2. Introduction – Pancreatic Cancer

Version 3.0 · March 2024 · AWMF 032/010OL
Leitlinienprogramm Onkologie · Deutsche Krebsgesellschaft · Deutsche Krebshilfe · AWMF

2.1 Scope and Purpose

2.1.1 Objective and Key Questions

The objective of the update for the Guideline “Exocrine Pancreatic Cancer” is to ensure evidence-based, comprehensive, optimal care for patients with exocrine pancreatic cancer. The update is ultimately intended to help prolong the survival of patients with resectable, borderline resectable, and non-resectable/metastatic pancreatic cancer, along with a good quality of life.

The key questions of the 2012/2013, 2020/2021 and 2021-2024 updates are listed in the table below. These were prioritized by the Guideline Groups at the beginning of each update.

Key questions of the 2012/2013 and 2020/2021 updates

Key Questions
Risk Factors/Screening/Risk Groups
Which screening examinations/programs should be offered to individuals with an increased risk of (a) sporadic and (b) familial/hereditary pancreatic cancer?	2021/2022
Which endogenous and exogenous risk conditions are associated with an increased risk of sporadic pancreatic cancer in the normal population? The content was restricted to the following topics: • Diseases • Lifestyle (smoking, alcohol, physical activity) • Nutrition	2021/2022
Which laboratory tests are appropriate for prevention/early diagnosis of pancreatic cancer in an asymptomatic normal population?	2020/2021
Which genetic tests allow detection of individuals at increased risk of hereditary pancreatic cancer?	2020/2021
Should these genetic tests be carried out in individuals with a positive family history of pancreatic cancer?	2020/2021
In the asymptomatic population, what imaging techniques allow prevention or early diagnosis of pancreatic cancer?	2020/2021
Diagnostics
Does PET-CT have advantages for assessing the preoperative spread of pancreatic cancer?	2020/2021
Should preoperative MRI of the liver with contrast be routinely performed in resectable pancreatic cancer to rule out hepatic metastasis?	2020/2021
Benefit of preoperative staging laparoscopy?	2012/2013
What diagnostic procedures should be carried out for further clarification of e.g. sonographically detected cystic lesions?	2020/2021
Surgical Therapy (Curative Intention)
What are the indications for a diagnostic laparoscopy? • High tumor marker value (CA 19-9 > 500 U/ml) for metastases that cannot be detected by imaging (peritoneum, liver) • For precise staging prior to neoadjuvant/palliative therapy • To confirm the diagnosis in the event of previous unsuccessful tumor confirmation by interventional biopsy (endosonography, sono-guided and CT-guided biopsy)	2021/2022
Expansion of the lymph node dissection during pylorus-preserving or classic duodeno-hemipancreatectomy (Whipple procedure).	2021/2022
Is there evidence for a benefit of minimum case numbers in surgery for pancreatic cancer?	2020/2021
Benefit of bile diversion by ERCP and stent in preoperative cholestasis?	2012/2013
What are criteria of tumor irresectability? Definition of borderline resectability?	2012/2013
What are criteria of resectability from patient's side? • Patient's age • ECOG Performance Status • Comorbidity (cardiopulmonary, liver cirrhosis + port. hypertension, renal function) • Other factors?	2020/2021
What are biological criteria of resectability from patient's side? • Regional lymph node metastases (biopsy/CT/PET-CT) • Tumor marker CA19-9	2020/2021
What are criteria of resectability or borderline resectability or locally advanced stage from the tumor side? • Extrapancreatic tumor manifestation • Infiltration of the celiac trunk • Infiltration of the superior mesenteric artery • Infiltration of portal vein • Infiltration of superior mesenteric vein	2020/2021
Should the primary tumor be resected despite evidence of distant metastases (organ metastases, peritoneal carcinomatosis, lymph node metastases considered distant metastases)?	2020/2021
Should resection of metastases from pancreatic cancer be performed? If yes – under what conditions?	2020/2021
What is the minimum resection margin from the macroscopic tumor margin that can be recommended?	2012/2013
Benefit of pylorus-preserving surgery for carcinoma of the pancreatic head?	2012/2013
Which procedure can be recommended in case of tumor adherence with surrounding organs?	2012/2013
Benefit of lymphadenectomy in resection of pancreatic cancer?	2012/2013
Is there an indication for ink marking of the resection margins or how should the resection specimen be processed?	2012/2013
Should resectable distant metastases that can be detected intraoperatively first be resected?	2012/2013
Should only intraoperatively detectable, resectable distant metastases be resected?	2020/2021
Benefit of laparoscopic surgical technique in the setting of pancreatic cancer surgery?	2012/2013
Is there an indication for laparoscopic/robotic surgical technique in the setting of pancreatic cancer surgery?	2020/2021
Benefit of intraoperative frozen section preparation in the setting of pancreatic cancer surgery?	2012/2013
Criteria of classification as R0 resection?	2012/2013
Necessary information provided by the pathologist?	2012/2013
Adjuvant and Neoadjuvant Non-surgical Therapy
Benefit of adjuvant chemotherapy after R0 resection, restrictions regarding age, comorbidity, ECOG status, and guidelines regarding duration, if applicable?	2012/2013
Benefit of additive chemotherapy after R1 resection?	2012/2013
