Clinical Applications of Immuno-PET in Lymphoma: A Systematic Review

Round 1

Reviewer 1 Report

This is a very interesting review, which intends to update a very challengeable filed of imaging in cancer, iPET for lymphoma. I suggest few items to overall improve the quality of this review.

First of all, inclusion criteria for their study are vague and not clearly defined. Writing a review based on 4 papers is remarkable but it has to have a stronger justification. Secondly, while the title addresses “lymphoma”, at the end of the day the authors discuss only iPET in B cell lymphoma. The title should be adjusted correspondingly. Thirdly, Discussion section must be updated with the personal points of view form the authors and further proposed research to improve the field (new targets, new tracers). The authors should also integrate in the Discussion section the other targets for B cell lymphoma like CD19, CD38, and especially CD274 (PD-L1). FInally, the authors should acknowledge the limitations of their work.

Author Response

POINT-BY-POINT REPLY OF THE AUTHORS TO THE REVIEWERS’ COMMENTS

Reviewer 1

#Q1

This is a very interesting review, which intends to update a very challengeable filed of imaging in cancer, iPET for lymphoma. I suggest few items to overall improve the quality of this review. First of all, inclusion criteria for their study are vague and not clearly defined. Writing a review based on 4 papers is remarkable but it has to have a stronger justification.

#A1

Our systematic review searched for evidence in the literature of clinical applications of immuno-PET in patients with lymphoma. As such, the title incorporates the criterium for articles to be included. We though recognize that the adjective “clinical” was not always specified in the sentences of the main text and we missed addressing the inclusion criteria more specifically. We therefore thank the Revisor for her/his suggestions and provide the text with an according adjustment (Abstract; Methods section, lines 111-113). As for a stronger justification to our work (and in coherence with further additions to the text that were made to answer the Revisor’s suggestions), we implemented the avowed aim (Introduction section, lines 102-103) with a wider reasoning for why we truly decided to perform this study.

#Q2

Secondly, while the title addresses “lymphoma”, at the end of the day the authors discuss only iPET in B cell lymphoma. The title should be adjusted correspondingly.

#A2

The original scope of our review was to assess clinical applications of immuno-PET in all histological types of lymphoma. The fact that the experiences that have been achieved (and therefore reported in our review) mainly regarded patients with B cell lymphoma, was a finding. In the doubt that these concepts were not clearly stated in the text for all readers, we added some specifications in the text (Methods section, line 113; Results section, lines 150-152)

#Q3

Thirdly, Discussion section must be updated with the personal points of view form the authors and further proposed research to improve the field (new targets, new tracers). The authors should also integrate in the Discussion section the other targets for B cell lymphoma like CD19, CD38, and especially CD274 (PD-L1).

Finally, the authors should acknowledge the limitations of their work.

#A3

The Revisor’s suggestions have been welcomed. The Discussion section has been implemented and the limitations acknowledged at the end of the same section accordingly.

Reviewer 2 Report

- The scope was to assess current  applications of immuno-PET in patients with lymphoma. Therefore, a systematic review of the published literature was performed.

- PubMed/Medline and Scopus databases were independently searched by two nuclear medicine physicians, to identify studies describing the use of immuno-PET in patients with lymphoma. Methodological quality of the included articles was assessed by using the Quality Assessment of Diagnostic Accuracy Studies criteria. Studies were then analyzed concerning the molecular target of interest.

- Initial search yielded 1407 articles. After elimination of duplicates, 1339 titles/abstracts were evaluated. Only 2 articles were found to comply with the inclusion criteria and 2 more were found during cross-reference check. Among the four included articles, 3 described the use of 89Zr-labelled antibodies targeting CD20+ relapsed/refractory B-cell lymphomas and 1 concerned the use of 68Ga-labelled mAb targeting CXCR4 in patients with Non-Hodgkin Lymphomas.

- Very limited literature data are currently available on the use of iPET in patients with lymphoma. This technique is encountering obstacles to a wider use, possibly because of the needing of specific facilities, unfavourable dosimetry, and unclear correlation of immunotracer biodistribution with patients’ clinical and tumors’ molecular characteristics. However, iPET may represent a useful tool to non-invasively visualize the heterogenous individual immunological environment, thus potentially guiding treatment-planning in lymphoma patients, and hence deserve further exploitation

Comments for author File: Comments.pdf

Author Response

Reviewer 2

Finally, we sincerely thank the Reviewer 2 for her/his constructive comments.

Round 2

Reviewer 1 Report

I would like to acknowledge the excellent work of the authors to respond to the reviewer questions. The manuscript appears to be ready for publication.