Interstitial Lung Diseases and Lung Cancer: A Review on Similarities, Common Pathogenesis and Therapeutic Approach
, Elisabetta Cocconcelli 1, Giuliana Grimaudo 1, Irene Di Leo 2, Serena Bellani 1, Giordano Fiorentù 1, Giacomo Giulianelli 1, Nicol Bernardinello 1, Elisabetta Balestro 1 and Paolo Spagnolo 1,*
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe manuscript entitled” Interstitial Lung Diseases and Lung Cancer: a Review on Similarities, Common Pathogenesis and Therapeutic Approach” was reviewed. This is a review article concerning the association between interstitial lung diseases and lung cancer. The manuscript is long and covers many fields in interstitial lung disease and lung cancer. Although the authors attempted to discuss this issue in detail, the manuscript is indeed a long one. However, in the past, there were several review articles published, such as “Lung cancer and interstitial lung disease: a literature review” (Naccache, J.M., Gibiot,Q.,, Monnet,I., Antoine, M., Wislez,M.,
Chouaid,C., Cadranel, J., J Thorac Dis 2018;10(6):3829-3844) and “Lung Cancer and Interstitial Lung Diseases” (Drakopanagiotakis, F., Krauss, E., Michailidou, I., Drosos, V., Anevlavis, V., Günther, A., Steiropoulos, P., Cancers 2024, 16, 2837. https://doi.org/10.3390/cancers16162837). These 2 references were not cited in this manuscript. The authors need to read these 2 previously published similar review articles and reorganize their contents to focus on the most recent advances in this topic.
And there is a major defect in this review article. It is well known that primary lung cancer can be classified into 2 major types: small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC). The latter can be further subgrouped into 1. Adenocarcinomas. 2. Squamous cell carcinomas. 3. Large cell carcinomas. There are other types of lung cancer, including bronchial carcinoids and cancers of supporting lung tissue such as smooth muscle, blood vessels, or cells involved in the immune response are rare in the lung. All these different primary lung cancers have different cell types, and their clinical characteristics also differ variably. Therefore, the authors need to discuss the issue individually, at least in selective parts of the manuscript. in current manuscript, only 1 or 2 sentences mentioned it.
Additionally, in Line 110-117, there are strange sentences “Materials and Methods should be described with sufficient details to allow others to replicate and build on the published results. Please note that the publication of your manuscript implies that you must make all materials, data, computer code, and protocols associated with the publication available to readers. Please disclose at the submission stage any restrictions on the availability of materials or information. New methods and protocols should be described in detail while well-established methods can be briefly described and appropriately cited.” These sentences seem to be the general guidelines for authors to prepare their manuscript. Please delete it.
- In this manuscript, please add a note following the first occurrence of the abbreviation “UIP”.
Author Response
Comment 1: The manuscript entitled” Interstitial Lung Diseases and Lung Cancer: a Review on Similarities, Common Pathogenesis and Therapeutic Approach” was reviewed. This is a review article concerning the association between interstitial lung diseases and lung cancer. The manuscript is long and covers many fields in interstitial lung disease and lung cancer. Although the authors attempted to discuss this issue in detail, the manuscript is indeed a long one. However, in the past, there were several review articles published, such as “Lung cancer and interstitial lung disease: a literature review” (Naccache, J.M., Gibiot,Q.,, Monnet,I., Antoine, M., Wislez,M., Chouaid,C., Cadranel, J., J Thorac Dis 2018;10(6):3829-3844) and “Lung Cancer and Interstitial Lung Diseases” (Drakopanagiotakis, F., Krauss, E., Michailidou, I., Drosos, V., Anevlavis, V., Günther, A., Steiropoulos, P., Cancers 2024, 16, 2837. https://doi.org/10.3390/cancers16162837). These 2 references were not cited in this manuscript. The authors need to read these 2 previously published similar review articles and reorganize their contents to focus on the most recent advances in this topic.
Response 1: We thank the reviewer for pointing out those two papers and helping us in bettering and differentiating our work. Naccache et al. was one of the basis of our work and was already cited several times in the paper (cit n. 16, former cit n 15), while Drakopanagiotakis et al. work was effectively not cited. We added the citation (n. 98) and read the article with interest and pleasure which helped improve our paper.
Comment 2: And there is a major defect in this review article. It is well known that primary lung cancer can be classified into 2 major types: small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC). The latter can be further subgrouped into 1. Adenocarcinomas. 2. Squamous cell carcinomas. 3. Large cell carcinomas. There are other types of lung cancer, including bronchial carcinoids and cancers of supporting lung tissue such as smooth muscle, blood vessels, or cells involved in the immune response are rare in the lung. All these different primary lung cancers have different cell types, and their clinical characteristics also differ variably. Therefore, the authors need to discuss the issue individually, at least in selective parts of the manuscript. in current manuscript, only 1 or 2 sentences mentioned it.