Should adjuvant chemotherapy be given for curatively resected pancreatic cancer?	2020/2021
Which patients benefit from adjuvant chemotherapy after resection (R0, R1, R2(?), T in situ, T1 N0 (?)?	2020/2021
Is there evidence for different therapies (gem mono, 5FU, gem & capecitabine, gem & nab-paclitaxel, mFolfirinox)?	2020/2021
What should be the duration of therapy (6 months or complete regimen)?	2020/2021
Benefit of adjuvant radiochemotherapy or radiotherapy after R0 resection? Benefit of additive radiochemotherapy after R1 resection?	2012/2013
Benefit of radiochemotherapy after adjuvant chemotherapy?	2012/2013
Benefit of adjuvant chemotherapy, radiochemotherapy, or radiotherapy after resection of distant metastases?	2012/2013
Within what time frames should adjuvant therapy be given?	2012/2013
When should therapy be started (< 6-8 weeks postoperatively, < 12 weeks postoperatively)?	2020/2021
Benefit of neoadjuvant radiochemotherapy or neoadjuvant chemotherapy for pancreatic cancer?	2012/2013
Benefit of chemotherapy, radiotherapy, radiochemotherapy, or combination therapy in locally advanced, unresectable pancreatic cancer to downsize the tumor with the goal of achieving secondary resectability (intention: potentially curative)?	2012/2013
Are there indications for neoadjuvant radiotherapy, radiation chemotherapy, or chemotherapy in pancreatic cancer?	2020/2021
When should neoadjuvant treatment be given? • resectable • borderline resectable (IAP definition, anatomic arterial vs. venous BR, biologic/conditional BR) • locally advanced	2020/2021
Should neoadjuvant systemic therapy be given alone or combined with local therapy (radiation)?	2020/2021
What is the evidence for the following systemic therapies: • Gemcitabine • Folfirinox • Gem & nab-paclitaxel	2020/2021
Should patients undergo surgical exploration after neoadjuvant therapy and at least stable disease on imaging?	2020/2021
What is the quality of imaging after neoadjuvant therapy?	2020/2021
Benefit of intraoperative radiotherapy in pancreatic cancer?	2012/2013
Benefit of new therapeutic modalities such as SIRT, hyperthermia, or proton therapy in adjuvant, neoadjuvant, or palliative therapy for pancreatic cancer?	2012/2013
Palliative Therapy
Benefit of palliative chemotherapy in locally advanced irresectable or metastatic pancreatic cancer (first-, second-, third-line), appropriate approach if any?	2012/2013
Which systemic palliative treatment is standard in first-line therapy? • Gemcitabine (conventional (1000 mg/m² over 30 min) or fixed dose rate infusion) • Gemcitabine plus nab-paclitaxel • FOLFIRINOX • NALIRIFOX • Other therapies	2020/2021/2023/2024
Are there criteria that suggest selection of a particular (systemic palliative) therapy?	2020/2021
Are there patients who particularly benefit from first-line combination chemotherapy?	2020/2021
Should further systemic palliative treatment be given after failure of first-line therapy? • OFF • mFOLFOX • mFOLFIRINOX • 5-FU/nal-Iri • Other therapies	2020/2021
Is there evidence suggesting a particular sequence in second-line therapy? a) Second-line therapy after gem b) Second-line therapy after gem/nab-paclitaxel c) Second-line therapy after FOLFIRINOX	2020/2021
Which progression parameters are useful for evaluating the clinical effectiveness of chemotherapy?	2020/2021
Usefulness of molecular markers for therapy management?	2012/2013
Usefulness of radiotherapy or chemotherapy for inoperable/resectable pancreatic cancer (locally advanced, non-metastatic)?	2012/2013
Are there indications for palliative radiotherapy in pancreatic cancer?	2020/2021
If there are indications for palliative radiotherapy in pancreatic cancer, according to which regimen(s) should they be applied?	2020/2021
If palliative radiotherapy is given, should it be combined with chemotherapy?	2012/2013
If radiotherapy is given in palliative care, should it be combined with chemotherapy?	2020/2021
Usefulness of a combination strategy (e.g., chemotherapy followed by radiation chemotherapy) for locally advanced, inoperable, or nonresectable tumor (intention: palliative)?	2012/2013
Benefit of primary simultaneous radiochemotherapy with no chance of secondary resectability?	2012/2013
Do targeted therapy approaches have a place in palliative therapy of pancreatic cancer?	2020/2021/2023/2024
Do immunotherapeutics such as checkpoint inhibitors have a place in palliative therapy of pancreatic cancer?	2020/2021
In which patient group and in which therapeutic situation is there an indication for therapy with immunotherapeutics?	2020/2021
Should MSI status in patients with advanced pancreatic cancer be investigated on a regular basis?	2020/2021
Which method should be used to determine MSI status?	2020/2021
Which therapeutics should be used in the presence of high microsatellite instability (MSI) in the tumor?	2020/2021
Do agents that interfere with DNA repair mechanisms - such as PARP inhibitors - have value in palliative therapy of pancreatic cancer?	2020/2021
In which patient group and in which therapeutic situation is there an indication for the use of substances that interfere with DNA repair mechanisms?	2020/2021
Should BRCA1/2 mutation status be regularly investigated in patients with advanced pancreatic cancer?	2020/2021
Which method should be used to determine BRCA1/2 mutation status?	2020/2021
Which therapeutic agents should be used in the presence of a BRCA1/2 mutation?	2020/2021

