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Strahlentherapie und Onkologie

, Volume 190, Issue 5, pp 485–490 | Cite as

Radiotherapy for patients with isolated local recurrence of primary resected pancreatic cancer

Prolonged disease-free interval associated with favorable prognosis
  • Akira NakamuraEmail author
  • Satoshi Itasaka
  • Kyoichi Takaori
  • Yoshiya Kawaguchi
  • Keiko Shibuya
  • Michio Yoshimura
  • Yukinori Matsuo
  • Takashi Mizowaki
  • Shinji Uemoto
  • Masahiro Hiraoka
Original article

Abstract

Background and purpose

To evaluate the treatment outcomes of radiotherapy and prognostic factors for recurrent pancreatic cancer.

Patients and methods

The study comprised 30 patients who developed a locoregional recurrence of primarily resected pancreatic cancer and received radiotherapy between 2000 and 2013 with a median dose of 54 Gy (range, 39–60 Gy). Concurrent chemotherapy included gemcitabine for 18 patients and S-1 for seven patients. The treatment outcomes and prognostic factors were retrospectively analyzed.

Results

The median follow-up after radiotherapy was 14.6 months. The 1-year overall survival, local control, and progression-free survival rates were 69 %, 67 %, and 32 %, respectively. The median overall survival and progression-free survival rates were 15.9 and 6.9 months, respectively. Tumor marker reduction and ≥ 50 % reduction were observed in 18 and two patients, respectively. Of the seven patients who exhibited pain symptoms, four and two patients were partly and completely relieved, respectively. Late grade 3 ileus and gastroduodenal bleeding were observed in one patient each. Among the clinicopathological factors evaluated, only a disease-free interval of greater than 18.9 months exhibited a significant association with improved overall survival (p = 0.017).

Conclusions

Radiotherapy for isolated locally recurrent pancreatic cancer resulted in encouraging local control, overall survival, and palliative effects with mild toxicity, particularly in patients with a prolonged disease-free interval. This treatment strategy should be prospectively evaluated.

Keywords

Pancreatic cancer Isolated local recurrence Chemoradiation therapy Prognostic factor Toxicity 

Radiotherapie für Patienten mit isoliertem lokalem Rezidiv eines primär resezierten Pankreaskarzinoms

Verlängerte krankheitsfreie Zeit mit besserer Prognose assoziiert

Zusammenfassung

Ziel

Beurteilung strahlentherapeutischer Behandlungsergebnisse und prognostischer Faktoren bei rezidivierendem Pankreaskrebs.

Material und Methoden

In dieser Studie wurden 30 Patienten aufgenommen, bei denen es nach primär reseziertem Pankreaskrebs zu lokoregionären Rezidiven kam und die zwischen 2000 und 2013 strahlentherapeutisch mit einer mittleren Dosis von 54 Gy (Bereich 39–60 Gy) behandelt wurden. Im Rahmen der gleichzeitig durchgeführten Chemotherapie wurde bei 18 Patienten Gemcitabin und bei 7 Patienten S-1 eingesetzt. Behandlungsergebnisse und prognostische Faktoren wurden retrospektiv analysiert.

Ergebnisse

Die durchschnittliche Beobachtungszeit nach Strahlentherapie betrug 14,6 Monate. Die 1-Jahres-Gesamtüberlebensrate, die lokale Kontrolle und die progressionsfreie Überlebensrate betrugen jeweils 69 %, 67 % bzw. 32 %. Die durchschnittliche Gesamtüberlebens- und progressionsfreie Überlebensrate betrugen jeweils 15,9 bzw. 6,9 Monate. Bei 18 bzw. 2 Patienten wurden jeweils eine Reduktion der Tumormarker und eine Reduktion ≥ 50 % beobachtet. Unter den 7 Patienten mit schmerzhaften Symptomen wurden jeweils 4 und 2 teilweise bzw. vollständig von den Schmerzen befreit. Bei jeweils einem Patienten wurde verzögerter Grad-3-Ileus und gastroduodenale Blutungen beobachtet. Unter den bewerteten klinisch pathologischen Faktoren zeigte nur das krankheitsfreie Intervall > 18,9 Monate einen signifikanten Zusammenhang mit einem verbessertem Gesamtüberleben (p = 0,017).

Schlussfolgerungen

Strahlentherapie führte bei lokal rezidivierendem Pankreaskrebs zu vielversprechender lokaler Kontrolle, Gesamtüberleben und palliativen Effekten mit milder Toxizität, insbesondere bei Patienten mit verlängertem krankheitsfreien Intervall. Diese Behandlungsstrategie sollte prospektiv ausgewertet werden.

Schlüsselwörter

Pankreaskrebs Isoliertes lokales Rezidiv Chemotherapie Prognostische Faktoren Toxizität 

