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NCCN Flash Updates: NCCN Guidelines and NCCN Templates Updated

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) and the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) for Gastric Cancer. These NCCN Guidelines^® are currently available as Version 5.2021.

Link directly to the Updates section of the NCCN Guidelines:
Gastric Cancer

• Principles of Systemic Therapy for Unresectable Locally Advanced, Recurrent or Metastatic Disease (GAST-F)
  • Second-Line or Subsequent Therapy; Useful in Certain Circumstances
    • Dostarlimab-gxly for MSI-H or dMMR tumors was added
  •  Footnote k is new: For patients that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.
• Principles of Systemic Therapy-Regimens and Dosing Schedules (GAST-F)
• The following dose schedule was added under Useful in Certain Circumstances: 
  • Dostarlimab-gxly (for MSI-H/dMMR tumors)
    Dostarlimab-gxly 500 mg IV every 3 weeks for 4 doses 
    followed by 1,000 mg IV every 6 weeks

Previous updates to the NCCN Guidelines for Gastric Cancer can be found in the UPDATES section of the current version.




NCCN has published updates to the NCCN Guidelines and the NCCN Compendium^® for Myelodysplastic Syndromes. These NCCN Guidelines are currently available as Version 1.2022

Add Link to the NCCN Guidelines: 
Myelodysplastic Syndrome

• Initial Evaluation (MDS-1)
  • Bullet 12 revised: ….particularly in patients younger than 40 patients years of age.
• Footnotes for Initial Evaluation of MDS (MDS-1A)
  • Footnote e revised: …Functional laboratory studies and constitutional (germline) genetic testing using large Next Generation Sequencing (NGS) panels to include genes listed on MDS-E whole exome or whole genome sequencing complemented with in silico copy number variant (CNV) calling and/or laboratory analysis for CNVs such as microarray testing is recommended for patients shown on MDS-D 5 of 5.  can assist in the diagnosis of these syndromes… 
  • Footnote f revised:  In patients younger than 40 patients years old of age, CSA is due to… CSA may appear late due to lyonization in X-linked sideroblastic anemia (not limited to younger patients and patients older than >60 years of age old at risk for germline DDX41 and short telomere syndromes). 
• Additional Testing and Classification (MDS-2)
  • Classification moved to middle column pathway.
• Prognostic Category:  IPSS-R Very Low, Low: IPSS: Low/Intermediate-1: WPSS: Very Low, Low Intermediate (MDS-3) 
  • Title changed:  Management of Lower-Risk Disease (IPSS-R Very Low, Low, Intermediate Risk Disease
  • Clinically significant cytopenia(s) or increased marrow blasts
  • No del(q) + other cytogenic abnormalities:  Added see MDS-4.  Removed Serum EPO < mU/mL; Serum EPO < 500 mU/mL.
• Clinically relevant thrombocytopenia or neutropenia or increased marrow blasts
  • Other recommended Decitabine or oral decitabine and cedazuridine.
• Footnote
  • Footnote t revised:  Oral decitabine and cedazuridine (DEC-C) could be considered as a substitution for intravenous decitabine in patients with IPSS intermediate-1 and above. (Also for MDS-5A, MDS-6A).
• Evaluation of Related Anemia/Treatment of Symptomatic Anemia/Follow-up (MDS-4)
  • Page order of MDS-4 and MDS-5 has been revised.
    • Follow-up, Lower pathway:  …with ring sideroblasts  >15% (or ring sideroblasts >5 % with an SF3B1 mutation).  No response, luspatercept-aamt, see pathway for Serum EPO >500 m/mL (poor probability to respond to IST) (See MDS-5)
    • Follow-up, Lower pathway:  …with ring sideroblasts >15% (or ring sideroblasts), >5%  with an SF3B1 mutation).  No response, consider lenalidomide, see pathway for Serum EPO >500 mU/mL (poor probability to respond to IST) (See MDS-5)
  • Footnote z revised: Except for patients with low neutrophil counts or low platelet counts. Recommended initial dose is: 10 mg/day for 21 out of 28 days or 28 days monthly for 2–4 months to assess response (See Discussion). Alternative option to lenalidomide may include an initial trial of ESAs in patients with serum EPO ≤500 mU/mL. Use caution for patients with low platelet and neutrophil counts; Alternative option…… (Also on MDS-5, MDS-5A)
• Prognostic Category: IPSS-R: Very Low, Low, Intermediate; IPSS: Low/Intermediate-1; WPSS: Very Low, Low Intermediate  (MDS-5)
  • Title changed:  Management of Lower-Risk Disease (IPSS-R Very Low-, Low-, Intermediate Risk Disease)
  • Serum EPO ≤500 mU/mL pathway: No response after 3 mo 6-8 weeks or erythroid response…No response after 4 mo 6-8 weeks…
  • Serum EPO ˃500 mU/mL pathway: Good probability to respond to IST
    • ATG or
    • ATG + cyclosporin A or
    • ATG + eltrombopag (category 2B) or
    • ATG + cyclosporin A + eltrombopag (category 2B).
  • Serum EPO <500 mU/mL pathway: Poor probability to respond to IST
    • Other Recommended, added: or Oral decitabine and cedazuridine.