There were no specific key questions for Chapter 9 „Palliative Care, Supportive Therapy and Follow-up Care“. The focus was on anticoagulation, rehabilitation aftercare, and nutrition.

2.1.2 Target Audience

The target group of users are physicians from all areas of care (specialists in particular) who treat patients with chronic pancreatic diseases, suspected pancreatic carcinoma, and diagnosed pancreatic carcinoma as outpatients and/or inpatients. This includes physicians from the fields of internal medicine with gastroenterology and oncology, as well as radiology, general and visceral surgery, palliative medicine, pathology, nuclear medicine, and radiotherapy. It serves as information for general practitioners and oncology nurses.

This Guideline applies to patients with exocrine pancreatic carcinoma regardless of age, gender, disease severity or comorbidity. It also applies to people at increased risk of developing pancreatic cancer, as far as this can be detected with currently available methods.
This Guideline applies to the outpatient and inpatient care sector, including follow-up and rehabilitation.

In accordance with the definition of guidelines, they are intended to support the joint decision-making of physician and patient in diagnostic and therapeutic measures. However, this Guideline does not release the physician from their obligation to assess the appropriate course of action on an individual basis, taking into account the patient's overall situation. Any deviation from this Guideline should be justifyable in the specific case.

The task is to continuously ensure the quality of treatment in curative and palliative care. By outlining which developments are necessary and which new, even cost-intensive substances should be used in the adjuvant and palliative situation, these Guidelines are also directed at those indirectly affected, such as payers and the medical service of the health insurance funds.

Dissemination and implementation of the guideline

This Guideline are published online on the websites of the German Guideline Program in Oncology (www.leitlinienprogramm-onkologie.de), the AWMF (www.awmf.org), the DGVS (www.dgvs.de), the German Cancer Aid (http://www.krebshilfe.de/) and the German Cancer Society (www.krebsgesellschaft.de/). A long version, a short version, and a guideline report are available there.

2.1.3 Validity and Update Process

S3 Guidelines are intended receive continuous updates. The Guidelines are valid for a maximum duration of 3 years (March 2027).

