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Published in: Radiation Oncology 1/2012

Open Access 01-12-2012 | Research

Radiation dose ≥54 Gy and CA 19–9 response are associated with improved survival for unresectable, non-metastatic pancreatic cancer treated with chemoradiation

Authors: Daniel W Golden, Caroline J Novak, Bruce D Minsky, Stanley L Liauw

Published in: Radiation Oncology | Issue 1/2012

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Abstract

Background

Unresectable pancreatic cancer (UPC) has low survival. With improving staging techniques and systemic therapy, local control in patients without metastatic disease may have increasing importance. We investigated whether the radiation dose used in chemoradiation (CRT) as definitive treatment for UPC and the CA 19–9 response to therapy have an impact on overall survival (OS).

Methods

From 1997–2009 46 patients were treated with CRT for non-metastatic UPC. Median prescribed RT dose was 54 Gy (range 50.4-59.4 Gy). All patients received concurrent chemotherapy (41: 5-fluorouracil, 5: other) and 24 received adjuvant chemotherapy.

Results

41 patients were inoperable due to T4 disease and 5 patients with T3 disease were medically inoperable. Five patients did not complete CRT due to progressive disease or treatment-related toxicity (median RT dose 43.2 Gy). Overall, 42 patients were dead of disease at the time of last follow-up. The median and 12 month OS were 8.8 months and 35%, respectively. By univariate analysis, minimum CA 19–9 post-CRT <90 U/mL was favorably associated with OS (12.3 versus 8.8 months, p = 0.012). Radiotherapy dose ≥54 Gy trended towards improved OS (11.3 versus 6.8 months, p = 0.089). By multivariable analysis, a delivered RT dose of ≥54 Gy (HR 0.47, p = 0.028) and minimum CA 19–9 post-CRT of <90 U/mL (HR 0.35, p = 0.008) were associated with OS.