    • No response within 6 cycles of azacitidine or 4 cycles of decitabine or oral decitabine and cedazuridine or intolerance.
• Footnotes (MDS-5A)
  • Footnote bb revised:  Encouraging Data are emerging have demonstrateding the effectiveness of luspatercept for treating the anemia of ring sideroblastic (RS) lower-risk MDS patients. Fenaux P, et al.  N Eng J Med 2020;382:140-151.  For lower-risk MDS patients lacking RS treated with luspatercept, encouraging albeit limited data have emerged (36% HI-E in 44 patients) in abstract form [Platzbecker U, et al. Clin Lymphoma Myeloma Leuk 2020;20:S319-320 Abstract MDS-191]. However, FDA approval has not yet occurred for use of the drug for RS negative patients. We recommend such patients enter clinical trials for use of luspatercept.
  • Footnote dd revised: ….transfusion requirement by 3 to 4 months 3 to 6 months of treatment.
  • Footnote gg revised:  …IST includes equine ATG ± cyclosporin A + eltrombopag (category 2B for eltrombopag combinations).
• Prognostic Category  IPSS-R: Intermediate, High, Very High; IPSS: Intermediate-2, High; WPSS: High, Very-High (MDS-6)
  • Title Changed:  Management of Higher-Risk Disease (IPSS-R Intermediate, High, Very High-Risk Disease)
  • Transplant candidate, added the following treatment options:
    • Oral decitabine and cedazuridine followed by allo-HCT
    • Clinical trial followed by allo-HCT
  • Not a transplant candidate, added:
    • Oral decitabine and cedazuridine as an option under Other recommended.
  • Relapse after allo-HCT or No response
    • Or oral decitabine and cedazuridine as an option under Other Recommendeded
  • The Categories of Preference have been applied to the treatment regimens
• Footnotes (MDS-6A)
  • Footnote ll revised:  Allogeneic hematopoietic cell transplantation from the most suitable donor (HLA-matched sibling or unrelated donor, HLA-haploidentical family member or cord blood). Early referral for transplant evaluation is recommended, to allow moving to transplant efficiently.  Pre-transplant debulking therapy to reduce marrow blasts to <5% with the goal of reducing post-transplant relapse (see footnote nn and Discussion)  is recommended, although the optimum strategy (azacitidine, decitabine, induction-type chemotherapy) has not been determined. To reduce the disease burden pre-transplant is particularly important in patients who will receive a reduced-intensity conditioning regimen (Festuccia M, et al. Biol Blood Marrow Transplant 2016;22:1227-1233). 2016;22:1227-1233). At some centers, failure to achieve <5% blasts with cytoreduction should not preclude from proceeding to transplant, as these patients appeared to derive survival benefit from transplant (Nakamura et al., ASH 2020, Schroeder et al., Biol Blood Marrow Transplant 75 (2019) 1550-1559).
  • Footnote nn revised:  Some emerging data have shown efficacy of novel agents including venetoclax in combination with hypomethylating agents or targeted IDH1/2 inhibitors for cytoreduction for patients with high-risk MDS who have HMA-refractory disease DiNardo C et al, New Eng J Med 2018) who have HMA-refractory disease.   Venetoclax, when used as cytoreduction for MDS, should not extend beyond 14 days. Repeat of marrow evaluation after 1-2 cycles is imperative to ensure recovery of hematopoiesis.  (Garcia J et al, Proc ASH 2020, #656). Clinical trials are preferred. (See Discussion).
• Supportive Care (MDS-7)
  • Bullet 1, Pre-Transplant new:
    • Sub-bullet 1 new: Transplant and non-transplant patients should receive support.
    • Sub-bullet 2 new: Transfusion products should be irradiated with 25 Gy.
    • Sub-bullet 3 new: Patients with ≥5% marrow blasts who are candidates for reduced intensity conditioning (RIC) should receive ‘debulking’ therapy with HMA or induction chemotherapy. Transplantation should be carried out as long as patients are responding; it should not be delayed until the response is lost.
• Supportive Care (MDS-8)
  • Cytokines
    • G-CSF sub-bullet 1 revised:  G-CSF refers to the following agents: filgrastim filgrastim-sndz, and tbo-filgrastim…
  • Bullet 3, Post-Transplant new
    • Sub-bullet 1 new: Patients should receive antibiotic prophylaxis at least as long as they are on immunosuppressive therapy.
    • Sub-bullet 2 new:  Detailed recommendations are provided in the Guidelines generated by the American Society of Transplantation and Cell Therapy (ASTCT, formerly  ASBMT).  See NCCN Guidelines for Hematopoietic Cell Transplantation.
  • Footnote ss new:  An FDA-approved biosimilar is an appropriate substitute for filgrastim.
• Myelodysplastic/Myeloproliferative Overlap Neoplasms (MDS/MPN), 2017 WHO Classification and Management (MDS-A, 3 of 4)
  • Row 7 moved down:  Atypical chronic myeloid leukemia (aCML) BCR-ABL negative. 
    Blood:  WBC >13x10⁹/L, neutrophil precursors;  dysgranulopoiesis; Bone Marrow:  Hypercellular, <20% blasts; Frequent mutations: SETBP1, ETNK1; Treatment Consider HMA and/or ruxolitinib and/or allogeneic HSCT.
    