In the third update 2021-2024, the following topics were addressed:

Risk factors/Risk groups/Screening (Chapter 4)
Surgical therapy (Chapter 6)
Palliative therapy for pancreatic carcinoma (Chapter 8)
Palliative care, supportive treatment, and follow-up care (Chapter 9)

The remaining topics will be revised in future updates. An annual update of the Guidelines is intended.
Comments and suggestions for the update process from practice are explicitly welcome and can be addressed to the DGVS Guidelines secretariat:
German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS), Olivaer Platz 7, 10707 Berlin, Germany.

E-mail: pankreaskarzinom@leitlinienprogramm-onkologie.de

Up-to-dateness of the recommendations

The first version of the interdisciplinary S3 Guidelines on exocrine pancreatic cancer was prepared in 2006. The first update was carried out in 2012/2013, followed by the second update in 2021, and the third update from 2021 to 2024.

Individual recommendations from the updated topic areas were adopted from the previous version. The guideline report contains an overview of the changes to the guideline recommendations as part of the second update 2020/2021 and the third update 2021-2024.
In the headers of the recommendations and statements, it was noted when they were created or updated and whether they were modified or newly created compared with the previous version.

2.2 Methodology

2.2.1 Levels of Evidence (LoE) According

Scheme of evidence grading according to Oxford

In the 2020/2021 update, the 2011 Oxford Centre for Evidence Based Medicine Levels of Evidence were used to classify the included studies (see Table 5). Studies with relevant methodologic deficiencies were not downgraded, analogous to the procedure used in the first update, but were marked with a minus sign. The evidence levels were retained for recommendations not reviewed in this update. The system used in each case was marked, e.g. 2011.

To classify the risk of bias of identified studies, the 2009 Oxford Centre for Evidence-based Medicine system listed in the following table was used for Chapters 6, 7, and 8, updated in 2012/1013. The classification of studies in the Oxford Centre for Evidence-based Medicine system provides for a downgrading of the level of evidence if the study has methodological deficiencies (e.g., drop out >20%, wide confidence intervals, inadequate randomization procedures). In the assessments in these Guidelines, studies were not downgraded in rank if they had relevant methodological flaws, but were marked with a minus sign (e.g., 1a-).

In preparing the remaining chapters in 2006, an older, modified version of the Oxford system was used (see Table 7)

Table 5: Evidence grading scheme for the 2020/2021 update (Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence).

Question	Step 1 *(Level 1)**	Step 2 *(Level 2)**	Step 3 *(Level 3)**	Step 4 *(Level 4)**	Step 5 (Level 5)
How common is the problem?	Local and current random sample surveys (or censuses)	Systematic review of surveys that allow matching to local circumstances**	Local non-random sample**	Case-series**	n/a
Is the diagnostic or monitoring test accurate? (Diagnosis)	Systematic review of cross-sectional studies with consistently applied reference standard and blinding	Individual cross-sectional studies with consistently applied reference standard and blinding	Non-consecutive studies, or studies without consistently applied reference standards**	Case-control studies or poor or non-independent reference standard**	Mechanism-based reasoning
What will happen if we do not add a therapy? (Prognosis)	Systematic review of inception cohort studies	Inception cohort studies	Cohort study or control arm of randomized trial*	Case-series or case-control studies, or poor quality prognostic cohort study**	n/a
Does the intervention help? (Treatment Benefits)	Systematic review of randomized trials or n-of-1 trials	Randomized trial or observational study with dramatic effect	Non-randomized controlled cohort/follow-up study**	Case-series, case-control studies, or historically controlled studies**	Mechanism-based reasoning
What are the COMMON harms? (Treatment Harms)	Systematic review of randomized trials, systematic review of nested case-control studies, n-of-1 trial with the patient you are raising the question about, or observational study with dramatic effect	Individual randomized trial or (exceptionally) observational study with dramatic effect	Non-randomized controlled cohort/follow-up study (post-marketing surveillance) provided there are sufficient numbers to rule out a common harm. (For long term harms the duration of follow-up must be sufficient.)**	Case-series, case-control studies, or historically controlled studies**	Mechanism-based reasoning
What are the RARE harms? (Treatment Harms)	Systematic review of randomized trials or n-of-1 trial	Randomized trial or (exceptionally) observational study with dramatic effect	Non-randomized controlled cohort/follow-up study (post-marketing surveillance) provided there are sufficient numbers to rule out a common harm. (For long term harms the duration of follow-up must be sufficient.)**	Case-series, case-control studies, or historically controlled studies**	Mechanism-based reasoning
Is this (early detection) test worthwhile? (Screening)	Systematic review of randomized trials	Randomized trial	Non-randomized controlled cohort/follow-up study**	Case-series, case-control studies, or historically controlled studies**	Mechanism-based reasoning
* Level may be graded down on the basis of study quality, imprecision, indirectness (study PICO does not match questions PICO), because of inconsistency between studies, or because the absolute effect size is very small; Level may be graded up if there is a large or very large effect size. ** As always, a systematic review is generally better than an individual study.