Conclusions

CRT as definitive treatment for UPC had low survival. However, our retrospective data suggest that patients treated to ≥54 Gy or observed to have a minimum post-CRT CA 19–9 <90 U/mL had improved likelihood of long-term survival.
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Literature
1.
go back to reference Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin 2010, 60: 277-300. 10.3322/caac.20073CrossRefPubMed Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin 2010, 60: 277-300. 10.3322/caac.20073CrossRefPubMed
2.
go back to reference Sener SF, Fremgen A, Menck HR, Winchester DP: Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985–1995, using the national cancer database. J Am Coll Surg 1999, 189: 1-7. 10.1016/S1072-7515(99)00075-7CrossRefPubMed Sener SF, Fremgen A, Menck HR, Winchester DP: Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985–1995, using the national cancer database. J Am Coll Surg 1999, 189: 1-7. 10.1016/S1072-7515(99)00075-7CrossRefPubMed
3.
go back to reference Ben-Josef E, Lawrence TS: Chemoradiotherapy for unresectable pancreatic cancer. Int J Clin Oncol 2008, 13: 121-126. 10.1007/s10147-007-0763-xCrossRefPubMed Ben-Josef E, Lawrence TS: Chemoradiotherapy for unresectable pancreatic cancer. Int J Clin Oncol 2008, 13: 121-126. 10.1007/s10147-007-0763-xCrossRefPubMed
4.
go back to reference Gutt R, Liauw SL, Weichselbaum RR: The role of radiotherapy in locally advanced pancreatic carcinoma. Nat Rev Gastroenterol Hepatol 2010, 7: 437-447. 10.1038/nrgastro.2010.98CrossRefPubMed Gutt R, Liauw SL, Weichselbaum RR: The role of radiotherapy in locally advanced pancreatic carcinoma. Nat Rev Gastroenterol Hepatol 2010, 7: 437-447. 10.1038/nrgastro.2010.98CrossRefPubMed
5.
go back to reference Iacobuzio-Donahue CA, Fu B, Yachida S, Luo M, Abe H, Henderson CM, Vilardell F, Wang Z, Keller JW, Banerjee P, et al.: DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 2009, 27: 1806-1813. 10.1200/JCO.2008.17.7188PubMedCentralCrossRefPubMed Iacobuzio-Donahue CA, Fu B, Yachida S, Luo M, Abe H, Henderson CM, Vilardell F, Wang Z, Keller JW, Banerjee P, et al.: DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 2009, 27: 1806-1813. 10.1200/JCO.2008.17.7188PubMedCentralCrossRefPubMed
6.
go back to reference Kamisawa T, Isawa T, Koike M, Tsuruta K, Okamoto A: Hematogenous metastases of pancreatic ductal carcinoma. Pancreas 1995, 11: 345-349. 10.1097/00006676-199511000-00005CrossRefPubMed Kamisawa T, Isawa T, Koike M, Tsuruta K, Okamoto A: Hematogenous metastases of pancreatic ductal carcinoma. Pancreas 1995, 11: 345-349. 10.1097/00006676-199511000-00005CrossRefPubMed
7.
go back to reference Huguet F, Andre T, Hammel P, Artru P, Balosso J, Selle F, Deniaud-Alexandre E, Ruszniewski P, Touboul E, Labianca R, et al.: Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies. J Clin Oncol 2007, 25: 326-331. 10.1200/JCO.2006.07.5663CrossRefPubMed Huguet F, Andre T, Hammel P, Artru P, Balosso J, Selle F, Deniaud-Alexandre E, Ruszniewski P, Touboul E, Labianca R, et al.: Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies. J Clin Oncol 2007, 25: 326-331. 10.1200/JCO.2006.07.5663CrossRefPubMed
8.
go back to reference Gastrointestinal Tumor Study Group: Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst 1988, 80: 751-755.CrossRef Gastrointestinal Tumor Study Group: Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst 1988, 80: 751-755.CrossRef
9.
go back to reference Loehrer PJ Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB 3rd: Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol 2011, 29: 4105-4112. 10.1200/JCO.2011.34.8904PubMedCentralCrossRefPubMed Loehrer PJ Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB 3rd: Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol 2011, 29: 4105-4112. 10.1200/JCO.2011.34.8904PubMedCentralCrossRefPubMed
10.
