|
Risikofaktoren/Screening/Risikofaktoren
|
|
Screening
|
|
ASCO 2019 [4]
|
Clinical evaluations of people (with or without pancreatic cancer) should include assessment for possible genetic predisposition syndromes, beginning
with a review of family history of cancer (including tumor types and ages at diagnosis
for all first- and second-degree relatives)
|
strong
|
n.a.
|
43. Lu KH, Wood ME, Daniels M, et al: American Society of Clinical Oncology expert
statement: Collection and use of a cancer family history for oncology providers. J
Clin Oncol 32:833–840, 2014
|
|
Pancreatic cancer surveillance can be considered for individuals who are first-degree
relatives of individuals with familial pancreatic cancer and/or individuals with a
family history of pancreatic cancer who carry a pathogenic germline variant in genes
associated with predisposition to pancreatic cancer.
The potential risks, benefits, uncertainties, and limitations of surveillance for
pancreatic cancer should be discussed in detail with individuals who are being considered
for pancreatic cancer surveillance prior to beginning such surveillance.
When possible, pancreatic surveillance should be performed at centers with the appropriate
expertise to manage individuals at increased risk for pancreatic cancer. Surveillance
may be performed with various modalities, including pancreas protocol magnetic resonance
imaging/magnetic resonance cholangiopancreatography and/or endoscopic ultrasound.
There are currently no approved biomarkers for screening and surveillance. CA 19–9
is not recommended as a screening test in the general population due to low specificity
and sensitivity; its potential utility in pancreatic screening of high-risk individuals
has not been established
|
Moderate
|
n.a.
|
2. Canto MI, Harinck F, Hruban RH, et al: International Cancer of the Pancreas Screening
(CAPS) consortium summit on the management of patients with increased risk for familial
pancreatic cancer. Gut 62:339–347, 2013
5. Hu C, Hart SN, Polley EC, et al: Association between inherited germline mutations
in cancer predisposition genes and risk of pancreatic cancer. JAMA 319:2401–2409,
2018
34. Bruenderman EH, Martin RC II: High-risk population in sporadic pancreatic adenocarcinoma:
Guidelines for screening. J Surg Res 194:212–219, 2015
37. Lu C, Xu CF, Wan XY, et al: Screening for pancreatic cancer in familial high-risk
individuals: A systematic review. World J Gastroenterol 21:8678–8686, 2015
52. Bartsch DK, Slater EP, Carrato A, et al: Refinement of screening for familial
pancreatic cancer. Gut 65:1314–1321, 2016
53. Canto MI, Almario JA, Schulick RD, et al: Risk of neoplastic progression in individuals
at high risk for pancreatic cancer undergoing long-term surveillance.
Gastroenterology155:740–751.e2, 2018
|
|
Pancreatic cancer surveillance can be considered for individuals who are first-degree
relatives of individuals with familial pancreatic cancer and/or individuals with a
family history of pancreatic cancer who carry a pathogenic germline variant in genes
associated with predisposition to pancreatic cancer.
|
Moderate
|
n.a.
|
|
Table 1. Genes Associated With Increased Risk for Pancreatic Cancer
|
|
Gene
|
Syndrome
|
Pancreatic Cancer Risk
%
|
Other Associated Cancers*
|
|
APC
|
Familial adenomatous polyposis
|
1–5
|
Colorectal, upper GI, thyroid, brain
|
|
ATM
|
Ataxia telangiectasia (biallelic)†
|
1–5
|
Breast, prostate, gastric
|
|
BRCA2
|
Hereditary breast ovarian cancer syndrome
|
5–10
|
Breast, ovary, prostate, melanoma
|
|
BRCA1
|
Hereditary breast ovarian cancer syndrome
|
2
|
Breast, ovary, prostate, melanoma
|
|
CDKN2A
|
Familial atypical multiple mole melanoma (FAMMM)
|
10–30
|
Melanoma
|
|
MLH1, MSH2, MSH6, PMS2, EPCAM
|
Lynch syndrome
|
5–10
|
Colorectal, uterine, upper GI, ovary, urinary tract, brain, sebaceous neoplasms
|
|
PALB2
|
|
5–10
|
Breast, prostate
|
|
STK11
|
Peutz Jeghers syndrome
|
10–30
|
Breast, colorectal, upper GI, lung, reproductive tract
|
|
TP53
|
Li Fraumeni syndrome
|
Not defined
|
Breast, brain, sarcoma, adrenocortical carcinoma
|
|
* Most commonly associated cancers.
† Biallelic ATM mutation carriers have ataxia telangiectasia, but a single ATM mutation is associated with increased risk for pancreatic cancer.
|
|
The potential risks, benefits, uncertainties, and limitations of surveillance for
pancreatic cancer should be discussed in detail with individuals who are being considered
for pancreatic cancer surveillance prior to beginning such surveillance.
When possible, pancreatic surveillance should be performed at centers with the appropriate
expertise to manage individuals at increased risk for pancreatic cancer. Surveillance
may be performed with various modalities, including pancreas protocol magnetic resonance
imaging/magnetic resonance cholangiopancreatography and/or endoscopic ultrasound.
There are currently no approved biomarkers for screening and surveillance. CA 19–9
is not recommended as a screening test in the general population due to low specificity
and sensitivity; its potential utility in pancreatic screening of high-risk individuals
has not been established.
|
|
Individuals with a family history of pancreatic cancer affecting two first-degree
relatives meet criteria for familial pancreatic cancer.
Individuals whose family history meets criteria for familial pancreatic cancer, those
with three or more diagnoses of pancreatic cancer in same side of the family, and
individuals meeting criteria for other genetic syndromes associated with increased
risk for pancreatic cancer have an increased risk for pancreatic cancer and are candidates
for genetic testing
Qualifying Statement.
It is important to note that for 90 % of families meeting criteria for familial pancreatic
cancer, genetic testing does not detect a pathogenic mutation; therefore, there may
be additional shared epigenetic, genetic, or environmental factors that contribute
to pancreatic cancer risk.
|
strong
|
n.a.
|
n.a.
|
|
An individual with a cancer diagnosis is often the best candidate in whom to initiate
genetic testing and has the highest likelihood of an informative test result; however,
if a cancer-affected individual is not available, testing may be performed in a pancreatic
cancer–unaffected individual following genetic risk assessment, with the understanding
that a negative test result is considered clinically uninformative.
The following cancer-unaffected individuals should be offered genetic risk evaluation:
-
Members of families with an identified pathogenic cancer susceptibility gene variant
-
Pancreatic cancer–unaffected individuals from families that meet criteria for genetic
evaluation for known hereditary syndromes that are linked to pancreatic cancer
Pancreatic cancer–unaffected individuals from families that meet criteria for familial
pancreatic cancer, as outlined in Provisional Clinical Opinion 1.2
|
strong
|
n.a.
|
n.a.
|
|
Several genes have been linked to risk for pancreatic cancer.
Unless a genetic diagnosis has previously been confirmed in a family member, germline
genetic testing should be performed using a multigene panel that includes the genes
listed in the table.
|
strong
|
n.a.
|
47. Robson ME, Bradbury AR, Arun B, et al: American Society of Clinical Oncology policy
statement update: Genetic and genomic testing for cancer susceptibility. J Clin Oncol
33:3660–3667, 2015
51. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation
of sequence variants: A joint consensus recommendation of the American College of
Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med
17:405–424, 2015
|
|
Table 1. Genes Associated With Increased Risk for Pancreatic Cancer
|
|
Gene
|
Syndrome
|
Pancreatic Cancer Risk
%
|
Other Associated Cancers*
|
|
APC
|
Familial adenomatous polyposis
|
1–5
|
Colorectal, upper GI, thyroid, brain
|
|
ATM
|
Ataxia telangiectasia (biallelic)†
|
1–5
|
Breast, prostate, gastric
|
|
BRCA2
|
Hereditary breast ovarian cancer syndrome
|
5–10
|
Breast, ovary, prostate, melanoma
|
|
BRCA1
|
Hereditary breast ovarian cancer syndrome
|
2
|
Breast, ovary, prostate, melanoma
|
|
CDKN2A
|
Familial atypical multiple mole melanoma (FAMMM)
|
10–30
|
Melanoma
|
|
MLH1, MSH2, MSH6, PMS2, EPCAM
|
Lynch syndrome
|
5–10
|
Colorectal, uterine, upper GI, ovary, urinary tract, brain, sebaceous neoplasms
|
|
PALB2
|
|
5–10
|
Breast, prostate
|
|
STK11
|
Peutz Jeghers syndrome
|
10–30
|
Breast, colorectal, upper GI, lung, reproductive tract
|
|
TP53
|
Li Fraumeni syndrome
|
Not defined
|
Breast, brain, sarcoma, adrenocortical carcinoma
|
|
* Most commonly associated cancers.
† Biallelic ATM mutation carriers have ataxia telangiectasia, but a single ATM mutation is associated with increased risk for pancreatic cancer.
|
|
A finding of a pathogenic or likely pathogenic germline variant can confer increased
risks of cancers beyond the pancreas for the probands and their families; finding
a germline variant of uncertain significance is not considered to be causative of
increased cancer susceptibility
|
|
CAPS 2019 [5]
|
Regardless of gene mutation status
-
If at least three affected blood relatives on the same side of the family, of whom
at least one is a first-degree relative to the individual considered for surveillance
-
If at least two affected blood relatives who are first-degree relatives to each other,
of whom at least one is a first-degree relative to the individual considered for surveillance
-
If at least two affected blood relatives on the same side of the family, of whom at
least one is an first-degree relative to the individual considered for surveillance
|
weak
|
n.a.
|
15 Klein AP, Brune KA, Petersen GM, et al. Prospective risk of pancreatic cancer in
familial pancreatic cancer kindreds. Cancer Res 2004;64:2634–2638.
