NCCN Flash Updates: NCCN Guidelines®, NCCN Compendium®, and NCCN Templates Updated
NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™), and the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for Esophageal and Esophagogastric Junction Cancers. These NCCN Guidelines® are currently available as Version 1.2021.
NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers
- Squamous Cell Carcinoma and Adenocarcinoma
- Workup: New bullet added, If sufficient tissue is available after the above testing has been completed, next-generation sequencing (NGS) may be considered. (ESOPH-1)
- Clinical Stages revised (ESOPH-1)
- Top pathway: Stage I–III, Stage I–IVA (locoregional disease, except T4b or unresectable N3) (Also for ESOPH- 2 and ESOPH-11)
- Stage IV IVA (includes T4b or unresectable N3 only) and IVB (metastatic disease) (Also for ESOPH-10 and ESOPH-19)
- Unresectable locally advanced, Locally recurrent, or Metastatic disease (ESOPH-10 and ESOPH-19)
- Third column: New bullet added, If sufficient tissue is available after the above testing has been completed, NGS may be considered.
- Adenocarcinoma
- Primary Treatment Options for Medically Fit Patients (ESOPH-13)
- Footnote "qq" is new: Repeat multidisciplinary consultation is recommended before proceeding to surgery for post-neoadjuvant T4a and bulky multiple nodal station N3.
- Surgical Outcomes/Clinical Pathologic Findings for Adenocarcinomas (Patients Have Not Received Preoperative Chemoradiation or Chemotherapy):
- R0 resection pathway: Revised, Node positive (pTis, pT1, pT2, pT3, pT4a) (Any T).
- Squamous Cell Carcinoma and Adenocarcinoma
- Principles of Pathologic Review and Biomarker Testing (ESOPH-B)
- Assessment of Overexpression or Amplification of HER2 in Esophageal and Esophagogastric Junction Cancers
- Revised: "...Next-generation sequencing (NGS) offers the opportunity to assess numerous mutations simultaneously, along with other molecular events such as amplification, deletions, tumor mutation burden, and microsatellite instability status. When limited diagnostic tissue is available for testing and the patient is unable to undergo additional procedures, NGS can be considered instead of sequential testing for single biomarkers when limited diagnostic tissue is available or when the patient is unable to undergo a traditional biopsy. It should be noted that NGS has several inherent limitations and thus whenever possible, the use of gold-standard assays (IHC/ISH) should be performed first and if sufficient tissue is available, additional NGS testing may be considered."
- Microsatellite Instability (MSI) or Mismatch Repair (MMR) Testing: Bullet revised, “…Patients with MSI-H or dMMR tumors may be referred to a genetics counselor for further assessment in the appropriate clinical context.”
- PD-L1 Testing: First bullet revised, "...An FDA-approved companion diagnostic test for use on FFPE tissue is available as an aid should be used in identifying patients for treatment with PD-1 inhibitors.
- Next-Generation Sequencing (NGS): Revised, "...Pembrolizumab is based on testing for MSI by PCR/ MMR by IHC, or PD-L1 expression by CPS or high tumor mutation burden (TMB) by NGS. The FDA granted approval for the use of select TRK inhibitors for NTRK gene fusion-positive solid tumors. When limited tissue is available for testing, or the patient is unable to undergo a traditional biopsy, sequential testing of single biomarkers or use of limited molecular diagnostic panels may quickly exhaust the sample. In these scenarios, comprehensive genomic profiling via a validated NGS assay performed in a CLIA-approved laboratory may be used for the identification of HER2 amplification, MSI, MMR mutations, TMB, and NTRK gene fusions. It should be noted that NGS has several inherent limitations and thus whenever possible, the use of gold-standard assays (IHC/FISH/targeted PCR) should be performed first and if sufficient tissue is available, additional NGS testing may be considered.
- Liquid Biopsy: Revised, "...Therefore, for patients who have metastatic or advanced esophageal/esophagogastric cancers and are unable to undergo a traditional biopsy..."
- Principles of Systemic Therapy (ESOPH-F)
- Systemic Therapy for Unresectable Locally Advanced, Recurrent or Metastatic Disease
- Second-Line or Subsequent Therapy
- Preferred regimens: The regimens in this section were reordered.
- Other recommended regimens
- Irinotecan and ramucirumab for adenocarcinoma was added.
- Fluorouracil and irinotecan + ramucirumab for adenocarcinoma moved from "Useful in Certain Circumstances" and changed from a category 2B to a category 2A recommendation.
- Useful in Certain Circumstances
- Entrectinib or larotrectinib for NTRK gene fusion-positive tumors was added. Previously it was listed under "Other recommended regimens"
- Pembrolizumab for MSI-H or dMMR tumors was added. Previously this indication was listed as a preferred
- Pembrolizumab for TMB high (≥10 mutations/megabase) tumors was added. This is a new indication.
