In the treatment of pancreatic carcinomas, one modality is intraoperative radiotherapy (IORT). A study was carried out to assess the feasibility of IORT alone or in a multimodality approach with postoperative adjuvant chemotherapy and external radiotherapy and to compare local control and survival of patients. Another objective of this retrospective study was to verify prognostic factors in resected patients treated with IORT.
Methods
From January 1985 through September 1992, 54 adenocarcinomas of the pancreas (unresectable and resected patients) were treated with IORT by electron beam at the San Raffaele Hospital and then analyzed. Comparison was also carried out between IORT-treated resected patients and a non-randomized control group of resected patients treated without IORT in the same period.
Results
In unresectable patients treated by laparotomy bypass and IORT, overall median survival was 6 months and 8 months in non-metastatic patients. Relief of severe pain present in 14 patients was observed in 85% within 12 days of IORT. As regards resected patients, the most important finding was that significantly better local control resulted from IORT. In fact, overall, local relapses were 25% in the IORT group and 55.8% in the non-IORT group (control group); instead, survival of the IORT group was not significantly longer than that of the control group. From a statistical analysis of resected patients treated with IORT and performed on prognostic factors on the basis of available data, survival was significantly influenced by tumor pathologic grading and diameter; postoperative adjuvant therapy was not a significant prognosis factor.
Conclusions
IORT has a role in local control of unresectable pancreatic carcinomas and in control of resultant severe pain. In resected patients, IORT is effective in decreasing local recurrences but has little impact on survival. To obtain more satisfactory results, new and more effective adjuvant therapies and better abdominal prophylaxis should be tested.
AbeM., ShibamotoY., TakahashiG., ManabeG., TobeT., InamotoI.: Intraoperative radiotherapy in carcinoma of the stomach and pancreas. World J. Surg., 11: 459–464, 1987.
2.
Ahmadu-SukaF., GilletteE.L., WithrowS.J., HustedP.W., NelsonA.W., WhitemanC.E.: Pathologic response of the pancreas and duodenum to experimental intraoperative irradiation. Int. J. Radiat. Oncol. Biol. Phys., 14: 1197–1204, 1988.
3.
Ahmadu-SukaF., GilletteE.L., WithrowS.J., HustedP.W., NelsonA.W., WhitemanC.E.: Exocrine pancreatic function following intraoperative irradiation of the canine pancreas. Cancer, 62: 1091–1095, 1988.
4.
BagneF.R., DobelbowerR.R.Jr., MilliganA.J., BronD.G.: Treatment of cancer of pancreas by intraoperative electron beam therapy: physical and biological aspects. Int. J. Radiat. Oncol. Biol Phys., 16: 231–242, 1989.
5.
BossetS.F., PavyJ.J., GilletM., MantionG., PelissierE., SchraubS.: Conventional external irradiation alone as adjuvant treatment in resectable pancreatic cancer: results of a prospective study. Radiother. Oncol., 24: 191–194, 1992.
6.
BrennanM., KinsellaT., FriedmanM.: Cancer of pancreas. in: Cancer. Principles and Practice of Oncology, De VitaC.V.Jr., HellmanS., RosenbergS.A. (Eds.), 3rd edn., pp. 800–835, Lippincott, Philadephia, 1989.
7.
CarterS.K., ComisR.L.: Adenocarcinoma of the pancreas, prognostic variables, and criteria of response. In: Cancer Therapy: Prognostic Factors and Criteria of Response, StaquetM.J. (Ed.), p. 237, Raven Press, New York, 1975.
8.
CattaneoG.M., FossatiV., ArdesiA., FiorinoC., LongobardiB., SignorottoP., CalandrinoR.: Development of IORT at San Raffaele Hospital in Milan: Physical aspects. In: Intraoperative Radiation Therapy, AbeM., TakahashiM. (Eds.), pp. 129–130, Pergamon Press, New York, 1991.
9.
ConnolyM.M., DawsonP.J., MichelassF., MoossaA.R., LowensteinF.: Survival in 1001 patients with carcinoma of the pancreas. Ann. Surg., 206: 366–373, 1987.