16 Jacobs EJ, Chanock SJ, Fuchs CS, et al. Family history of cancer and risk of pancreatic
cancer: a pooled analysis from the pancreatic cancer cohort Consortium (PanScan).
Int J Cancer 2010;127:1421–1428.
17 Mukewar SS, Sharma A, Phillip N, et al. Risk of pancreatic cancer in patients with
pancreatic cysts and family history of pancreatic cancer. Clin Gastroenterol Hepatol
2018.
18 Tanaka M, Fernandez-del Castillo C, Adsay V, et al. International consensus guidelines
2012 for the management of IPMN and McN of the pancreas. Pancreatology 2012;12:183–197.
19 European Study Group on Cystic Tumours of the Pancreas. European evidence-based
guidelines on pancreatic cystic neoplasms. Gut 2018;67:789–804.
20 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:7–34.
21 Owens DK, Davidson KW, Krist AH, et al. Screening for pancreatic cancer: US preventive
services task force reaffirmation recommendation statement. JAMA 2019;322:438–444.
|
|
Germline mutation carriers
|
Strong
|
n.a.
|
22 Goggins M, Schutte M, Lu J, et al. Germline BRCA2 gene mutations in patients with
apparently sporadic pancreatic carcinomas. Cancer Res 1996;56:5360–5364.
23 Roberts NJ, Jiao Y, Yu J, et al. ATM mutations in patients with hereditary pancreatic
cancer. Cancer Discov 2012;2:41–46. 24 Jones S, Hruban RH, Kamiyama M, et al. Exomic
sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 2009;324:217.
25 Kastrinos Fet al. Risk of pancreatic cancer in families with Lynch syndrome. JAMA
2009;302:1790–1795.
26 Roberts NJ, Norris AL, Petersen GM, et al. Whole genome sequencing defines the
genetic heterogeneity of familial pancreatic cancer. Cancer Discov 2016;6:166–175.
27 Rosendahl J, Witt H, Szmola R, et al. Chymotrypsin C (CTRC) variants that diminish
activity or secretion are associated with chronic pancreatitis. Nat Genet 2008;40:78–82.
28 Witt H, Beer S, Rosendahl J, et al. Variants in CPA1 are strongly associated with
early onset chronic pancreatitis. Nat Genet 2013;45:1216–1220.
29 Lowenfels AB, Maisonneuve P, DiMagno EP, et al. Hereditary pancreatitis and the
risk of pancreatic cancer. International hereditary pancreatitis study group. J Natl
Cancer Inst 1997;89:442–446.
30 Whitcomb DC. Genetic risk factors for pancreatic disorders. Gastroenterology 2013;144:1292–1302.
31 Tamura K, Yu J, Hata T, et al. Mutations in the pancreatic secretory enzymes CPA1
and CPB1 are associated with pancreatic cancer. Proc Natl Acad Sci U S A 2018;115:4767–4772.
32 Chaffee KG, Oberg AL, McWilliams RR, et al. Prevalence of germ-line mutations in
cancer genes among pancreatic cancer patients with a positive family history. Genet
Med 2018;20.
33 Grant RC, Selander I, Connor AA, et al. Prevalence of germline mutations in cancer
predisposition genes in patients with pancreatic cancer. Gastroenterology 2015;148:556–564.
34 Shindo K, Yu J, Suenaga M, et al. Deleterious germline mutations in patients with
apparently sporadic pancreatic adenocarcinoma. J Clin Oncol 2017;35:3382–3390.
35 Hu C, Hart SN, Polley EC, et al. Association between inherited germline mutations
in cancer predisposition genes and risk of pancreatic cancer. JAMA 2018;319:2401–2409.
36 Lowery MA, Wong W, Jordan EJ, et al. Prospective evaluation of germline alterations
in patients with exocrine pancreatic neoplasms. J Natl Cancer Inst 2018;110:1067–1074.
37 Wood LD, Yurgelun MB, Goggins MG. Genetics of familial and sporadic pancreatic
cancer. Gastroenterology 2019;156:2041–2055.
38 Yurgelun MB, Chittenden AB, Morales-Oyarvide V, et al. Germline cancer susceptibility
gene variants, somatic second hits, and survival outcomes in patients with resected
pancreatic cancer. Genet Med 2019;21:213–223.
39 Bannon SA, Montiel MF, Goldstein JB, et al. High prevalence of hereditary cancer
syndromes and outcomes in adults with early-onset pancreatic cancer. Cancer Prev Res
(Phila) 2018;11:679–686.
40 Lucas AL, Frado LE, Hwang C, et al. BRCA1 and BRCA2 germline mutations are frequently
demonstrated in both high-risk pancreatic cancer screening and pancreatic cancer cohorts.
Cancer 2014;120:1960–1967.
41 Abe T, Blackford AL, Tamura K, et al. Deleterious germline mutations are a risk
factor for neoplastic progression among high-risk individuals undergoing pancreatic
surveillance. J Clin Oncol. 2019;37:1070–1080.
42 Konings ICAW, Harinck F, Poley J-W, et al. Prevalence and progression of pancreatic
cystic precursor lesions differ between groups at high risk of developing pancreatic
cancer. Pancreas 2017;46:28–34.
43 Stoffel EM, McKernin SE, Brand R, et al. Evaluating susceptibility to pancreatic
cancer: ASCO provisional clinical opinion. J Clin Oncol 2019;37:153–164.
44 Vasen HF, Gruis NA, Frants RR, et al. Risk of developing pancreatic cancer in families
with familial atypical multiple mole melanoma associated with a specific 19 deletion
of p16 (p16-Leiden). Int J Cancer 2000;87:809–811.
45 Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl
Cancer Inst 1999;91:1310–1316.
46 Risch HA, McLaughlin JR, Cole DEC, et al. Population BRCA1 and BRCA2 mutation frequencies
and cancer penetrances: a kin–cohort study in Ontario, Canada. J Natl Cancer Inst
2006;98:1694–1706.
47 Roch AM, Schneider J, Carr RA, et al. Are BRCA1 and BRCA2 gene mutation patients
underscreened for pancreatic adenocarcinoma? J Surg Oncol 2019;119:777–783.
48 Ginsburg GS, Wu RR, Orlando LA. Family health history: underused for actionable
risk assessment. The Lancet 2019;394:596–603.
|
|
Germline mutation carriers
|
strong
|
n.a.
|
|
Germline mutation carriers
Carriers of a germline BRCA2, BRCA1, PALB2, ATM, MLH1, MSH2, or MSH6 gene mutation
with at least one affected first-degree blood relative
|
Weak
|
n.a.
|
|
Age to initiate surveillance
-
Familial pancreatic cancer kindred (without a known germline mutation): Start at age
50 or 55* or 10 years younger than the youngest affected blood relative
-
For CDKN2A†, Peutz-Jegher syndrome, start at age 40 or 10 years younger than the youngest
affected blood relative
-
BRCA2, ATM, PALB2 BRCA1, MLH1 / MSH2 start at age 45 or 50 or 10 years younger than
youngest affected blood relative
|
Weak
|
n.a.
|
|
Tests at baseline
|
Weak
|
n.a.
|
62 Sah RP, Sharma A, Nagpal S, et al. Phases of metabolic and soft tissue changes
in months preceding a diagnosis of pancreatic ductal adenocarcinoma. Gastroenterology
2019;156:1742–1752.
69 O’Brien DP, Sandanayake NS, Jenkinson C, et al. Serum CA19–9 is significantly upregulated
up to 2 years before diagnosis with pancreatic cancer: implications for early disease
detection. Clin Cancer Res 2015;21:622–631.
70 Jenkinson C, Elliott VL, Evans A, et al. Decreased serum thrombospondin-1 levels
in pancreatic cancer patients up to 24 months prior to clinical diagnosis: association
with diabetes mellitus. Clin Cancer Res 2016;22:1734–1743.
71 Nolen BM, Brand RE, Prosser D, et al. Prediagnostic serum biomarkers as early detection
tools for pancreatic cancer in a large prospective cohort study. PLoS One 2014;9:e94 928.
72 Siu AL, U S Preventive Services Task Force. Screening for abnormal blood glucose
and type 2 diabetes mellitus: U.S. preventive services task force recommendation statement.
Ann Intern Med 2015;163:861–868.
73 Chari S, Leibson C, Rabe K, et al. Probability of pancreatic cancer following diabetes:
a population-based study. Gastroenterology 2005;129:504–511.
74 Chari ST, Leibson CL, Rabe KG, et al. Pancreatic cancer–associated diabetes mellitus:
prevalence and temporal association with diagnosis of cancer. Gastroenterology 2008;134:95–101.
75 Setiawan VW, Stram DO, Porcel J, et al. Pancreatic cancer following incident diabetes
in African Americans and Latinos: the multiethnic cohort. J Natl Cancer Inst 2019;111:27–33.
76 Sharma A, Kandlakunta H, Nagpal SJS, et al. Model to determine risk of pancreatic
cancer in patients with new-onset diabetes. Gastroenterology 2018;155:730–739.
