Seegenschmiedt M H, Keilholz L, Altendorf-Hofmann A, Urban A, Schell H, Hohenberger W, Sauer R
The Department of Radiation Oncology, University Erlangen-Nürnberg, Erlangen, Germany.
Int J Radiat Oncol Biol Phys. 1999 Jun 1;44(3):607-18. doi: 10.1016/s0360-3016(99)00066-8.
Radiotherapy is used as a "last resort" for patients with advanced cutaneous malignant melanoma. We have analyzed our 20-year clinical experience with respect to different endpoints and prognostic factors in patients with locally advanced, recurrent, or metastatic malignant melanoma.
From 1977 to 1995, 2,917 consecutive patients were entered in the melanoma registry of our hospital. Radiotherapy was indicated in 121 patients (56 females, 65 males) for palliative reasons in advanced malignant melanoma stages UICC IIB/III/IV. The histology of the primary lesion was nodular in 51 patients, superficial spreading in 35, acral-lentiginous in 8, and lentigo maligna melanoma in 4 patients. Eleven patients had primary or recurrent lesions which were either not eligible for surgery or had residual disease (R2) after resection of a primary or recurrent lesion (UICC IIB); 57 patients had lymph node (n = 33) or in-transit metastases (n = 24) (UICC III), and 53 had distant organ metastases (7 M1a; 46 M1b) (UICC IV). Time from first diagnosis to on-study radiotherapy averaged 19 (median: 18; range: 3-186) months. In most cases, conventional RT was applied with 2-6 Gy single fractions up to a median total radiation dose of 48 (mean: 45; range: 20-66) Gy.
At 3 months follow-up, complete response (CR) was achieved in 7 (64%) and overall response [complete (CR) and partial response (PR)] in all (100%) UICC IIB patients, in 25 (44%) and 44 (77%) of 57 UICC III patients, and in 9 (17%) and 26 (49%) of 53 UICC IV patients. Tumor progression during radiotherapy occurred in 25 (21%) patients. Patients with CR survived longer (median: 40 months) than those without CR (median 10 months) (p < 0.01). At last follow-up (Dec 31, 1996), 26 patients were still alive: 6 (55%) UICC IIB, 17 (30%) UICC III, and 3 (6%) UICC IV patients (p < 0.01). Univariate analysis revealed the following prognostic factors for complete response and long-term survival: UICC stage (p < 0.001), primary location in the head and neck region, total radiation dose above 40 Gy (all p < 0.05), while age, gender, and histology had no impact. In multivariate analysis, UICC stage was the only independent prognostic factor (p < 0.001).
External beam radiotherapy can provide long-term local control and effective palliation in malignant melanoma UICC stages IIB-IV. The current UICC staging system is an excellent prognostic factor for initial and long-term tumor response in metastatic melanoma. Therefore, prospective randomized trials using external radiotherapy with or without adjuvant therapy for advanced malignant melanoma are justified.
放射治疗被用作晚期皮肤恶性黑色素瘤患者的“最后手段”。我们分析了20年来局部晚期、复发或转移性恶性黑色素瘤患者在不同终点和预后因素方面的临床经验。
1977年至1995年，我院黑色素瘤登记处连续纳入2917例患者。121例患者（56例女性，65例男性）因晚期恶性黑色素瘤UICC IIB/III/IV期的姑息治疗而接受放射治疗。原发灶组织学类型为结节型51例，浅表扩散型35例，肢端雀斑样痣型8例，恶性雀斑样黑色素瘤4例。11例患者的原发或复发病变不符合手术条件，或在原发或复发病变切除后有残留疾病（R2）（UICC IIB）；57例患者有淋巴结转移（n = 33）或区域淋巴结转移（n = 24）（UICC III），53例有远处器官转移（7例M1a；46例M1b）（UICC IV）。从首次诊断到开始研究性放射治疗的时间平均为19个月（中位数：18个月；范围：3 - 186个月）。在大多数情况下，采用常规放疗，单次剂量2 - 6 Gy，总辐射剂量中位数为48 Gy（平均：45 Gy；范围：20 - 66 Gy）。
在3个月的随访中，UICC IIB期患者中7例（64%）达到完全缓解（CR），所有患者（100%）达到总体缓解[完全缓解（CR）和部分缓解（PR）]；UICC III期57例患者中分别有25例（44%）和44例（77%）达到CR和PR；UICC IV期53例患者中分别有9例（17%）和26例（49%）达到CR和PR。25例（21%）患者在放疗期间出现肿瘤进展。达到CR的患者生存时间更长（中位数：40个月），未达到CR的患者生存时间中位数为10个月（p < 0.01）。在最后随访（1996年12月31日）时，26例患者仍存活：UICC IIB期6例（55%），UICC III期17例（30%），UICC IV期3例（6%）（p < 0.01）。单因素分析显示，以下因素是完全缓解和长期生存的预后因素：UICC分期（p < 0.001），头颈部原发部位，总辐射剂量高于40 Gy（所有p < 0.05），而年龄、性别和组织学类型无影响。多因素分析中，UICC分期是唯一的独立预后因素（p < 0.001）。
外照射放疗可在UICC IIB - IV期恶性黑色素瘤中提供长期局部控制和有效的姑息治疗。当前的UICC分期系统是转移性黑色素瘤初始和长期肿瘤反应的优秀预后因素。因此，开展关于晚期恶性黑色素瘤使用或不使用辅助治疗的外照射放疗的前瞻性随机试验是合理的。
