Advertisement

Annals of Surgical Oncology

, Volume 21, Issue 2, pp 662–669 | Cite as

Neoadjuvant Chemoradiation and Duration of Chemotherapy Before Surgical Resection for Pancreatic Cancer: Does Time Interval Between Radiotherapy and Surgery Matter?

  • Kathryn T. Chen
  • Karthik Devarajan
  • Barton N. Milestone
  • Harry S. Cooper
  • Crystal Denlinger
  • Steven J. Cohen
  • Joshua E. Meyer
  • John P. Hoffman
Pancreatic Tumors

Abstract

Background

Neoadjuvant chemoradiation and chemotherapy provided for borderline or locally advanced, potentially resectable pancreatic adenocarcinoma improves resectability rates. Response to therapy is also an important prognostic factor. There are no data in the literature regarding optimal time interval or duration of chemotherapy after chemoradiation before surgery, and pathologic response rates. Using our database, we evaluated these relationships and the effect on overall and progression-free survival.

Methods

We retrospectively analyzed the records of 83 patients who underwent neoadjuvant chemoradiation for locally advanced, potentially resectable, and borderline resectable pancreatic cancers before definitive resection. We divided patients into three groups according to time interval between completion of chemoradiation and resection: group A (0–10 weeks), group B (11–20 weeks), and group C (>20 weeks). After chemoradiation, patients underwent ongoing chemotherapy before resection. Pathologic response was defined as major (>95 % fibrosis), partial (50–94 % fibrosis), or minor (<50 % fibrosis).

Results

There were 56 patients in group A, 17 patients in group B, and 10 patients in group C. Patients in groups B and C were significantly more likely to experience a major response than group A (p < 0.013). Patients in group C had significantly increased median progression-free and overall survival (p < 0.05). Multivariable classification and regression tree analysis demonstrated pathologic response to be the only significant factor in overall survival.

Conclusions

Patients who underwent a prolonged time interval after neoadjuvant chemoradiation with ongoing chemotherapy were more likely to have an improved pathologic response at time of surgical resection, which was associated with improved median overall survival.

Keywords

Overall Survival Gemcitabine Pathologic Response Additional Chemotherapy Pathologic Response Rate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

DISCLOSURE

The authors declare no conflict of interest.

