Skip to main content
SpringerLink
Log in

Strategien für präoperatives Downsizing bei inoperablem Pankreaskarzinom

Strategies for preoperative downsizing in patients with local nonresectable pancreatic cancer

  • Leitthema
  • Published:
Der Chirurg Aims and scope Submit manuscript

Zusammenfassung

Bei ca. 30–40% der Patienten mit Pankreaskarzinomen zeigt sich bei Erstdiagnose ein lokal fortgeschrittenes Tumorstadium ohne Fernmetastasierung; durch die Ummauerung der umliegenden Gefäßstrukturen liegt hier oft eine primäre Inoperabilität vor. Neoadjuvante Behandlungskonzepte, wie die neoadjuvante kombinierte Radio-Chemo-Therapie, bieten die Möglichkeit einer signifikanten Tumorverkleinerung, sodass eine sekundäre kurative Resektabilität ermöglicht werden kann. Daher sollte die Therapieentscheidung im interdisziplinären Kontext gemeinsam evaluiert werden.

In Zukunft bieten innovative Studienkonzepte sowie neue Strahlqualitäten, wie die Schwerionentherapie, neue Behandlungshorizonte für diese Patientenpopulation. Ebenso könnten molekulare Marker bei einer Therapiestratifizierung helfen.

Abstract

In about 30–40% of all patients with pancreatic cancer a locally advanced lesion without distant metastases is found at primary diagnosis and the tumor is mostly nonresectable due to the close vicinity to blood vessels. Neoadjuvant treatment strategies, such as neoadjuvant radiochemotherapy offer the possibility to achieve substantial tumor reduction so that secondary resectability can be achieved. Therefore, treatment decisions should be made in an interdisciplinary context. In the future, innovative study protocols as well as novel radiation modalities, such as carbon ions can open new horizons in the treatment of this patient population. Additionally, molecular markers may help to stratify patients for different treatment schedules.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4

Literatur

  1. Jemal A, Siegel R, Ward Eet al (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249

    Article  PubMed  Google Scholar 

  2. Heinemann V, Boeck S, Hinke A et al (2008) Meta-analysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer. BMC Cancer 8:82

    Article  PubMed  Google Scholar 

  3. Sultana A, Tudur SC, Cunningham D et al (2008) Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer: results of secondary end points analyses. Br J Cancer 99:6–13

    Article  PubMed  CAS  Google Scholar 

  4. Sultana A, Smith CT, Cunningham D et al (2007) Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J Clin Oncol 25:2607–2615

    Article  PubMed  Google Scholar 

  5. Sultana A, Tudur SC, Cunningham D et al (2007) Systematic review, including meta-analyses, on the management of locally advanced pancreatic cancer using radiation/combined modality therapy. Br J Cancer 96:1183–1190

    Article  PubMed  CAS  Google Scholar 

  6. Butturini G, Pisano M, Scarpa A et al (2011) Aggressive approach to acinar cell carcinoma of the pancreas: a single-institution experience and a literature review. Langenbecks Arch Surg 396:363–369

    Article  PubMed  Google Scholar 

  7. Stoeltzing O, Loss M, Huber E et al (2010) Staged surgery with neoadjuvant 90Y-DOTATOC therapy for down-sizing synchronous bilobular hepatic metastases from a neuroendocrine pancreatic tumor. Langenbecks Arch Surg 395:185–192

    Article  PubMed  Google Scholar 

  8. Tempero M, Arnoletti JP, Ben Josef E et al (2007) Pancreatic adenocarcinoma. Clinical practice guidelines in oncology. J Natl Compr Canc Netw 5:998–1033

    PubMed  Google Scholar 

  9. Gaedcke J, Gunawan B, Grade M et al (2010) The mesopancreas is the primary site for R1 resection in pancreatic head cancer: relevance for clinical trials. Langenbecks Arch Surg 395:451–458

