortality rate (RR, 0.25) were reduced to about 25%. Subgroup analysis revealed that RAI improved the survival of patients with DM at presentation (RR, 0.17) and improved the LR control rate in patients who had no DM at presentation (RR, 0.13). For patients who underwent total thyroidectomy with negative resection margins, RAI significantly reduced the rate of LR recurrence (RR, 0.05). Patients with the minimally invasive type of FTC had a good prognosis. The 10-year rates for CSS, LR control, and freedom from DM were 97.6%, 100%, and 90.6%, respectively. The prognosis of patients with frankly invasive FTC was much poorer. The 10-year rates for CSS, LR control, and freedom from DM were 66.7%, 100%, and 45%, respectively. CONCLUSIONS: RAI is an effective treatment for patients with FTC. It was associated with improved survival rates and fewer recurrences.

Differentiated thyroid carcinoma: comparison between papillary and follicular carcinoma in a single institute.

PURPOSE: To compare and contrast the clinical presentation and treatment outcome of patients with papillary and follicular thyroid carcinoma and to study the pattern of practice of treatment of differentiated thyroid carcinoma in Hong Kong. METHOD: The clinical presentation and treatment outcomes were reviewed for 1057 patients with differentiated thyroid cancers who were treated at the Queen Elizabeth Hospital, Hong Kong, from 1960 to 1997. Eight hundred forty-two patients had papillary thyroid carcinomas (PTC), and 215 had follicular thyroid carcinomas (FTC). The mean follow-up was 9.2 years. RESULTS: The differences in the clinical factors of PTC to FTC were as follows: PTC had a higher incidence (3.9:1); these patients were younger at presentation (median age, 44 vs 49), showed a higher female-male ratio (4.5 vs 2.9) and smaller primary tumor size (median 2 cm vs 3.5 cm), and a higher incidence of multifocal disease (28.3% vs 18.1%), extrathyroidal extension (39.4% vs 14%), and more lymph node metastases (33.3% vs 12.1%). The incidence of distant metastases was higher for patients with FTC (28.8% vs 8.9%), and cause-specific survival rates were lower (p =.001). The locoregional control rates were not significantly different (p =.2). The 10-year cause-specific survival, freedom from distant metastasis, and locoregional failure figures for PTC compared with FTC were 92.1% vs 81%, 90.8% vs 72.3%, and 78.5% vs 83%. CONCLUSIONS: Although patients with PTC tend to have more advanced locoregional disease compared with those with FTC, the likelihood of locoregional control is similar, and the probability of cure is better.

Cervical nodal metastases from occult primary: undifferentiated carcinoma versus squamous cell carcinoma.

PURPOSE/OBJECTIVE: Controversy exists regarding the management of cervical lymph node metastases from occult primary. Oncologists face a major challenge in adopting an optimal approach. This study attempted to compare the clinical course of two different histologic findings of this disease entity. MATERIALS AND METHODS: A retrospective analysis was performed for all patients referred to our institution between 1988 and 1998 with cervical lymph node metastases from an unknown primary. Case records of consecutive unselected patients with histologically confirmed carcinoma in cervical lymph nodes were reviewed. Those with histologic findings other than squamous cell carcinoma (SCC) or undifferentiated carcinoma (UDC) and lymphadenopathies at the supraclavicular fossa alone or below the clavicles at the time of diagnosis were excluded. There were 45 patients identified with a mean follow-up of 36 months (range, 4-110 months). Thirty-seven were men and eight were women. The mean age was 57 (range, 29-91). There were 32 patients with SCC and 13 patients with UDC. Treatment modality included surgery (S) alone in 1 patient (2%), radiotherapy (RT) alone in 24 patients (53%), and combined modality in 20 patients (45%). (Twelve patients (27%) had combined S and RT, 8 patients (18%) had combined chemotherapy and RT.) Twenty-eight patients (62%) were treated with radical intent. For those patients treated by radical RT, the RT field covered both sides of the neck and the potential mucosal primary (PMP) sites, including the entire pharyngeal axis. The median radiation doses to the lymph nodes and the PMP were 65 Gy (range, 60-70 Gy) and 60 Gy (range, 40-70 Gy), respectively. RESULTS: At the time of analysis, ultimate control of disease above the clavicles according to N stage, treatment intent, and histologic type was as follows: N1s, 7 of 7 (100%); N2s, 15 of 26 (58%); N3s, 1 of 12 (8%); radical intent, 19 of 28 (68%); palliative intent, 3 of 17 (18%); UDC, 11 of 13 (85%); SCC,11 of 32 (34%). Eleven patients remained alive and disease free, with a median follow-up of 79 months (range, 27-110 months). The 5-year disease-specific survival (DSS) for the radical treatment group and the palliative treatment group were 67% and 18%, respectively (p =.0011). Significant difference in 5-year DSS was observed among the different N groups: 100% for N1s, 55% for N2s, and 0% for N3s, respectively (p =.0001). There was also a significant difference in the 5-year DSS between UDC and SCC: 81% for UDC vs 34% for SCC (p =.01). No significant difference in the 5-year DSS was observed on the basis of treatment modality in the radically treated group: 63% for RT alone vs 75% for S + RT (p =.711). CONCLUSIONS: UDC histologic findings in our series are associated with better locoregional control and DSS than SCC. Our results in local control, emergence of primary tumor, and DSS are comparable with other published data. However, disease control of advanced nodal stage remains poor; more aggressive treatment approaches, like the use of concurrent chemoradiation or altered fractionation scheme, should be explored.

Papillary thyroid carcinoma: prognostic factors and the role of radioiodine and external radiotherapy.

PURPOSE: To evaluate the role of radioiodine and external radiotherapy treatment in papillary thyroid carcinoma (PTC). METHODS AND MATERIALS: This is a retrospective study of 842 patients with the diagnosis of PTC registered from 1960 to 1997 at the Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong. The mean follow-up was 9.2 years. The stage distribution according to UICC/AJCC TNM staging was as follows: 58.6%, Stage I; 9.6%, Stage II; 26.1%, Stage III; 2.3%, Stage IV; and 3.4%, not stated. RESULTS: The 10-year cause-specific survival (CSS) rates were as follows: Stage I, 99.8%; Stage II, 91.8%; Stage III, 77.4%; and Stage IV, 37.1%. Multivariate analysis showed that the statistically significant poor prognostic factors for CSS were as follows: age older than 45, postoperative gross locoregional (LR) residual disease, distant metastasis (DM) at presentation, and lack of radioactive iodine (RAI) treatment. In patients with no DM and no postoperative LR disease, adjuvant RAI ablation reduced both LR failure (RR [relative risk] = 0.29) and DM (RR = 0.2), although the CSS was not affected. In the subgroup of T1N0 M0 disease, no patient with RAI treatment had a relapse. External radiotherapy reduced the risk of LR failure to 0.35. Subgroup analysis revealed that external radiotherapy was particularly effective in increasing the probability of LR control of disease in patients with gross postoperative LR disease (RR = 0.36). CONCLUSIONS: Both RAI and external radiotherapy were effective treatment in PTC. Total or near-total thyroidectomy followed by RAI treatment appears to result in the best outcome. External radiotherapy to improve LR control is indicated in patients with gross postoperative residual disease. Treatment should be individualized for patients with T1N0 M0 disease.