77 Boursi B, Finkelman B, Giantonio BJ, et al. A clinical prediction model to assess
risk for pancreatic cancer among patients with new-onset diabetes. Gastroenterology
2017;152:840–850.e3.
|
|
Diagnostik
|
|
Differentialdiagnostik zystischer Prozesse/Radiologie
|
|
European evidence-based guidelines 2018 [1]
|
Pancreatic MRI is the preferred method for follow-up of PCN
|
weak
|
low
|
25. Sainani NI, Saokar A, Deshpande V, et al. Comparative performance of MDCT and
MRI with MR cholangiopancreatography in characterizing small pancreatic cysts. AJR
Am J Roentgenol 2009;193:722–731.
33. Sahani DV, Kambadakone A, Macari M, et al. Diagnosis and management of cystic
pancreatic lesions. AJR Am J Roentgenol 2013;200:343–354.
34. Chaudhari VV, Raman SS, Vuong NL, et al. Pancreatic cystic lesions: discrimination
accuracy based on clinical data and high resolution CT features. J Comput Assist Tomogr
2007;31:860–867.
35. de Jong K, Nio CY, Mearadji B, et al. Disappointing interobserver agreement among
radiologists for a classifying diagnosis of pancreatic cysts using magnetic resonance
imaging. Pancreas 2012;41:278–282.
36. Waters JA, Schmidt CM, Pinchot JW, et al. CT vs MRCP: optimal classification of
IPMN type and extent. J Gastrointest Surg 2008;12:101–109.
37. Pilleul F, Rochette A, Partensky C, et al. Preoperative evaluation of intraductal
papillary mucinous tumors performed by pancreatic magnetic resonance imaging and correlated
with surgical and histopathologic findings. J Magn Reson Imaging 2005;21:237–244.
38. Berland LL, Silverman SG, Gore RM, et al. Managing incidental findings on abdominal
CT: white paper of the ACR incidental findings committee. J Am Coll Radiol 2010;7:754–773.
39. Sodickson A, Baeyens PF, Andriole KP, et al. Recurrent CT, cumulative radiation
exposure, and associated radiation-induced cancer risks from CT of adults. Radiology
2009;251:175–184.
|
|
In general, MRI is the preferred method for the investigation of patients with PCN.
Multimodality imaging should be considered in cases where the identification of calcification
is important, for tumour staging, or for diagnosing postoperative recurrent disease
|
weak
|
low
|
|
No definite MRI or CT protocol can be recommended for the diagnosis or surveillance
of patients with PCN because of the wide spread of published data and the lack of
dedicated comparative studies
|
weak
|
low
|
|
MRI is the preferred imaging modality for the follow-up of IPMN. EUS can be used in
selected cases
|
strong
|
moderate
|
|
Differentialdiagnostik zystischer Prozesse/Endoskopie
|
|
European evidence-based guidelines 2018 [1]
|
EUS is recommended as an adjunct to other imaging modalities
EUS is helpful for identifying PCN with features that should be considered for surgical
resection. Similar to MRI and CT (see 3.1 statement), EUS is imperfect at identifying
the exact type of PCN
EUS is recommended if the PCN has either clinical or radiological features of concern
identified during the initial investigation or follow-up
|
weak
|
low
|
45. Donahue TR, Hines OJ, Farrell JJ, et al. Cystic neoplasms of the pancreas: results
of 114 cases. Pancreas 2010;39:1271–1276.
46. Kim JH, Eun HW, Park HJ, et al. Diagnostic performance of MRI and EUS in the differentiation
of benign from malignant pancreatic cyst and cyst communication with the main duct.
Eur J Radiol 2012;81:2927–2935.
47. Gress F, Gottlieb K, Cummings O, et al. Endoscopic ultrasound characteristics
of mucinous cystic neoplasms of the pancreas. Am J Gastroenterol 2000;95:961–965.
48. Yamao K, Nakamura T, Suzuki T, et al. Endoscopic diagnosis and staging of mucinous
cystic neoplasms and intraductal papillary-mucinous tumors. J Hepatobiliary Pancreat
Surg 2003;10:142–146.
49. Ahmad NA, Kochman ML, Lewis JD, et al. Can EUS alone differentiate between malignant
and benign cystic lesions of the pancreas? Am J Gastroenterol 2001;96:3295–3300.
50. Ahmad NA, Kochman ML, Brensinger C, et al. Interobserv er agreement among endosonographers
for the diagnosis of neoplastic versus non-neoplastic pancreatic cystic lesions. Gastrointest
Endosc 2003;58:59–64.
51. Kamata K, Kitano M, Omoto S, et al. Contrast-enhanced harmonic endoscopic ultrasonography
for differential diagnosis of pancreatic cysts. Endoscopy 2016;48:35–41.
52. Harima H, Kaino S, Shinoda S, et al. Differential diagnosis of benign and malignant
branch duct intraductal papillary mucinous neoplasm using contrast-enhanced endoscopic
ultrasonography. World J Gastroenterol 2015;21:6252–6260.
53. Fusaroli P, Kypraios D, Mancino MG, et al. Interobserver agreement in contrast
harmonic endoscopic ultrasound. J Gastroenterol Hepatol 2012;27:1063–1069.
54. de Jong K, van Hooft JE, Nio CY, et al. Accuracy of preoperative workup in a prospective
series of surgically resected cystic pancreatic lesions. Scand J Gastroenterol 2012;47:1056–1063.
55. Ardengh JC, Lopes CV, de Lima-Filho ER, et al. Impact of endoscopic ultrasoundguided
fine-needle aspiration on incidental pancreatic cysts. A prospective study. Scand
J Gastroenterol 2014;49:114–120.
56. Gillis A, Cipollone I, Cousins G, et al. Does EUS-FNA molecular analysis carry
additional value when compared to cytology in the diagnosis of pancreatic cystic neoplasm?
A systematic review. HPB (Oxford) 2015;17:377–386.
57. Al-Haddad M, DeWitt J, Sherman S, et al. Performance characteristics of molecular
(DNA) analysis for the diagnosis of mucinous pancreatic cysts. Gastrointest Endosc
2014;79:79–87.
58. Brugge WR, Lewandrowski K, Lee-Lewandrowski E, et al. Diagnosis of pancreatic
cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology
2004;126:1330–1336.
59. Cizginer S, Turner BG, Turner B, Bilge AR, et al. Cyst fluid carcinoembryonic
antigen is an accurate diagnostic marker of pancreatic mucinous cysts. Pancreas 2011;40:1024–1028.
60. Gaddam S, Ge PS, Keach JW, et al. Suboptimal accuracy of carcinoembryonic antigen
in differentiation of mucinous and nonmucinous pancreatic cysts: results of a large
multicenter study. Gastrointest Endosc 2015;82:1060–1069.
61. Jin DX SA, Vollmer CM, Jhala N, et al. A lower cyst fluid CEA cut-off increases
diagnostic accuracy in identifying mucinous pancreatic cystic lesions. J Pancreas
2015;16:271–277.
62. Kadayifci A, Al-Haddad M, Atar M, et al. The value of KRAS mutation testing with
CEA for the diagnosis of pancreatic mucinous cysts. Endosc Int Open 2016;4:E391–E396.
63. Khalid A, Zahid M, Finkelstein SD, et al. Pancreatic cyst fluid DNA analysis in
evaluating pancreatic cysts: a report of the PANDA study. Gastrointest Endosc 2009;69:1095–1102.
64. Winner M, Sethi A, Poneros JM, et al. The role of molecular analysis in the diagnosis
and surveillance of pancreatic cystic neoplasms. JOP 2015;16:143–149.
65. Ngamruengphong S, Bartel MJ, Raimondo M. Cyst carcinoembryonic antigen in differentiating
pancreatic cysts: a meta-analysis. Dig Liver Dis 2013;45:920–926.
66. Sedlack R, Affi A, Vazquez-Sequeiros E, et al. Utility of EUS in the evaluation
of cystic pancreatic lesions. Gastrointest Endosc 2002;56:543–547.
67. Koito K, Namieno T, Nagakawa T, et al. Solitary cystic tumor of the pancreas:
EUSpathologic correlation. Gastrointest Endosc 1997;45:268–276.
68. Morris-Stiff G, Lentz G, Chalikonda S, et al. Pancreatic cyst aspiration analysis
for cystic neoplasms: mucin or carcinoembryonic antigen--which is better? Surgery
2010;148:638–645. discussion 44–5.
69. Tarantino I, Fabbri C, Di Mitri R, et al. Complications of endoscopic ultrasound
fine needle aspiration on pancreatic cystic lesions: final results from a large prospective
multicenter study. Dig Liver Dis 2014;46:41–44.
70. Barresi L, Tarantino I, Traina M, et al. Endoscopic ultrasound-guided fine needle
aspiration and biopsy using a 22-gauge needle with side fenestration in pancreatic
cystic lesions. Dig Liver Dis 2014;46:45–50.
71. Al-Haddad M, Wallace MB, Woodward TA, et al. The safety of fine-needle aspiration
guided by endoscopic ultrasound: a prospective study. Endoscopy 2008;40:204–208.
72. Lee LS, Saltzman JR, Bounds BC, et al. EUS-guided fine needle aspiration of pancreatic
cysts: a retrospective analysis of complications and their predictors. Clin Gastroenterol
Hepatol 2005;3:231–236.
73. Varadarajulu S, Eloubeidi MA. Frequency and significance of acute intracystic
hemorrhage during EUS-FNA of cystic lesions of the pancreas. Gastrointest Endosc 2004;60:631–635.
74. O’Toole D, Palazzo L, Arotçarena R, et al. Assessment of complications of EUS-guided
fine-needle aspiration. Gastrointest Endosc 2001;53:470–474.