- Principles of Systemic Therapy-Regimens and Dosing Schedules
- The dosing schedules were updated to reflect the changes in the algorithm.
- Principles of Surveillance (ESOPH-I)
- Table 1: pT1b (N0 on EUS); ER/ablation: Recommendation changed, "Once eradication of all neoplasia/high-risk preneoplasia cancer/high-grade dysplasia has been achieved..."
- Stage II or III (T2–T4,N0–N+,T4b) treated with trimodality therapy: Revised, "... therefore, EGD surveillance is not recommended as clinically indicated after trimodality therapy. Most luminal recurrences are detected by other imaging modalities. The risk..."
NCCN has published updates to the NCCN Guidelines, the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™), and the NCCN Compendium® for Gastric Cancers. These NCCN Guidelines are currently available as Version 1.2021.
NCCN Guidelines for Gastric Cancers
- Workup (GAST-1)
- 9th bullet revised: Universal testing for MSI by PCR/MMR by IHC testing if metastatic disease is documented/suspected is recommended in all newly diagnosed patients.
- New bullet added: If sufficient tissue is available after the above testing has been completed, next-generation sequencing (NGS) may be considered.
- Unresectable locally advanced, Locally recurrent or metastatic disease; Third column; Recommendation added, If sufficient tissue is available after the above testing has been completed, NGS may be considered
- Principles of Pathologic Review and Biomarker Testing (GAST-B)
- Pathologic Review (Table 1); Analysis/Interpretation/Reporting; New bullets added: Analysis/Interpretation/Reporting; New bullets added:
- Biopsy: Universal testing for MSI by PCR/MMR by IHC is recommended in all newly diagnosed patients.
- Endoscopic mucosal resection: Universal testing for MSI by PCR/MMR by IHC is recommended in all newly diagnosed patients.
- Gastrectomy, without prior chemoradiation: Universal testing for MSI by PCR/MMR by IHC is recommended in all newly diagnosed patients, if not previously performed.
- Assessment of Overexpression or Amplification of HER2 in Gastric Cancer
- Revised: "... NGS offers the opportunity to assess numerous mutations simultaneously, along with other molecular events such as amplification, deletions, tumor mutation burden, and microsatellite instability status. When limited diagnostic tissue is available for testing and the patient is unable to undergo additional procedures, NGS can be considered instead of sequential testing for single biomarkers when limited diagnostic tissue is available or when the patient is unable to undergo a traditional biopsy. It should be noted that NGS has several inherent limitations and thus whenever possible, the use of gold-standard assays (IHC/ISH) should be performed first and if sufficient tissue is available, additional NGS testing may be considered."
- Microsatellite Instability (MSI) or Mismatch Repair (MMR):
- Revised, Universal testing for MSI by polymerase chain reaction (PCR) or MMR by IHC should be considered on locally advanced, recurrent, or metastatic gastric cancer in patients who are candidates for treatment with PD-1 inhibitors. performed for all newly diagnosed gastric cancers. The testing...Patients with MSI-H or dMMR tumors should may be referred to a genetics counselor for further assessment in the appropriate clinical context. PD-L1 Testing: Revised, "...An FDA-approved companion diagnostic test for use should be used on FFPE tissue is available as an aid in identifying patients for treatment with PD-1 inhibitors."
- Next-Generation Sequencing (NGS):
- Revised, "Pembrolizumab is based on testing for MSI by PCR/MMR by IHC, or PD-L1 expression by CPS, or high tumor mutation burden (TMB) by NGS. The FDA granted approval for the use of select TRK inhibitors for NTRK gene fusion-positive solid tumors. When limited tissue is available for testing, or the patient is unable to undergo a traditional biopsy, sequential testing of single biomarkers or use of limited molecular diagnostic panels may quickly exhaust the sample. In these scenarios, comprehensive genomic profiling via a validated NGS assay performed in a CLIA-approved laboratory may be used for the identification of HER2 amplification, MSI, MMR mutations, TMB, and NTRK gene fusions. It should be noted that NGS has several inherent limitations and thus whenever possible, the use of gold-standard assays (IHC/FISH/targeted PCR) should be performed first and if sufficient tissue is available, additional NGS testing may be considered."
- Liquid Biopsy:
- Revised, "...Therefore, for patients who have metastatic or advanced gastric cancer and are unable to undergo a traditional biopsy..."
- Principles of Surgery
- Resectable Tumors
- 1st bullet revised: "...EMR or ESD if they meet appropriate criteria (in experienced centers)."
- 2nd bullet revised: "... to achieve negative microscopic margins along with lymphadenectomy."
- 3rd bullet revised: T4 T4b tumors require en bloc resection of involved structures.
- 6th bullet revised: "Consider placing feeding tube in select patients undergoing total gastrectomy (especially..."