10.
CoxD.R.: Regression models and life tables, J. Sta. Soc. Ser. B., 34: 187–222, 1972.
11.
CrileG.Jr.: The advantages of bypass operative over radical pancreaticduodenectomy in the treatment of pancreatic carcinoma. Surg. Gynecol. Obstet., 130: 1049–1053, 1970.
12.
CromackD.T., MaherM.N., HoekstraH., KinsellaR.J., SindelarW.F.: Are complications in intraoperative radiation therapy more frequent than in conventional treatment? Arch. Surg., 124: 229–234, 1989.
13.
Di CarloV., ChiesaR., PontiroliA.E., CarlucciM., StaudacherC., ZerbiA.: Pancreatoduodenectomy with occlusion of the residual stump by neoprene injection. World J. Surg., 13: 105–111, 1988.
14.
DobelbowerR.R.Jr., HowardJ.M., BagneF.R., EitakiA., MerrickH.W.: Treatment of cancer of the pancreas by precision high dose (PHD) external photon beam and intraoperative electrom beam therapy (IOEBT). Int J. Radiat. Oncol. Biol. Phys., 16: 205–209, 1989.
15.
FortnerJ.G.: Regional pancreatectomy for cancer of the pancreas, ampulla and other related sites. Ann. Surg., 199: 418–425, 1984.
16.
FossatiV., CattaneoG.M., PessinaP., CarlucciM., FerlaG., OlmiL., ParolinD., StaudacherC., ZerbiA., BissiA., CalandrinoR., Di CarloB., GalliE., TorriG., VolterraniF., MartinenghiC.: Institutional experience of IORT by electron beam at S. Raffaele Hospital in Milan: Clinical Results. In: Intraoperative Radiation Therapy, AbeM., TakahashiM. (Eds.), pp. 129–130, Pergamon Press, New York, 1991.
17.
Gastrointestinal Tumor Study Group: Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer, 59: 2006–2010, 1987.
18.
GerardJ.P., PartenskyC., RomestaingP., De LarocheG., LaassamiR.: La radiothérapie post-opératoire des cancers résécables du pancréas exocrine. Expérience lyonnaise. Bull. Cancer. Radiother., 78: 33–38, 1991.
19.
GilletteE.L., PowersB.E., McChesneyS.L., ParkR.D., WithrowS.J.: Response of aorta and branch arteries to experimental intraoperative irradiation. Int. J. Radiat. Oncol. Biol. Phys., 17: 1247–1255, 1989.
20.
GriffinJ.F., SmalleyS.R., JewellW., ParadiloJ.C., ReymondR.D., HassaneinR.E.S., EvansR.G.: Patterns of failure after curative resection of pancreatic carcinomaCancer, 66: 56–61, 1990.
21.
GudjonssonB.: Cancer of the pancreas. 50 years of surgery. Cancer, 60: 2284–2303, 1987.
22.
GudjonssonB., LivstoneE.M., SpiroH.M.: Cancer of the pancreas. Diagnostic accuracy and survival statistics. Cancer, 42: 2494–2506, 1978.
23.
GundersonL.L., ShipleyW.U., SuitH.D., EppE.R., NardiG., WoodW., CohenA., NelsonJ., BattitG., BiggsP.J., RussellA., RockettA., ClarkD.: Intraoperative irradiation: a pilot study combining external beam photons with “boost” dose intraoperative electrons. Cancer, 49: 2259–2266, 1982.
HataK.: Researches for the widening of indications in intraoperative radiation therapy. Annual report of cancer research. Japan: Ministry of Health and Welfare, pp. 242–245, 583–585, 1988.
26.
HiraokaT.: Extended radical resection of cancer of the pancreas with intraoperative radiotherapy. Clin. Gastroenterol., 4: 985–993, 1990.
27.
HiraokaR., WatanabeE., MochinagaM., TashiroS., MiyauchiY., NakamuraI.: Intraoperative irradiation combined with radical resection for cancer of the head of the pancreas. World. J. Surg., 8: 766–771, 1984.