75. Bournet B, Migueres I, Delacroix M, et al. Early morbidity of endoscopic ultrasound:
13 years’ experience at a referral center. Endoscopy 2006;38:349–354.
76. Guarner-Argente C, Shah P, Buchner A, et al. Use of antimicrobials for EUS-guided
FNA of pancreatic cysts: a retrospective, comparative analysis. Gastrointest Endosc
2011;74:81–86.
77. Suzuki R, Thosani N, Annangi S, et al. Diagnostic yield of EUS-FNA-based cytology
distinguishing malignant and benign IPMNs: a systematic review and meta-analysis.
Pancreatology 2014;14:380–384.
78. Siech M, Tripp K, Schmidt-Rohlfing B, et al. Cystic tumours of the pancreas: diagnostic
accuracy, pathologic observations and surgical consequences. Langenbecks Arch Surg
1998;383:56–61.
79. Hara T, Yamaguchi T, Ishihara T, et al. Diagnosis and patient management of intraductal
papillary-mucinous tumor of the pancreas by using peroral pancreatoscopy and intraductal
ultrasonography. Gastroenterology 2002;122:34–43.
80. Navez J, Hubert C, Gigot JF, et al. Impact of intraoperative pancreatoscopy with
intraductal biopsies on surgical management of intraductal papillary mucinous neoplasm
of the pancreas. J Am Coll Surg 2015;221:982–987.
81. Konda VJ, Meining A, Jamil LH, et al. A pilot study of in vivo identification
of pancreatic cystic neoplasms with needle-based confocal laser endomicroscopy under
endosonographic guidance. Endoscopy 2013;45:1006–1013.
82. Nakai Y, Iwashita T, Park DH, et al. Diagnosis of pancreatic cysts: EUS-guided,
through-the-needle confocal laser-induced endomicroscopy and cystoscopy trial: DETECT
study. Gastrointest Endosc 2015;81:1204–1214.
83. Le Pen C, Palazzo L, Napoléon B. A health economic evaluation of needle-based
confocal laser endomicroscopy for the diagnosis of pancreatic cysts. Endosc Int Open
2017;5:E987–E995.
84. Napoléon B, Lemaistre AI, Pujol B, et al. A novel approach to the diagnosis of
pancreatic serous cystadenoma: needle-based confocal laser endomicroscopy. Endoscopy
2015;47:26–32.
|
|
CH-EUS* should be considered for further evaluation of mural nodules. CH-EUS is also
helpful in assessing vascularity within the cyst and septations
The presence of hyperenhancement of a mural nodule, solid mass, or septations on CH-EUS
raises concern for malignant transformation, and EUS-fine needle aspiration (FNA)
of the lesion should be considered
* Contrast-enhanced harmonic endoscopic ultrasound
|
weak
|
low
|
|
EUS-FNA improves diagnostic accuracy in PCN for differentiating mucinous versus non-mucinous
PCN, and malignant versus benign PCN, in cases where CT or MRI are unclear
A combined analysis of cyst fluid CEA, cyst fluid lipase levels, and cytology provides
the highest accuracy for differentiating mucinous from non-mucinous PCN (GRADE 2C)
EUS-FNA should only be performed when the results are expected to change clinical
management
EUS-FNA should not be performed if the diagnosis is already established by cross-sectional
imaging, or where there is a clear indication for surgery (GRADE 2C)
Relative contraindications for EUS-FNA in PCN is a distance of > 10 mm between the
cyst and the transducer, the presence of a high-risk of bleeding due to bleeding disorder,
or the use of dual antiplatelet drugs
|
weak
|
low
|
|
Evaluation of cyst fluid CEA, combined with cytology, or KRAS/GNAS mutation analyses
(although the latter is not yet standard management), may be considered for differentiating
an IPMN or MCN from other PCN (GRADE 2C)
To differentiate benign PCN from those harbouring high-grade dysplasia or cancer,
EUS-FNA may be considered, and any solid component or thickened cyst wall targeted
for cytology (GRADE 2C)
Brush cytology, and forceps biopsy are not recommended owing to a lack of high-quality
evidence. Further studies are required before these tests can be considered in clinical
practice (GRADE 1C)
|
strong to weak
|
low
|
|
EUS morphology alone has a modest diagnostic yield (GRADE 2C)
EUS-FNA is recommended to achieve a better performance for diagnosing PCN (GRADE 1C).
|
strong to weak
|
low
|
|
EUS-FNA for PCN is a safe procedure with a relatively low risk (3.4 %) of complications
(GRADE 2B, strong agreement). No specific measures are suggested to minimise the risk
of complications in EUS-FNA
|
weak
|
low
|
|
ERCP should not be used as a diagnostic modality for differentiating PCN (GRADE 1C)
Pancreatoscopy may be used in selected cases to provide information on the location
and extent of main duct (MD)-IPMN and can be useful in differentiating chronic pancreatitis
from MD-IPMN (GRADE 2C)
nCLE should not be used for the differential diagnosis of PCN (GRADE 1C)
|
strong to weak
|
low
|
|
Differentialdiagnostik zystischer Prozesse/Biomarker
|
|
European evidence-based guidelines 2018 [1]
|
There are no available DNA, RNA or protein biomarkers in blood for clinical use to
differentiate pancreatic cyst type or identify high-grade dysplasia or cancer. Serum
cancer antigen (CA) 19.9 may be considered in IPMN where there is concern for malignant
transformation (GRADE 2C)
DNA markers, in particular, mutations in GNAS and KRAS, have shown promise in identifying
mucin-producing cysts. In cases in which the diagnosis is unclear, and a change in
diagnosis will alter management, analysis of these mutations using highly sensitive
techniques, such as next-generation sequencing (NGS), may be considered (GRADE 2C)
Currently, there is insufficient evidence to support the use of RNA or non-carcinoembryonic
antigen (CEA) protein markers in pancreatic cysts (GRADE 1B)
|
strong to weak
|
moderate to low
|
14. Jang JY, Park T, Lee S, et al. Proposed nomogram predicting the individual risk
of malignancy in the patients with branch duct type intraductal papillary mucinous
neoplasms of the pancreas. Ann Surg 2017;266:1062–1068.
15. Wang W, Zhang L, Chen L, et al. Serum carcinoembryonic antigen and carbohydrate
antigen 19–9 for prediction of malignancy and invasiveness in intraductal papillary
mucinous neoplasms of the pancreas: a meta-analysis. Biomed Rep 2015;3:43–50.
16. Kim JR, Jang JY, Kang MJ, et al. Clinical implication of serum carcinoembryonic
antigen and carbohydrate antigen 19–9 for the prediction of malignancy in intraductal
papillary mucinous neoplasm of pancreas. J Hepatobiliary Pancreat Sci 2015;22:699–707.
17. Singhi AD, Nikiforova MN, Fasanella KE, et al. Preoperative GNAS and KRAS testing
in the diagnosis of pancreatic mucinous cysts. Clin Cancer Res 2014;20:4381–4389.
18. Springer S, Wang Y, Dal Molin M, et al. A combination of molecular markers and
clinical features improve the classification of pancreatic cysts. Gastroenterology
2015;149:1501–1510.
19. Singhi AD, Zeh HJ, Brand RE, et al. American Gastroenterological Association guidelines
are inaccurate in detecting pancreatic cysts with advanced neoplasia: a clinicopathologic
study of 225 patients with supporting molecular data. Gastrointest Endosc 2016;83:1107–1117.
20. Kadayifci A, Atar M, Wang JL, et al. Value of adding GNAS testing to pancreatic
cyst fluid KRAS and carcinoembryonic antigen analysis for the diagnosis of intraductal
papillary mucinous neoplasms. Dig Endosc 2017;29:111–117.
21. Al-Rashdan A, Schmidt CM, Al-Haddad M, et al. Fluid analysis prior to surgical
resection of suspected mucinous pancreatic cysts. A single centre experience. J Gastrointest
Oncol 2011;2:208–214.
22. van der Waaij LA, van Dullemen HM, Porte RJ. Cyst fluid analysis in the differential
diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointest Endosc2005;62:383–389.
|
|
Chirurgische Therapie
|
|
Resektabilitätskriterien
|
|
ASCO 2016 [6]
|
Primary surgical resection of the primary tumor and regional lymph nodes is recommended
for patients with potentially curable pancreatic cancer who meet all of the following
criteria:
-
no clinical evidence for metastatic disease,
-
a performance status and comorbidity profile appropriate for a major abdominal operation,
-
no radiographic interface between primary tumor and mesenteric vasculature on high-definition
cross-sectional imaging, and
-
an acceptable CA 19–9 level in (absence of jaundice) suggestive of localized disease
|
strong
|
inter-mediate
|
16. Oettle H, Post S, Neuhaus P, et al: Adjuvant chemotherapy with gemcitabine vs
observation in patients undergoing curative-intent resection of pancreatic cancer:
A randomized controlled trial. JAMA 297:267–277, 2007
17. Smeenk HG, van Eijck CH, Hop WC, et al: Long-term survival and metastatic pattern
of pancreatic and periampullary cancer after adjuvant chemoradiation or observation:
Long-term results of EORTC trial 40 891. Ann Surg 246:734–740, 2007
20. Yamada S, Fujii T, Sugimoto H, et al: Aggressive surgery for borderline resectable
pancreatic cancer: Evaluation of National Comprehensive Cancer Network guidelines.
Pancreas 42:1004–1010, 2013
36. Kalser MH, Ellenberg SS: Pancreatic cancer: Adjuvant combined radiation and chemotherapy
following curative resection. Arch Surg 120:899–903, 1985 37.
