Prevalence and Significance of Incidental PET/CT Findings of Cancer Detected in Patients Evaluated for Their Primary Hematologic Malignancy: A Systematic Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a systematic review of the predictive value of PET/CT for synchronous cancers in patients with hematological malignancies. It is a useful review, providing a clear summary of the literature on this topic, although no definite conclusion can be drawn in terms of recommendations, limited by the relatively small number of studies, significant variations in reporting of data, as well as global variations in access to testing and clinical practice. It would be useful for the authors to provide a summary of the role of PET/CT in staging of the different hematological malignancies- this is clear in lymphomas but not so much for myeloma until the more recent era (EMD and other). It would have been useful to discuss the limitations of PET/CT in sensitivity/ specificity of malignant lesions- what is the expected SUV max for malignancies, vs infections/ inflammation- what is the false positive/ negative of malignant lesions. This would provide a good lead in to the discussion of the variation in clinical practice of biopsies of suspicious lesions, and perhaps allow firmer conclusions to be drawn from the review. 

Overall, this is a well written and relevant review in the era of increasing utility of PET/CT in hematological malignancies and is of interest to readers.

Author Response

Comment 1: It would be useful for the authors to provide a summary of the role of PET/CT in staging of the different hematological malignancies- this is clear in lymphomas but not so much for myeloma until the more recent era (EMD and other).

Response 1: Thank you for taking the time to review our paper. We greatly appreciate your feedback and have incorporated your suggestions into the revised manuscript. In our initial manuscript, the differences in PET/CT interpretations for lymphoma vs plasma cell disorders are discussed in lines 267-275. Based on your recommendations, we have extended this discussion to cover the roles of PET/CT in the staging process, found in the introduction on lines 43-50.

Comment 2: Discuss the limitations of PET/CT in sensitivity/specificity of malignant lesions—what is the expected SUV max for malignancies, vs infections/inflammation— what is the false positive/negative of malignant lesions. 

Response 2: In our revised manuscript, we have included more discussion on lines 284-294 surrounding the nuances of using SUVmax to identify malignancies. This may highlight the need to take into consideration a combination of clinical judgement, radiology, and laboratory results when investigating a PET/CT finding suspicious for malignancy. 

Reviewer 2 Report

Comments and Suggestions for Authors

The authors of this manuscript performed a systematic review on the prevalence and significance of incidental PET/CT findings of cancer detected in patients evaluated for their primary hematologic malignancy.

Thirteen studies published between 2008-2022 were reviewed, including conference abstracts (n = 8) and journal articles (n = 5)

The manuscript is well-structured in each section and the topic is timely. I agree with the authors that meta-analysis is not appropriate due to the heterogeneity among the studies included in this review.

Here below you find some suggestions to further improve the quality of this manuscript:

- please report the filled PRISMA checklist as Supplemental file

- As PET/CT can be performed using different radiotracers it is relevant to specify in the whole manuscript the type of PET tracer used (fluorine-18 fluorodeoxyglucose). Therefore the name of the PET tracer (or its abbreviation: FDG) should be reported in the title and in the whole mansuscript (e.g. FDG PET/CT)

- Even if not mandatory, a figure illustrating a case of incidental cancer detected by FDG PET/CT performed in a patient with hematological malignany could be reported

Author Response

Comment 1: Please report the filled PRISMA checklist as a Supplemental file

Response 1: Thank you for taking the time to review our paper. We greatly appreciate your feedback and have incorporated your suggestions into the revised manuscript. As per your comment, we have attached our PRISMA checklist as a supplemental file (please see attached). Accordingly, we have modified a few elements of the formatting to better fit the checklist. Notably, we listed our extracted data items (in section 2.2.4 under methods) and reorganized our explanation of the risk of bias methodology by moving a paragraph from section 3.4 to section 2.2.5. We hope this provides greater clarity and congruence with the PRISMA checklist. 

 

Comment 2: As PET/CT can be performed using different radiotracers it is relevant to specify in the whole manuscript the type of PET tracer used (fluorine-18 fluorodeoxyglucose). Therefore the name of the PET tracer (or its abbreviation: FDG) should be reported in the title and in the whole manuscript (e.g. FDG PET/CT)

Response 2: While our study design did not limit inclusion to FDG tracers (refer to “Intervention” section of Table 1), we noticed that 10 out of the 13 eligible studies used FDG PET/CT. We have included a statement to clarify this on lines 159-161.  

 

Comment 3: Even if not mandatory, a figure illustrating a case of incidental cancer detected by FDG PET/CT performed in a patient with hematological malignancy could be reported

Response 3: We acknowledge that it could be helpful to include an imaging example of an incidental cancer detected by PET/CT. However, the overarching purpose of this review is to identify and summarize primary manuscripts that report on incidental second primary malignancies when FDG PET/CTs are performed as opposed to illustrating a specific case. We suggest that this addition would detract from the essence of the manuscript – a systematic review; as such we have declined to include this in the body of our manuscript. We appreciate your understanding.

Author Response File: Author Response.pdf