Wiegel T, Runkel N, Frommhold H, Rübe C, Hinkelbein W
Abteilung Strahlentherapie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin.
Strahlenther Onkol. 2000 Jul;176(7):299-306. doi: 10.1007/s000660050011.
The prognosis of patients with adenocarcinoma of the pancreas remains poor. Only patients with small tumors and complete resection have a curative chance. The value of combined radio-chemotherapy adjuvant or even palliative in case of unresectable tumors is controversial due to the short median survival times of all patients ranging from 8 to 15 months. Within the last years, significant new treatment modalities were introduced into the multimodality approach. Even the intraoperative boost therapy (IORT) with fast electrons remains still controversial.
Since the publication of the results of the historic GITSG study, in the US postoperative adjuvant radio-chemotherapy with 5-FU remains the treatment of choice. Successor studies of the ESPAC and the EORTC have been closed or are recruiting patients, the results are still pending. Neoadjuvant treatment modalities were investigated within the last 3 years, mostly in case of primary operable but also in unresectable tumors. Using 3-D-treatment planning, the total dose of radiotherapy was increased from 40 up to 45 to 50 Gy. In centers with great experience, an IORT was added to these combined modalities. More modern chemotherapeutic agents like gemcitabine or the taxanes are under investigation, using combined radio-chemotherapy in phase-II protocols in patients with unresectable tumors.
In case of both, adjuvant or neoadjuvant radio-chemotherapy following or before pancreaticoduodenectomy, median survival times range from 15 to 25 months. The neoadjuvant radio-chemotherapy seems to reduce the rate of positive surgical margins and the rate of patients with positive lymph nodes. For the moment, there is no proven survival advantage or increase of local control (about 80% in both cases) for patients treated with neoadjuvant radio-chemotherapy compared with adjuvant radio-chemotherapy. However, about 25% of the patients don't receive adjuvant therapy due to the perioperative morbidity. Because prolongation of survival with adjuvant therapy is only 5 to 10 months, in Europe adjuvant radio-chemotherapy is not accepted as the treatment standard. Combined radio-chemotherapy in patients with unresectable tumors results in significant improvement of survival. 5-FU continuous infusion with 250 mg/m2 seems to be the treatment of choice. IORT is effective in achieving long-term local control and an effective pain palliation. More modern chemotherapeutic agents seem to be effective in vitro as radio-sensitizers. In first reported results, the MTD was not found. Toxicity seems not to be increased with single radiotherapy doses of 1.8 to 2 Gy. However, higher single doses should not be used.
Due to the worse prognosis of patients with adenocarcinoma of the pancreas, new combined treatment modalities as adjuvant and neoadjuvant radio-chemotherapy, particularly with more modern chemotherapeutic agents, for patients with resectable and unresectable tumors are under investigation. For some reasons, the neoadjuvant setting seems to be better. However, these results are not proven by prospective randomized clinical trials. Therefore, these trials are necessary to define the treatment of choice in these patients. IORT is a helpful tool to improve local control. However, these aggressive multimodality approaches are only indicated in a minority of patients. In patients with unresectable tumors and good condition, combined radio-chemotherapy remains the treatment of choice.
胰腺癌患者的预后仍然很差。只有肿瘤较小且能完全切除的患者才有治愈的机会。对于无法切除的肿瘤，辅助性甚至姑息性联合放化疗的价值存在争议，因为所有患者的中位生存时间较短，为8至15个月。在过去几年中，多模式治疗方法引入了重要的新治疗方式。即使是使用快速电子的术中强化治疗（IORT）也仍然存在争议。
自具有历史意义的胃肠道肿瘤研究组（GITSG）研究结果发表以来，在美国，术后使用5-氟尿嘧啶（5-FU）进行辅助性放化疗仍然是首选治疗方法。欧洲癌症研究与治疗组织（EORTC）和英国胰腺癌研究组（ESPAC）的后续研究已经结束或正在招募患者，结果仍未可知。在过去3年中对新辅助治疗方式进行了研究，主要针对原发性可手术切除但也包括无法切除的肿瘤。使用三维治疗计划，放疗总剂量从40 Gy增加到45 Gy，再到50 Gy。在经验丰富的中心，这些联合治疗方式中增加了IORT。正在研究更现代的化疗药物，如吉西他滨或紫杉烷类，在无法切除肿瘤的患者的II期方案中使用联合放化疗。
在胰十二指肠切除术后进行辅助性或新辅助性放化疗的情况下，中位生存时间为15至25个月。新辅助放化疗似乎能降低手术切缘阳性率和淋巴结阳性患者的比例。目前，与辅助性放化疗相比，新辅助放化疗治疗的患者在生存优势或局部控制率提高方面（两种情况均约为80%）尚无确凿证据。然而，约25%的患者由于围手术期发病率未接受辅助治疗。由于辅助治疗使生存延长仅5至10个月，在欧洲，辅助性放化疗未被接受为治疗标准。无法切除肿瘤的患者进行联合放化疗可显著提高生存率。持续输注250 mg/m² 的5-FU似乎是首选治疗方法。IORT在实现长期局部控制和有效缓解疼痛方面有效。更现代的化疗药物似乎在体外作为放射增敏剂有效。在首次报告的结果中，未发现最大耐受剂量（MTD）。单次放疗剂量为1.8至2 Gy时毒性似乎未增加。然而，不应使用更高的单次剂量。
由于胰腺癌患者预后较差，正在研究针对可切除和不可切除肿瘤患者的新的联合治疗方式，如辅助性和新辅助性放化疗，特别是使用更现代的化疗药物。由于某些原因，新辅助治疗方案似乎更好。然而，这些结果尚未得到前瞻性随机临床试验的证实。因此，需要这些试验来确定这些患者的首选治疗方法。IORT是改善局部控制的有用工具。然而，这些积极的多模式治疗方法仅适用于少数患者。对于无法切除肿瘤且身体状况良好的患者，联合放化疗仍然是首选治疗方法。