37. Klinkenbijl JH, Jeekel J, Sahmoud T, 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 230:776–782,
1999
38. Mayo SC, Gilson MM, Herman JM, et al: Management of patients with pancreatic adenocarcinoma:
National trends in patient selection, operative management, and use of adjuvant therapy.
J Am Coll Surg 214:33–45, 2012
39. Davila JA, Chiao EY, Hasche JC, et al: Utilization and determinants of adjuvant
therapy among older patients who receive curative surgery for pancreatic cancer. Pancreas
38:e18–e25, 2009
40. Merkow RP, Bilimoria KY, Tomlinson JS, et al: Postoperative complications reduce
adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg 260:372–377, 2014
41. Wu W, He J, Cameron JL, et al: The impact of postoperative complications on the
administration of adjuvant therapy following pancreaticoduodenectomy for adenocarcinoma.
Ann Surg Oncol 21:2873–2881, 2014
42. Gleisner AL, Assumpcao L, Cameron JL, et al: Is resection of periampullary or
pancreatic adenocarcinoma with synchronous hepatic metastasis justified? Cancer 110:2484–2492,
2007
43. Ferrone CR, Finkelstein DM, Thayer SP, et al: Perioperative CA19–9 levels can
predict stage and survival in patients with resectable pancreatic adenocarcinoma.
J Clin Oncol 24:2897–2902, 2006
44. Ballehaninna UK, Chamberlain RS: The clinical utility of serum CA 19–9 in the
diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based
appraisal. J Gastrointest Oncol 3: 105–119, 2012
45. Kang CM, Kim JY, Choi GH, et al: The use of adjusted preoperative CA 19–9 to predict
the recurrence of resectable pancreatic cancer. J Surg Res 140:31–35, 2007
46. Sugiura T, Uesaka K, Kanemoto H, et al: Serum CA19–9 is a significant predictor
among preoperative parameters for early recurrence after resection of pancreatic adenocarcinoma.
J Gastrointest Surg 16: 977–985, 2012
47. Kim TH, Han SS, Park SJ, et al: CA 19–9 level as indicator of early distant metastasis
and therapeutic selection in resected pancreatic cancer. Int J Radiat Oncol Biol Phys
81:e743–e748, 2011
48. Hallemeier CL, Botros M, Corsini MM, et al: Preoperative CA 19–9 level is an important
prognostic factor in patients with pancreatic adenocarcinoma treated with surgical
resection and adjuvant concurrent chemoradiotherapy. Am J Clin Oncol 34:567–572, 2011
49. Duffy MJ, Sturgeon C, Lamerz R, et al: Tumor markers in pancreatic cancer: A European
Group on Tumor Markers (EGTM) status report. Ann Oncol 21: 441–447, 2010
|
|
Primary surgical resection of the primary tumor and regional lymph nodes is recommended
for patients with potentially curable pancreatic cancer who meet all of the following
criteria:
-
no clinical evidence for metastatic disease,
-
a performance status and comorbidity profile appropriate for a major abdominal operation,
-
no radiographic interface between primary tumor and mesenteric vasculature on high-definition
cross-sectional imaging, and
-
an acceptable CA 19–9 level in (absence of jaundice) suggestive of localized disease
|
strong
|
Inter-mediate
|
|
Primary surgical resection of the primary tumor and regional lymph nodes is recommended
for patients with potentially curable pancreatic cancer who meet all of the following
criteria:
-
no clinical evidence for metastatic disease,
-
a performance status and comorbidity profile appropriate for a major abdominal operation,
-
no radiographic interface between primary tumor and mesenteric vasculature on high-definition
cross-sectional imaging, and
-
an acceptable CA 19–9 level in (absence of jaundice) suggestive of localized disease
|
strong
|
inter-mediate
|
|
Palliative Therapie
|
|
Systemische Therapie Erstlinie
|
|
ASCO 2016 [7]
|
Gemcitabine alone is recommended for patients who have either an ECOG PS of 2 or a
comorbidity profile that precludes more aggressive regimens and who wish to pursue
cancer-directed therapy. The addition of either capecitabine or erlotinib to gemcitabine
may be offered in this setting
|
strong
|
inter-mediate
|
8. Conroy T, Desseigne F, Ychou M, et al: FOLFIRINOX versus gemcitabine for metastatic
pancreatic cancer. N Engl J Med 364:1817–1825, 2011
9. Von Hoff DD, Ervin T, Arena FP, et al: Increased survival in pancreatic cancer
with nabpaclitaxel plus gemcitabine. N Engl J Med 369: 1691–1703, 2013
21. Cunningham D, Chau I, Stocken DD, et al: Phase III randomized comparison of gemcitabine
versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer.
J Clin Oncol 27: 5513–5518, 2009
26. 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 25: 1960–1966,
2007
38. Ma C, Bandukwala S, Burman D, et al: Interconversion of three measures of performance
status: An empirical analysis. Eur J Cancer 46:3175–3183, 2010
39. Mahaseth H, Brutcher E, Kauh J, et al: Modified FOLFIRINOX regimen with improved
safety and maintained efficacy in pancreatic adenocarcinoma. Pancreas 42:1311–1315,
2013
40. 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 387: 545–557,
2016
41. Burris HA III, 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 15:2403–2413, 1997
|
|
Gemcitabine plus nanoparticle albuminbound (NAB) -paclitaxel is recommended for patients
who meet all of the following criteria:
-
ECOG PS 0 to 1,
-
relatively favorable comorbidity profile, and
-
patient preference and support system for relatively aggressive medical therapy
|
strong
|
inter-mediate
|
|
Leucovorin, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) is recommended
for patients who meet all of the following criteria:
-
ECOG PS 0 to 1,
-
favorable comorbidity profile,
-
patient preference and support system for aggressive medical therapy, and
-
access to chemotherapy port and infusion pump management services
|
strong
|
inter-mediate
|
|
Patients with an ECOG PS > 3 or with poorly controlled comorbid conditions despite
ongoing active medical care should be offered cancer-directed therapy only on a case-by-case
basis. The major emphasis should be on optimizing supportive care measures
|
moderate
|
inter-mediate
|
|
Initial systemic therapy with combination regimens is recommended for most patients
who meet the following criteria:
-
Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1,
-
a favorable comorbidity profile, and
-
patient preference and a support system for aggressive medical therapy.
There is no clear evidence to support one regimen over another, and physicians may
offer therapy on the basis of extrapolation from data derived from studies in the
metastatic setting. For some patients, chemoradiotherapy (CRT) or stereotactic body
radiation therapy (SBRT) may be offered up front, on the basis of patient and physician
preference
|
strong
|
inter-mediate
|
6. Von Hoff DD, Ervin T, Arena FP, et al: Increased survival in pancreatic cancer
with nabpaclitaxel plus gemcitabine. N Engl J Med 369:1691–1703, 2013
9. Mukherjee S, Hurt CN, Bridgewater J, et al: Gemcitabine-based or capecitabine-based
chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): A multicentre,
randomised, phase 2 trial. Lancet Oncol 14:317–326, 2013
10. Hurt CN, Mukherjee S, Bridgewater J, et al: Health-related quality of life in
SCALOP, a randomized phase 2 trial comparing chemoradiation therapy regimens in locally
advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 93:810–818, 2015
14. Ueno H, Ioka T, Ikeda M, et al: Randomized phase III study of gemcitabine plus
S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic
pancreatic cancer in Japan and Taiwan:GEST study. J Clin Oncol 31:1640–1648, 2013
16. Loehrer PJ Sr., Feng Y, Cardenes H, et al: Gemcitabine alone versus gemcitabine
plus radiotherapy in patients with locally advanced pancreatic cancer: An Eastern
Cooperative Oncology Group trial. J Clin Oncol 29:4105–4112, 2011
17. Huang J, Robertson JM, Margolis J, et al: Long-term results of full-dose gemcitabine
with radiation therapy compared to 5-fluorouracil with radiation therapy for locally
advanced pancreas cancer. Radiother Oncol 99:114–119, 2011
20. Boeck S, Vehling-Kaiser U, Waldschmidt D, et al: Erlotinib 150 mg daily plus chemotherapy
in advanced pancreatic cancer: An interim safety analysis of a multicenter, randomized,
cross-over phase III trial of the ‘Arbeitsgemeinschaft Internistische Onkologie’.
Anticancer Drugs 21:94–100, 2010
24. Cunningham D, Chau I, Stocken DD, et al: Phase III randomized comparison of gemcitabine
versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer.