    Article  PubMed  CAS  Google Scholar 

  10. Gastrointestinal Tumor Study Group (1987) Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer 59:2006–2010

    Article  Google Scholar 

  11. Bakkevold KE, Arnesjo B, Dahl O, Kambestad B (1993) Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater – results of a controlled, prospective, randomised multicentre study. Eur J Cancer 29(A):698–703

    Article  Google Scholar 

  12. Klinkenbijl JH, Jeekel J, Sahmoud T et al (1999) 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 230:776–782

    Article  PubMed  CAS  Google Scholar 

  13. Neoptolemos JP, Stocken DD, Friess H et al (2004) A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350:1200–1210

    Article  PubMed  CAS  Google Scholar 

  14. Oettle H, Post S, Neuhaus P et al (2007) Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297:267–277

    Article  PubMed  CAS  Google Scholar 

  15. Takada T, Amano H, Yasuda H et al (2002) Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 95:1685–1695

    Article  PubMed  Google Scholar 

  16. Adler G, Seufferlein T, Bischoff SC et al (2007) S3-Guidelines „Exocrine pancreatic cancer“ 2007. Z Gastroenterol 45:487–523

    Article  PubMed  CAS  Google Scholar 

  17. National Comprehensive Cancer Network (2011) NCCN Clinical Practice Guidelines V.2.2010 Pancreatic adenocarcinoma. NCCN Guidelines 2011

  18. Gillen S, Schuster T, Meyer Zum BC et al (2010) Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 7:e1000267

    Article  PubMed  Google Scholar 

  19. Morganti AG, Massaccesi M, La Torre G et al (2010) A systematic review of resectability and survival after concurrent chemoradiation in primarily unresectable pancreatic cancer. Ann Surg Oncol 17:194–205

    Article  PubMed  Google Scholar 

  20. Zhu CP, Shi J, Chen YX et al (2011) Gemcitabine in the chemoradiotherapy for locally advanced pancreatic cancer: a meta-analysis. Radiother Oncol 99:108–113

    Article  PubMed  CAS  Google Scholar 

  21. Crane CH, Winter K, Regine WF et al (2009) Phase II study of bevacizumab with concurrent capecitabine and radiation followed by maintenance gemcitabine and bevacizumab for locally advanced pancreatic cancer: Radiation Therapy Oncology Group RTOG 0411. J Clin Oncol 27:4096–4102

    Article  PubMed  CAS  Google Scholar 

  22. Krempien R, Muenter MW, Huber PE et al (2005) Randomized phase II–study evaluating EGFR targeting therapy with cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer–PARC: study protocol [ISRCTN56652283]. BMC Cancer 5:131

    Article  PubMed  CAS  Google Scholar 

  23. Crane CH, Varadhachary GR, Yordy JS et al (2011) Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression. J Clin Oncol 29:3037–3043

    Article  PubMed  CAS  Google Scholar 

  24. Breslin TM, Hess KR, Harbison DB et al (2001) Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann Surg Oncol 8:123–132

    Article  PubMed  CAS  Google Scholar 

  25. Evans DB, Varadhachary GR, Crane CH et al (2008) Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol 26:3496–3502

    Article  PubMed  CAS  Google Scholar 

  26. Mornex F, Girard N, Delpero JR, Partensky C (2005) Radiochemotherapy in the management of pancreatic cancer–part I: neoadjuvant treatment. Semin Radiat Oncol 15:226–234

    Article  PubMed  Google Scholar 

  27. White RR, Hurwitz HI, Morse MA et al (2001) Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas. Ann Surg Oncol 8:758–65

    Article  PubMed  CAS  Google Scholar 

  28. Varadhachary GR, Tamm EP, Abbruzzese JL et al (2006) Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol 13:1035–1046

    Article  PubMed  Google Scholar 

  29. Matsui Y, Asano T, Kenmochi T et al (2004) Effects of carbon-ion beams on human pancreatic cancer cell lines that differ in genetic status. Am J Clin Oncol 27:24–28

