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Acute meyloid leukemia (Non-APL)
Consider molecular analyses to identify the following genetic abnormalities: - ASXL11
- CEBPA1,2
- DNMT3A1
- FLT3 (ITD and TKD)1,2
- IDH1 and IDH21
- KIT1
- MLL gene2
- NPM11,2
- RUNX11
- TP531
Consider cytogenetic analyses to identify the following genetic abnormalities: - chromosomal translocations: t(8;21)(q22;q22.1), t(16;16)(p13.1;q22), t(9;11)(p21.3;q23.2), t(6;9)(p23;q34.1), t(v;11q23.3), t(9;22), (q34.1;q11.2), t(3;3)(q21.3;q26.2)
- chromosomal inversions: inv(16)(p13.1q22), inv(3)(q21.3;q26.2)
- chromosomal deletions: del(5q), -5, -7, -17/abn(17p)
Footnotes 1 NCCN 2019. NCCN Clinical Practice Guidelines in Oncology. Acute Myeloid Leukemia. Version 1.2020. August 13, 2019. Accessed online 8/23/19
2 ESMO 2013. Fey MF, et al. Acute Myeloblastic Leukaemias in Adult Patients: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. Ann Oncol. 2013 Oct;24 Suppl6:vi138-43. Accessed online 7/10/19
3 WHO 2016. The 2016 Revision to the World Health Organization Classification of Myeloid Neoplasms and Acute Leukemia. Blood. 2016 May 19; 127(20):2391-405.
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If noninvasive breast CA, consider: - tumor estrogen receptor (ER) status1-4
If invasive/inflammatory breast CA, consider: - tumor estrogen receptor (ER) status:1-4 AND
- tumor progesterone receptor (PR) status1-4 AND
- HER2 status testing on metastatic site by validated IHC assay or by validated dual-probe ISH assay1
Footnotes 1 NCCN 2019. NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Version 2.2019. July 2, 2019. Accessed online 8/23/19
2 ASCO 2019. American Society of Clinical Oncology. Fabrice A, et al. Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update—Integration of Results From TAILORx. J Clin Oncol.. Published online May 31, 2019. PDF
3 ESO-ESMO 2018. Cardoso F, et al. 4th European School of Oncology, European School for Medical Oncology. ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4). Ann Oncol. 2018 Aug 1;29(8):1634-1657. PDF
4 ASCO 2015. American Society of Clinical Oncology. Van Poznak C, et al. Use of Biomarkers to Guide Decisions on Systemic Therapy for Women With Metastatic Breast Cancer. J Clin Oncol. 2015 Aug 20;33(24):2695-704. PDF
Subsequent testing (if ER/PR/HER2 status already known) If ER/PR(+)/HER2(-) breast CA AND node-negative status, consider:1,2 - EndoPredict (12-gene assay): to guide decisions for adjuvant systemic chemotherapy2
- MammaPrint (70-gene assay): for pts who ALSO have high clinical risk as defined by MINDACT categorization to inform decisions on withholding adjuvant systemic chemotx2
- Oncotype DX (21-gene assay):1,2
- PAM50 (50-gene assay): recommended in conjunction w/ other clinicopathologic variables to guide decisions about adjuvant systemic tx2
- Breast Cancer Index (BCI): to guide decisions about adjuvant systemic tx2
- uPA and PAI-1: to guide decisions about adjuvant systemic tx2
If ER/PR(+)/HER2(-) breast CA AND node-positive status, consider:1 - EndoPredict (12-gene assay)1
- MammaPrint (70-gene assay): recommended in pts w/ 1-3 positive nodes who ALSO have high clinical risk as defined by MINDACT categorization to inform decisions on withholding adjuvant systemic chemotx2
- Oncotype DX (21-gene assay)1
- PAM50 (50-gene assay)1
If triple-negative invasive breast CA, consider: - PD-L1 biomarker status on tumor-infiltrating immune cells1
If recurrent or Stage IV HER2(-) invasive breast CA AND candidate for chemo tx, consider: - germline BRCA 1/2 testing1
Footnotes 1 NCCN 2019. NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Version 1.2019. March 14, 2019. Accessed online 6/1/19
2 ASCO 2019. American Society of Clinical Oncology. Fabrice A, et al. Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update—Integration of Results From TAILORx. J Clin Oncol.. Published online May 31, 2019. PDF
3 ESO-ESMO 2018. Cardoso F, et al. 4th European School of Oncology, European School for Medical Oncology. ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4). Ann Oncol. 2018 Aug 1;29(8):1634-1657. PDF
4 ASCO 2015. American Society of Clinical Oncology. Van Poznak C, et al. Use of Biomarkers to Guide Decisions on Systemic Therapy for Women With Metastatic Breast Cancer. J Clin Oncol. 2015 Aug 20;33(24):2695-704. PDF