J Clin Oncol 27: 5513–5518, 2009
25. Allendorf JD, Lauerman M, Bill A, et al: Neoadjuvant chemotherapy and radiation
for patients with locally unresectable pancreatic adenocarcinoma: Feasibility, efficacy,
and survival. J Gastrointest Surg 12:91–100, 2008
28. Herrmann R, Bodoky G, Ruhstaller T, et al: Gemcitabine plus capecitabine compared
with gemcitabine alone in advanced pancreatic cancer: A randomized, multicenter, phase
III trial of the Swiss Group for Clinical Cancer Research and the Central European
Cooperative Oncology Group. J Clin Oncol 25:2212–2217, 2007
34. Berlin JD, Catalano P, Thomas JP, et al: Phase III study of gemcitabine in combination
with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma:
Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol 20:3270–3275, 2002
41. Zhu CP, Shi J, Chen YX, et al: Gemcitabine in the chemoradiotherapy for locally
advanced pancreatic cancer: A meta-analysis. Radiother Oncol 99: 108–113, 2011
42. Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F, et al: Impact of FOLFIRINOX
compared with gemcitabine on quality of life in patients with metastatic pancreatic
cancer: Results from the PRODIGE 4/ACCORD 11 randomized trial. J Clin Oncol 31:23–29,
2013
|
|
NiCE 2018 [8]
|
Consider gemcitabine for people with locally advanced pancreatic cancer who are not
well enough to tolerate combination chemotherapy
|
weak
|
low to very low
|
Cantore M, Fiorentini G, Luppi G et al. (2004) Gemcitabine versus FLEC regimen given
intra- arterially to patients with unresectable pancreatic cancer: a prospective,
randomized phase III trial of the Italian Society for Integrated Locoregional Therapy
in Oncology. Journal of Chemotherapy 16(6): 589–594
Heinemann V, Ebert MP, Laubender RP et al. (2013) Phase II randomised proof-of-concept
study of the urokinase inhibitor upamostat (WX-671) in combination with gemcitabine
compared with gemcitabine alone in patients with non-resectable, locally advanced
pancreatic cancer. British Journal of Cancer 108(4): 766–770
|
|
Offer gemcitabine to people who are not well enough to tolerate combination chemotherapy.
(metastatic pancreatic cancer)
|
strong
|
high to very low
|
Abou-Alfa GK, Letourneau R, Harker G et al. (2006) Randomized phase III study of exatecan
and Gemcitabine compared with Gemcitabine single-agent in untreated advanced pancreatic
cancer. Journal of Clinical Oncology 24(27): 4441–4447
Berlin JD, Catalano P, Thomas JP et al. (2002) Phase III study of Gemcitabine in combination
with fluorouracil versus Gemcitabine single-agent in patients with advanced pancreatic
carcinoma: Eastern Cooperative Oncology Group Trial E2297. Journal of Clinical Oncology
20(15): 3270–3275
Bernhard J, Dietrich D, Scheithauer W et al. (2008) Clinical benefit and quality of
life in patients with advanced pancreatic cancer receiving Gemcitabine + capecitabine
versus Gemcitabine single-agent: a randomized multicenter phase III clinical trial--SAKK
44/00-CECOG/PAN13 001. Journal of Clinical Oncology 26(22): 3695–3701
Bramhall SR, Schulz J, Nemunaitis J et al. (2002) A double-blind placebo-controlled,
randomised study comparing Gemcitabine and marimastat with Gemcitabine and placebo
as first line therapy in patients with advanced pancreatic cancer. British Journal
of Cancer 87(2): 161–167
Burris HA, Moore MJ, Andersen J et al. (1997) Improvements in survival and clinical
benefit with Gemcitabine as first-line therapy for patients with advanced pancreas
cancer: a randomized trial. Journal of Clinical Oncology 15(6): 2403–2413
Colucci G, Labianca R, Di Costanzo F et al. (2010) Randomized phase III trial of Gemcitabine
plus cisplatin compared with single-agent Gemcitabine as first-line treatment of patients
with advanced pancreatic cancer: the GIP-1 study. Journal of Clinical Oncology 1 28(10):
1645–1651
Conroy T, Desseigne F, Ychou M et al. (2011) FOLFIRINOX versus Gemcitabine for metastatic
pancreatic cancer. New England Journal of Medicine 364(19): 1817–1825
Chao Y, Wu CY, Wang JP et al. (2013) A randomized controlled trial of Gemcitabine
plus cisplatin versus Gemcitabine single-agent in the treatment of metastatic pancreatic
cancer. Cancer Chemotherapy and Pharmacology 72(3): 637–642
Cunningham D, Chau I, Stocken DD et al. (2009) Phase III randomized comparison of
Gemcitabine versus Gemcitabine plus capecitabine in patients with advanced pancreatic
cancer. Journal of Clinical Oncology 27(33): 5513–5518
Deplanque G, Demarchi M, Hebbar M et al. (2015) A randomized, placebo-controlled phase
III trial of masitinib + Gemcitabine in the treatment of advanced pancreatic cancer.
Annals of Oncology 26(6): 1194–1200
Eckhardt SG, De Porre P, Smith D et al. (2009) Patient-reported outcomes as a component
of the primary endpoint in a double-blind, placebo-controlled trial in advanced pancreatic
cancer. Journal of Pain Symptom Management 37(2): 135–143
Fuchs CS, Azevedo S, Okusaka T et al. (2015) A phase 3 randomized, double-blind, placebo-controlled
trial of ganitumab or placebo in combination with Gemcitabine as first-line therapy
for metastatic adenocarcinoma of the pancreas: the GAMMA trial. Annals of Oncology
26(5): 921–927
Gonçalves A, Gilabert M, François E et al. (2012) BAYPAN study: a double-blind phase
III randomized trial comparing Gemcitabine plus sorafenib and Gemcitabine plus placebo
in patients with advanced pancreatic cancer. Annals of Oncology 23(11): 2799–2805
Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F et al. (2013) Impact of FOLFIRINOX
compared with Gemcitabine on quality of life in patients with metastatic pancreatic
cancer: results from the PRODIGE 4/ACCORD 11 randomized trial. Journal of Clinical
Oncology 31(1): 23–29
Heinemann V, Quietzsch D, Gieseler F et al. (2006) Randomized phase III trial of Gemcitabine
plus cisplatin compared with Gemcitabine single-agent in advanced pancreatic cancer.
Journal of Clinical Oncology 24(24): 3946–3952
Heinemann V, Ursula V-K, Dirk W et al. (2012) Gemcitabine plus erlotinib followed
by capecitabine versus capecitabine plus erlotinib followed by Gemcitabine in advanced
pancreatic cancer: final results of a randomised phase 3 trial of the ‘Arbeitsgemeinschaft
Internistische Onkologie’ (AIO-PK0104). Gut 62(5): 751–759
Herrmann R, Bodoky G, Ruhstaller T et al. (2007) Gemcitabine plus capecitabine compared
with Gemcitabine single-agent in advanced pancreatic cancer: a randomized, multicenter,
phase III trial of the Swiss Group for Clinical Cancer Research and the Central European
Cooperative Oncology Group. Journal of Clinical Oncology 25(16): 2212–2217
Kindler HL, Ioka T, Richel DJ et al. (2011) Axitinib plus Gemcitabine versus placebo
plus Gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind
randomised phase 3 study. Lancet Oncology 12(3): 256–262
Kindler HL, Niedzwiecki D, Hollis D et al. (2010) Gemcitabine plus bevacizumab compared
with Gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III
trial of the Cancer and Leukemia Group B (CALGB 80 303). Journal of Clinical Oncology
28(22): 3617–3622
Lee HS, Chung MJ, Park JY et al. (2017) A randomized, multicenter, phase III study
of gemcitabine combined with capecitabine versus gemcitabine alone as first-line chemotherapy
for advanced pancreatic cancer in South Korea. Medicine 96(1): e5702
Louvet C, Labianca R, Hammel P et al. (2005). Gemcitabine in combination with oxaliplatin
compared with Gemcitabine single-agent in LA or metastatic pancreatic cancer: results
of a GERCOR and GISCAD phase III trial. Journal of Clinical Oncology 23(15): 3509–3516
Maraveyas A, Waters J, Roy R et al. (2012) Gemcitabine versus Gemcitabine plus dalteparin
thromboprophylaxis in pancreatic cancer. European Journal of Cancer 48(9): 1283–1292
Middleton G, Palmer DH, Greenhalf W et al. (2017) Vandetanib plus gemcitabine versus
placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP):
a prospective, randomised, double-blind, multicentre phase 2 trial. Lancet Oncology
18(4): 486–499
Moinpour CM, Vaught NL, Goldman B et al. (2010) Pain and emotional well-being outcomes
in Southwest Oncology Group-directed intergroup trial S0205: a phase III study comparing
Gemcitabine plus cetuximab versus Gemcitabine as first-line therapy in patients with
advanced pancreas cancer. Journal of Clinical Oncology 28(22): 3611–3616
Moore MJ, Goldstein D, Hamm J et al. (2007) Erlotinib plus Gemcitabine compared with
Gemcitabine single-agent in patients with advanced pancreatic cancer: a phase III
trial of the National Cancer Institute of Canada Clinical Trials Group. Journal of
Clinical Oncology 25(15): 1960–1966
Moore MJ, Hamm J, Dancey J et al. (2003) Comparison of Gemcitabine versus the matrix
metalloproteinase inhibitor BAY 12–9566 in patients with advanced or metastatic adenocarcinoma
of the pancreas: a phase III trial of the National Cancer Institute of Canada Clinical
Trials Group. Journal of Clinical Oncology 21(17): 3296–3302
Oettle H, Richards D, Ramanathan RK et al. (2006) A phase III trial of pemetrexed
plus Gemcitabine versus Gemcitabine in patients with unresectable or metastatic pancreatic
cancer. Annals of Oncology 16(10): 1639–1645
Pelzer U, Opitz B, Deutschinoff G et al. (2015) Efficacy of Prophylactic Low-Molecular
Weight Heparin for Ambulatory Patients With Advanced Pancreatic Cancer: Outcomes From
the CONKO-004 Trial. Journal of Clinical Oncology 33(18): 2028–2034
Philip PA, Benedetti J, Corless CL et al. (2010) Phase III study comparing Gemcitabine
plus cetuximab versus Gemcitabine in patients with advanced pancreatic adenocarcinoma:
Southwest Oncology Group-directed intergroup trial S0205. Journal of Clinical Oncology
28(22): 3605–3610
Poplin E, Levy DE, Berlin J et al. (2006) Phase III trial of Gemcitabine (30-minute
infusion) versus Gemcitabine (fixed-dose-rate infusion [FDR]) versus Gemcitabine oxaliplatin
(GEMOX) in patients with advanced pancreatic cancer (E6201). Journal of Clinical Oncology
24: 933S
Reni M, Cordio S, Milandri C et al. (2005) Gemcitabine versus cisplatin, epirubicin,
fluorouracil, and Gemcitabine in advanced pancreatic cancer: a randomised controlled
multicentre phase III trial. Lancet Oncology 6(6): 369–376
Riess H, Helm A, Niedergethmann M et al. (2005) A randomised, prospective, multicenter,
phase III trial of Gemcitabine, 5-fluorouracil (5-FU), folinic acid versus Gemcitabine
single-agent in patients with advanced pancreatic cancer. Journal of Clinical Oncology
23(16 suppl): 4009
Rocha Lima CM, Green MR, Rotche R et al. (2004) Irinotecan plus Gemcitabine results
in no survival advantage compared with Gemcitabine monotherapy in patients with LA
or metastatic pancreatic cancer despite increased tumor response rate. Journal of
Clinical Oncology 22(18): 3776–3783
Rougier P, Riess H, Manges R et al. (2013) Randomised, placebo-controlled, double-blind,
parallel-group phase III study evaluating aflibercept in patients receiving first-line
treatment with Gemcitabine for metastatic pancreatic cancer. European Journal of Cancer
49(12): 2633–2642
Smith D and Gallagher N (2003) A phase II/III study comparing intravenous ZD9331 with
Gemcitabine in patients with pancreatic cancer. European Journal of Cancer 39(10):
1377–1383
Stathopoulos GP, Syrigos K, Aravantinos G et al. (2006) A multicenter phase III trial
comparing irinotecan-Gemcitabine (IG) with Gemcitabine (G) monotherapy as first-line
treatment in patients with LA or metastatic pancreatic cancer. British Journal of
Cancer 95(5):587–592
Sudo K, Ishihara T, Hirata N et al. (2014) Randomized controlled study of Gemcitabine
plus S-1 combination Chemotherapy versus Gemcitabine for unresectable pancreatic cancer.
