Critical Issues for Patients and Caregivers in Neuro-Oncology during the COVID-19 Pandemic: What We Have Learnt from an Observational Study

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Congratulations on an interesting study!

To consider:

-Changing PTS as it is not an acronym for neuro-oncological patients. 

-Adding citations for definition of caregiver. 

-Explain why Spearman correlations were used instead of Pearson (ex between PTS and caregiver anxiety).

-Were any of your medical/demographic variables (ex. age, time since diagnosis) related to dependent variables?

-Note a limitation of your QoL scale is that is is skewed positively. You had 4 possible positive responses (satisfactory, good, very good, excellent) and only one negative one (not at all satisfactory). This biases the responses choice for your participants.

-"Examples of strategies adopted to deal with cancer anxiety" should not be introduced in the discussion when it was not included in the results.

 

Comments on the Quality of English Language

This was a very interesting study! Reading through the manuscript was extremely challenging though. Possibly Word document or some other software could be used to improve editing.

Author Response

Authors' Responses to Reviewer's Comments (Reviewer 1)

We addressed in details the questions highlighted by Reviewer 1.

Changing PTS as it is not an acronym for neuro-oncological patients. 

As the authors’ instruction asked, we defined the abbreviation “PTS” at first mention in the text. However, we proceeded to report the patient full name, as suggested by the reviewer, if this was not sufficiently descriptive.

-Adding citations for definition of caregiver. 

As the reviewer pointed out, we added in the manuscript the citation of the official definition of caregiver reported by the Americ Cancer Society such as https://www.cancer.org/cancer/caregivers/what-a-caregiver-does/who-and-what-are-caregivers.html.

-Explain why Spearman correlations were used instead of Pearson (ex between PTS and caregiver anxiety).

We used Spearman correlation because one variable(resources)showed a non-normal distribution. We made both Pearson and Spearman analysis and, as the results were almost the same (difference at 3rd decimal level), we presented the most conservative one.

-Were any of your medical/demographic variables (ex. age, time since diagnosis) related to dependent variables?

We performed analysis to verify possible relation between medical/demographic variables and dependent variables (Qol, Tumor anxiety, Covid anxiety) but no significant relation was found in our sample.

-Note a limitation of your QoL scale is that is is skewed positively. You had 4 possible positive responses (satisfactory, good, very good, excellent) and only one negative one (not at all satisfactory). This biases the responses choice for your participants.

The reviewer highlighted the disproportion between positive rates vs negative in QoL scale. However, we would like to report that also other authors (Nayak et al, doi: 10.4103/IJPC.IJPC_82_17) used distribution of quality of life of cancer patient including higher number of positive status than negative.

-"Examples of strategies adopted to deal with cancer anxiety" should not be introduced in the discussion when it was not included in the results.

As the reviewer properly suggested, we added a sentence (regarding anxiety coping strategies) also in the results.

Reviewer 2 Report

Comments and Suggestions for Authors

I appreciate the opportunity to review this work.  This prospective cross-sectional study, conducted by Anghileri et al., addresses the important issues of neurooncological patients’ and caregivers’ emotional state, future perceptions, and needs during the COVID-pandemic. The manuscript is well written with an appropriately detailed introduction and thoughtful discussion. Despite the high relevance and direct implications for clinical care, I think that the greatest strength of the paper is that it aims to not only shed light on the patients’ perspective but also includes caregivers’ views. Also, it deserves to be mentioned that the survey’s response rate is relatively high compared to similar studies, which further strengthens the implications of the authors’ findings.  

In general, I find this manuscript suitable for publication in “Current Oncology”. However, there are a few remarks for minor revisions. Also, I have added some suggestions that the authors might be easily able to answer with their data and which might further improve the manuscript. If those issues can not be addressed due to the limitations of the data, I would suggest a short discussion of those topics; however, I would still consider the manuscript to be of high interest to the scientific community nonetheless.

1)     Although the manuscript is well written and easy to understand, there are a few typos or small grammatical errors throughout it and partially in the translated survey (e.g., “reinforce” in line 34 or “During the pandemic” in line 90). Therefore, I highly suggest a thorough review of wording and grammar.

2)     The authors included patients and caregivers with a multitude of different diagnoses and disease duration. Did the authors find any differences/trends between different subgroups (e.g. gliomas v.s. meningiomas; newly diagnosed patients v.s. patients with a disease duration > 5 years). As the prognosis and the burden of disease appear to differ significantly between those groups, it would be interesting to investigate whether COVID-19 might also have impacted/affected those groups differently.

