eBulletin Newsletter

NCCN Flash Updates: NCCN Guidelines Updated for Pancreatic Adenocarcinoma

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), the NCCN Drugs & Biologics Compendium (NCCN Compendium®) and the NCCN Radiation Therapy Compendium™, for Pancreatic Adenocarcinoma. These NCCN Guidelines® are currently available as Version 1.2024.

Link directly to the Updates section of the NCCN Guidelines: Pancreatic Adenocarcinoma

Terminologies in all NCCN Guidelines are being actively modified to advance the goals of equity, inclusion, and representation. 

Global Changes

  • References updated throughout the Guidelines.

PANC-1

  • Clinical Presentation and Workup
    • No metastatic disease
      • 4th bullet modified: Consider PET/CT or PET/MRI in patients with high risk.

PANC-1A

  • Footnote b modified: Imaging with contrast as appropriate for disease management (unless contraindicated). (Also for PANC-3)
  • Footnote d modified: PET/CT scan may be considered after formal pancreatic CT protocol in patients with high risk to detect extra-pancreatic metastases. It is not a substitute for high-quality, contrast-enhanced CT. For neoadjuvant therapy, consider PET/CT scan before and after initiation to assess response to systemic therapy and for restaging. See Principles of Diagnosis, Imaging, and Staging (PANC-A).
  • Footnote f modified: Elevated CA 19-9 does not necessarily indicate cancer or advanced disease. CA 19-9 may be elevated as a result of biliary infection (cholangitis), inflammation, or obstruction, benign or malignant. In addition, CA 19-9 will be undetectable in Lewis antigen-negative individuals (carcinoembryonic antigen [CEA] and CA-125 in nonsecreting patients who are nonsecreting or those with normal CA 19-9 levels). (Discussion). (Also for PANC-2, PANC-4, PANC-8)
  • Footnote i modified: Tumor/somatic molecular profiling is recommended for patients with locally advanced/metastatic disease who are candidates for anti-cancer therapy to identify uncommon mutations. Consider specifically testing for potentially actionable somatic findings including, but not limited to: fusions (ALK, NRG1, NTRK, ROS1, FGFR2, and RET), mutations (BRAF, BRCA1/2, KRAS, and PALB2), amplifications (HER2), microsatellite instability (MSI), mismatch repair deficiency (dMMR), or tumor mutational burden (TMB) via an FDA-approved and/or validated next-generation sequencing (NGS)-based assay. RNA sequencing assays are preferred for detecting RNA fusions because gene fusions are better detected by RNA-based NGS. ... (Also for PANC-5, PANC-6A, PANC-9, PANC-10, PANC-11)

PANC-2

  • This page was extensively revised.

PANC-3

  • New algorithm extracted from PANC-2 and PANC-4

PANC-4

  • This page was extensively revised.

PANC-6A

  • Footnote w modified: Serial imaging as indicated to assess disease response. See Principles of Diagnosis, Imaging, and Staging (PANC-A). (Also for PANC-10, PANC-11)

PANC-8

  • Surveillance modified: Surveillance as appropriate every 3–6 mo for 2 years, then every 6–12 mo as clinically indicated:

PANC-9

  • This page was moved to this location from PANC-10.

PANC-A 1 OF 8

  • 2nd bullet modified: High-quality dedicated imaging of the pancreas should be performed at presentation (even if standard CT imaging is already available), preferably within 4 weeks of surgery, and following neoadjuvant treatment to provide adequate staging and assessment of resectability status. Imaging should be done prior to stenting, when possible. Imaging with contrast as appropriate for disease management (unless contraindicated).

PANC-A 2 OF 8

  • 1st bullet modified: PET/CT or PET/MRI scan may be considered after formal pancreatic CT protocol in patients with high risk to detect extra-pancreatic metastases. It is not a substitute for high-quality, contrast-enhanced CT.
  • 2nd bullet added: For neoadjuvant therapy, consider PET/CT scan before and after initiation to assess response to systemic therapy and for restaging.
  • Footnote b modified: Indicators of patients with high risk may include equivocal or indeterminate imaging findings, borderline resectable disease, markedly elevated CA 19-9, large primary tumors, or large regional lymph nodes.

PANC-A 3 OF 8

  • MDCT Pancreatic Adenocarcinoma Protocol
    • Parameters, 2nd row modified: Section Slice thickness.
    • Details, 3rd row modified: Same as section slice thickness (no gap)

PANC-F 1 OF 12

  • 3rd bullet added: Consider testing for potentially actionable somatic findings including, but not limited to: fusions (ALK, NRG1, NTRK, ROS1, FGFR2, and RET), mutations (BRAF, BRCA1/2, KRAS, and PALB2), amplifications (HER2), microsatellite instability (MSI), mismatch repair deficiency (dMMR), or tumor mutational burden (TMB) via an FDA-approved and/or validated NGS-based assay.