References

  1. 1.
    Habermehl D, Kessel K, Welzel T, Hof H, Abdollahi A, Bergmann F, et al. Neoadjuvant chemoradiation with Gemcitabine for locally advanced pancreatic cancer. Radiat Oncol. 2012;7:28.Google Scholar
  2. 2.
    Chun YS, Milestone BN, Watson JC, Cohen SJ, Burtness B, Engstrom PF, et al. Defining venous involvement in borderline resectable pancreatic cancer. Ann Surg Oncol. 2010;17:2832–8.Google Scholar
  3. 3.
    Yeung RS, Weese JL, Hoffman JP, Solin LJ, Paul AR, Engstrom PF, et al. Neoadjuvant chemoradiation in pancreatic and duodenal carcinoma. A phase II study. Cancer. 1993;72:2124–33.Google Scholar
  4. 4.
    White RR, Hurwitz HI, Morse MA, Lee C, Anscher MS, Paulson EK, et al. Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas. Ann Surg Oncol. 2001;8:758–65.Google Scholar
  5. 5.
    Takai S, Satoi S, Yanagimoto H, Toyokawa H, Takahashi K, Terakawa N, et al. Neoadjuvant chemoradiation in patients with potentially resectable pancreatic cancer. Pancreas. 2008;36:e26–32.Google Scholar
  6. 6.
    Hoffman JP, Lipsitz S, Pisansky T, Weese JL, Solin L, Benson AB 3rd, et al. Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology Group Study. J Clin Oncol. 1998;16:317–23.Google Scholar
  7. 7.
    Snady H, Bruckner H, Cooperman A, Paradiso J, Kiefer L. Survival advantage of combined chemoradiotherapy compared with resection as the initial treatment of patients with regional pancreatic carcinoma. An outcomes trial. Cancer. 2000;89:314–27.Google Scholar
  8. 8.
    Hazard L. The role of radiation therapy in pancreas cancer. Gastrointest Cancer Res. 2009;3:20–8.Google Scholar
  9. 9.
    Moutardier V, Magnin V, Turrini O, Viret F, Hennekinne-Mucci S, Gonçalves A, et al. Assessment of pathologic response after preoperative chemoradiotherapy and surgery in pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys. 2004;60:437–43.Google Scholar
  10. 10.
    Klinkenbijl JH, Jeekel J, Sahmoud T, van Pel R, Couvreur ML, Veenhof CH, et al. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg. 1999;230:776–82.Google Scholar
  11. 11.
    Spitz FR, Abbruzzese JL, Lee JE, Pisters PW, Lowy AM, Fenoglio CJ, et al. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol. 1997;15:928–37.Google Scholar
  12. 12.
    Krishnan S, Rana V, Janjan NA, Varadhachary GR, Abbruzzese JL, Das P, et al. Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy. Cancer. 2007;110:47–55.Google Scholar
  13. 13.
    Huguet F, Andre T, Hammel P, Artru P, Balosso J, Selle F, 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;25:326–31.Google Scholar
  14. 14.
    Rumstadt B, Schwab M, Schuster K, Hagmuller E, Trede M. The role of laparoscopy in the preoperative staging of pancreatic carcinoma. J Gastrointest Surg. 1997;1:245–50.Google Scholar
  15. 15.
    Shikama N, Sasaki S, Nishikawa A, Koiwai K, Yoshino F, Hirase Y, et al. Risk factors for local-regional recurrence following preoperative radiation therapy and surgery for head and neck cancer (stage II–IVB). Radiology. 2003;228:789–94.Google Scholar
  16. 16.
    Francois Y, Nemoz CJ, Baulieux J, Vignal J, Grandjean JP, Partensky C, et al. Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol. 1999;17:2396.Google Scholar
  17. 17.
    Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer. Medical Research Council Rectal Cancer Working Party. Lancet. 1996;348(9042):1605–10.Google Scholar
  18. 18.
    Garcia-Aguilar J, Smith DD, Avila K, Bergsland EK, Chu P, Krieg RM, et al. Optimal timing of surgery after chemoradiation for advanced rectal cancer: preliminary results of a multicenter, nonrandomized phase II prospective trial. Ann Surg. 2011;254:97–102.Google Scholar
  19. 19.
    Esiashvili N, Landry J, Matthews RH. Carcinoma of the anus: strategies in management. Oncologist. 2002;7:188–99.Google Scholar
  20. 20.
    Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol. 2009;16:1727–33.Google Scholar
  21. 21.
    Ishikawa O, Ohigashi H, Imaoka S, Furukawa H, Sasaki Y, Fujita M, et al. Preoperative indications for extended pancreatectomy for locally advanced pancreas cancer involving the portal vein. Ann Surg. 1992;215:231–6.Google Scholar
  22. 22.
    Tian F, Appert HE, Myles J, Howard JM. Prognostic value of serum CA 19-9 levels in pancreatic adenocarcinoma. Ann Surg. 1992;215:350–5.Google Scholar
  23. 23.
    Evans DB, Erickson BA, Ritch P. Borderline resectable pancreatic cancer: definitions and the importance of multimodality therapy. Ann Surg Oncol. 2010;17:2803–5.Google Scholar
  24. 24.
    Evans DB, Rich TA, Byrd DR, Cleary KR, Connelly JH, Levin B, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 1992;127:1335–9.Google Scholar
  25. 25.
    Hartman DJ, Krasinskas AM. Assessing treatment effect in pancreatic cancer. Arch Pathol Lab Med. 2012;136:100–9.Google Scholar
  26. 26.
    White RR, Xie HB, Gottfried MR, Czito BG, Hurwitz HI, Morse MA, et al. Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer. Ann Surg Oncol. 2005;12:214–21.Google Scholar
  27. 27.
    Chatterjee D, Katz MH, Rashid A, Varadhachary GR, Wolff RA, Wang H, et al. Histologic grading of the extent of residual carcinoma following neoadjuvant chemoradiation in pancreatic ductal adenocarcinoma: a predictor for patient outcome. Cancer. 2012;118:3182–90.Google Scholar
  28. 28.
    Chun YS, Cooper HS, Cohen SJ, Konski A, Burtness B, Denlinger CS, et al. Significance of pathologic response to preoperative therapy in pancreatic cancer. Ann Surg Oncol. 2011;18:3601–7.Google Scholar
  29. 29.
    Heinrich S, Pestalozzi BC, Schafer M, Weber A, Bauerfeind P, Knuth A, et al. Prospective phase II trial of neoadjuvant chemotherapy with gemcitabine and cisplatin for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26:2526–31.Google Scholar
  30. 30.
    Pisters PW, Wolff RA, Janjan NA, Cleary KR, Charnsangavej C, Crane CN, et al. Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome. J Clin Oncol. 2002;20:2537–44.Google Scholar

Copyright information

© Society of Surgical Oncology 2013

Authors and Affiliations

  • Kathryn T. Chen
    • 1
  • Karthik Devarajan
    • 2
  • Barton N. Milestone
    • 3
  • Harry S. Cooper
    • 4
  • Crystal Denlinger
    • 5
  • Steven J. Cohen
    • 5
  • Joshua E. Meyer
    • 6
  • John P. Hoffman
    • 1
  1. 1.Department of Surgical OncologyFox Chase Cancer CenterPhiladelphiaUSA
  2. 2.Department of BiostatisticsFox Chase Cancer CenterPhiladelphiaUSA
  3. 3.Department of Diagnostic ImagingFox Chase Cancer CenterPhiladelphiaUSA
  4. 4.Department of PathologyFox Chase Cancer CenterPhiladelphiaUSA
  5. 5.Department of Medical OncologyFox Chase Cancer CenterPhiladelphiaUSA
  6. 6.Department of Radiation OncologyFox Chase Cancer CenterPhiladelphiaUSA

Personalised recommendations