Cancer Chemotherapy and Pharmacology 73(2): 389–396
Ueno H, Ioka T, Ikeda M et al. (2013) Randomized phase III study of Gemcitabine plus
S-1, S-1 alone, or Gemcitabine single-agent in patients with LA and metastatic pancreatic
cancer in Japan and Taiwan: GEST study. Journal of Clinical Oncology 31(13): 1640–1648
Van Cutsem E, van de Velde H, Karasek P et al. (2004) Phase III trial of Gemcitabine
plus tipifarnib compared with Gemcitabine plus placebo in advanced pancreatic cancer.
Journal of Clinical Oncology 15;22(8): 1430–1438
Van Cutsem E, Vervenne WL, Bennouna J et al. (2009) Phase III trial of bevacizumab
in combination with Gemcitabine and erlotinib in patients with metastatic pancreatic
cancer. Journal of Clinical Oncology 27(13): 2231–2237
Von Hoff DD, Ervin T, Arena FP et al. (2013) Increased survival in pancreatic cancer
with nab-paclitaxel plus Gemcitabine. New England Journal of Medicine 369(18): 1691–1703
Yamaue H, Tsunoda T, Tani M et al. (2015) Randomized phase II/III clinical trial of
29 elpamotide for patients with advanced pancreatic cancer: PEGASUS-PC Study. Cancer
30 Science 106(7): 883–890
|
|
Offer FOLFIRINOX to people with metastatic pancreatic cancer and an Eastern Cooperative
Oncology Group (ECOG) performance status of 0–1.
|
strong
|
high to very low
|
|
Consider gemcitabine combination therapy for people who are not well enough to tolerate
FOLFIRINOX.
|
weak
|
high to very low
|
|
Systematische Therapie Zweitlinie
|
|
ASCO 2016 [7]
|
No data exist on the duration of cancer directed therapy. An ongoing discussion of
goals of care and assessment of treatment response and tolerability should guide decisions
to continue or hold/terminate cancer-directed therapy
|
strong
|
low
|
keine
|
|
Refer people with LAPC who have not benefited from treatment and have disease progression
for a clinical trial
|
strong
|
Inter-mediate
|
keine
|
|
ASCO 2018 [9]
|
Gemcitabine or fluorouracil can be considered as second-line therapy for patients
who have either an ECOG PS of 2 or a comorbidity profile that precludes more aggressive
regimens and who wish to pursue cancer-directed therapy
|
moderate
|
low
|
13. Oettle H, Riess H, Stieler JMet al: Second-line oxaliplatin, folinic acid, and
fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory
pancreatic cancer: Outcomes from the CONKO-003 trial. J Clin Oncol 32:2423–2429, 2014
40. 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 387: 545–557,
2016
42. Rahma OE, Duffy A, Liewehr DJ, et al: Second-line treatment in advanced pancreatic
cancer: A comprehensive analysis of published clinical trials. Ann Oncol 24:1972–1979,
2013
|
|
PD-1 immune checkpoint inhibitor pembrolizumab is recommended as second-line therapy
for patients who have tested positive for dMMR or MSI-H.
|
moderate
|
inter-mediate
|
6. Le DT, Durham JN, Smith KN, et al: Mismatch repair deficiency predicts response
of solid tumors to PD-1 blockade. Science 357:409–413, 2017
8. US Food and Drug Administration: FDA approves first cancer treatment for any solid
tumor with a specific genetic feature. May 23, 2017 https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm560167.htm
9. Hu ZI, Shia J, Stadler ZK, et al: Evaluating mismatch repair deficiency in pancreatic
adenocarcinoma: Challenges and recommendations. Clin Cancer Res 24:1326–1336, 2018
|
|
Routine testing for deficiency in mismatch repair (dMMR) or high microsatellite instability
(MSI-H) is recommended, using immunohistochemistry (IHC), polymerase chain reaction
(PCR), or next-generation sequencing (NGS), for patients who are considered to be
candidates for checkpoint inhibitor therapy
|
moderate
|
low
|
|
Fluorouracil plus nanoliposomal irinotecan, or fluorouracil plus irinotecan where
the former combination is unavailable, is preferred as second-line therapy, for patients
who meet all of the following criteria:
-
first-line treatment with gemcitabine plus NAB-paclitaxel,
-
an ECOG PS of 0 to 1,
-
a relatively favorable comorbidity profile,
-
patient preference and a support system for aggressive medical therapy, and
-
access to chemotherapy port and infusion pump management services
Qualifying statement
A recent phase III trial comparing mFOLFOX6 with FU + LV demonstrated a higher rate
of grade 3 or 4 adverse events and significantly reduced OS within the mFOLFOX6 arm
of the trial.7 However, previous phase III data have demonstrated a benefit with the
OFF regimen compared with FU + LV.10 Considering the inconsistency of these results,
although fluorouracil plus nanoliposomal irinotecan is preferred, the Expert Panel
continues to support the use of fluorouracil plus oxaliplatin as an option where the
availability of fluorouracil plus nanoliposomal irinotecan is limited or where residual
toxicity from first-line therapy or comorbidities preclude the use of fluorouracil
plus nanoliposomal irinotecan.
|
moderate
|
low
|
7. Gill S, Ko YJ, Cripps C, et al: PANCREOX: A randomized phase III study of fluorouracil/leucovorin
with or without oxaliplatin for second-line advanced pancreatic cancer in patients
who have received gemcitabine-based chemotherapy. J Clin Oncol 34: 3914–3920, 2016
10. Oettle H, Riess H, Stieler JM, et al: Secondline oxaliplatin, folinic acid, and
fluorouracil versus folinic acid and fluorouracil alone for gemcitabinerefractory
pancreatic cancer: Outcomes from the CONKO-003 trial. J Clin Oncol 32:2423–2429, 2014
11. 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 387:545–557,
2016
|
|
Fluorouracil plus oxaliplatin may be considered as second-line therapy for patients
who meet all of the following criteria:
-
first-line treatment with gemcitabine plus NAB-paclitaxel,
-
an ECOG PS of 0 to 1,
-
a relatively favorable comorbidity profile,
-
patient preference and a support system for aggressive medical therapy, and
-
access to chemotherapy port and infusion pump management services
Qualifying statement
A recent phase III trial comparing mFOLFOX6 with FU + LV demonstrated a higher rate
of grade 3 or 4 adverse events and significantly reduced OS within the mFOLFOX6 arm
of the trial.7 However, previous phase III data have demonstrated a benefit with the
OFF regimen compared with FU + LV.10 Considering the inconsistency of these results,
although fluorouracil plus nanoliposomal irinotecan is preferred, the Expert Panel
continues to support the use of fluorouracil plus oxaliplatin as an option where the
availability of fluorouracil plus nanoliposomal irinotecan is limited or where residual
toxicity from first-line therapy or comorbidities preclude the use of fluorouracil
plus nanoliposomal irinotecan.