- New bullets were added regarding Minimally invasive surgical approaches (MIS) and Hyperthermic intraperitoneal chemotherapy (HIPEC) or laparoscopic HIPEC.
- Principles of Genetic Assessment for Gastric Cancer (GAST-C)
- Hereditary Cancer Predisposition Syndromes Associated with an Increased Risk for Gastric Cancers
- Hereditary Diffuse Gastric Cancer; Arrow sub-bullet: The criteria for genetic testing for CDH1 mutations was updated and significantly revised.
- Screening Recommendations table; Hereditary diffuse gastric cancer: New bullet added, For those patients without a strong family history of DGC, genetics counseling with multidisciplinary review is indicated.
- Principles of Systemic Therapy (GAST-F)
- Preferred Regimens: All regimens were removed and currently no regimens are listed as preferred.
- Other Recommended Regimens:
- Fluorouracil and oxaliplatin was added and changed from category 1 to a category 2B recommendation. Previously it was listed as preferred.
- Fluorouracil and cisplatin was added and changed from category 1 to a category 2B recommendation. Previously it was listed as preferred.
- Fluoropyrimidine (fluorouracil or capecitabine) was added as a category 2B recommendation.
- Fluoropyrimidine (fluorouracil or capecitabine) and paclitaxel was removed as an option.
- Second-Line or Subsequent Therapy
- Preferred regimens:
- The regimens for this section were reordered.
- Revised: "Pembrolizumab for third-line or subsequent therapy for gastric adenocarcinoma cancer with..."
- Other recommended regimens
- Irinotecan and ramucirumab was added.
- Fluorouracil and irinotecan + ramucirumab moved from "Useful in Certain Circumstances" and changed from a category 2B to a category 2A recommendation.
- Useful in Certain Circumstances
- Entrectinib or larotrectinib for NTRK gene fusion-positive tumors was added. Previously it was listed under "Other recommended regimens".
- Pembrolizumab for MSI-H or dMMR tumors was added. Previously this indication was listed as a preferred regimen.
- Pembrolizumab for TMB high (≥10 mutations/megabase) tumors was added. This is a new indication.
- New footnote m added: Based on consensus opinion, the panel revised the doses and schedule studied in level C of the GO2 trial.
- Principles of Systemic Therapy-Regimens and Dosing Schedules
- The dosing schedules were updated to reflect the changes in the algorithm.
- Principles of Survivorship (GAST-I)
- Management of Long-Term Sequelae of Disease or Treatment
- Under Chemotherapy-induced neuropathy, new diamond sub-bullet added: Consider referral to occupational, rehabilitation, and/or physical therapy for patients with chemotherapy-induced neuropathy at risk for falls.
NCCN has published updates to the NCCN Chemotherapy Order Templates (NCCN Templates®) for Non-Small Cell Lung Cancer to reflect the currently published NCCN Guidelines for Non-Small Cell Lung Cancer v2.2021.
- Changes to the Indication section have been made on the following NCCN Templates®:
- NSC76: Pembrolizumab + PEMEtrexed/CARBOplatin
- NSC84: Pembrolizumab + PEMEtrexed/CISplatin
- NSC85a: Atezolizumab and Bevacizumab + PACLitaxel/CARBOplatin followed by Atezolizumab and Bevacizumab Maintenance - Atezolizumab and Bevacizumab + PACLitaxel/CARBOplatin Course
- NSC86: Pembrolizumab + PACLitaxel/CARBOplatin followed by Pembrolizumab Maintenance
- NSC88: Pembrolizumab + Albumin-bound PACLitaxel/CARBOplatin followed by Pembrolizumab Maintenance
- NSC97: Nivolumab + Ipilimumab
- NSC98: Atezolizumab + Albumin-bound PACLitaxel/CARBOplatin followed by Atezolizumab Maintenance
- NSC104: Nivolumab + Ipilimumab + PEMEtrexed/CARBOplatin
- NSC105: Nivolumab + Ipilimumab + PEMEtrexed/CISplatin
- NSC106: Nivolumab + Ipilimumab + PACLitaxel/CARBOplatin
NCCN has updated the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™) to reflect recommendations within the following NCCN Guidelines:
- Systemic Mastocytosis version 1.2020
For the complete updated versions of the NCCN Guidelines, NCCN Guidelines with NCCN Evidence Blocks™, the NCCN Drugs & Biologics Compendium (NCCN Compendium®), the NCCN Biomarkers Compendium®, the NCCN Chemotherapy Order Templates (NCCN Templates®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™), please visit NCCN.org.
To view the NCCN Guidelines for Patients®, please visit NCCN.org/patientguidelines.
Free NCCN Guidelines apps for iPhone, iPad, and Android devices are now available! Visit NCCN.org/apps.
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