Feasibility and efficacy of combination therapy with preoperative full-dose gemcitabine, concurrent three-dimensional conformal radiation, surgery, and postoperative liver perfusion chemotherapy for T3-pancreatic cancer.
OBJECTIVE
To evaluate both the feasibility and efficacy of our combined therapy, which consisted of preoperative chemoradiation, surgery, and postoperative liver perfusion chemotherapy (LPC) for patients with T3 (extended beyond the pancreatic confines) cancer of the pancreas.


BACKGROUND
Because of the high incidence of local recurrence and liver metastasis, long-term outcomes for patients after resection of T3-pancreatic cancer are extremely poor.


METHODS
During the period from 2002 to 2007, 38 patients with T3-pancreatic cancers consented to receive a combination of preoperative chemoradiation, surgery, and postoperative LPC. With the aid of 3D radiation planning, irradiation fields were constructed that included both the primary pancreatic tumor and retropancreatic tissues while taking care to exclude any section of the gastrointestinal tract. The total dose of radiation was 50 Gy (2 Gy x 25 fractions/5 weeks) and was administered in combination with gemcitabine treatments (1000 mg/m/week x 9/3 months). Preoperative restaging via computerized tomography and intraoperative inspection were used to determine if pancreatectomy was indicated. For respected cases, one catheter was placed into the gastroduodenal artery and another one into the superior mesenteric vein. Postoperatively, 5-FU (125 mg/day x 28 days) was infused via each of these 2 routes.


RESULTS
Preoperative chemoradiation was completed for all 38 patients, including 3 patients who required gemcitabine-dose reduction. Seven patients (18%) did not undergo surgical resection because either distant metastases or progressive local tumors had been detected after chemoradiation. The remaining 31 patients (82%) underwent pancreatectomy plus postoperative LPC, without postoperative or in-hospital mortality. The 5-year survival rate after pancreatectomy was 53%, with low incidences of both local recurrence (9%) and liver metastasis (7%). Postoperative histopathologic study revealed a marked degenerative change in cancer tissue, showing negative surgical margins (R0) for 30 patients (96%) and negative nodal involvement for 28 patients (90%).


CONCLUSIONS
Results of this trial suggest that a combination of preoperative full-dose gemcitabine, concurrent 3D-conformal radiation, surgery, and postoperative LPC is feasible for the treatment of T3-pancreatic cancer. Using the method described in this article, we were able to effectively reduce the incidence of both local and liver recurrence. Therefore, this type of combination therapy seems promising for improving long-term outcomes for patients with T3-cancers of the pancreas. This study is registered with University hospital Medical information Network clinical trials Registry number, UMIN000001804.
Ohigashi
Hiroaki
H
Departments of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashi-nari-ku, Osaka 537-8511, Japan. oohigasi-hi@mc.pref.osaka.jp
Ishikawa
Osamu
O
Eguchi
Hidetoshi
H
Takahashi
Hidenori
H
Gotoh
Kunihito
K
Yamada
Terumasa
T
Yano
Masahiko
M
Nakaizumi
Akihiko
A
Uehara
Hiroyuki
H
Tomita
Yoshihiko
Y
Nishiyama
Kinji
K
D000230:Adenocarcinoma / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D015918:Infusion Pumps, Implantable; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D010477:Perfusion; D018714:Radiotherapy, Adjuvant; D020266:Radiotherapy, Conformal; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine