A Trial Comparing USG-HIFU vs AS in Management of Low-risk PTMC
A Trial Comparing USG-HIFU vs AS in Management of Low-risk PTMC
Papillary thyroid microcarcinoma (PTMC) is a common tumor in Hong Kong. Early immediate
 surgery has traditionally been recommended. However, given its excellent prognosis, some have
 recommended Active Surveillance (AS) as an alternative. AS involves monitoring the patients
 who have PTMC until the tumor progresses. On the other hand, a new technology of ablation has
 been developing to be an alternative treatment for thyroid nodules comparing with traditional
 surgery, named High intensity focused ultrasound (HIFU). In our previous study, HIFU is
 proved in shrinking the size of target site by 6 months gradually and effectively.

 The investigator hypothesize that HIFU is an effective treatment for PTMC. Compared to AS,
 HIFU may be a better option as it not only halts disease progression but also has a longer
 progression-free survival, longer time to tumor progression and is less likely to harbor
 active disease.
Differentiated thyroid cancer has been rising in incidence and is expected to be a leading
 cancer by the year 2030 . However, the rise has been mostly attributed to an increased
 detection of incidentally-discovered papillary thyroid microcarcinoma (PTMC). PTMC is a
 papillary thyroid carcinoma (PTC) measuring ≤ 10mm in its greatest dimension. Previous
 screening and autopsy studies have confirmed these lesions are common and could be found in
 up to 15% of normal healthy individuals.

 However, since the incidence of clinically-significant PTC has historically been <0.5% (i.e.
 100 times less than the occult rate), most occult PTMCs probably do not cause harm in one's
 life-time and could be safely observed without immediate surgery.

 As a result, several groups of investigators worldwide began evaluating the feasibility and
 safety of observing PTMC without surgery. Rather than offering immediate surgery, well
 selected patients with low-risk PTMC (i.e. no extrathyroidal extension, nodal and distant
 metastases) were followed with regular ultrasound (USG) alone and only proceeded to
 definitive to surgery when the PTMC showed progression. As expected, >90% PTMCs did not
 progress and of those who progressed and had surgery, all were cured. This meant even when
 the initial surgery was deferred, there was no compromise in the chance of cure.

 With a recent shift towards a more conservative approach in the management of PTC, it has
 become increasingly accepted that perhaps active surveillance (AS) might be a safe
 alternative in well selected low-risk PTMCs.

 However, despite the fact that AS is a viable alternative, there are issues and challenges.
 First, although the majority of occult tumors do not progress initially, the accumulative
 risk of tumor progression increases with time. From an analysis of the 1479 PTMCs observed
 over 5 years, 212 (14.3%) eventually met the progression criteria (such as tumor enlargement,
 local invasion, new lymph node metastasis or becoming clinical disease) and had surgery.
 Therefore, with longer observation, a greater proportion of patients would end up having
 surgery. Second some patients tend to find it difficult to accept AS as a treatment. Even if
 they do initially, the "wait and see" approach may distress patients leading to
 non-compliance. To date, little is known how this may affect patients' well-being and
 health-related quality of life (HRQOL) over time. Third, since there are no clinical or
 molecular parameters to predict which tumors are more likely to progress, patients often need
 life-long follow-up. However, this may be challenging because patients may move to different
 places. Lastly, there are now less invasive, non-surgical options available to potentially
 eradicate PTMCs. Image-guided thermal ablation (IGTA) using laser ablation or radiofrequency
 ablation appears promising. With technological advances, they may eventually replace surgery
 in the future. However, reports have so far been non-randomized, uncontrolled and short
 follow-up. Furthermore, despite being less-invasive, they still require a small skin
 incision.

 High intensity focused ultrasound (HIFU) is a form of IGTA that needs no skin incision or
 needle insertion and so, is a truly noninvasive treatment. Under USG guidance, it is able to
 cause irreversible tissue destruction deep to the skin and subcutaneous layer. Apart from
 being non-invasive, it is less dependent on the operator's skill as the treatment could be
 controlled by an automated program. In fact, HIFU is highly successful in a number of solid
 cancers. In the thyroid, it induces tissue damage via the cavitation and thermal effects. To
 date, several groups (including us) have confirmed that HIFU ablation is highly effective in
 inducing shrinkage of benign thyroid nodules.
Inclusion Criteria:

 -  Have a thyroid nodule ≤10mm in the largest dimension that is confirmed on FNAC to be
 PTC (Bethesda class VI cytology) or suspicious of PTC (Bethesda V cytology). For the
 latter, the nodule needs to have an additional suspicious sonographic feature (i.e.
 marked hypoechogenicity, irregular margins, height-to-wide ratio >1 and intravascular
 microcalcifications);

 -  Have not expressed a strong desire for immediate surgery after PTMC has been
 confirmed.

 Exclusion Criteria:

 -  Age ≤ 18 or ≥ 75 years old;

 -  Have another thyroid nodule that is either indeterminate or malignant on FNAC;

 -  Have concomitant hypo- or hyperthyroidism (i.e. thyroid stimulating hormone (TSH)
 and/or free thyroxine levels outside the normal ranges)

 -  Have sonographic evidence of chronic lymphocytic thyroiditis (because this generally
 makes it difficult to assess and reassess tumor size accurately on USG alone)

 -  Have a tumor considered not suitable for AS. This includes a PTMC with extrathyroidal
 extension, concomitant nodal or distant metastasis or a PTMC located within 3mm from
 trachea-esophageal groove or recurrent laryngeal nerve.

 -  Have a condition considered not suitable for HIFU treatment (pregnancy, history of
 neck irradiation, known contralateral vocal cord palsy, a tumor with coarse,
 macroscopic intranodular calcifications or located outside the treatable depth of 5-30
 mm from the skin, family history of non-medullary thyroid carcinoma and medical
 conditions precluding intravenous sedation).