    Footnote e revised:  CMML patients with JAK2 mutations may respond to ruxolitinib…
• References (MDS-A, 4 of 4)
  • References updated
• Genes Frequently Somatically Mutated in MDS (MDS-C, 2 of 3)
  • Mutated Gene: SETBP1:  Clinical Significance revised: … More frequent in aCML (24%); …
• References: MDS-C (3 of 3)
  • References updated
• Genetic Familiar High-Risk Assessment: Hereditary Myeloid Malignancy Predisposition Syndromes (MDS-D, 1 of 5)
  • Bullet 1 revised:  Recognition of these predisposition syndromes is clinically relevant. Patients…..clonal hematopoiesis, often  rarely respond poorly …….
  • Bullet 3 revised:  ….germline DDX41 mutations. Patients younger than 40 Younger patients years with MDS …..
• Genetic Familial High-Risk Assessment: Hereditary Myeloid Malignancy Predisposition Syndromes (MDS-D, 2 of 5)
  • Bullet 1 revised:  … Consultation with a hereditary….below;
  • Bullet 5 new:  Limitations of the proposed approach
  • Bullet 6 new:  Surveillance
• Genetic Familial High-Risk Assessment: Hereditary Myeloid Malignancy Predisposition Syndromes (MDS-D, 4 of 5)
  • Bullet 5 new:  Limitations of the proposed approach
    • Sub-bullet 1 new:  The current criteria are focused mainly on known genetic predisposition syndromes to MDS or AML. The proposed age threshold of 50 years at the time of diagnosis is arbitrary and conditions known to be diagnosed at older ages (DDX41) with predisposition to MDS or AML due to germline may be missed.  Additionally, there are certainly genetic aberrations predisposing to the development of myeloid neoplasms that have not yet been identified and as such, some patients may not fit the aforementioned criteria. Any clinical suspicion of a hereditary condition not included in these guidelines may still warrant a referral to an institution with expertise in the field.
  • Bullet 6 new:  Surveillance
    • Individuals who fulfill the clinical diagnostic criteria for a myeloid neoplasm with a germline predisposition, even if the pathogenic genetic variant is undetermined. 
    • Individuals with a deleterious or likely deleterious genetic variant associated with a germline redisposition, regardless of clinical presentation.
• Genetic Familiar High-Risk Assessment: Hereditary Myeloid Malignancy Predisposition Syndromes (MDS-D, 5 of 5)
  • Whom to Test?
    • Bullet 1 new:  Aberrations of chromosome 7 and age <50 
    • Bullet 7 revised:  Allogeneic sibling related donor 
  • Subsequent Steps
    • Arrow 3 revised:  If chromosomal…..DNA or whole exome or genome
    • Footnote e revised:  Genetic counseling… Feurstein S, et al. Leukemia 2021;35:2439-2444.
• Gene Mutations Associated with Hereditary Myeloid Malignancies (MDS-E, 1 of 6)
  • Disorder: Xeroderma Pigmentosa Pigmentosum C (XPC); Gene XPCd^elTG; Hematologic Findings/Myeloid Malignancy:  Increased myeloid malignancies and T-cell acute lymphoblastic leukemia in people aged 7 to 29 years; Other Phenotypes and Clinical Features:  Sensitivity to UV light, experiencing severe sunburns with minutes of exposure, dry skin (xeroderma), freckling (pigmentosum), hearing loss, poor coordination, loss of intellectual function, seizures, and development of squamous cell carcinomas and melanomas often as early as 10 years old in sun-exposed areas.
  • Disorder:  ERCC6L2 new:  Gene:  ERCC6L2; Hematologic Findings/Myeloid Malignancy; Marrow failure, MDS, AML, Other Phenotypes and Clinical Features;  Skeletal/cardiac abnormalities, neurological defects also associated with somatic TP53 mutations and erythroleukemia. Pre-existing cytopenias, microcephaly, developmental delay, and other congenital abnormalities
  • Footnote a revised: The list of genes associated with inherited myeloid malignancy predisposition is continually evolving. Not all of the listed individual genes under the Gene column have been reported in myeloid malignancies.
• Gene Mutations Associated with Hereditary Myeloid Malignancies (MDS-E, 2 of 6)
  • LIG-4 syndrome new:  Gene LIG-4:  Hematologic Findings/Myeloid Malignancy:  Marrow failure, lymphoid malignancy;  Other Phenotypes and Clinical Features:  Short stature, microcephaly, combined immunodeficiency.
• Gene Mutations Associated with Hereditary Myeloid Malignancies -  References (MDS-E,         5 of 6, 6 of 6)
  • References updated
• Spectrum of Indolent Myeloid Hematopoietic Disorders (MDS-F)
  • Page moved to MDS-B (3 of 3)