|
moderate
|
low
|
|
Gemcitabine plus NAB-paclitaxel can be offered as second-line therapy to patients
who meet all of the following criteria:
-
first-line treatment with FOLFIRINOX,
-
an ECOG PS of 0 to 1,
-
a relatively favorable comorbidity profile, and
-
patient preference and a support system for aggressive medical therapy
|
moderate
|
low
|
13. Oettle H, Riess H, Stieler JMet al: Second-line oxaliplatin, folinic acid, and
fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory
pancreatic cancer: Outcomes from the CONKO-003 trial. J Clin Oncol 32:2423–2429, 2014
40. 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 387: 545–557,
2016
42. Rahma OE, Duffy A, Liewehr DJ, et al: Second-line treatment in advanced pancreatic
cancer: A comprehensive analysis of published clinical trials. Ann Oncol 24:1972–1979,
2013
|
|
NICE 2018 [8]
|
Consider gemcitabine-based chemotherapy as second-line treatment for people whose
cancer has progressed after first-line FOLFIRINOX.
|
weak
|
moderate to very low
|
Azmy A, Abdelwahab S, Yassen M (2013) Oxaliplatin and Bolus-Modulated 5-Fluorouracil
as a Second-Line Treatment for Advanced Pancreatic Cancer: Can Bolus Regimens Replace
FOLFOX When Considered for Second Line? ISRN Oncology Article ID 358 538
Ciuleanu TE, Pavlovsky AV, Bodoky G et al. (2009) A randomised Phase III trial of
glufosfamide compared with best supportive care in metastatic pancreatic adenocarcinoma
previously treated with Gemcitabine. European Journal of Cancer 45(9): 1589–1596
Dahan L, Bonnetain F, Ychou M et al. (2010) Combination 5-fluorouracil, folinic acid
and cisplatin (LV5FU2-CDDP) followed by Gemcitabine or the reverse sequence in metastatic
pancreatic cancer: final results of a randomised strategic phase III trial (FFCD 0301).
Gut 59(11): 1527–1534
Gill S, Ko YJ, Cripps C et al. (2016) PANCREOX: A Randomized Phase III Study of 5-Fluorouracil/Leucovorin
With or Without Oxaliplatin for Second-Line Advanced Pancreatic Cancer in Patients
Who Have Received Gemcitabine-Based Chemotherapy. Journal of Clinical Oncology. 2016
Heinemann V, Ursula V-K, Dirk W et al. (2012) Gemcitabine plus erlotinib followed
by capecitabine versus capecitabine plus erlotinib followed by Gemcitabine in advanced
pancreatic cancer: final results of a randomised phase 3 trial of the ‘Arbeitsgemeinschaft
Internistische Onkologie’ (AIO-PK0104). Gut 62(5): 751–759
Oettle H, Riess H, Stieler JM et al. (2014) Second-line oxaliplatin, folinic acid,
and fluorouracil versus folinic acid and fluorouracil alone for Gemcitabine-refractory
pancreatic cancer: outcomes from the CONKO-003 trial. Journal of Clinical Oncology
32(23): 2423–2429
Ulrich-Pur H, Raderer M, Kornek GV et al. (2003) Irinotecan plus raltitrexed vs raltitrexed
alone in patients with Gemcitabine -pretreated advanced pancreatic adenocarcinoma.
British Journal of Cancer 88(8): 1180–1184
|
|
Consider oxaliplatin-based chemotherapy as second-line treatment for people who have
not had first-line oxaliplatin
|
weak
|
moderate to very low
|
|
Systemische Therapie Drittlinie
|
|
ASCO 2018 [9]
|
No data are available to recommend third-line (or greater) therapy with a cytotoxic
agent. Clinical trial participation is encouraged
|
moderate
|
low
|
13. Oettle H, Riess H, Stieler JMet al: Second-line oxaliplatin, folinic acid, and
fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory
pancreatic cancer: Outcomes from the CONKO-003 trial. J Clin Oncol 32:2423–2429, 2014
40. 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 387: 545–557,
2016
42. Rahma OE, Duffy A, Liewehr DJ, et al: Second-line treatment in advanced pancreatic
cancer: A comprehensive analysis of published clinical trials. Ann Oncol 24:1972–1979,
2013
|
|
Strahlentherapie/Strahlenchemotherapie
|
|
ASCO 2016 [7]
|
If there is local disease progression after induction chemotherapy, but without evidence
of systemic spread, then CRT may be offered to patients who meet the following criteria:
-
first-line chemotherapy treatment is completed or terminated;
-
ECOG PS < 2;
-
a comorbidity profile that is adequate, including adequate hepatic and renal function
and hematologic status; and
-
patient preference
|
strong
|
inter-mediate
|
4. Gillen S, Schuster T, Meyer Zum Buschenfelde C, et al: Preoperative/neoadjuvant
therapy in pancreatic cancer: A systematic review and meta-analysis of response and
resection percentages. PLoS Med 7:e1000 267, 2010
9. Mukherjee S, Hurt CN, Bridgewater J, et al: Gemcitabine-based or capecitabine-based
chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): A multicentre,
randomised, phase 2 trial. Lancet Oncol 14:317–326, 2013
10. Hurt CN, Mukherjee S, Bridgewater J, et al: Health-related quality of life in
SCALOP, a randomized phase 2 trial comparing chemoradiation therapy regimens in locally
advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 93:810–818, 2015
16. Loehrer PJ Sr., Feng Y, Cardenes H, et al: Gemcitabine alone versus gemcitabine
plus radiotherapy in patients with locally advanced pancreatic cancer: An Eastern
Cooperative Oncology Group trial. J Clin Oncol 29:4105–4112, 2011
41. Zhu CP, Shi J, Chen YX, et al: Gemcitabine in the chemoradiotherapy for locally
advanced pancreatic cancer: A meta-analysis. Radiother Oncol 99: 108–113, 2011
43. Li CP, Chao Y, Chi KH, et al: Concurrent chemoradiotherapy treatment of locally
advanced pancreatic cancer: Gemcitabine versus 5-fluorouracil, a randomized controlled
study. Int J Radiat Oncol Biol Phys 57:98–104, 2003
44. Moningi S, Dholakia AS, Raman SP, et al: The Role of stereotactic body radiation
therapy for pancreatic cancer: A single-institution experience. Ann Surg Oncol 22:2352–2358,
2015
|
|
CRTor SBRTmay be offered to patients who have responded to an initial 6 months of
chemotherapy or have stable disease but have developed unacceptable chemotherapy-related
toxicities or show a decline in performance status, as a consequence of chemotherapy
toxicity
|
strong
|
inter-mediate
|
|
If there is response or stable disease after 6 months of induction chemotherapy, CRTor
SBRT may be offered as an alternative to continuing chemotherapy alone for any patient
with LAPC
|
strong
|
inter-mediate
|
|
Clinicians may offer SBRT for treatment of patients with LAPC, although the evidence
quality is intermediate so additional prospective and/or randomized trials are required
to definitively compare results of SBRT with chemotherapy alone and SBRT
SBRT = stereotactic body radiation therapy
|
Moderate
|
inter-mediate
|
45. Parekh A, Rosati LM, Chang DT, et al: Stereotactic body radiation for pancreatic
cancer: results of an international survey of practice patterns. International Journal
of Radiation Oncology Biology Physics 93:E132, 2015
46. Koong AC, Le QT, Ho A, et al: Phase I study of stereotactic radiosurgery in patients
with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 58:1017–1021,
2004
47. Schellenberg D, Goodman KA, Lee F, et al: Gemcitabine chemotherapy and single-fraction
stereotactic body radiotherapy for locally advanced pancreatic cancer. Int J Radiat
Oncol Biol Phys 72: 678–686, 2008
48. Schellenberg D, Kim J, Christman-Skieller C, et al: Single-fraction stereotactic
body radiation therapy and sequential gemcitabine for the treatment of locally advanced
pancreatic cancer. Int J Radiat Oncol Biol Phys 81:181–188, 2011
49. Herman JM, Chang DT, Goodman KA, et al: Phase 2 multi-institutional trial evaluating
gemcitabine and stereotactic body radiotherapy for patients with locally advanced
unresectable pancreatic adenocarcinoma. Cancer 121:1128–1137, 2015
50. Mahadevan A, Jain S, Goldstein M, et al: Stereotactic body radiotherapy and gemcitabine
for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 78:735–742, 2010
51. Mahadevan A, Miksad R, Goldstein M, et al: Induction gemcitabine and stereotactic
body radiotherapy for locally advanced nonmetastatic pancreas cancer. Int J Radiat
Oncol Biol Phys 81: e615–e622, 2011
52. Hoyer M, Roed H, Sengelov L, et al: Phase-II study on stereotactic radiotherapy
of locally advanced pancreatic carcinoma. Radiother Oncol 76:48–53,2005
|
|
A short course of palliative radiotherapy (conventional RTor SBRT) may be offered
to patients with LAPC who meet the following criteria:
-
prominent local symptoms, such as abdominal pain and/or worsening jaundice and/or
GI bleeding;
-
local infiltration into the GI tract causing impending gastric outlet or duodenal
obstruction; and
-
patient preference
|
moderate
|
inter-mediate
|
53. Morganti AG, Trodella L, Valentini V, et al: Pain relief with short-term irradiation
in locally advanced carcinoma of the pancreas. J Palliat Care 19:258–262, 2003
|
|
NICE 2018 [8]
|
When using chemoradiotherapy, consider capecitabine as the radiosensitiser.
|
weak
|
high to very low
|
Khan K, Cunningham D, Peckitt C et al. (2016) miR-21 expression and clinical outcome
in locally advanced pancreatic cancer: exploratory analysis of the pancreatic cancer
Erbitux, radiotherapy and UFT (PERU) trial. Oncotarget 7(11): 12 672–12 681
Mukherjee S, Hurt CN, Bridgewater J et al. (2013) Gemcitabine-or capecitabine-chemoradiotherapy
for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase
2 trial. Lancet Oncology 14(4): 317–326
|