3)      The authors state that they developed telehealth interventions as a safe and easy way for patients to access their doctors. Did the authors obtain data on which of their patients participated in telehealth consultations and whether their answers to the survey differed? A previous study (10.3390/cancers15164054) reported that similar telehealth interventions for neuro-oncological patients may improve patients’ and caregivers’ mental well-being. Did the authors observe a similar effect?

Comments on the Quality of English Language

See above.

Author Response

The answers are in the attached file.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

Very good paper

Author Response

Thanks for your comments.

Reviewer 4 Report

Comments and Suggestions for Authors

Anghileri et al report INR questionnaire based study on-oncologic patient's and caregivers regarding their tumor care and emotional functioning during the COVID-19 pandemic.  Patients and their caregivers were provided with questionnaires that presented questions with regard to tumor related anxiety and COVID related anxiety,

This was a prospective study that was approved by a medical review board.

Abstract: The abstract adequately summarized the results.  the  term QoL is presented without a definition.  Please defined this as quality of life.

Introduction: The introduction contains a reasonable description of concerns that cancer patients and their caregivers and the possible ways the COVID-19 pandemic may have changed them.  The authors described the aim of the study to better understand the impact on cancer patients and caregivers in the COVID-19 pandemic but did not provide an actual hypothesis.

Materials and methods: The materials and method section does not provide any inclusion criteria.  This is problematic as the study was appears to have been open to anybody with intracranial tumor regardless of malignancy or lack thereof and there may be a fundamental differences between a patient with a meningioma who is being observed and a patient with a glioblastoma receiving myelosuppressive chemotherapy.  Perspectives regarding the role of the pandemic in care may not allow for an accurate evaluation of patient concerns.  The study likely should be limited to patients receiving some form of treatment that may increase the risk of infection (steroids, radiation therapy).  The other concern was the baseline performance status of these patients.  Were patients with aphasia allowed to participate? They would have difficulty reading and completing the questionnaire.  Were patients with low Karnofsky/high ECOG scores allowed to participate? Performance status was not even listed with demographics and a patient with a Karnofsky performance score of less than 70 or and ECGO score greater than 2 may not be able to accurately complete the questionnaire. The authors need to state all patients were able to independently complete the questionnaire.

Results: Patient and caregiver demographics were provided in table format.  However, questionnaire results were not, and were provided in narrative format, and I found it difficult to have an actual sense of what the results were.  Also, was there information available on similar questionnaires for patients with primary intracranial tumors with regard to discomfort, lifestyle, quality of life and concerns regarding tumor management from before the pandemic?  If so what were the results?

Discussion: The discussion section adequately addressed the data, though my concerns regarding the inclusion criteria that contain patients who have a range of tumors from very benign to very malignant tumors some of whom may not be receiving treatment that would place them  at risk with Covid 19 makes the overall data difficult to interpret  There was no discussion why caretaker involvement was much less than that of patients involvement.

Conclusions: adequately reflects the text of the discussion.

References:  Adequate for the subject matter.

Tables and figures: Adequate with no redundancy.

In order to obtain the data that adequately reflects concerns regarding the role of the COVID-19 pandemic with regard to concerns about treatment, illness and survival, the population survey needs to be more homogeneous with regard to diagnosis and performance status.  Patients with meningiomas will have different concerns than that of patients with glioblastoma or medulloblastoma, which would require surveys of additional patients.   Also, other concerns addressed with regard to the ability of patients to accurately complete the survey, the lack caregiver input, and concerns regarding performance status needs to be addressed..  My recommendation would be for rejection with encouragement to rework this study and resubmit.

 

Comments on the Quality of English Language

Minor findings, misspelling of words and inappropriate use of the direct object ("the")

Author Response

The answers are in the attached file.

Thank you

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review this interesting manuscript. It is much improved. Please see comments below, mostly for minor editing. 

 

 

 

Abstract :

1.          “ The COVID-19 pandemic inferred on neuro-oncological patients and the 23

caregivers regarding tumor care and emotional functioning, including the Quality of Life (QoL) 24

referred as an individual's perception of their position in life in the context of the culture and value 25 systems.” Do you mean the pandemic had a significant impact on medical care, emotional functioning and quality of life for neuro-oncological patients and their caregivers? I would not include a definition of QOL here, but rather put in introduction. 