28.
HoekstraH.J., RestrepoC., KinsellaT.J., SindelarW.F.: Histopathological effects of intraoperative radiotherapy on pancreas and adjacent tissues: a postmortem analysisJ Surg Oncol., 37: 104–108, 1988.
29.
IhseI., LilijaP., ArnesjoB., BengmarkK.S.: Total pancreatectomy for cancer. An appraisal of 65 cases. Ann Surg186: 675–680, 1977.
30.
IshikawaO., OhhigashiH., SasakiY., KabutoR., FukudaI., FurukawaH., ImaokaS., IwanagaT.: Practical usefulness of lymphatic and connective tissue clearance for the carcinoma of the pancreas head. Ann. Surg., 208: 215–220, 1988.
31.
KaiserM.H., EllenbergS.S.: Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch. Surg., 120: 899–903, 1985.
32.
KaplanE.L., MeierP.: Non parametric estimation from incomplete observations. J. Am. Stat. Assoc., 53: 457–481, 1958.
33.
KowamuraM., KataokaM., FujiiT., ItohH., InshineM., HamamotoK., YokoyamaS., TakashimaS., SatohM., InoueK.: Electron beam intraoperative radiation therapy (EBIORT) for localized pancreatic carcinoma. Int J. Radiat. Oncol. Biol. Phys., 23: 751–757, 1992.
34.
KloppelG.: Cancer of the pancreas: morphological and biological aspects. In: Cancer of the Bile Ducts and Pancreas, PreeceP.E., CuschieriA., RosinR.D. (Eds.), pp. 113–138, W.B. Saunders, Philadelphia, 1989.
KopelsonG.: Curative surgery for adenocarcinoma of the pancreas/ampulla of Vater: the role of adjuvant pre or postoperative radiation therapy. Int. J. Radiat. Oncol. Biol. Phys., 9: 911–915, 1983.
37.
LevinP.L., ConnelyR.R., De VesaS.S.: Demographic characteristics of cancer of the pancreas: mortality, incidence and survival. Cancer, 47: 1456–1468, 1981.
38.
LygidakisN.J., van der Hyde, HoutheffH.J., SchipperM.E.I., HuibregtseK., TytgatG.N.: Resectional surgical procedures for adenocarcinoma of the head of the pancreas. Surg. Gynecol. Obstet., 168: 157–165, 1989.
39.
McChesney-GilletteS., GilletteE.L., PowersB.E., LeCouteurR.A., ParkR.D., WithrowS.J.: Late normal tissue response after intraoperative therapy (IORT) alone and combined with external beam radiotherapy (EBRT). In: Intraoperative Radiation Therapy, AbeM., TakahashiM. (Eds.), pp. 399–400, Pergamon Press, New York, 1991.
ManabeR., OhshioG., BabaN.: Radical pancreatectomy for ductal cell carcinoma of the head of the pancreas. Cancer, 64: 1132–1137, 1989.
42.
MantelN.: Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother. Rep., 50: 163–170, 1966.
43.
MillerA.B., HoogstratenB., StaquetM., WinklerA.: Reporting results of cancer treatment. Cancer, 47: 207–214, 1981.
44.
NakaseA., MatsumotoY., UchidaK., HonjoI.: Surgical treatment of cancer of the pancreas and the periampullary region: cumulative results in 57 institutions in Japan. Ann. Surg., 185: 52–57, 1977.
45.
OnoderaT.: Multimodal treatment utilizing intraoperative radiotherapy for advanced cancer of the pancreas. Jpn. J. Cancer Chemother., 9: 1512–1517, 1982.
46.
OzakiH., KinoshitaT., KosugeT., EgawaS., KishiK.: Effectiveness of multimodality treatment for resectable pancreatic cancer. Int. J. Pancreatol., 7: 195–200, 1990.
47.
RoldanF.E., GundersonL.L., NagorneyD.M., MartinJ.K., IlstrupD.M., HoldbrookM.A.: External beam versus intraoperative and external beam irradiation for locally advanced pancreatic cancer. Cancer, 61: 1110–1116, 1988.