PANC-F 3 OF 12

  • Locally Advanced Disease (First-Line Therapy), Good PS 0–1
    • Preferred Regimens
      • Moved here from Other Recommended Regimens: Liposomal irinotecan + 5-FU + leucovorin + oxaliplatin (NALIRIFOX)
    • Useful in Certain Circumstances
      • Regimen added: Dabrafenib + trametinib (if BRAF V600E mutation positive)
      • Regimen added: Entrectinib (if NTRK gene fusion positive) (Also for PANC-F 5)
      • Regimen added: Larotrectinib (if NTRK gene fusion positive) (Also for PANC-F 5)
      • Regimen added: Pembrolizumab (if MSI-H, dMMR, or TMB-H [≥10 mut/Mb])
      • Regimen added: Selpercatinib (if RET gene fusion-positive) (Also for PANC-F 5)

PANC-F 4 OF 12

  • Locally Advanced Disease (First-Line Therapy)
    • Intermediate PS 2
      • Useful in Certain Circumstances
        • Regimen removed: NALIRIFOX (category 2B) (Also for PANC-F 6)
        • Regimen added: Dabrafenib + trametinib (if BRAF V600E mutation positive)
        • Regimen added: Entrectinib (if NTRK gene fusion positive)
        • Regimen added: Larotrectinib (if NTRK gene fusion positive)
        • Regimen added: Pembrolizumab (if MSI-H, dMMR, or TMB-H [≥10 mut/Mb])
        • Regimen added: Selpercatinib (if RET gene fusion-positive)
    • Poor PS modified: Poor PS 3–4 (Also for PANC-F 6, PANC-F 9)

PANC-F 5 OF 12

  • Metastatic Disease (First-Line Therapy), Good PS 0-1
    • Preferred Regimens
      • Moved here from Other Recommended Regimens: NALIRIFOX (category 1) (category of evidence changed from 2A to 1)
    • Useful in Certain Circumstances
      • Moved here from Other Recommended Regimens: Dabrafenib + trametinib (if BRAF V600E mutation positive)

PANC-F 6 OF 12

  • Metastatic Disease (First-Line Therapy), Intermediate PS 2
    • Preferred Regimens
      • Regimens added: If unable to tolerate FOLFIRINOX, consider: FOLFOX, FOLFIRI, CapeOx
    • Useful in Certain Circumstances
      • Regimen added: Entrectinib (if NTRK gene fusion positive)
      • Regimen added: Larotrectinib (if NTRK gene fusion positive)
      • Regimen added: Pembrolizumab (if MSI-H, dMMR, or TMB-H [≥10 mut/Mb])
      • Regimen added: Selpercatinib (if RET gene fusion-positive)
      • Regimen added: Dabrafenib + trametinib (if BRAF V600E mutation positive)
  • Footnote removed: While NCCN recognizes that there is high-level evidence supporting the use of NALIRIFOX over gemcitabine and albumin-bound paclitaxel, it should be recognized that this regimen does not appear to have an advantage over FOLFIRINOX and adds considerably more expense compared to FOLFIRINOX.

PANC-F 7 OF 12

  • Footnote added: For oncogenic or likely oncogenic mutations in BRCA1, BRCA2, and PALB2, refer to definitions at oncokb.org, cbioportal.org, mycancergenome.org, pmkb.weill.cornell.edu, genie.cbioportal.org, ckb.jax.org, cancer.sanger.ac.uk/cosmic, brcaexchange.org, ncbi.nlm.nih.gov/clinvar or sift.bii.a-star.edu.sg.

PANC-F 8 OF 12

  • Subsequent Therapy for Locally Advanced/Metastatic Disease and Therapy for Recurrent Disease, Good PS 0-1
    • Preferred Regimens
      • Subheading added: If no prior immunotherapy (Also for Other Recommended Regimens, PANC-F 8. Also mentioned on PANC-9 Useful/PS2 and Preferred PS 3)
    • Other Recommended Regimens
      • If prior gemcitabine-based therapy
        • Regimen added: Bolus 5-FU + leucovorin.

PANC-F 9 OF 12

  • Subsequent Therapy for Locally Advanced/Metastatic Disease and Therapy for Recurrent Disease, Intermediate PS 2
    • Useful in Certain Circumstances
      • Regimen added: Dabrafenib + trametinib (if BRAF V600E mutation positive)
      • Regimen added: Entrectinib (if NTRK gene fusion positive)
      • Regimen added: Larotrectinib (if NTRK gene fusion positive)
      • Regimen added: Pembrolizumab (if MSI-H, dMMR, or TMB-H [≥10 mut/Mb])

PANC-G 3 OF 6

  • Footnote a moved here from PANC-G 1: It is not known whether one regimen is necessarily more effective than another in the five clinical scenarios mentioned above. Therefore, the following recommendations are given as examples of commonly utilized regimens. However, other recommendations based on similar principles are acceptable. See Principles of Systemic Therapy (PANC-F) for details on chemotherapy regimens used for chemoradiation.

PANC-H 1 OF 2

  • Pain row
    • Therapy
      • 4th bullet added: Celiac plexus radiation/radiosurgery.
      • 5th bullet added: SBRT.
  • Anorexia row added.

PANC-H 2 OF 2

  • Footnote e added: Yaacov YR, et al. J Clin Oncol 2023;41(4_suppl):Abstract 662; Jacobson G, et al. BMJ Open 2022;12:e050169.
  • Footnote f added: Sandhya L, et al. J Clin Oncol 2023;41:2617-2627.

 

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