Incidence of non-Hodgkin’s lymphoma among adults in Sardinia, Italy

Giorgio Broccia; Jonathan Carter; Cansu Ozsin-Ozler; Federico Meloni; Sara De Matteis; Pierluigi Cocco

doi:10.1371/journal.pone.0260078

Peer Review History

Original SubmissionMarch 18, 2021
6 Jun 2021 Decision Letter - Francesco Bertolini, Editor PONE-D-21-08974 Incidence of non Hodgkin lymphoma among adults in Sardinia, Italy PLOS ONE Dear Dr. Cocco, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process by the two Reviewers. Please submit your revised manuscript by Jul 21 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Please remove your figures from within your manuscript file, leaving only the individual TIFF/EPS image files, uploaded separately. These will be automatically included in the reviewers’ PDF. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? 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Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: No Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: corrections to English, Non Hodgkin's would be better than Non Hodgkin. line 88 - only a fraction of cases not but line 249 - confirms validity not confirm line 250- and indicates not indicate line 251 - with what was observed not what observed Reviewer #2: This manuscript is about a population based study of lymphoma cases diagnosed in Sardinia during a very long time frame. The manuscript is full of observations and is mainly hypothesis generating. The used approach is interesting and adds value to the work. Nevertheless the study result are severely affected by diagnostic biases caused by the important changes made to the classification of lymphomas during the last 30 years. This problem is only partly hide by the analysis of lymphoma as a whole that represent a second major concern that severely limits the transferability of these data to the clinic. Lymphomas are currently seen as a group of separate entities and every effort should be done to refer data also from cancer based registries to single entities, at least for the most frequent ones. Are there any lymphoma specifica data available at least for the most recent diagnoses, to try to identify if some lymphoma subtype was the cause of different geographical distribution? A second comment is related to possible temporal changes in the epidemiology of lymphomas during the study period. it would be interesting to analyze this trend separating the study frame in 2 or 3 periods and if number are not to small to identify and explain possible changes. Finally it would be useful to compare these epidemiological data (i.e. world standardized incidence) with other available from other cancer registries in Italy and to discuss about the comparison (i.e. Luminari et al. Hematologiacl Oncology 2007). ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes:** Kalyan Saginala Reviewer #2: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0260078.r001
Revision 1
10 Aug 2021 Author Response PLoS One Manuscript # PONE-D-21-08974 “Incidence of non-Hodgkin’s lymphoma among adults in Sardinia, Italy” Response to the Editor 1. “…ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming” Title page, main text, and file names do now comply with PLOS ONE’s style requirements. 2. “data from this study …available upon request” We took note of the Journal’s requirement for data availability, and we uploaded the file with the aggregated data as a supplementary file in submitting the revised version. 3. “Figure 2 … contains map images which may be copyrighted” We contacted the person who created the map of the administrative borders of the Italian communes and made it available on the web site https:\\\\umap.geonue.com/en/map/confini-e-dati-statistici-dei-comuni-ditalia _297#8/40.102/8.973. As reported in the screenshot of the web page we accessed, the map was based on a software created by the National Association of the Italian Communes (ANCITEL) under an Open Database License (ODbL). As reported in the web site https:// opendatacommons.org/licenses/odbl/1-0/index.html, the ODbL license is a license agreement that allows users to freely share, modify, and use under the understanding that the resulting product will also made freely available to the public, and with the condition that the attribution of the original work would be acknowledged to the authors, the product would be shared alike, and the database would be kept open. Such conditions seem to us compatible with the CC BY 4.0 license. Therefore, in the revised version, we added a sentence acknowledging the authors of the map and the creator of the software used for the purpose under the ANCITEL ODbL license. In Submitting the revised manuscript, we also uploaded the screenshot of the web page we accessed (in Italian), along with its translation to English, as an “other” file. 4. The “… ethics statement should only appear in the Methods section …” The ethics statement is now the last paragraph of the Methods section. 5. “…remove your figures from within …[the]… manuscript file, leaving only the individual TIFF/EPS image files, uploaded separately.” We removed Fig 2 from the manuscript file, and uploaded separately its parts as individual TIFF image files. Response to the reviewers’ comments Reviewer 1. Grammatical errors. We are grateful to the reviewer for picking some grammatical errors in the text. We amended those and a few others. However, the plural form of the verbs “to confirm” (line 249) and “to indicate” (line 250) is correct as the subject (Cancer Registry data) is plural. Reviewer 2. 1. “…diagnostic biases caused by the important changes made to the classification of lymphomas during the last 30 years”. We dedicated an entire paragraph, the first under the subheading “Limitations” from line 309 to 328 on page 10 to discuss this point. As we explain in the text, having the first author, himself a senior hematologist, collecting and revising each diagnosis of the incident hematological malignancies in 1974-2003 should reassure us and the readers about diagnostic bias due to the changes in the lymphoma classification that occurred along the study period. 2. ”…the analysis of lymphoma as a whole …[is]… a second major concern that severely limits the transferability of these data to the clinic. Lymphomas are currently seen as a group of separate entities and every effort should be done to refer data also from cancer based registries to single entities”. “Are there any lymphoma specific data available at least for the most recent diagnoses, to try to identify if some lymphoma subtype was the cause of different geographical distribution?”