Table 6: Scheme of evidence grading in the 2012/2013 update (Oxford scheme)

Level	Therapy / Prevention, Etiology / Harm	Prognosis	Diagnosis	Differential diagnosis / symptom prevalence study	Economic and decision analyses
1a	SR (with homogeneity) of RCTs	SR (with homogeneity) of inception cohort studies; CDR validated in different populations	SR (with homogeneity) of level 1 diagnostic studies; CDR with 1b studies from different clinical centers	SR (with homogeneity) of prospective cohort studies	SR (with homogeneity) of Level 1 economic studies
1b	Individual RCT (with narrow Confidence Interval)	Individual inception cohort study with > 80% follow-up; CDR validated in a single population	Validating cohort study with good reference standards; or CDR tested within one clinical centre	Prospective cohort study with good follow-up	Analysis based on clinically sensitive costs or alternatives; systematic review(s) of the evidence; and including multi-way sensitivity analyses
1c	All or none	All or none case-series	Absolute SpPins and SnNouts	All or none case-series	Absolute better-value or worse-value analyses
2a	SR (with homogeneity) of cohort studies	SR (with homogeneity ) of either retrospective cohort studies or untreated control groups in RCTs	SR (with homogeneity ) of level >2 diagnostic studies	SR (with homogeneity ) of 2b and better studies	SR (with homogeneity) of Level >2 economic Studies
2b	Individual cohort study (including low quality RCT; e.g., <80% follow-up)	Retrospective cohort study or follow-up of untreated control patients in an RCT; derivation of CDR or validated on split-sample only	Exploratory cohort study with good reference standards; CDR after derivation, or validated only on split-sample or databases	Retrospective cohort study, or poor follow-up	Analysis based on clinically sensitive costs or alternatives; limited review(s) of the evidence, or single studies; and including multi-way sensitivity analyses
2c	"Outcomes" research; Ecological studies	"Outcomes" research		Ecological studies	Audit or outcomes Research
3a	SR (with homogeneity) of case control studies		SR (with homogeneity ) of 3b and better studies	SR (with homogeneity ) of 3b and better studies	SR (with homogeneity*) of 3b and better studies
3b	Individual case-control Study		Non-consecutive study; or without consistently applied reference standards	Non-consecutive cohort study, or very limited population	Analysis based on limited alternatives or costs, poor quality estimates of data, but including sensitivity analyses incorporating clinically sensitive variations.
4	Case-series (and poor quality cohort and case control studies)	Case-series (and poor quality prognostic cohort studies)	Case-control study, poor or non-independent reference standard	Case-series or superseded reference standards	Analysis with no sensitivity analysis
5	Expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles".	Expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles".	Expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles".	Expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles".	Expert opinion without explicit critical appraisal, or based on economic theory or "first principles".

Table 7: Scheme of evidence grading in the preparation of the Guideline in 2006

Level of Evidence (LoE)	Definition
1	Systematic review (SR) with homogeneity (no heterogeneity in the results of individual studies) of randomized controlled trials (RCT)
2a 2b	Systematic review with homogeneity of cohort studies Individual cohort studies plus RCTs of low quality (e.g., follow-up < 80%):
3	Systematic reviews with homogeneity of case-control studies plus Individual case-control studies.
4	Case series and cohort studies plus low-quality case-control studies (i.e., cohort: no clearly defined comparison group, no outcome/exposure measurement in experimental and control groups, insufficient follow-up; case-control s.: no clearly defined comparison group).
5	Expert opinion or inconsistent or inconclusive studies of any level of evidence.