go back to reference Tempero MA, Arnoletti JP, Behrman S, Ben-Josef E, Benson AB 3rd, Berlin JD, Cameron JL, Casper ES, Cohen SJ, Duff M, et al.: Pancreatic adenocarcinoma. J Natl Compr Canc Netw 2010, 8: 972-1017.PubMedCentralPubMed Tempero MA, Arnoletti JP, Behrman S, Ben-Josef E, Benson AB 3rd, Berlin JD, Cameron JL, Casper ES, Cohen SJ, Duff M, et al.: Pancreatic adenocarcinoma. J Natl Compr Canc Netw 2010, 8: 972-1017.PubMedCentralPubMed
11.
go back to reference Yoo T, Lee WJ, Woo SM, Kim TH, Han SS, Park SJ, Moon SH, Shin KH, Kim SS, Hong EK, et al.: Pretreatment carbohydrate antigen 19-9 level indicates tumor response, early distant metastasis, overall survival, and therapeutic selection in localized and unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2011, 81: e623-e630. 10.1016/j.ijrobp.2011.02.063CrossRefPubMed Yoo T, Lee WJ, Woo SM, Kim TH, Han SS, Park SJ, Moon SH, Shin KH, Kim SS, Hong EK, et al.: Pretreatment carbohydrate antigen 19-9 level indicates tumor response, early distant metastasis, overall survival, and therapeutic selection in localized and unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2011, 81: e623-e630. 10.1016/j.ijrobp.2011.02.063CrossRefPubMed
12.
go back to reference Moertel CG, Frytak S, Hahn RG, O'Connell MJ, Reitemeier RJ, Rubin J, Schutt AJ, Weiland LH, Childs DS, Holbrook MA, et al.: Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer 1981, 48: 1705-1710. 10.1002/1097-0142(19811015)48:8<1705::AID-CNCR2820480803>3.0.CO;2-4CrossRefPubMed Moertel CG, Frytak S, Hahn RG, O'Connell MJ, Reitemeier RJ, Rubin J, Schutt AJ, Weiland LH, Childs DS, Holbrook MA, et al.: Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer 1981, 48: 1705-1710. 10.1002/1097-0142(19811015)48:8<1705::AID-CNCR2820480803>3.0.CO;2-4CrossRefPubMed
13.
go back to reference Crane CH, Beddar AS, Evans DB: The role of intraoperative radiotherapy in pancreatic cancer. Surg Oncol Clin N Am 2003, 12: 965-977. 10.1016/S1055-3207(03)00090-5CrossRefPubMed Crane CH, Beddar AS, Evans DB: The role of intraoperative radiotherapy in pancreatic cancer. Surg Oncol Clin N Am 2003, 12: 965-977. 10.1016/S1055-3207(03)00090-5CrossRefPubMed
14.
go back to reference Milano MT, Chmura SJ, Garofalo MC, Rash C, Roeske JC, Connell PP, Kwon OH, Jani AB, Heimann R: Intensity-modulated radiotherapy in treatment of pancreatic and bile duct malignancies: toxicity and clinical outcome. Int J Radiat Oncol Biol Phys 2004, 59: 445-453. 10.1016/j.ijrobp.2003.11.003CrossRefPubMed Milano MT, Chmura SJ, Garofalo MC, Rash C, Roeske JC, Connell PP, Kwon OH, Jani AB, Heimann R: Intensity-modulated radiotherapy in treatment of pancreatic and bile duct malignancies: toxicity and clinical outcome. Int J Radiat Oncol Biol Phys 2004, 59: 445-453. 10.1016/j.ijrobp.2003.11.003CrossRefPubMed
15.
go back to reference Ben-Josef E, Schipper M, Francis IR, Hadley S, Ten-Haken R, Lawrence T, Normolle D, Simeone DM, Sonnenday C, Abrams R, et al.: A phase I/II trial of intensity modulated radiation (IMRT) dose escalation with concurrent fixed-dose rate gemcitabine (FDR-G) in patients with unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2012. Article in press Ben-Josef E, Schipper M, Francis IR, Hadley S, Ten-Haken R, Lawrence T, Normolle D, Simeone DM, Sonnenday C, Abrams R, et al.: A phase I/II trial of intensity modulated radiation (IMRT) dose escalation with concurrent fixed-dose rate gemcitabine (FDR-G) in patients with unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2012. Article in press
16.
go back to reference Koong AC, Christofferson E, Le QT, Goodman KA, Ho A, Kuo T, Ford JM, Fisher GA, Greco R, Norton J, Yang GP: Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2005, 63: 320-323. 10.1016/j.ijrobp.2005.07.002CrossRefPubMed Koong AC, Christofferson E, Le QT, Goodman KA, Ho A, Kuo T, Ford JM, Fisher GA, Greco R, Norton J, Yang GP: Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2005, 63: 320-323. 10.1016/j.ijrobp.2005.07.002CrossRefPubMed
