Radiotherapy-Related Clinical and Functional Sequelae in Lung Cancer Survivors

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

In the current study the authors have done a comprehensive analysis of the clinical effects of radiotherapy on lung cancer survivors. The study is significant as this will help clinicians formulate future treatment plans and supportive care. The authors draw conclusions about the quality of life based on the clinical effects.

I found the study lacking in the following aspects.  I suggest the following changes will enhance the quality of the manuscript :

1. The conclusion section is too short. The authors should add a sentence or two about how the findings might benefit clinicians.

2. This study-doi:10.3238/arztebl.m2021.0024 also has a section about - " The risk of cognitive impairment following RT" . The authors should cite this study and compare their conclusions.

3. A more detailed description between the relationship about the type of RT received vs the extent of sequelae if any should be mentioned.  Is one type of RT better than the other ?

4. Where the rest of the 54% of patients all females ?

5. A more detailed information about - what kind of physical activity was affected in the patients in the long term would be useful.

Author Response

Comment 1: The conclusion section is too short. The authors should add a sentence or two about how the findings might benefit clinicians.

Response: We acknowledge the reviewer´ comment. According with her/his suggestion, we have improved the conclusion section to make the article more adequate. (Line 292)

Comment 2: This study-doi:10.3238/arztebl.m2021.0024 also has a section about - " The risk of cognitive impairment following RT". The authors should cite this study and compare their conclusions.

Response: We acknowledge the reviewer´ comment. We have read the recommended study and it has been used to discuss with our results. (Line 244)

Comment 3: A more detailed description between the relationship about the type of RT received vs the extent of sequelae if any should be mentioned. Is one type of RT better than the other?

Response: Thank you for your comment. We agree with the reviewer that clarifying these aspects could be very interesting in this study. So we have assessed the mentioned relationship, but no significant differences has been observed between the application of the types of RT. Here we attach the results found.

 

	VMAT + IGRT N = 33	SBRT + IGRT N = 15	External N = 12	F (p)
Symptoms
Dyspnea	4,52 ± 2,06	4,47 ± 1,76	3,42 ± 1,92	1,47  (0,24)
Cough	5,52 ± 4,37	6,53 ± 4,50	5,25 ± 2,52	0,41 (0,66)
Fatigue
Behavioral	3,01 ± 1,62	2,89 ± 1,36	4,34 ± 1,68	3,63 (0,055)
Affective	4,84 ± 2,15	5,15 ± 2,16	5,49 ± 2,20	0,43 (0,65)
Cognitive	5,40 ± 2,12	5,72 ± 1,41	6,15 ± 2,44	0,61 (0,544)
Sensory	4,73 ± 0,97	4,61 ±  0,61	5,47 ± 1,32	3,01 (0,057)
Physical Activity
Walking	708,33 ± 592,50	422,33 ± 437,36	308,87 ± 468,49	3,08 (0,053)
Moderate	228,67 ± 417,12	38,23 ± 86,67	249,00 ± 295,63	1,87 (0,164)
Vigorous	83,04 ± 82,80	91,28 ± 63,53	40,69 ± 56,80	1,83 (0,169)
Total	1020,04 ± 794,16	551,85 ± 489,43	598,57 ± 454,62	3,29 (0,054)
Minutes / sitting	449,29 ± 167,94	455,36 ± 143,12	454,47 ± 114,29	0,010 (0,99)
Barriers to P.A.	25,00 ± 4,92	25,47 ± 4,68	26,58 ± 4,42	0,48 (0,618)
Muscle Mass (RFCSA)	0,93 ± 0,30	1,04 ± 0,23	1,07 ± 0,18	1,71 (0,189)
Quality of Life
Mobility subscore	2,12 ± 0,960	1,87 ± 0,91	2,25 ± 0,75	0,65 (0,525)
Self-care subscore	1,79 ± 1,08	1,47 ± 0,74	1,75 ± 0,75	0,61 (0,547)
Activities daily life subscore	1,97 ± 0,91	1,93 ± 0,70	2,00 ± 0,73	0,02 (0,979)
Pain subscore	2,27 ± 0,91	2,27 ± 0,70	2,33 ± 0,77	0,02 (0,973)
Anxiety-Depression subscore	1,85 ± 0,90	1,87 ± 1,12	1,58 ± 0,66	0,41 (0,664)
VAS subscore (0-100)	57,27 ± 23,72	64,33 ± 15,22	66,67 ± 11,54	1,26 (0,289)

 

 

Comment 4: Where the rest of the 54% of patients all females ?