Response 2: We thank the reviewer for raising this concept. We added both an introduction of different histotypes of LC and presented the NSCLC and SCLC parts more in detail in the “4.Distribution and Histopathology of Lung Cancer in Interstitial Lung Diseases” section. Due to the primary aim of our paper, we did not create selective parts of the manuscript for the singular entities, however, we hope to have provided a sufficiently detailed description of the epidemiology of these entities associated with ILD.
Comment 3:Additionally, in Line 110-117, there are strange sentences “Materials and Methods should be described with sufficient details to allow others to replicate and build on the published results. Please note that the publication of your manuscript implies that you must make all materials, data, computer code, and protocols associated with the publication available to readers. Please disclose at the submission stage any restrictions on the availability of materials or information. New methods and protocols should be described in detail while well-established methods can be briefly described and appropriately cited.” These sentences seem to be the general guidelines for authors to prepare their manuscript. Please delete it.
Response 3: We are sorry for the mistake. There was an issue with uploading the document in the journal’s required format. The problem has been amended.
Comment 4:In this manuscript, please add a note following the first occurrence of the abbreviation “UIP”.
Response 4: We thank the reviewer for pointing out this mistake, we amended it as suggested.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe paper is a very interesting review about ILDs. It is very informative, well written, the figure is simple but gives all information needed. Nevertheless, there are some minor issues that could be ameliorated.
Please explain all abbreviations when you mention them for the first time.
Line 18: please explain the term “scar-cinoma”
Line 39: is it the only reason why there are more cases of ILDs? Please discuss a bit and add maybe some other reasons or refer to other parts of the manuscript.
Line 43: maybe it would be an idea to write a bit about these categories or refer to other parts of the manuscript.
Fig. 1 Mutations are usually associated with genes, consider to reformulate.
Lines 94-99: consider to reformulate this paragraph. For the moment, it is not clear if smoking is the main risk factor and/or inducer of pathomechanisms. Now it sounds like “it is but it’s not”.
Line 110-117: delete this part, it seems to be a part of the template.
Line 152: consider to add examples of these cytokines and nitro derivatives.
Line 175-177: consider to reformulate or divide into 2 separate sentences.
Line 228: do you mean the JAK-STAT pathway?
Table 1: consider to reformulate the table or present the content in another way; now it is difficult to understand. Maybe another form of the table would be clearer.
Line 407: I do not really understand the need of presence of this section. In fact, its content refers rather to all severe and life-threatening diseases, not only ILD&LC. Why have you decided to put it into the text? Nevertheless, if you think that this section is indispensable in the review, leave it but consider to add a sentence about the need of such section in this paper.
Author Response
Comment 1: Please explain all abbreviations when you mention them for the first time.
Response 1: We reviewed all the paper and amended whenever necessary the abbreviations used and/or added the correct explanations.
Comment 2: Line 18: please explain the term “scar-cinoma”
Response 2: Dear reviewer, we expanded the definition of scar-cinoma as requested in lines 18-19.
Comment 3: Line 39: is it the only reason why there are more cases of ILDs? Please discuss a bit and add maybe some other reasons or refer to other parts of the manuscript.
Response 3: Dear reviewer, we agree that the perceived increased incidence and prevalence of ILD patients may have several reasons. In literature there are no clear explanations further than the increased interest in the topic among the scientific community. In any case we smoothened the affirmation and added a new citation to explain the concept better (lines 40-44).
Comment 3: Line 43: maybe it would be an idea to write a bit about these categories or refer to other parts of the manuscript.
Response 3: We thank the reviewer for this kind suggestion. We expanded as requested the explanation of the categories (lines 46-49)
Comment 4: Fig. 1 Mutations are usually associated with genes, consider to reformulate.
Response 4: We thank the reviewer for the clarification; we have made the change as requested.
Comment 5: Lines 94-99: consider to reformulate this paragraph. For the moment, it is not clear if smoking is the main risk factor and/or inducer of pathomechanisms. Now it sounds like “it is but it’s not”.
Response 5: We thank the reviewer for the help in clarifying this complex point. In fact smoke seems to be the main character in the majority of ILD-LC instances, however, in conditions such as SSc-ILD, inflammation and immune processes seems more related to the development of the combined diseases. We tried to explain better the concept in the text (lines 101-110)
Comment 6: Line 110-117: delete this part, it seems to be a part of the template.
Response 6: We are sorry for the mistake. There was an issue with uploading the document in the journal’s required format. The problem has been amended.
Comment 7: Line 152: consider to add examples of these cytokines and nitro derivatives.
Response 7: In lines 153-162 we already briefly presented TGFbeta and nitric oxidative (NO) derivatives as related to both ILD and LC. We hope the reviewer agrees to this as sufficient examples.
Comment 8: Line 175-177: consider to reformulate or divide into 2 separate sentences.
Response 8: As suggested we divided the statement in two separate sentences.
Comment 9: Line 228: do you mean the JAK-STAT pathway?