17.
go back to reference Chang DT, Schellenberg D, Shen J, Kim J, Goodman KA, Fisher GA, Ford JM, Desser T, Quon A, Koong AC: Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas. Cancer 2009, 115: 665-672. 10.1002/cncr.24059CrossRefPubMed Chang DT, Schellenberg D, Shen J, Kim J, Goodman KA, Fisher GA, Ford JM, Desser T, Quon A, Koong AC: Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas. Cancer 2009, 115: 665-672. 10.1002/cncr.24059CrossRefPubMed
18.
go back to reference Hoyer M, Roed H, Sengelov L, Traberg A, Ohlhuis L, Pedersen J, Nellemann H, Kiil Berthelsen A, Eberholst F, Engelholm SA, von der Maase H: Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma. Radiother Oncol 2005, 76: 48-53. 10.1016/j.radonc.2004.12.022CrossRefPubMed Hoyer M, Roed H, Sengelov L, Traberg A, Ohlhuis L, Pedersen J, Nellemann H, Kiil Berthelsen A, Eberholst F, Engelholm SA, von der Maase H: Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma. Radiother Oncol 2005, 76: 48-53. 10.1016/j.radonc.2004.12.022CrossRefPubMed
19.
go back to reference Schellenberg D, Goodman KA, Lee F, Chang S, Kuo T, Ford JM, Fisher GA, Quon A, Desser TS, Norton J, et al.: Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2008, 72: 678-686. 10.1016/j.ijrobp.2008.01.051CrossRefPubMed Schellenberg D, Goodman KA, Lee F, Chang S, Kuo T, Ford JM, Fisher GA, Quon A, Desser TS, Norton J, et al.: Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2008, 72: 678-686. 10.1016/j.ijrobp.2008.01.051CrossRefPubMed
20.
go back to reference Goyal K, Einstein D, Ibarra RA, Yao M, Kunos C, Ellis R, Brindle J, Singh D, Hardacre J, Zhang Y, et al.: Stereotactic body radiation therapy for nonresectable tumors of the pancreas. J Surg Res 2012, 174: 319-325. 10.1016/j.jss.2011.07.044PubMedCentralCrossRefPubMed Goyal K, Einstein D, Ibarra RA, Yao M, Kunos C, Ellis R, Brindle J, Singh D, Hardacre J, Zhang Y, et al.: Stereotactic body radiation therapy for nonresectable tumors of the pancreas. J Surg Res 2012, 174: 319-325. 10.1016/j.jss.2011.07.044PubMedCentralCrossRefPubMed
21.
go back to reference Mahadevan A, Miksad R, Goldstein M, Sullivan R, Bullock A, Buchbinder E, Pleskow D, Sawhney M, Kent T, Vollmer C, Callery M: Induction gemcitabine and stereotactic body radiotherapy for locally advanced nonmetastatic pancreas cancer. Int J Radiat Oncol Biol Phys 2011, 81: e615-e622. 10.1016/j.ijrobp.2011.04.045CrossRefPubMed Mahadevan A, Miksad R, Goldstein M, Sullivan R, Bullock A, Buchbinder E, Pleskow D, Sawhney M, Kent T, Vollmer C, Callery M: Induction gemcitabine and stereotactic body radiotherapy for locally advanced nonmetastatic pancreas cancer. Int J Radiat Oncol Biol Phys 2011, 81: e615-e622. 10.1016/j.ijrobp.2011.04.045CrossRefPubMed
22.
go back to reference Ko AH, Quivey JM, Venook AP, Bergsland EK, Dito E, Schillinger B, Tempero MA: A phase II study of fixed-dose rate gemcitabine plus low-dose cisplatin followed by consolidative chemoradiation for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2007, 68: 809-816. 10.1016/j.ijrobp.2007.01.005CrossRefPubMed Ko AH, Quivey JM, Venook AP, Bergsland EK, Dito E, Schillinger B, Tempero MA: A phase II study of fixed-dose rate gemcitabine plus low-dose cisplatin followed by consolidative chemoradiation for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2007, 68: 809-816. 10.1016/j.ijrobp.2007.01.005CrossRefPubMed
23.
go back to reference Krishnan S, Rana V, Janjan NA, Varadhachary GR, Abbruzzese JL, Das P, Delclos ME, Gould MS, Evans DB, Wolff RA, Crane CH: Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy. Cancer 2007, 110: 47-55. 10.1002/cncr.22735CrossRefPubMed Krishnan S, Rana V, Janjan NA, Varadhachary GR, Abbruzzese JL, Das P, Delclos ME, Gould MS, Evans DB, Wolff RA, Crane CH: Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy. Cancer 2007, 110: 47-55. 10.1002/cncr.22735CrossRefPubMed
24.