2.2.2 Grades of Recommendation (GoR)

In these Guidelines, the level of evidence of the underlying studies (according to the Oxford scheme, see Chapter 2.2.1) and, in the case of recommendations, the strength of the recommendation (degree of recommendation) are shown for all Evidence-based statements (see Chapter 2.2.3) and recommendations.

With regard to the strength of the recommendation, the 2006 version used the four grades of recommendation proposed at that time by the Oxford Centre for Evidence-based Medicine (A-D, see Table 8). These reflect, in summary form, the underlying study types or grades of evidence.

Table 8: Recommendation grading scheme for the 2006 recommendations.

Recommendation grade	Meaning
A	Consistent Studies with evidence level 1 available
B	Consistent studies with evidence level 2 or 3 or extrapolations of studies with evidence level 1 available
C	Studies with evidence level 4 or extrapolations of studies with evidence level 2 or 3 available
D	Expert opinion or inconsistent or inconclusive studies of any level of evidence

In contrast, the three grades of recommendation commonly used in the GGPO program were distinguished for the updates (see Table 9), which are also reflected in the wording of the recommendations in each case. In addition to the design and quality of the underlying studies, the following aspects were taken into account in the grading of recommendations in all versions of the Guidelines:

Consistency of study results
Clinical relevance of the endpoints and effect sizes
Benefit-risk ratio (weighing of desirable and undesirable effects)
Ethical, legal, and economic considerations
Patient preferences
Applicability to the patient target group and the German healthcare system, feasibility in everyday life/different healthcare settings.

Therefore, in appropriately justified cases, the level of evidence may deviate from the level of recommendation (see in detail the AWMF rulebook [1]).

The GGPO methodology provides for the assignment of grades of recommendation by the Guideline authors within the framework of a formal consensus procedure. Accordingly, a multipart nominal group process moderated by the AWMF was conducted (see Guidelines Report). At the end of this group process, the recommendations were formally voted on by the voting mandate holders (see Chapter 1.9). The results of the respective votes are assigned to the recommendations according to the categories in Table 10.

Table 9: Recommendation scheme for the updated recommendations from 2013 and 2021.

Grade of recommendation	Description	Expression
A	Strong recommendation	shall
B	Recommendation	should
0	Open recommendation	can/may

Table 10: Consensus strength

Consensus Strength	Percentage consensus
Strong consensus	> 95% of those voting
Consensus	> 75 – 95% of those eligible to vote
Majority agreement	> 50 – 75% of those eligible to vote
Dissent	< 50% of those eligible to vote

2.2.3 Statements

Statements are presentations or explanations of specific facts or issues without an immediate call to action. They are adopted in accordance with the procedure for recommendations as part of a formal consensus process and can be based either on study results or on expert opinions.

2.2.4 Expert Consensus

In the 2021 Guideline update, Good Clinical Practice (GCP) was replaced by Expert Consensus (EC).

Statements/recommendations for which editing based on expert consensus of the Guideline Group was decided are identified as Expert Consensus.

No systematic literature search was carried out for these recommendations (the studies cited in the background texts, if any, were selected by the participating subject matter experts).

For recommendations based on expert consensus, no symbols or letters are used to represent the strength of recommendation and quality of evidence. The strength of the recommendation is determined here solely by the wording used (shall/should/may/can) according to the scheme in Table 9.

2.2.5 Independence and Disclosure of Possible Conflicts of Interest

The German Cancer Aid provided the financial resources for the update through the German Guideline Program in Oncology. These funds were used for personnel costs, office supplies, procurement of literature, preparation of evidence reports, and the consensus conference (technology, moderators, fees), whereby the authors of the guideline worked exclusively on a voluntary basis.

The 3rd update was carried out with editorial independence from the funding organization.

All authors of the 3rd update submitted at least one written declaration of any existing conflicts of interest during the guideline process. An overview of the disclosed conflicts of interest and further information on dealing with conflicts of interest can be found in the guideline report on the guideline.

We would therefore like to thank all those involved for their exclusively voluntary work, without which the S3 guideline would not have been possible.

References

[1] Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften - Ständige Kommission, Leitlinien, AWMF-Regelwerk "Leitlinien", 2. Auflage, 2020., http://www.awmf.org/leitlinien/awmf-regelwerk/awmf-regelwerk.html