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

Background: The prognosis of patients with adenocarcinoma of the pancreas r emains 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 t he multimodality approach. Even the intraoperative boost therapy (IORT) wit h 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 EOR TC have been closed or are recruiting patients, the results are still pendi ng. Neoadjuvant treatment modalities were investigated within the last 3 ye ars, mostly in case of primary operable but also in unresectable tumors. Us ing S-D-treatment planning, the total dose of radiotherapy was increased fr om 40 up to 45 to 50 Gy. In centers with great experience, an IORT was adde d to these combined modalities. More modern chemotherapeutic agents like ge mcitabine or the taxanes are under investigation, using combined radio-chem otherapy in phase-II protocols in patients with unresectable tumors. Results: In case of both, adjuvant or neoadjuvant radio-chemotherapy follow ing or before pancreaticoduodenectomy, median survival times range from 15 to 25 months. The neoadjuvant radio-chemotherapy seems to reduce the rate o f positive surgical margins and the rate of patients with positive lymph no des. For the moment, there is no proven survival advantage or increase of l ocal control (about 80% in both cases) for patients treated with neoadjuvan t radiochemotherapy compared with adjuvant radio-chemotherapy, However, abo ut 25% of the patients don't receive adjuvant therapy due to the perioperat ive morbidity. Because prolongation of survival with adjuvant therapy is on ly 5 to 10 months, in Europe adjuvant radio-chemotherapy is not accepted as the treatment standard. Combined radio-chemotherapy in patients with unres ectable tumors results in significant improvement of survival. 5-FU continu ous 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 pallia tion. More modern chemotherapeutic agents seem to be effective in vitro as radio-sensitizers. In first reported results, the MTD was not found. Toxici ty 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 investigati on. For some reasons, the neoadjuvant setting seems to be better. However, these results are not proven by prospective randomized clinical trials. The refore, these trials are necessary to define the treatment of choice in the se patients. IORT is a helpful tool to improve local control. However, thes e aggressive multimodality approaches are only indicated in a minority of p atients. In patients with unresectable tumors and good condition, combined radio-chemotherapy remains the treatment of choice.