. We definitely agree with the reviewer that every effort should be addressed to explore individual subtypes. However, the point is that the epidemiological analysis of time trends requires using a uniform definition of the disease entity across the time span object of the investigation. This imposes keeping using the initial definition. For the same reason, the IARC CI5 volumes and the Cancer Registries also keep using the NHL definition. A few studies have explored time trends, although within a still limited time frame (Morton L et al. Blood 2006;107(1):265-276; Luminari S et al. Hematol Oncol 2007;25:189-197; van Leeuwen MT et al. Int J Cancer 2014;135(9):2146-2156; Lim RB et al. Int J Cancer. 2015;137(11):2674-2687) or survival from (Al-Hamadani M et al. Am J Hematol 2015;90: 790–795; Ye X et al. BMJ Open 2017;7(7):e015106), major B-cell lymphoma subtypes. To the best of our knowledge, enough information might be currently available to explore the spatial distribution of lymphoma subtypes as well. We hope that for the future IARC would promote the registration of lymphoma subtypes besides keeping the old NHL definition, so to make possible what the reviewer proposes at a larger scale. 2. “…possible temporal changes in the epidemiology of lymphomas during the study period. it would be interesting to analyze this trend separating the study frame in 2 or 3 periods and if number are not too small to identify and explain possible changes.” We are grateful to the reviewer for raising this interesting comment. To identify any joinpoint in the regression of NHL incidence against time, we plotted the residuals against the values predicted by the regression equation. As shown in figure 1, high or low residuals did not cluster in a specific range of predicted values. Therefore, we interpreted the upward trend we observed as continuous, with no evidence of a sudden change in slope, which might have been related to introduction of new diagnostic tests, or upgrade or new opening of onco-haematology facilities, or any acute environmental event. We added a new sentence at the end of the Time trend in NHL incidence paragraph of the Results section. Figure 1. Residuals vs values predicted by the regression equation of 1974-2003 NHL incidence in Sardinia. 4. “… compare these epidemiological data (i.e. world standardized incidence) with other available from other cancer registries in Italy and to discuss about the comparison (i.e. Luminari et al. Hematol Oncol 2007).” We again grateful to the reviewer for its useful suggestion. We retrieved the paper by Luminari et al., we extracted the corresponding figures from our data set, and we compared the age standardized incidence rates (World standard population) in males and females for the corresponding period. Rates from the Modena Cancer Registry were substantially higher in both genders. In the revised version, we added a paragraph under the subheading “Time trend in NHL incidence” to present and comment about such comparison. Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0260078.r002
27 Sep 2021 Decision Letter - Francesco Bertolini, Editor PONE-D-21-08974R1Incidence of non-Hodgkin's lymphoma among adults in Sardinia, ItalyPLOS ONE Dear Dr. Cocco, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process by Reviewer #1. Please submit your revised manuscript by Nov 11 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. 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Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Additional Editor Comments (if provided): [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: 38th page - suggests not suggest 42 page - the communes associated with posterior probability are located on the extreme right of the incidence distribution curve of the 356 communes in the region would be better way to phrase and write than the current original one Reviewer #2: (No Response) ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Kalyan Saginala Reviewer #2: Yes:** Stefano Luminari [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0260078.r003
Revision 2
8 Oct 2021 Author Response Reviewer 1. 1. Grammatical error (“38th page - suggests not suggest”). The plural form of the present tense of the verb “to suggest” is used twice: one in the abstract (line 10) and one on page 10 of the manuscript (last line). In both instances, the plural form is correct as the subject (Cancer Registry data) is plural. 2. “42 page - the communes associated with posterior probability are located on the extreme right of the incidence distribution curve of the 356 communes in the region would be better way to phrase and write than the current original one” We rephrased the statements that describe the location of high incidence communes in the graph and in the map as it follows: “Another 22 communes are located on the extreme right of the incidence distribution curve of the 356 communes in the region, with a posterior probability of an excess NHL incidence in the total population ranging 80 – 94%. On the map, these communes tended to concentrate in the northern (20/35 communes) and central (12/35) areas of the island, with only three in southern Sardinia, including the major urban area of Cagliari.” We are grateful for the reviewer suggestion, and we hope the sentence sounds better. Attachments Attachment Submitted filename: Broccia G etalR2 - Response to reviewers.docx https://doi.org/10.1371/journal.pone.0260078.r004
3 Nov 2021 Decision Letter - Francesco Bertolini, Editor Incidence of non-Hodgkin's lymphoma among adults in Sardinia, Italy PONE-D-21-08974R2 Dear Dr. Cocco, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Francesco Bertolini, MD, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: interesting article, very well summarized the epidemiological background and incidence of NHL among adults in Sardinia, Italy, title is appropriate ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes:** kalyansaginala https://doi.org/10.1371/journal.pone.0260078.r005
Formally Accepted
21 Jan 2022 Acceptance Letter - Francesco Bertolini, Editor PONE-D-21-08974R2 Incidence of non-Hodgkin’s lymphoma among adults in Sardinia, Italy Dear Dr. Cocco: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Francesco Bertolini Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0260078.r006

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