References

  1. 1.
    Combs SE, Habermehl D, Kessel K et al (2013) Intensity modulated radiotherapy as neoadjuvant chemoradiation for the treatment of patients with locally advanced pancreatic cancer: outcome analysis and comparison with a 3D-treated patient cohort. Strahlenther Onkol 189:738–744PubMedCrossRefGoogle Scholar
  2. 2.
    Habermehl D, Brecht IC, Bergmann F et al (2013) Chemoradiation in patients with isolated recurrent pancreatic cancer therapeutical efficacy and probability of re-resection. Radiat Oncol 8:27PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Haeno H, Gonen M, Davis MB et al (2012) Computational modeling of pancreatic cancer reveals kinetics of metastasis suggesting optimum treatment strategies. Cell 148:362–375PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Hamidian Jahromi A, Sangster G, Zibari G et al (2013) Accuracy of multi-detector computed tomography, fluorodeoxyglucose positron emission tomography-CT, and CA 19-9 Levels in detecting recurrent pancreatic adenocarcinoma. JOP 14:466–468PubMedGoogle Scholar
  5. 5.
    Hashimoto K, Ueno H, Ikeda M et al (2009) Do recurrent and metastatic pancreatic cancer patients have the same outcomes with gemcitabine treatment? Oncology 77:217–223PubMedCrossRefGoogle Scholar
  6. 6.
    Hidalgo M (2010) Pancreatic cancer. N Engl J Med 362:1605–1617PubMedCrossRefGoogle Scholar
  7. 7.
    Hishinuma S, Ogata Y, Tomikawa M et al (2006) Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings. J Gastrointest Surg 10:511–518PubMedCrossRefGoogle Scholar
  8. 8.
    Iacobuzio-Donahue CA, Fu B, Yachida S et al (2009) DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 27:1806–1813PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Kalser MH, Ellenberg SS (1985) Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120:899–903PubMedCrossRefGoogle Scholar
  10. 10.
    Kleeff J, Reiser C, Hinz U et al (2007) Surgery for recurrent pancreatic ductal adenocarcinoma. Ann Surg 245:566–572PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    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, discussion 782–784Google Scholar
  12. 12.
    Neoptolemos JP, Dunn JA, Stocken DD et al (2001) Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet 358:1576–1585PubMedCrossRefGoogle Scholar
  13. 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 350:1200–1210PubMedCrossRefGoogle Scholar
  14. 14.
    [no authors listed] (1987) Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer 59:2006–2010CrossRefGoogle Scholar
  15. 15.
    Oshima M, Okano K, Muraki S et al (2013) Immunohistochemically detected expression of 3 major genes (CDKN2A/p16, TP53, and SMAD4/DPC4) strongly predicts survival in patients with resectable pancreatic cancer. Ann Surg 258:336–346PubMedCrossRefGoogle Scholar
  16. 16.
    Regine WF, Winter KA, Abrams RA et al (2008) Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA 299:1019–1026PubMedCrossRefGoogle Scholar
  17. 17.
    Seelig MH, Janot M, Chromik AM et al (2009) Redo-surgery following curative resection of pancreatic carcinoma: the difference between true and suspected recurrence. Dig Surg 26:222–228PubMedCrossRefGoogle Scholar
  18. 18.
    Strobel O, Hartwig W, Hackert T et al Re-resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with encouraging survival. Ann Surg Oncol 20:964–972Google Scholar
  19. 19.
    Tempero MA, Arnoletti JP, Behrman SW et al (2012) Pancreatic adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines. J Natl Compr Canc Netw 10:703–713PubMedCentralPubMedGoogle Scholar
  20. 20.
    Therneau TM, Grambsch PM, Fleming TR (1990) Martingale-based residuals for survival models. Biometrika 77:147–160CrossRefGoogle Scholar
  21. 21.
    Thomas RM, Truty MJ, Nogueras-Gonzalez GM et al (2012) Selective reoperation for locally recurrent or metastatic pancreatic ductal adenocarcinoma following primary pancreatic resection. J Gastrointest Surg 16:1696–1704.PubMedCrossRefGoogle Scholar
  22. 22.
    Van den Broeck A, Sergeant G, Ectors N et al (2009) Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma. Eur J Surg Oncol; 35:600PubMedCrossRefGoogle Scholar
  23. 23.
    Van Laethem JL, Hammel P, Mornex F et al (2010) Adjuvant gemcitabine alone versus gemcitabine-based chemoradiotherapy after curative resection for pancreatic cancer: a randomized EORTC-40013–22012/FFCD-9203/GERCOR phase II study. J Clin Oncol 28:4450–4456PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Wilkowski R, Thoma M, Bruns C et al (2006) Combined chemoradiotherapy for isolated local recurrence after primary resection of pancreatic cancer. JOP 7:34–40PubMedGoogle Scholar
  25. 25.
    Winter JM, Tang LH, Klimstra DS et al (2013) Failure patterns in resected pancreas adenocarcinoma: lack of predicted benefit to SMAD4 expression. Ann Surg 258:331–335PubMedCrossRefGoogle Scholar
  26. 26.
    Yoon H, Oh D, Park HC et al (2013) Predictive factors for gastroduodenal toxicity based on endoscopy following radiotherapy in patients with hepatocellular carcinoma. Strahlenther Onkol 189:541–546PubMedCrossRefGoogle Scholar
  27. 27.
    Zamboglou C, Messmer MB, Becker G et al (2012) Stereotactic radiotherapy in the liver hilum. Basis for future studies. Strahlenther Onkol 188:35–41PubMedCrossRefGoogle Scholar
  28. 28.
    Zhang Y, Frampton AE, Kyriakides C et al (2012) Loco-recurrence after resection for ductal adenocarcinoma of the pancreas: predictors and implications for adjuvant chemoradiotherapy. J Cancer Res Clin Oncol 138:1063–1071PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Akira Nakamura
    • 1
    Email author
  • Satoshi Itasaka
    • 1
  • Kyoichi Takaori
    • 2
  • Yoshiya Kawaguchi
    • 2
  • Keiko Shibuya
    • 3
  • Michio Yoshimura
    • 1
  • Yukinori Matsuo
    • 1
  • Takashi Mizowaki
    • 1
  • Shinji Uemoto
    • 2
  • Masahiro Hiraoka
    • 1
  1. 1.Department of Radiation Oncology and Image-Applied Therapy, Graduate School of MedicineKyoto UniversityKyotoJapan
  2. 2.Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
  3. 3.Department of Therapeutic RadiologyYamaguchi University Graduate School of MedicineYamaguchiJapan

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