NCCN has published updates to the NCCN Guidelines and the NCCN Compendium for Gestational Trophoblastic Neoplasia. These NCCN Guidelines^® are currently available as Version 1.2022.

Link directly to the Updates section of the NCCN Guidelines:
Gestational Trophoblastic Neoplasia

Hydatidiform Mole (Noninvasive)

• Monitoring (HM-1)
  • 3rd bullet revised: “Systemic hormonal contraception (oral contraceptives....)”
  • Footnote b is new: If hCG is elevated with no evidence of disease on imaging, consider possibility of luteinizing hormone (LH) crossover, pituitary hCG, or phantom hCG. Consult with laboratory medicine/pathology to test for phantom hCG with serial dilution study or comparison of serum to urine hCG.
  • Footnote g revised: Oral contraceptives pills are preferred over intrauterine devices (IUDs) because they suppress endogenous LH/follicle-stimulating hormone (FSH), which may interfere with hCG measurement at low levels. (Also for GTN-2)
• Findings (HM-2)
  • Top pathway; Revised language: "One or more of the following indicating persistent post-molar GTN:..."
    • Bullet removed: hCG persistence 6 months after molar evacuation
  • Bottom pathway: Revised language: "Histopathologic diagnosis of choriocarcinoma, PSTT/ETT, and/or..."
  • Staging; 3rd bullet revised: Chest x-ray changed to "Imaging (chest x-ray or chest/abdomen/pelvis CT scan"
  • Footnote i revised: "...If the chest x-ray shows metastases, CT scan of the chest/abdomen/pelvic CT scan and brain MRI of the brain are indicated.

Gestational Trophoblastic Neoplasia (GTN)

• Low-risk GTN (GTN-2)
  • Response Assessment; Normal hCG level bullet revised: Continue systemic therapy for 2–3 treatment cycles (3 preferred) past hCG normalization.
  • Footnote j revised: "Hysterectomy with salpingectomy or repeat endometrial curettage may be considered if there is localized disease in the uterus. Hysterectomy is preferred and where fertility preservation is not desired..." (Also for GTN-3)

• Treatment for Persistent GTN (GTN-3)
  • First column language revised
    • Good response to initial therapy followed by hCG level plateau or re-elevation (hCG <300 1000)
      • Response Assessment; Top pathway; Normal hCG level:
      • Continue systemic therapy for 2–3 (3 preferred) treatment cycles past normalization
    • "Good response to initial therapy followed by rapid rise in hCG level (hCG ≥300 1000)..."
      • Response assessment; Bottom pathway: Normal hCG levels:
        • Continue systemic therapy for 2–3 (2 preferred) treatment cycles past normalization
        • Additional Treatment: "Administer etoposide/platinum-based regimens..."
• High-risk GTN (GTN-4)
  • Incomplete response to treatment pathway; Additional treatment revised: "Consider alternative Chemotherapy for patients who are intolerant to EP/EMA: Etoposide/Platinum-based regimens with bleomycin, ifosfamide, or paclitaxel, and..."
• Intermediate trophoblastic tumor: PSTT and ETT (GTN-5)
  • Metastatic pathway; Treatment: "Chemotherapy with a platinum/etoposide-containing platinum-based regimen, such as..."