2.          Please rephrase and clarify what is meant by “Cancer treatment schedule was changed in 18.5%, including for patient’s decision.”

 

Introduction:

1.            “Cancer diagnosis as well as COVID risk or disease described a context of high fragility.” Edit to “Cancer diagnosis as well as COVID risk or disease are described as contexts of high fragility”

2.           “They sustained that frailty” change to “they reported that frailty”

3.           What is meant by “(as positive reinforce)”

 

Discussion:

 

1. “To manage such issues as well as to protect PATIENTS from SARS-CoV-2 exposure” please correct to “patients”

2. I do not see my previous comment re the potential positive bias of the scale being addressed in the discussion. 

Comments on the Quality of English Language

See above.

Author Response

Abstract :

1. “ The COVID-19 pandemic inferred on neuro-oncological patients and the 23

caregivers regarding tumor care and emotional functioning, including the Quality of Life (QoL) 24

referred as an individual's perception of their position in life in the context of the culture and value 25 systems.” Do you mean the pandemic had a significant impact on medical care, emotional functioning and quality of life for neuro-oncological patients and their caregivers? I would not include a definition of QOL here, but rather put in introduction.

 

As you suggested we postponed QoL definition in the introduction chapter.

2. Please rephrase and clarify what is meant by “Cancer treatment schedule was changed in 18.5%, including for patient’sdecision.”

 As you kindly suggested, we now changed in “in 18.5% the treatment schedule was changed, either by patient’s or medical decision.”

Introduction:

1. “Cancer diagnosis as well as COVID risk or disease described a context of high fragility.” Edit to “Cancer diagnosis as well as COVID risk or disease are described as contexts of high fragility”
2. “They sustained that frailty” change to “they reported that frailty”
3. What is meant by “(as positive reinforce)”

As you pointed out, we corrected 1. and 2. and we modified the sentence (3.) from: “We also focused on the level of resilience and possible flourishing “(as positive reinforce)” to  “We also focused on the level of resilience and possible flourishing “( that can develop as positive reaction).

 

Discussion:

1.“To manage such issues as well as to protect PATIENTS from SARS-CoV-2 exposure” please correct to “patients”

As you pointed out, we corrected the graphic.

 

2. I do not see my previous comment re the potential positive bias of the scale being addressed in the discussion. 

 Dear reviewer, unintentionally the answer to your previous question [“Note: a limitation of your QoL scale is that is skewed positively. You had 4 possible positive responses (satisfactory, good, very good, excellent) and only one negative one (not at all satisfactory). This biases the responses choice for your participants”] did not show up.

Now I reported it: thanks to your comment we discovered a terrible mistake in Fig.2: we wrongly reported as “Satisfactory” the label of the translation of the Italian “poco soddisfacente” which correct translation is “Unsatisfactory”. We have now changed the Fig.2.

We apologise for the inconvenience we caused. The disproportion between positive rates vs negative in QoL scale is less unbalanced than previously suggested by our (wrong) presentation.  

Reviewer 2 Report

Comments and Suggestions for Authors

In lines 293 and 297 the word 'patients' has been included in capital letters ('PATIENTS'). If there is no specific reason for this, I would suggest changing the spelling to small letters.
Apart from this minor detail the authors offered sufficient explanations and revised their manuscript to satisfactorily meet the standard required for publication in 'Current Oncology'.

Author Response

In lines 293 and 297 the word 'patients' has been included in capital letters ('PATIENTS'). If there is no specific reason for this, I would suggest changing the spelling to small letters.
Apart from this minor detail the authors offered sufficient explanations and revised their manuscript to satisfactorily meet the standard required for publication in 'Current Oncology'.

Dear reviewer, thanks to appreciate our revision work and the overall manuscript.

As you pointed out, we corrected the word from capital letter to lower case letter.

Reviewer 4 Report

Comments and Suggestions for Authors

The population studied remains too heterogeneous for me to draw any conclusions.  A study such as this should concentrate on one population, such as GBM or malignant glioma in general.  I am having difficulty determining how the conclusions are derived from the results.  The conclusion also provides no information that is not already apparent. My major concerns were not adequately addressed and my prior recommendation for "rework" implied concentrating on a larger and more homogeneous cohort.  My recommendation has not changed except that resubmission with the current design is not feasible.