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For all CRC pts, consider: - DNA Mismatch Repair (MMR) genes (MLHI, MSH2, MSH6 or PMS2 mutations)1,2 leading to lack of protein expression; to identify CRC pts at high risk for Lynch syndrome and/or prognostic stratification;3 recommended in all pts w/ personal Hx of colon/rectal CA1,2
- Microsatellite Instability (MSI)1,2 to identify CRC pts at high risk for Lynch syndrome and/or prognostic stratification;3 recommended in all pts w/ personal Hx of colon/rectal CA;1,2 MSI testing may be accomplished w/ a validated NGS panel (esp in pts w/ metastatic dz who require genotyping of RAS and BRAF)
If advanced or metastatic CRC dz, consider the following additional tests: - BRAF V600E mutational analysis:1-3 of the primary colorectal CAs and/or the metastasis to determine tumor gene status;1,2 perform testing only in CLIA-certified "high-complexity" labs and on formalin-fixed paraffin-embedded tissue;1,2 perform in CRC tissue of pts w/ CRC for prognostic stratification and/or in deficient MMR tumors w/ loss of MLH1 to evaluate for Lynch syndrome risk3
- HER2 status:1,2 to identify candidates for trastuzumab, pertuzumab, or lapatinib
- NTRK (neurotrophic receptor tyrosine kinase) gene testing: to identify candidates for larotrectinib1,2
- RAS (KRAS and NRAS) mutation testing:1-3 specifically KRAS condons 12 and 13 exon 2 mutation of the primary colorectal CAs and/or the metastasis to determine tumor gene status;1,2 perform testing for KRAS, NRAS, and BRAF mutations only in CLIA-88-certified "high-complexity" labs and on formalin-fixed paraffin-embedded tissue;1,2 if CRC pt being considered for anti-EGFR tx, perform RAS mutation testing that includes KRAS and NRAS codons 12, 13 of exon 2; 59, 61 of exon 3; and 117 and 146 of exon 4 ("expanded" or "extended" RAS)3
Footnotes 1 NCCN 2019. [NCCN Recommendation 2A] NCCN Clinical Practice Guidelines in Oncology. Colon Cancer. Version 2.2019. May 15, 2019. Accessed online 6/1/19
2 NCCN 2019. [NCCN Recommendation 2A] NCCN Clinical Practice Guidelines in Oncology. Rectal Cancer. Version 2.2019. May 15, 2019. Accessed online 6/1/19
3 ASCO 2017. American Society of Clinical Oncology. Sepulveda AR, et al. Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society of Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology. J Oncol Pract. 2017 May;13(5):3330337. Accessed online 6/10/19.
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If metastatic dz, consider: - BRAF1,2
- KIT1,2
- NRAS1,2
- PD-L11,2
If advanced dz (unresectable stage III or stage IV): - BRAF mutation testing:1,2 mandatory for pts for whom BRAF-directed tx may be an option
If high-risk resected dz stage IIc or stage IIIb-IIIc: - BRAF mutation testing:2 highly recommended
If resected stage I-II cutaneous melanoma: - BRAF mutation testing: only if testing informs clinical trial participation1,2
Footnotes 1 NCCN 2019. NCCN Clinical Practice Guidelines in Oncology. Cutaneous Melanoma. Version 2.2019. March 12, 2019. Accessed online 6/1/19
2 ESMO 2015. Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Dummer R, et al. Ann Oncol. 2015 Sep;26 Suppl 5:v126-32. PDF
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If advanced or metastatic dz, consider: - HER2:1,2 Test tumor tissue of pts w/ advanced GEA who are potential candidates for HER2-targeted tx;3 request HER2 testing on tumor tissue or resection specimens (primary or metastasis) preferably before initiating trastuzumab tx; acceptable alternative: testing on FNA specimens (cell blocks)3
- MSI/MMR1,2
- PD-L11,2
Footnotes 1 NCCN 2019. NCCN Clinical Practice Guidelines in Oncology. Gastric Cancer. Version 2.2019. June 3, 2019. Accessed online 7/1/19
2 NCCN 2019. NCCN Clinical Practice Guidelines in Oncology. Esophageal and Esophagogastric Junction Cancers. Version 2.2019. Accessed online 7/1/19
3 ASCO 2017. American Society of Clinical Oncology. Bartley AN, et al. HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. Journal of Clinical Oncology. Volume 35. Number 4. February 1, 2017. PDF
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For all NSCL CA pts: Strongly consider broad molecular profiling to identify rare drive mutations for which effective drugs may already be available, to better counsel pts re clinical trial availability1 or for any non-small cell histology where clinical features indicate a higher probability of an ocongenic driver (eg, young age <50 yo, light or absent tobacco exposure)2 If adenocarcinoma/large cell/NSCLC not otherwise specified AND advanced/metastatic dz, then consider, at minimum: - ALK testing (category 1)1,2
