Initial Experiences of Selective RET Inhibitor Selpercatinib in Adults with Metastatic Differentiated Thyroid Carcinoma and Medullary Thyroid Carcinoma: Real-World Case Series in Korea

Round 1

Reviewer 1 Report

A different slice of the CT scan for the figure 1 letter H vs I should be better select, because the hilar lesion are different at the baseline and after 6 months.

Author Response

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Reviewer 2 Report

Thanks for the opportunity to review this article;

Treatment-resistant thyroid cancer is a problem that some patients suffer from and finding a cure for it is very helpful. In this study, 2 patients with medullary thyroid cancer and 2 patients with papillary thyroid cancer have been presented who have received promising results from this drug.

The nomenclature of Figure 1 and the marking of Figure 4 should be revised.

Author Response

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Reviewer 3 Report

In this paper the authors reported an interesting real life case series about the use of selpercatinib as second line treatment in patients with progressive and metastatic medullary and papillary thyroid carcinoma. The good clinical responses of selpercatinib are not a novelty however, the description of the cases outside the clinical trials could be useful for the readers to give information about the real-life management. However, several information are missing in these cases and several issues need to be clarified.

Major comments

Introduction section – “It has been suggested that minor RET…”. This concept could be misleading, please rephrase as follows…”It has been suggested that other RET alteration with less frequency, such as indels…”

Case 1:

The phrase “This case was presented at review article from one of the authors” is not useful.

Please change six years ago with six years before

Please report data about histology of this patient, T and N at the time of surgery and if surgery was radical (R0) or not.

Please report data about the dimension of the suspicious lung metastases.

The authors should clarify why the presence of lung metastases was relevant for performing germline RET mutation test. Regardless of the presence of metastases, RET germline mutation test must be offered to all patients with a confirmed histology of MTC, as suggested by all the guidelines, to discover the familial cases. Please clarify.

“Despite Vandetanib…”, the sentence is not so clear, had the patient decrease the dose or not? How long time the patient remained on vandetanib treatment? Which was the clinical response on vandetanib treatment? Please specify, it is important for the readers to report these data.

After vandetanib withdrawal, why the patient did not perform other MKI and remained one year without treatment despite progression? Please specify.

Please specify the clinical and radiological behavior of the bone lesions on selpercatinib treatment.

The authors stated that a PEG was positioned. However, the drugs that is possible to administered through the PEG are usually liquids or crushed tablets. Conversely, selpercatinib has a capsule, how the authors administered the drug through the PEG? Please clarify.

Case 2

Please change “ago” with “before”

The same information about histology are missing also for this case, as far as for case 1.

The same consideration for RET germline testing should be due also for this case

Please report how the metastatic lesions responded (or not) to the treatment with selpercatinib. 

Please specify why in this case selpercatinib was not started at the suggested initial dosage of 160 mg/BID.

Case 3 and case 4 led to the same considerations of the 2 previous cases. The authors should detail histologic information, also regarding PTC (tumor dimension, histologic variant, number, site and dimension of the metastatic lymph nodes…and so on)

Discussion section

“metastatic hepatic nodule despite germline mutation was not detected”…the use of “despite” makes no sense. The research for somatic RET mutation should be performed only on germline RET negative cases, so, please rephrase.

Concerning adverse events, the authors highlighted that the safety profile of selpercatinib was very good, however it should be mentioned that several and new emerging TEAEs are being observed, particularly as chylous effusions (PMID: 35788405, PMID: 36314655). For this reason, the authors should report also that, since these drugs are relatively “young”, the late adverse events are still little known, and the monitoring of the patients should be carefully continued.

Minor comments

The paper needs of an extensive revision by a native English writer

Author Response

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Round 2

Reviewer 3 Report

I thank the authors because answering all my questions