When Two Maladies Meet: Disease Burden and Pathophysiology of Stroke in Cancer

Round 1

Reviewer 1 Report

In this review, Sun and Bhaskar have extensively discussed about stroke in cancer with a focus on their burden and pathophysiology. This is a timely review that provides up-dated information to readers. The authors also provide important inputs to researchers working in the filed. I have some suggestions and corrections of the review before it is accepted for publication as follows:

 

1.      The abbreviations should be defined when their full names appeared for the first time. Also, avoid repeating definitions. For example, “AIHW” and “low- and middle-income countries (LMIC)” in Page 5.

2.      In the Abstract, the authors mentioned that stroke is a “chronic disease”. However, stroke was always regarded as an acute disorder. And also, I don’t think that stroke and cancer have “common aetiopathological mechanisms”, strongly suggest the authors put it another way.

3.      In the section of “Direct Impact of the Tumour”, it is lack of sufficient argumentation support.

4.      The fonts in Page 24 are different.

Author Response

We thank the reviewer for the favorable review of our work and comments. The comments received have helped us to improve the manuscript significantly. 

We have made significant efforts to incorporate the feedback from the reviewer. Please find our point-by-point rebuttal below as well as the revised manuscript that is attached for your perusal.

C#: In this review, Sun and Bhaskar have extensively discussed about stroke in cancer with a focus on their burden and pathophysiology. This is a timely review that provides up-dated information to readers. The authors also provide important inputs to researchers working in the filed. I have some suggestions and corrections of the review before it is accepted for publication as follows:

Reply# We thank the reviewer for the review of our work and positive remarks. 

C#1. The abbreviations should be defined when their full names appeared for the first time. Also, avoid repeating definitions. For example, “AIHW” and “low- and middle-income countries (LMIC)” in Page 5.

Reply# We thank the reviewer for indicating this. We have now updated all the abbreviations, as advised.

 

C#2: In the Abstract, the authors mentioned that stroke is a “chronic disease”. However, stroke was always regarded as an acute disorder. And also, I don’t think that stroke and cancer have “common aetiopathological mechanisms”, strongly suggest the authors put it another way.

Reply# We have made appropriate changes in the abstract as seen below.

"Stroke and cancer are disabling diseases with an enormous global burden, disproportionately affecting vulnerable populations and low- and middle-income countries. Both these diseases share common risk factors which warrant concerted attention toward reshaping population health approaches and the conducting of fundamental studies"

C#3: In the section of “Direct Impact of the Tumour”, it is lack of sufficient argumentation support.

Reply# We thank the reviewer for the suggestion. We have expanded this section as below. The manuscript has been updated.

"Direct Impact of the Tumour

The effect of the tumor itself in contributing to vascular events cannot be overlooked [35]. Stroke due to the direct impact of the tumor, is relatively rare, albeit, challenging to diagnose in clinical settings. Direct effects of tumor can manifest in varying forms [35], including compression of the blood vessel by tumor, invasion of arterial and venous sinus by leptomeningeal infiltrates or tumor mass, or bleeding within the tumor, also referred to as intratumoral hemorrhage (ITH) [38,39]."

C#4: The fonts in Page 24 are different.

Reply# The font has been changed

 

Author Response File: Author Response.pdf

Reviewer 2 Report

This work presents review paper important for the field of neurobiology and medicine. The text is correctly conceived, the cited literature is adequate and recent. In this extensive manuscript, the authors present an overview of contemporary knowledge about association of stroke and cancer, including epidemiological trends in the prevalence and burden of these diseases, underlying biological mechanisms and clinical risk factors. Various tools available for risk prediction and prognosis are described. In addition, recommendations for future research are elaborated, with the aim of bridging existing gaps in our understanding of pathophysiology of both disorders, particularly of stroke in cancer patients. The authors the authors pointed out that future research should be directed at the investigation of the causes that predispose increased risk of stroke and/or cancer, and at biomarkers that can be used to predict associated morbidity and mortality. Bearing in mind all the foregoing, and importance of such a review paper for both scientists and clinicians, I truly suggest that the manuscript be published in its current form. 

Author Response

We thank the reviewer for the critical review of our work and positive remarks. 

 

Round 2

Reviewer 1 Report

The authors have fully addressed all my concerns raised in the review process.No further comments.