Hydatidiform Mole (Noninvasive) and GTN

• Principles of Pathology (GTN-A)
  • Procedure: Pelvic exenteration removed
  • Immunohistochemical Markers for Differential Diagnosis of GTN Table
    • New statement added: GATA-3 is a sensitive marker for both benign and malignant trophoblast proliferations, and may be useful in distinguishing GTN from non-GTN tumors.
    • First column: Entry revised to "Gestational choriocarcinoma"
• Systemic Therapy for GTN (GTN-B)
  • Dosing schedules revised throughout section.
  • High-Risk GTN: Therapy for Methotrexate-Resistant GTN
    • Preferred regimens
      • BEP; Comments/Considerations: 
        • Bullet revised: Pulmonary function testing should be performed prior to initiation of therapy and every fourth dose thereafter Assessment of pulmonary function tests (PFTs), typically spirometry and diffusing capacity for carbon monoxide (DLCO), at baseline prior to treatment and monitoring PFTs prior to each new treatment cycle as clinically indicated.
        • Bullet removed: Lifetime dose of bleomycin should not exceed 270 units.
  • High-Risk GTN: Additional Agents/Regimens Shown to Have Some Activity in Treating Multiagent Chemotherapy-Resistant GTN)
    • The following Useful in Certain Circumstances regimens were removed (also for Intermediate Trophoblastic Tumor PSTT and ETT)
      • 5-fluorouracil–based regimens
      • Gemcitabine ± carboplatin 
  • Intermediate Trophoblastic Tumor (PSTT and ETT)
    • “TP/TE: Paclitaxel, cisplatin/paclitaxel, etoposide” moved from Other Recommended Regimens to Preferred Regimens
• Principles of Gynecologic Survivorship (GTN-C)
  • Clinical approach:
    • New bullet added: For premenopausal patients, hormone replacement therapy should be considered.

NCCN has published updates to the NCCN Chemotherapy Order Templates (NCCN Templates^®) for Gestational Trophoblastic Neoplasia to reflect the currently published NCCN Guidelines for Gestational Trophoblastic Neoplasia v1.2022.

• The following NCCN Templates^® have been DELETED:
  • GTN11: CARBOplatin/Gemcitabine
  • GTN15: Fluorouracil

NCCN has published updates to the NCCN Templates for Non-Small Cell Lung Cancer to reflect the currently published NCCN Guidelines for Non-Small Cell Lung Cancer v 6.2021.

• The following New NCCN Template has been published:
  • NSC112: Mobocertinib

NCCN has published updates to the NCCN Templates for Myelodysplastic Syndromes to reflect the currently published NCCN Guidelines for Myelodysplastic Syndromes v1.2022.

• Changes to the Indication section have been made on the following NCCN Templates:
  • MDS1: Lenalidomide
  • MDS2: AzaCITIDine
  • MDS4: Decitabine
  • MDS5: ATG (Antithymocyte globulin, equine)/CycloSPORINE
  • MDS6: ATG (Antithymocyte globulin, equine)
  • MDS10: Imatinib
  • MDS12: Midostaurin
  • MDS19: Oral Decitabine and Cedazuridine
• References have been updated on the following template:
  • MDS1: Lenalidomide
• Emetic risk has been updated on the following template:
  • MDS19: Oral Decitabine and Cedazuridine
• Changes to the Chemotherapy Regimen section have been made on the following templates:
  • MDS1: Lenalidomide
  • MDS2: AzaCITIDine
  • MDS4: Decitabine
  • MDS9: Decitabine
  • MDS15: Decitabine + Ruxolitinib
• Drug information notes for the following agents have been updated in the Supportive Care, Monitoring and Hold Parameters, and/or Safety Parameters and Special Instructions sections:
  • ATG (Antithymocyte globulin, equine)
  • CycloSPORINE
  • Lenalidomide

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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