Successful Alectinib Treatment for Carcinoma of Unknown Primary with EML4-ALK Fusion Gene: A Case Report
Round 1
Reviewer 1 Report
This case report is an impressive and informative report in CUP patient. However, I have the following questions.
- The authors should show histology of Lymph node in low and high magnification with AE1.3, CD31 and CK7.
- Have you performed liver biopsy in this patient?
- Did NGS show other informative fusion genes which are associated with molecular target therapy?
Author Response
Response to Reviewer 1 Comments
We wish to express our appreciation to the reviewer for their insightful comments our paper. The comments have helped our article more informative.
Point 1: The authors should show histology of Lymph node in low and high magnification with AE1.3, CD31, and CK7.
Response 1: We thank you for your suggestion. We have added the image illustrating IHC results of AE1.3, CD31, and CK7 in the manuscript (Figure 2).
Point 2: Have you performed liver biopsy in this patient?
Response 2: We thank you for the comment. We did not perform a liver biopsy. As the effectiveness of FOLFOX or alectinib, an ALK kinase inhibitor, is the same in the liver and other lesions, we considered that all lesions, except for early colorectal adenocarcinoma, were of the same origin.
Point 3: Did NGS show other informative fusion genes which are associated with molecular target therapy?
Response 3: We thank you for this comment. Apart from the EML4-ALK fusion gene, actionable mutation and remarkable findings including microsatellite instability and TMB-high were not detected. We have added this information in lines 76–77.
Author Response File: 
Author Response.docx
Reviewer 2 Report
Thank you for asking me to review this case report which, as a clinician who treats lung cancer and CUP as my primary sites, was particularly interesting.
I find this report to be relevant to the management of CUP, and further encourages the use of NGS where possible in these patients.
I was pleased to see reference to CUP of favorable and unfavorable subtypes, and the case report outlines a comprehensive workup of a CUP patient, including PET scan, colonoscopy, comprehensive IHC and then the NGS panel. It is also worthwhile emphasizing the emergence and importance of institutional molecular oncology case conferences to discuss patients like this.
I have no significant recommendations for improvement. My only comment to consider would be that I did not find the PET image in Figure 1 to be particularly easy to view, in contrast to the PET image after treatment response in Figure 3. Maybe the authors could use the same PET image settings in Figure 1.
Author Response
Response to Reviewer 2 Comments
We wish to express our appreciation to the reviewer for their insightful comments our paper. We are pleased that the reviewer of our paper is a highly specialized in the field of lung cancer and CUP.
Point 1: Thank you for asking me to review this case report which, as a clinician who treats lung cancer and CUP as my primary sites, was particularly interesting.
I find this report to be relevant to the management of CUP, and further encourages the use of NGS where possible in these patients.
I was pleased to see reference to CUP of favorable and unfavorable subtypes, and the case report outlines a comprehensive workup of a CUP patient, including PET scan, colonoscopy, comprehensive IHC and then the NGS panel. It is also worthwhile emphasizing the emergence and importance of institutional molecular oncology case conferences to discuss patients like this.
I have no significant recommendations for improvement. My only comment to consider would be that I did not find the PET image in Figure 1 to be particularly easy to view, in contrast to the PET image after treatment response in Figure 3. Maybe the authors could use the same PET image settings in Figure 1
Response 1: We thank you for evaluating our case report. We believe that kinase inhibitors against driver oncogenes in non-small-cell-lung cancer are effective for the treatment of patients with CUP, based on a series of reports published after the conduction of a clinical trial. Regarding PET image (Figure 1), this patient was referred from another hospital to our institute, and the PET-CT at baseline was not performed in our hospital; therefore, the image is different from that depicted in Figure 2. We hope that this is acceptable.
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
Your manuscript has been revised and you answered my questions. Please add the following information.
- I ask you to add HE pictures with low and high magnification.
- You should add magnification of each picture to the figure legend.
Author Response
Point 1: Your manuscript has been revised and you answered my questions. Please add the following information.
- I ask you to add HE pictures with low and high magnification.
- You should add magnification of each picture to the figure legend.
Response 1: Thank you for your comments. Per your suggestions, I have added the images of the HE staining and the magnification of each picture.
