Dtsch Med Wochenschr 2021; 146(04): 246-252
DOI: 10.1055/a-1221-7306
Dossier

Diagnostik und Therapie des Pankreaskarzinoms

Diagnostics and therapy of pancreatic carcinoma
Patrick Wenzel
,
Guido von Figura

Das Pankreaskarzinom bleibt trotz moderner Diagnostik und zielgerichteter Therapien prognostisch sehr ungünstig. Gründe sind das bei Diagnose häufig fortgeschrittene oder metastasierte Stadium und die Tumorbiologie. Der Beitrag gibt einen Überblick über Differenzialdiagnosen, eine sinnvolle Diagnostik, die Verbesserung der operativen Therapie, Möglichkeiten palliativer Chemotherapien sowie die Therapie bei BRCA-Mutation.

Abstract

Ductal pancreatic carcinoma is expected to become one of the most common malignant diseases worldwide in the coming decades. However, the prognosis of the disease remains very poor and has improved only slightly over the last decade. The 5-year survival rate of all patients with ductal adenocarcinoma has been increased to approximately 10 percent. The reasons for the very poor prognosis are the advanced stage of the disease at diagnosis with metastases already present in many cases, the anatomical location of the pancreas and the tumor biology. Therapeutically, chemotherapy remains the basis of systemic therapy. Intensive combinations with FOLFIRINOX (oxaliplatin, irinotecan, leucovorin/5-FU) and nanoparticel albumin bound (nab)paclitaxel/gemcitabine lead to an improvement in overall survival in the palliative situation; used preoperatively, they can increase the rate of secondary resections. Targeted therapies and immune checkpoint inhibitors could not be established. In patients with a proven germline mutation in the BRCA gene, a therapy with the PARP inhibitor olaparib is in the approval process.

This article provides an overview of differential diagnoses, meaningful diagnostics, therapeutic concepts to improve surgical treatment, possibilities of palliative chemotherapy and targeted therapy in the presence of a BRCA mutation.



Publication History

Article published online:
16 February 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • Literatur

  • 1 Zentrum für Krebsregisterdaten und Gesellschaft der Epidemioloschigen Krebsregister in Deutschland e.V. Krebs in Deutschland für 2015/2016. Robert Koch Inst; 2019 12. 1-161 . Im Internet (Stand: 06.12.2020): https://www.krebsdaten.de/Krebs/DE/Content/Publikationen/Krebs_in_Deutschland/kid_2019 / krebs_in_deutschland_2019.pdf?__blob=publicationFile
  • 2 Tummers WS, Groen JV, Sibinga Mulder BG. et al. Impact of resection margin status on recurrence and survival in pancreatic cancer surgery. Br J Surg 2019; 106: 1055-1065
  • 3 Raimondi S, Maisonneuve P, Lowenfels AB. Epidemiology of pancreatic cancer: An overview. Nat Rev Gastroenterol Hepatol 2009; 6: 699-708
  • 4 Al-Hawary MM, Francis IR, Chari ST. et al. Pancreatic ductal adenocarcinoma radiology reporting template: Consensus statement of the society of abdominal radiology and the american pancreatic association. Radiology 2014; 270: 248-260
  • 5 Guarneri G, Gasparini G, Crippa S. et al. Diagnostic strategy with a solid pancreatic mass. Press Medicale 2019; 48: e125-e145 . doi:org/10.1016/j.lpm.2019.02.026
  • 6 Oettle H, Neuhaus P, Hochhaus A. et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: The CONKO-001 randomized trial. JAMA – J Am Med Assoc 2013; 310: 1473-1481
  • 7 Neoptolemos JP, Palmer DH, Ghaneh P. et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet 2017; 389: 1011-1024
  • 8 Conroy T, Hammel P, Hebbar M. et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med 2018; 379: 2395-2406
  • 9 Tempero MA, Reni M, Riess H. et al. APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma. J Clin Oncol 2019; 37 (15) 4000
  • 10 Ahmad SA, Duong M, Sohal DPS. et al. Surgical Outcome Results From SWOG S1505. Ann Surg 2020; 272: 481-486
  • 11 Suker M, Beumer BR, Sadot E. et al. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol 2016; 17: 801-810
  • 12 Philip PA, Lacy J, Portales F. et al. Nab-paclitaxel plus gemcitabine in patients with locally advanced pancreatic cancer (LAPACT): a multicentre, open-label phase 2 study. Lancet Gastroenterol Hepatol 2020; 5: 285-294
  • 13 Kunzmann V, Algül H, Goekkurt E. et al. Conversion rate in locally advanced pancreatic cancer (LAPC) after nab-paclitaxel/gemcitabine- or FOLFIRINOX-based induction chemotherapy (NEOLAP): Final results of a multicenter randomised phase II AIO trial. Ann Oncol 2019; 30: v253
  • 14 Picozzi V, Alseidi A, Winter J. et al. Gemcitabine/nab-paclitaxel with pamrevlumab: a novel drug combination and trial design for the treatment of locally advanced pancreatic cancer. ESMO open 2020; 5: e000668
  • 15 Burris HA, Moore MJ, Andersen J. et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial. J Clin Oncol 1997; 15: 2403-2413
  • 16 Moore MJ, Goldstein D, Hamm J. et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: A phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007; 25: 1960-1966
  • 17 Haas M, Siveke JT, Schenk M. et al. Efficacy of gemcitabine plus erlotinib in rash-positive patients with metastatic pancreatic cancer selected according to eligibility for FOLFIRINOX: A prospective phase II study of the ‘Arbeitsgemeinschaft Internistische Onkologie’. Eur J Cancer 2018; 94: 95-103
  • 18 Conroy T, Desseigne F, Ychou M. et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364: 1817-1825
  • 19 Von Hoff DD, Ervin T, Arena FP. et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369: 1691-1703
  • 20 Wang-Gillam A, Li CP, Bodoky G. et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): A global, randomised, open-label, phase 3 trial. Lancet 2016; 387: 545-557
  • 21 Van Cutsem E, Tempero MA, Sigal D. et al. Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma. J Clin Oncol 2020; 38 (27) 3185-3194
  • 22 Ramanathan RK, McDonough SL, Philip PA. et al. Phase IB/II randomized study of FOLFIRINOX plus pegylated recombinant human hyaluronidase versus FOLFIRINOX alone in patients with metastatic pancreatic adenocarcinoma: SWOG S1313. J Clin Oncol 2019; 37: 1062
  • 23 Renouf DJ, Knox JJ, Kavan P. et al. LBA65 The Canadian Cancer Trials Group PA. 7 trial: Results of a randomized phase II study of gemcitabine (GEM) and nab-paclitaxel (Nab-P) vs GEM, nab-P, durvalumab (D) and tremelimumab (T) as first line therapy in metastatic pancreatic ductal adenocarcin. Ann Oncol 2020; 31: S1195
  • 24 Bailey P, Chang DK, Nones K. et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 2016; 531: 47-52
  • 25 Golan T, Hammel P, Reni M. et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med 2019; 381: 317-327
  • 26 Ducreux M, Cuhna AS, Caramella C. et al. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015; 26: v56-v68
  • 27 Khorana AA, McKernin SE, Berlin J. et al. Potentially curable pancreatic adenocarcinoma: ASCO clinical practice guideline update. J Clin Oncol 2019; 37: 2082-2088