Patient Management Using Thyroseq V3

  • The ThyroSeq test results refine cancer probability in thyroid nodules with indeterminate cytology, informing the most appropriate management of these patients.

There are two classes of negative test results:

ThyroSeq test result: NEGATIVE

  •  According to the NCCN guidelines:
    • If molecular testing, in conjunction with clinical and ultrasound features:
      • Predicts a risk of cancer comparable to the risk of malignancy seen in a benign FNA cytology (approximately 5% or less):
        • Observation can be considered.
    • Therefore, in those clinical situations where the pre-test probability of cancer in nodules with Bethesda III and IV cytology is <45%:
      • A negative ThyroSeq test results:
        • Would confer the cancer probability of 5% or less:
          • Justifying observation in lieu of surgical management in appropriately selected cases.
        • Because the probability of cancer in such nodules is comparable to that of benign FNA cytology:
          • The management of patients may follow the recommendations for nodules with benign cytology, which, based on the 2015 ATA guidelines:
            • Should be determined based on ultrasound (US) pattern:
              • Specifically, the recommendation for nodules that have:
                • High suspicion US pattern:
                  • Is repeat US and US-guided FNA within 12 months
                • For nodules with low to intermediate suspicion US pattern:
                  • Repeat US at 12 to 24 months and if sonographic evidence of growth or development of new suspicious sonographic features, the FNA could be repeated or observation continued with repeat US, with repeat FNA in case of continued growth (ATA Recommendation #23).
  • In nodules with Bethesda V cytology and negative ThyroSeq result:
    • The residual cancer risk of approximately 20% does not allow to avoid surgical management:
      • Thyroid lobectomy may be sufficient initial treatment for many of these patients as the majority of these nodules are expected to be benign.

ThyroSeq test result: CURRENTLY NEGATIVE

  • Test results are reported as currently negative:
    • When the sample is found positive for a low-risk gene mutation that alone is not sufficient for full cancer development (eg. PTEN, EIF1AX) and found in a subpopulation of cells.
    • Although at the time of sampling most of these nodules are benign:
      • Some of them may undergo clonal expansion and acquire additional mutations.
    • In the absence of high-suspicion US pattern or other clinical risk factors:
      • Many of these patients are likely to benefit from active surveillance with potential repeat of FNA and possibly molecular testing in 1 year.

ThyroSeq test result: POSITIVE

  • For these nodules, the type and level of mutation(s) provide further refinement of the probability of cancer and estimate cancer aggressiveness / risk:
    • According to the ATA risk stratification system for thyroid cancer:
      • The risk of structural disease recurrence can be:
        • Low (1% to 5%)
        • Intermediate (10% to 20%)
        • High (30% to 55%)
  • ThyroSeq test positive for an isolated RAS or RAS-like mutation:
    • Predicts a high probability (approximately 80%) of either:
      • Low-risk cancer or a pre-cancerous tumor, NIFTP.
    • Many of these nodules may be managed by therapeutic lobectomy:
      • Which is currently recommended by the ATA guidelines for low-risk papillary and follicular carcinomas (ATA Recommendation #35) and NIFTP.
  • ThyroSeq test positive for an isolated BRAF V600E or BRAF V600E-like mutation:
    • Confers a very high (greater than 95%) probability of cancer that typically is of intermediate risk for recurrence:
      • According to the ATA guidelines:
        • BRAF-mutated less than 1 cm unifocal intrathyroidal carcinoma:
          • Is of low risk for disease recurrence:
            • Therefore may be treated with thyroid lobectomy alone
        • Whereas 1 cm to 4 cm intrathyroidal BRAF-positive PTC:
          • Is an intermediate-risk tumor:
            • Where total thyroidectomy or lobectomy should be considered based on clinical and US findings.
  • ThyroSeq test positive for multiple high-risk mutations:
    • Is virtually diagnostic of cancer and predicts an elevated risk of disease recurrence.
    • Most of these patients would likely benefit from:
      • Total thyroidectomy, with possible consideration for regional lymph node dissection if one of the mutations is BRAF V600E.

#Arrangoiz #ThyroidSurgeon #ThyroidCancer #ThyroidExpert #CancerSurgeon #HeadandNeckSurgeon #ThyroidNodules #Thyroseq

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