- BRAF V600E testing1,2
- EGFR mutation testing (category 1): NCCN recommends EFGR (exon 19 deletions, p.L858R point mutation in exon 21 assoc w/ responsiveness to EGFR TKI tx);1 but ASCO strongly recommends against evaluating EFGR by immunohistochemistry for selection of pts for EGFR-targeted therapy2
- NTRK gene fusion testing1
- PD-L1 testing (category 1)1
- ROS1 testing1,2
If squamous cell carcinoma AND advanced/metastatic dz, then consider, at minimum: - ALK testing1 in never smokers or small bx specimens, or mixed histology2
- BRAF V600E testing1 in small bx specimens or mixed histology2
- EGFR mutation testing1 in never smokers or small bx specimens, or mixed histology2
- KRAS1-2 prognostic; not indicated as routine stand-alone assay as a sole determinant of targeted tx; appropriate to include KRAS as part of larger testing panels performed either initially or when routine EFGR, ALK, BRAF, and ROS1 testing is negative2
- NTRK gene fusion testing1
- PD-L1 testing (category 1)1
- ROS1 testing1 in small bx specimens or mixed histology2
Also consider these emerging biomarkers to identify novel therapies: - ERBB2 (HER2) molecular testing: Not indicated as routine stand-alone assay outside the context of a clinical trial; perform as part of a larger testing panel either initially or when routine EFGR, ALK, BRAF, and ROS1 testing is negative2
- High-level MET amplification of MET exon 14 skipping mutation: Not indicated as routine stand-alone assay outside the context of a clinical trial; perform as part of a larger testing panel either initially or when routine EFGR, ALK, BRAF, and ROS1 testing is negative2
- KRAS1-2 prognostic; not indicated as routine stand-alone assay as a sole determinant of targeted tx; appropriate to include KRAS as part of larger testing panels performed either initially or when routine EFGR, ALK, BRAF, and ROS1 testing is negative2
- RET molecular testing1,2 Not recommended as a routine stand-alone assay outside of context of clinical trial, but appropriate to include RET as part of larger testing panels performed either initially or when routine EGFR, ALK, BRAF, and ROS1 testing is negative2
- Tumor mutational burden (TMB)
Footnotes 1 NCCN 2019. NCCN Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer. Version 6.2019. August 12, 2019. Accessed online 8/23/19
2 ASCO 2018. American Society of Clinical Oncology. Kalemkerian GP, et al. Molecular Testing for the Selection of Patients With Lung Cancer for Treatment With Targeted Tyrosine Kinase Inhibitors Guideline Endorsement. J Oncol Pract. 2018 May;14(5):323-327. PDF
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For all CRC pts, w/ any of the following: - positive FHx1
- high-risk, very-high-risk, regional, or metastatic prostate CA, regardless of FHx
- Ashkenazi Jewish ancestry
- intraductal histology
Consider the following germline genetic testing: - ATM
- BRCA 1/2
- CHEK2
- MMR (MLH1, MSH2, MSH6, PMS2)
- PALB2
If regional or metastatic dz, consider the following somatic genetic testing: - ATM
- BRCA 1/2
- CHEK2
- FANCA
- MMR (MLH1, MSH2, MSH6, PMS2)
- MSI
- PALB2
- RAD51D
If clinically low-risk or favorable intermediate-risk dz w/ life expectancy ≥10 yo, consider the following tumor multigene molecular testing: - Decipher
- Oncotype Dx Prostate
- Prolaris
- ProMark
Footnotes 1 NCCN 2019. FHx criteria/considerations prompting genetic testing: - strong FHx of prostate CA consists of: brother/father/multiple family members diagnosed w/ prostate CA (but not clinically localized Grade Group 1) at <60 yo or who died from prostate CA
- Ashkenazi Jewish ancestry
- ≥3 cancers on same side of family, esp diagnoses ≤50 yo; bile duct, breast, colorectal, endometrial, gastric, kidney, melanoma, ovarian, pancreatic, prostate (but not clinically localized Grade Group 1), small bowel, or urothelial CA.
NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer. Version 4.2019. August 19, 2019. Accessed online 8/22/19
2 NCCN 2019. NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer. Version 4.2019. August 19, 2019. Accessed online 8/22/19
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