Author Response

Comments and Suggestions for Authors

The population studied remains too heterogeneous for me to draw any conclusions.  A study such as this should concentrate on one population, such as GBM or malignant glioma in general.  I am having difficulty determining how the conclusions are derived from the results.  The conclusion also provides no information that is not already apparent. My major concerns were not adequately addressed and my prior recommendation for "rework" implied concentrating on a larger and more homogeneous cohort.  My recommendation has not changed except that resubmission with the current design is not feasible.

The reviewer pointed out the heterogeneity of our sample. However, the purpose of our work was to provide an overall picture of patients affected by lower as well as higher grade primary cerebral tumors. In particular, our Institute is a highly specialised neuro-oncological Centre to which patients from all over Italy are referred, and may be well representative of the neuro-oncological Italian population in the context of COVID-19 pandemic. Similarly, others addressed the COVID-19 impact in neuro-oncological population on a global scale (Voisin et al ,2020).

The psychological impact combined with the strict recommendation of social distancing due to COVID-19 pandemic was dramatic for the overall neuro-oncological population who is extremely frail. We then decided to evaluate their worries and their resources, as well as the care changing (Weller at al, 2020).

Moreover, even if our purpose was general, we made some preliminary statistical analyses to verify homogeneity of our population. The result of chi-square and Anova test to compare benign vs. malignant tumours for anxiety and QoL were statistically non-significant and we went on with analyses on the whole population. We did not think as necessary to include these results in the discussion.

Although the COVID-19 pandemic emergency is nowadays concluded, we deduce that the results about emotional status and disease burden in such patients should be taken into account for the daily patient care management, and could be useful to better define a dedicated care pathway.

As the reviewer suggested, we have now modified the conclusion of main manuscript as follows: “Based on the WHO biopsychosocial model of «health», the medical good disease management must include the patients and their caregivers’ psychological needs, that can be coped also by a proactive support program. In our data patients and caregivers were satisfied with information on Covid19 effects provided by their oncologists; in this regard, we must consider communication as a key tool to ensure the best possible care for the patients and their caregivers. Our data also outline that results about emotional status and disease burden in such patients should be taken into account for the daily patient care management, and could be useful to better define a dedicated care pathway. It was more relevant in neuro-oncological setting during COVID-19 pandemic but we need to improve the routinely use of anxiety and QoL scale score as indicator of our clinical work.

We will need to ensure that pts-clinician relation is part of the care and reflects the style of relation chosen by the pts: in such way we will act as allies in the continuum of care.”

 

REFERENCES

Voisin MR, Oliver K, Farrimond S, Chee T, Arzbaecher J, Kruchko C, Maher ME, Tse C, Cashman R, Daniels M, Mungoshi C, Lamb S, Granero A, Lovely M, Baker J, Payne S, Zadeh G. Brain tumors and COVID-19: the patient and caregiver experience. Neurooncol Adv. 2020 Aug 23;2(1):vdaa104. doi: 10.1093/noajnl/vdaa104.

Weller M, Preusser M. How we treat patients with brain tumour during the COVID-19 pandemic. ESMO Open. 2020 May;4(Suppl 2):e000789. doi: 10.1136/esmoopen-2020-000789 

Round 3

Reviewer 4 Report

Comments and Suggestions for Authors

While some concerns were adequately addressed, I do not see how the conclusion that "Such data reinforce the need to build a proficient alliance between patients and health professionals" is derived directly from the data reviewed.  This cannot be fixed without a larger and more homogeneous cohort (such as all high grade gliomas).

Author Response

 

1.“To manage such issues as well as to protect PATIENTS from SARS-CoV-2 exposure” please correct to “patients”

As you pointed out, we corrected the graphic.

PAGE 9, PARAGRAPH 4, ROW 283 (clean version)

 

2. I do not see my previous comment re the potential positive bias of the scale being addressed in the discussion. 

 

Dear reviewer, unintentionally the answer to your previous question [“Note: a limitation of your QoL scale is that is skewed positively. You had 4 possible positive responses (satisfactory, good, very good, excellent) and only one negative one (not at all satisfactory). This biases the responses choice for your participants”] did not show up.

Now I reported it: thanks to your comment we discovered a terrible mistake in Fig.2: we wrongly reported as “Satisfactory” the label of the translation of the Italian “poco soddisfacente” which correct translation is “Unsatisfactory”. We have now changed the Fig.2.

We apologise for the inconvenience we caused. The disproportion between positive rates vs negative in QoL scale is less unbalanced than previously suggested by our (wrong) presentation.  

PAGE 6, FIG. 2 AND LEGEND 2, ROW 209 (clean version)