    Article  PubMed  Google Scholar 

  30. Schulz-Ertner D, Tsujii H (2007) Particle radiation therapy using proton and heavier ion beams. J Clin Oncol 25:953–964

    Article  PubMed  Google Scholar 

  31. Hong TS, Ryan DP, Blaszkowsky LS et al (2011) Phase I study of preoperative short-course chemoradiation with proton beam therapy and capecitabine for resectable pancreatic ductal adenocarcinoma of the head. Int J Radiat Oncol Biol Phys 79:151–157

    Article  PubMed  CAS  Google Scholar 

  32. Yamada S, Shinoto M, Imada H et al (2010) Carbon ion radiotherapy for patients with gastrointestinal cancer. PTCOG 49, Chiba

  33. Combs SE, Ellerbrock M, Haberer T et al (2010) Heidelberg Ion Therapy Center (HIT): Initial clinical experience in the first 80 patients. Acta Oncol 49:1132–1140

    Article  PubMed  Google Scholar 

  34. Combs SE, Jakel O, Haberer T, Debus J (2010) Particle therapy at the Heidelberg Ion Therapy Center (HIT) – Integrated research-driven university-hospital-based radiation oncology service in Heidelberg, Germany. Radiother Oncol 95:41–44

    Article  PubMed  Google Scholar 

  35. Rieken S, Habermehl D, Nikoghosyan A et al (2011) Assessment of early toxicity and response in patients treated with proton and carbon ion therapy at the Heidelberg Ion Therapy Center using the raster scanning technique. Int J Radiat Oncol Biol Phys

  36. Mori S, Hara R, Yanagi T et al (2009) Four-dimensional measurement of intrafractional respiratory motion of pancreatic tumors using a 256 multi-slice CT scanner. Radiother Oncol 92:231–237

    Article  PubMed  Google Scholar 

  37. Mori S, Yanagi T, Hara R et al (2010) Comparison of respiratory-gated and respiratory-ungated planning in scattered carbon ion beam treatment of the pancreas using four-dimensional computed tomography. Int J Radiat Oncol Biol Phys 76:303–312

    Article  PubMed  Google Scholar 

  38. Bert C, Durante M (2011) Motion in radiotherapy: particle therapy. Phys Med Biol 56:R113-R144

    Article  PubMed  CAS  Google Scholar 

  39. Bert C, Gemmel A, Saito N et al (2010) Dosimetric precision of an ion beam tracking system. Radiat Oncol 5:61

    Article  PubMed  Google Scholar 

  40. Bert C, Gemmel A, Saito N, Rietzel E (2009) Gated irradiation with scanned particle beams. Int J Radiat Oncol Biol Phys 73:1270–1275

    Article  PubMed  Google Scholar 

  41. Bert C, Grozinger SO, Rietzel E (2008) Quantification of interplay effects of scanned particle beams and moving targets. Phys Med Biol 53:2253–2265

    Article  PubMed  Google Scholar 

  42. Bert C, Saito N, Schmidt A et al (2007) Target motion tracking with a scanned particle beam. Med Phys 34:4768–4771

    Article  PubMed  Google Scholar 

  43. Bert C, Rietzel E (2007) 4D treatment planning for scanned ion beams. Radiat Oncol 2:24

    Article  PubMed  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Abteilung RadioOnkologie und Strahlentherapie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 400, 69120 , Heidelberg, Deutschland

    S.E. Combs, D. Habermehl & J. Debus

  2. Allgemein-, Viszeral- und Transplantationschirurgie, Chirurgische Universitätsklinik, Heidelberg, Deutschland

    J. Werner & M.W. Büchler

Authors
  1. S.E. Combs
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Habermehl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Werner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M.W. Büchler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Debus
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S.E. Combs.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Combs, S., Habermehl, D., Werner, J. et al. Strategien für präoperatives Downsizing bei inoperablem Pankreaskarzinom. Chirurg 82, 981–988 (2011). https://doi.org/10.1007/s00104-011-2129-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00104-011-2129-1

Schlüsselwörter

Keywords

Search

Navigation