48.
ShibamotoY., ManabeT., BabaN., SasaiK., TakahashiM., TobeT., AbeM.: High dose external beam and intraoperative radiotherapy in the treatment of resectable and unresectable pancreatic cancer. Int. J. Radiat. Oncol. Biol. Phys., 19: 605–611, 1990.
49.
ShipleyW.U., WoodW.C., TepperJ.E., WarshawA.L., OrlowE.L., KaufmanS.D., BattitG.E., NardiG.L.: Intraoperative electron beam irradiation for patients with unresectable pancreatic carcinoma. Ann. Surg., 200: 289–294, 1984.
50.
SindelarW.F., KinsellaT.J.: Randomized trial of intraoperative radiotherapy in resected carcinoma of the pancreas. Int. J. Radiat. Oncol. Biol. Phys., 12 (Suppl. I): 110, 1986.
51.
SindelarW.F., HoekstraH.J., KinsellaT.J.: Surgical approaches and techniques in intraoperative radiotherapy for intraabdominal retroperitoneal and pelvic neoplasms. Surgery, 103: 247–256, 1988.
52.
SindelarW.F.: Intraoperative radiotherapy in carcinoma of the stomach and pancreas. Recent Results Cancer Res., 110: 226–243, 1988.
53.
SindelarW.F.: Clinical experience with regional pancreatectomy for adenocarcinoma of the pancreas. Arch. Surg., 124: 127–132, 1989.
54.
SmithI.E., CourtenayV.D., MillsJ., PeckmanM.J.: In vitro radiation response of cells from four human tumours propagated to immune-suppressed mice. Cancer Res., 38: 390–395, 1978.
55.
TepperJ., NardiG., SuitH.: Carcinoma of the pancreas: review of MGH experience from 1963 to 1973. Analysis of surgical failure and implications for radiation therapy. Cancer, 37: 1519–1524, 1976.
56.
TepperJ.E., NoyesD., KrallJ.M., SauseW.T., WolkovH.B., DobelbowerR.R., ThomsonJ., OwensJ., HanksG.E.: Intraoperative radiation therapy of pancreatic carcinoma: a report of RTOG–8505. Int. J. Radiat. Oncol. Biol. Phys., 21: 1145–1149, 1991.
57.
TradeM.: The surgical treatment of pancreatic carcinoma. Surgery, 97: 28–35, 1985.
58.
TucsonW.B., GoldsonA.L., AshayeriE., Halyard-RichardsonM., DeWittyR.L., LeffalL.D.Jr.: Intraoperative radiotherapy for patients with carcinoma of the pancreas. Ann. Surg., 207: 648–654, 1981.
Van HeerdenJ.A.: Pancreatic resection for carcinoma of the pancreas: Whipple versus total pancreatectomy – an institutional perspective. World. J. Surg., 8: 880–888, 1984.
61.
WarrenK.W., ChoeD.S., PlazaJ., RelihanM.: Results of radical resection for periampullary cancer. Ann. Surg., 181: 534–540, 1975.
62.
WarshawA.L., SwansonR.S.: Pancreatic cancer in 1988: possibilities and probabilities. Ann. Surg., 208: 541–553, 1988.
63.
WatanapaP., WilliamsonR.C.N.: Surgical palliation for pancreatic cancer: developments during the past two decades. Br. J. Surg., 79: 8–20, 1992.
64.
WhittingtonR., DobelbowerR.R., MohiuddinM., RosatoF.E., WeissS.M.: Radiotherapy of unresectable pancreatic carcinoma: a six-year experience with 104 patients. Int. J. Radiat. Oncol. Biol. Phys., 52: 808–813, 1983.
65.
WilliamsJ.A., CubillaA., MacleanB.J., FortnerJ.G.: Twenty-two-year experience with periampullary carcinoma at Memorial Sloan-Kettering Cancer Center. Am. J. Surg., 138: 662–665, 1979.
