Lee D S, White D E, Hurst R, Rosenberg S A, Yang J C
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cancer J Sci Am. 1998 Mar-Apr;4(2):86-93.
The purpose of this study was to examine the pattern of relapse and the treatment of relapse with either surgery or repeat immunotherapy in patients with metastatic melanoma or renal cell carcinoma who had previously responded to interleukin-2-based therapy.
Over a 10-year period 1051 patients with metastatic melanoma or renal cell carcinoma were treated with interleukin-2-based immunotherapy at a single institution. One hundred fifty-nine patients who relapsed after an initial partial response or complete response to interleukin-2-based immunotherapy formed the study population for this retrospective review. Medical records, physical examination forms, and relevant radiographs were reviewed to determine response, relapse site(s), and response to treatment for relapse.
Relapse after an initial response to interleukin-2-based therapy occurred in 84 (80%) of 105 patients with metastatic melanoma and in 75 (70%) of 107 patients with metastatic renal cell carcinoma. Relapse after an initial partial response involved 71 (97%) of 73 patients with metastatic melanoma and 55 (86%) of 64 patients with metastatic renal cell carcinoma. The initial site(s) of relapse after a partial response involved a new site(s), old site(s), or both old and new sites with relatively even distribution. Relapse after an initial complete response occurred in 13 (41%) of 32 patients with metastatic melanoma and in 20 (47%) of 43 completely responding patients with metastatic renal cell carcinoma. Surprisingly, the initial site of relapse after a complete response involved only new sites of disease in 70% of patients. Retreatment of relapses with the same interleukin-2-based therapy originally used was effective in only one (2%) of 54 selected patients, but a different interleukin-2-based therapy in 35 patients resulted in five responders (a 14% secondary response rate). Most re-responders, however, responded to treatment with tumor-infiltrating lymphocytes and interleukin-2, and only one of 20 patients responded to retreatment with interleukin-2 alone. Surgical metastasectomy with therapeutic intent in 25 selected melanoma patients and in 31 selected renal cell cancer patients resulted in a 2-year progression-free survival of 18% in patients with metastatic melanoma and 37% in patients with metastatic renal cell carcinoma.
In patients with metastatic melanoma or renal cell carcinoma, tumor relapse was common after a partial response to an interleukin-2-based therapy and included previously identified sites of disease in most patients. Relapse after a complete response was less frequent and involved only new sites in a majority of patients. In selected patients who relapsed, repeat treatment with the same interleukin-2-based therapy that provided the initial response was rarely effective. However, with a different interleukin-2-based therapy, usually using tumor-infiltrating lymphocytes, repeat treatment induced secondary responses in some patients. In addition, salvage metastasectomy resulted in durable progression-free survival in selected patients.
本研究旨在探讨转移性黑色素瘤或肾细胞癌患者在先前对白介素 - 2 为基础的治疗有反应后复发的模式，以及采用手术或重复免疫疗法对复发进行治疗的情况。
在 10 年期间，1051 例转移性黑色素瘤或肾细胞癌患者在单一机构接受了以白介素 - 2 为基础的免疫治疗。159 例在对白介素 - 2 为基础的免疫治疗最初出现部分缓解或完全缓解后复发的患者构成了本次回顾性研究的人群。对病历、体格检查表格及相关影像学资料进行回顾，以确定反应情况、复发部位以及对复发治疗的反应。
105 例转移性黑色素瘤患者中有 84 例（80%）在对白介素 - 2 为基础的治疗最初反应后复发，107 例转移性肾细胞癌患者中有 75 例（70%）复发。最初部分缓解后复发的情况在 73 例转移性黑色素瘤患者中有 71 例（97%），在 64 例转移性肾细胞癌患者中有 55 例（86%）。部分缓解后复发的初始部位涉及新部位、旧部位或新旧部位均有，分布相对均匀。32 例转移性黑色素瘤完全缓解患者中有 13 例（41%）复发，43 例转移性肾细胞癌完全缓解患者中有 20 例（47%）复发。令人惊讶的是，完全缓解后复发的初始部位在 70%的患者中仅涉及新的疾病部位。对 54 例选定患者用最初使用的相同白介素 - 2 为基础的疗法对复发进行再治疗，仅 1 例（2%）有效，但对 35 例患者采用不同的白介素 - 2 为基础的疗法导致 5 例有反应者（继发反应率为 14%）。然而，大多数再反应者对肿瘤浸润淋巴细胞和白介素 - 2 的治疗有反应，20 例患者中仅 1 例对单独用白介素 - 2 再治疗有反应。对 25 例选定的黑色素瘤患者和 31 例选定的肾细胞癌患者进行有治疗意图的手术切除转移灶，转移性黑色素瘤患者的 2 年无进展生存率为 18%，转移性肾细胞癌患者为 37%。
在转移性黑色素瘤或肾细胞癌患者中，对白介素 - 2 为基础的治疗出现部分缓解后肿瘤复发很常见，且大多数患者复发包括先前已确定的疾病部位。完全缓解后复发较少见，且大多数患者仅涉及新部位。在选定的复发患者中，用提供最初反应的相同白介素 - 2 为基础的疗法重复治疗很少有效。然而，采用不同的白介素 - 2 为基础的疗法，通常使用肿瘤浸润淋巴细胞，重复治疗在一些患者中诱导了继发反应。此外，挽救性转移灶切除术在选定患者中导致了持久的无进展生存。