Response 9: We thank the reviewer for pointing out this mistake, we amended it as suggested.
Comment 10: Table 1: consider to reformulate the table or present the content in another way; now it is difficult to understand. Maybe another form of the table would be clearer.
Response 10: Reviewing the table we agreed with the reviewer that it was complex to understand. Therefore we tried to simplify the concepts by grouping better the prevalences of mutations in the ILD-LC and LC populations. We hope that now the table is better rendered.
Comment 11: Line 407: I do not really understand the need of presence of this section. In fact, its content refers rather to all severe and life-threatening diseases, not only ILD&LC. Why have you decided to put it into the text? Nevertheless, if you think that this section is indispensable in the review, leave it but consider to add a sentence about the need of such section in this paper.
Response 11: Dear reviewer, we absolutely agree in the concept that every severe and life-threatening disease has a need for a correct approach in the palliative and end-of-life treatment. However, several publications underlined that this approach remains an unmet need in the IPF/ILD population. Furthermore the LC overlap on an ILD background may accelerate the need for palliative care referral. Therefore, we deemed to add this paragraph essential to underline the importance of this topic in the ILD-LC population. We also added as requested a new sentence to explain this concept also to the reader (lines 461-462).
Reviewer 3 Report
Comments and Suggestions for AuthorsThanks for the opportunity to review the manuscript by Gioele Castelli and colleagues. In this, the authors evaluate the main pathogenetic mechanisms, clinical presentations, and treatment implications.
In general, the main idea for summarizing the clinical presentations and treatment implications is very well described and includes relevant information. However, the pathogenic mechanisms should be revised in detail and improved; most descriptions are superficial.
Next, some comments to be addressed for the authors:
A most appropriate description for "environmental exposures" in Figure 1 is: Tobacco smoking (not just "smoking"), and in the case of "e-cig", should be corrected to electronic nicotine delivery systems (ENDS) and heated tobacco products (HTP), which are different devices, and have been described to affect lung function (PMID: 33924379).
Remove the paragraph in line 112 "Please note that the publication of your manuscript implicates that you must make all materials..." since this is part of the paper template. Be careful, please, in your revised version.
The section "5. Genetic Mutations: similarities and common pathways" is vague and imprecise; the authors should refine these concepts and content. The "mutations" you argue in the SFTPA, SFTPA2, "p53" (TP53), and STPFA1 genes should be carefully described. Please remember that not all genetic variants are mutations; most are single-nucleotide variants with different effects. Include a depicting table including gene(s), variants "rs ID" (if applicable), gene location, effect, and reference. Do not forget to use the correct symbols for human genes, as specified by the HGNC (https://www.genenames.org/).
Expand and improve the information about telomere shortening, as it is currently imprecise and superficial.
Author Response
In general, the main idea for summarizing the clinical presentations and treatment implications is very well described and includes relevant information. However, the pathogenic mechanisms should be revised in detail and improved; most descriptions are superficial.
Next, some comments to be addressed for the authors:
Comment 1: A most appropriate description for "environmental exposures" in Figure 1 is: Tobacco smoking (not just "smoking"), and in the case of "e-cig", should be corrected to electronic nicotine delivery systems (ENDS) and heated tobacco products (HTP), which are different devices, and have been described to affect lung function (PMID: 33924379).
Response 1: We thank the reviewer for the clarification; we have modified Figure 1 as requested.
Comment 2: Remove the paragraph in line 112 "Please note that the publication of your manuscript implicates that you must make all materials..." since this is part of the paper template. Be careful, please, in your revised version.
Response 2: We are sorry for the mistake. There was an issue with uploading the document in the journal’s required format The problem has been amended.
Comment 3: The section "5. Genetic Mutations: similarities and common pathways" is vague and imprecise; the authors should refine these concepts and content. The "mutations" you argue in the SFTPA, SFTPA2, "p53" (TP53), and STPFA1 genes should be carefully described. Please remember that not all genetic variants are mutations; most are single-nucleotide variants with different effects. Include a depicting table including gene(s), variants "rs ID" (if applicable), gene location, effect, and reference. Do not forget to use the correct symbols for human genes, as specified by the HGNC (https://www.genenames.org/).
Response 3: We thank you for this comment and suggestion. We modified the symbols for human genes according to the HGNC. We tried to expand the presentation of the genetic mutation and variants in the surfactant and telomere related genes, expliciting when a mutation was found and when only a genetic variant. We also tried to be specific on the activity of the mutation, when presented in the original cited papers. We preferred to avoid a genetic table, which would be out of the scope of this review.
Comment 4: Expand and improve the information about telomere shortening, as it is currently imprecise and superficial.
Response 4: We expanded as suggested the informations about telomere shortening and telomere related genes.
Round 2
Reviewer 3 Report
Comments and Suggestions for AuthorsThanks for addressing my previous concerns. Just ensure that all gene symbols are in italic font wherever they are mentioned, including in tables and figures.
