Mazzaferri E L, Jhiang S M
Ohio State University College of Medicine, Columbus.
Am J Med. 1994 Nov;97(5):418-28. doi: 10.1016/0002-9343(94)90321-2.
To determine the long-term impact of medical and surgical treatment of well differentiated papillary and follicular thyroid cancer.
Patients with papillary and follicular cancer (n = 1,355) treated either in U.S. Air Force or Ohio State University hospitals over the past 40 years were prospectively followed by questionnaire or personal examination to determine treatment outcomes. Outcomes were analyzed by Kaplan-Meier survival curves and Cox proportional-hazard regression model.
Median follow-up was 15.7 years; 42% (568) of the patients were followed for 20 years and 14% (185) for 30 years. After 30 years, the survival rate was 76%, the recurrence rate was 30%, and the cancer death rate was 8%. Recurrences were most frequent at the extremes of age (< 20 and > 59 years). Cancer mortality rates were lowest in patients younger than 40 years and increased with each subsequent decade of life. Thirty-year cancer mortality rates were greatest in follicular cancer patients, who were more likely to have adverse prognostic factors: older age, larger tumors, more mediastinal node involvement, and distant metastases. When patients with distant metastases at diagnosis were excluded, follicular and papillary cancer mortality rates were similar (10% versus 6%, P not significant [NS]). In a Cox regression model that excluded patients who presented with distant metastases, the likelihood of cancer death was (1) increased by age > or = 40 years, tumor size > or = 1.5 cm, local tumor invasion, regional lymph-node metastases, and delay in therapy > or = 12 months; (2) reduced by female sex, surgery more extensive than lobectomy, and 131I plus thyroid hormone therapy; and (3) unaffected by tumor histologic type. Following 131I therapy given only to ablate normal thyroid gland remnants, the recurrence rate was less than one third the rate after thyroid hormone therapy alone (P < 0.001). No patient treated in this way with 131I has died of thyroid cancer. Low 131I doses (29 to 50 mCi) were as effective as high doses (51 to 200 mCi) in controlling tumor recurrence (7% versus 9%, P = NS). Following 131I therapy, whether given for thyroid remnant ablation or cancer therapy, recurrence and the likelihood of cancer death were reduced by at least half, despite the existence of more adverse prognostic factors in patients given 131I. At 30 years, the cumulative cancer mortality rate following 131I therapy, regardless of the reason for its use, was one third that in patients not so treated (P = 0.03).
Over the long term, for tumors > or = 1.5 cm that are not initially metastatic to distant sites, near-total thyroidectomy followed by 131I plus thyroid hormone therapy confers a distinct outcome advantage. This therapy reduces tumor recurrence and mortality sufficiently to offset the augmented risks incurred by delayed therapy, age > or = 40 at the time of diagnosis, and tumors that are much larger than 1.5 cm, multicentric, locally invasive, or regionally metastatic.
确定分化型甲状腺乳头状癌和滤泡状癌的内科及外科治疗的长期影响。
对过去40年在美国空军医院或俄亥俄州立大学医院接受治疗的乳头状癌和滤泡状癌患者（n = 1355）进行前瞻性随访，通过问卷调查或个人检查来确定治疗结果。采用Kaplan-Meier生存曲线和Cox比例风险回归模型对结果进行分析。
中位随访时间为15.7年；42%（568例）的患者随访了20年，14%（185例）随访了30年。30年后，生存率为76%，复发率为30%，癌症死亡率为8%。复发在年龄两端（<20岁和>59岁）最为常见。40岁以下患者的癌症死亡率最低，并随年龄每增加一个十年而上升。滤泡状癌患者的30年癌症死亡率最高，他们更可能具有不良预后因素：年龄较大、肿瘤较大、更多纵隔淋巴结受累以及远处转移。当排除诊断时有远处转移的患者后，滤泡状癌和乳头状癌的死亡率相似（10%对6%，P无显著性差异[NS]）。在一个排除有远处转移患者的Cox回归模型中，癌症死亡的可能性为：（1）因年龄≥40岁、肿瘤大小≥1.5 cm、局部肿瘤侵犯、区域淋巴结转移以及治疗延迟≥12个月而增加；（2）因女性、手术范围超过叶切除术以及131I加甲状腺激素治疗而降低；（3）不受肿瘤组织学类型影响。仅为消融正常甲状腺残余组织而给予131I治疗后，复发率不到仅接受甲状腺激素治疗后的三分之一（P<0.001）。接受这种方式131I治疗的患者中没有死于甲状腺癌的。低剂量131I（29至50 mCi）在控制肿瘤复发方面与高剂量（51至200 mCi）同样有效（7%对9%，P = NS）。接受131I治疗后，无论其用于甲状腺残余组织消融还是癌症治疗，复发率和癌症死亡可能性至少降低一半，尽管接受131I治疗的患者存在更多不良预后因素。30年后，无论使用131I的原因如何，接受131I治疗后的累积癌症死亡率是未接受该治疗患者的三分之一（P = 0.03）。
从长期来看，对于初始未远处转移且肿瘤≥1.5 cm的患者，次全甲状腺切除术后给予131I加甲状腺激素治疗具有明显的预后优势。这种治疗充分降低了肿瘤复发率和死亡率，足以抵消因治疗延迟、诊断时年龄≥40岁以及肿瘤远大于1.5 cm、多中心、局部侵犯或区域转移所带来的增加风险。
