Radiotherapeutic strategies in the multimodality approach of resectable and non-resectable pancreatic carcinoma

Background: 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. Material and Methods: 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 S-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. Results: 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 radiochemotherapy 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/m(2) 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. Conclusions: 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.