Response: Thank you for comment. We are not sure what the reviewer is referring to, we believe that the question is about sex distribution and there has been misleading data in table 1. We understand that this table is not clear enough, for this reason we have modified the detailed information regarding sex distribution. (Table 1)

Comment 5: A more detailed information about - what kind of physical activity was affected in the patients in the long term would be useful.

Response: Thank you for your comment. We agree with the reviewer that clarifying these aspects will be useful. We have modified the Future research section adding this fact as an important knowledge gap for research. (Line 273).

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

In this manuscript, Alejandro Heredia-Ciuró et al. investigate the clinical and functional outcomes of lung cancer survivors following radiotherapy. The research revealed significant increases in symptoms such as dyspnea, cough, and fatigue, alongside a marked decline in physical activity levels and muscle mass, as well as a decrease in quality of life. Patients showed heightened barriers to physical activity and greater sedentary behavior post-treatment. These findings underscore the need for targeted interventions, such as rehabilitation programs, to mitigate long-term sequelae and enhance the quality of life for lung cancer survivors.

 

1. My biggest concern about current study is lack of control group. Control groups are essential in biological experiments as they provide a baseline that allows researchers to compare and analyze the results. In this study, the control group of lung cancer patients who did not receive radiotherapy or received alternative treatments should be included. Without the control group, it is difficult to attribute the observed changes solely to radiotherapy rather than other concurrent treatments or natural disease progression.
2. Moreover, include other groups receiving different treatments, such as chemotherapy or immunotherapy, to better isolate the specific impacts of radiotherapy and understand how different modalities affect patient outcomes. This is a suggestion, optional.
3. Some molecular experiments are also recommended to briefly explain and support current results. There are some proteins or pathways you can try: P53, ATM/ATR, BRCA1/BRCA2 (DDR pathway); NF-κB, IL-6 (inflammation); Bcl-2, Caspases (Apoptosis). Above mentioned proteins or pathways are just suggestions, and it is more than welcome if you have other proteins or pathways to investigate to support and explain your data.
4. Minor concern: There are still some language issues in the article.

 

Comments on the Quality of English Language

Moderate editing of English language required

Author Response

Dear Editor and Reviewer,

Please find a revision of our manuscript entitled " Radiotherapy-related Clinical and Functional sequelae in Lung Cancer Survivors." We would like to thank the editor and reviewer for the comments. Changes have been highlighted in yellow in the revised manuscript. An itemized point-by-point response to comments is presented below.

 

Comment 1: My biggest concern about current study is lack of control group. Control groups are essential in biological experiments as they provide a baseline that allows researchers to compare and analyze the results. In this study, the control group of lung cancer patients who did not receive radiotherapy or received alternative treatments should be included. Without the control group, it is difficult to attribute the observed changes solely to radiotherapy rather than other concurrent treatments or natural disease progression. 

Response:  We agree with the reviewers´ comment. When the study design was proposed, we did not consider a case-control study since it was a directional research question. Therefore, a one-group study could detect smaller differences, making them more sensitive to the effects of the independent variable (Hales AH. One-tailed tests: Let's do this (responsibly). Psychol Methods. 2023. doi: 10.1037/met0000610). However, we agree with the reviewer that using single-group designs may lead to bias. For this reason, we have highlighted in the Limitations section that the comparison with a control group might have been more beneficial to the study. (Line 265)

 

Comment 2: Moreover, include other groups receiving different treatments, such as chemotherapy or immunotherapy, to better isolate the specific impacts of radiotherapy and understand how different modalities affect patient outcomes. This is a suggestion, optional.

Response: We acknowledge the reviewer´ comment. We agree with the reviewer that clarifying these aspects will be useful. We will take it into account for future studies.

 

Comment 3: Some molecular experiments are also recommended to briefly explain and support current results. There are some proteins or pathways you can try: P53, ATM/ATR, BRCA1/BRCA2 (DDR pathway); NF-κB, IL-6 (inflammation); Bcl-2, Caspases (Apoptosis). Above mentioned proteins or pathways are just suggestions, and it is more than welcome if you have other proteins or pathways to investigate to support and explain your data. 

Response: We agree with the reviewer that including these aspects could have been very interesting. Unfortunately, this analysis was not initially raised. This is now acknowledged in the Future studies section and we have mentioned previous research in relation to these facts. (Line 277)

 

Comment 4: Minor concern: There are still some language issues in the article. Moderate editing of English language required.

Response: We acknowledge the reviewer´ comment. We are agree with you, I apologize for our grammar. The manuscript has been sent to a native editor-reviewer who has checked the grammar of the English language.