go back to reference Slim N, Passoni P, Cattaneo M, Cereda S, Reni M, Longobardi B, Landoni C, Bettinardi V, Alongi F, Di Muzio N: Hypofractionated image-guided tomotherapy concomitant to capecitabine in advanced pancreatic adenocarcinoma. Preliminary results of a phase II study. Int J Radiat Oncol Biol Phys 2010, 78: S194.CrossRef Slim N, Passoni P, Cattaneo M, Cereda S, Reni M, Longobardi B, Landoni C, Bettinardi V, Alongi F, Di Muzio N: Hypofractionated image-guided tomotherapy concomitant to capecitabine in advanced pancreatic adenocarcinoma. Preliminary results of a phase II study. Int J Radiat Oncol Biol Phys 2010, 78: S194.CrossRef
25.
go back to reference Wakatsuki T, Irisawa A, Terashima M, Shibukawa G, Takagi T, Imamura H, Takahashi Y, Sato A, Sato M, Ikeda T, et al.: ATP assay-guided chemosensitivity testing for gemcitabine with biopsy specimens obtained from unresectable pancreatic cancer using endoscopic ultrasonography-guided fine-needle aspiration. Int J Clin Oncol 2011, 16: 387-394. 10.1007/s10147-011-0197-3CrossRefPubMed Wakatsuki T, Irisawa A, Terashima M, Shibukawa G, Takagi T, Imamura H, Takahashi Y, Sato A, Sato M, Ikeda T, et al.: ATP assay-guided chemosensitivity testing for gemcitabine with biopsy specimens obtained from unresectable pancreatic cancer using endoscopic ultrasonography-guided fine-needle aspiration. Int J Clin Oncol 2011, 16: 387-394. 10.1007/s10147-011-0197-3CrossRefPubMed
26.
go back to reference Stokes JB, Nolan NJ, Stelow EB, Walters DM, Weiss GR, de Lange EE, Rich TA, Adams RB, Bauer TW: Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer. Ann Surg Oncol 2011, 18: 619-627. 10.1245/s10434-010-1456-7CrossRefPubMed Stokes JB, Nolan NJ, Stelow EB, Walters DM, Weiss GR, de Lange EE, Rich TA, Adams RB, Bauer TW: Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer. Ann Surg Oncol 2011, 18: 619-627. 10.1245/s10434-010-1456-7CrossRefPubMed
27.
go back to reference Katz A, Hanlon A, Lanciano R, Hoffman J, Coia L: Prognostic value of CA 19–9 levels in patients with carcinoma of the pancreas treated with radiotherapy. Int J Radiat Oncol Biol Phys 1998, 41: 393-396. 10.1016/S0360-3016(98)00058-3CrossRefPubMed Katz A, Hanlon A, Lanciano R, Hoffman J, Coia L: Prognostic value of CA 19–9 levels in patients with carcinoma of the pancreas treated with radiotherapy. Int J Radiat Oncol Biol Phys 1998, 41: 393-396. 10.1016/S0360-3016(98)00058-3CrossRefPubMed
28.
go back to reference Micke O, Bruns F, Kurowski R, Horst E, DeVries AF, Hausler JW, Willich N, Schafer U: Predictive value of carbohydrate antigen 19–9 in pancreatic cancer treated with radiochemotherapy. Int J Radiat Oncol Biol Phys 2003, 57: 90-97. 10.1016/S0360-3016(03)00524-8CrossRefPubMed Micke O, Bruns F, Kurowski R, Horst E, DeVries AF, Hausler JW, Willich N, Schafer U: Predictive value of carbohydrate antigen 19–9 in pancreatic cancer treated with radiochemotherapy. Int J Radiat Oncol Biol Phys 2003, 57: 90-97. 10.1016/S0360-3016(03)00524-8CrossRefPubMed
29.
go back to reference Turrini O, Schmidt CM, Moreno J, Parikh P, Matos JM, House MG, Zyromski NJ, Nakeeb A, Pitt HA, Lillemoe KD: Very high serum CA 19–9 levels: a contraindication to pancreaticoduodenectomy? J Gastrointest Surg 2009, 13: 1791-1797. 10.1007/s11605-009-0916-5CrossRefPubMed Turrini O, Schmidt CM, Moreno J, Parikh P, Matos JM, House MG, Zyromski NJ, Nakeeb A, Pitt HA, Lillemoe KD: Very high serum CA 19–9 levels: a contraindication to pancreaticoduodenectomy? J Gastrointest Surg 2009, 13: 1791-1797. 10.1007/s11605-009-0916-5CrossRefPubMed
Metadata
Title
Radiation dose ≥54 Gy and CA 19–9 response are associated with improved survival for unresectable, non-metastatic pancreatic cancer treated with chemoradiation
Authors
Daniel W Golden
Caroline J Novak
Bruce D Minsky
Stanley L Liauw
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2012
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/1748-717X-7-156

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