An Analysis of Clinical and Systemic Factors Associated with Palliative Radiotherapy Delivery and Completion at the End of Life in Alberta, Canada

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

In the article "Factors Associated with Completion of Palliative Radiotherapy at the End of Life" Gouta et al. addresses a neglected and interesting subject both through the economic-financial implications and access to radiotherapy. The article identifies a 10% rate of non-completion of palliative radiotherapy and the benefit of using the reduced number of fractions for patients near the end of life. The factors predicting the completion of the radiotherapy course are identified and presented in detail, as well as the characteristics of the patients included in the study. The authors also identify the limits of the analysis and the difficulty of identifying whether the reduction in the number of fractions is the effect of the analysis on radiation oncolytic or a global trend identified in palliative radiotherapy. I would also add a discussion on the possible benefit of a course of incomplete palliative radiotherapy near end of life (is it partially effective or futile? - a short discussion about the timing and amplitude of symptom mitigation if it exists), but the article can also be published in this form .

Author Response

REVIEWER 1: "I would also add a discussion on the possible benefit of a course of incomplete palliative radiotherapy near end of life (is it partially effective or futile? - a short discussion about the timing and amplitude of symptom mitigation if it exists), but the article can also be published in this form.:

Response: Thank you for your comments and suggestions. We have added to our discussion and included a statement on potential symptom mitigation.

Reviewer 2 Report

Comments and Suggestions for Authors

This is a very well written manuscript.  The result confirms what has been reported in the literature, that a significant number of patients did not complete palliative radiotherapy and patients were more likely to complete palliative single fraction radiotherapy.  It, however, is unclear the rationale of selecting 347 of 2040 patients for analysis.  The reason for incompletion and the type/site of palliative radiotherapy were not described, making the conclusion more challenging to generalize.  Further analysis by site (bone vs. brain vs. other palliative RT for example) may further characterize the utility of palliative RT, as treatment fractionation tends to differ. 

Author Response

REVIEWER 2: "It, however, is unclear the rationale of selecting 347 of 2040 patients for analysis. "

Response: Clarified

"The reason for incompletion and the type/site of palliative radiotherapy were not described, making the conclusion more challenging to generalize.  Further analysis by site (bone vs. brain vs. other palliative RT for example) may further characterize the utility of palliative RT, as treatment fractionation tends to differ." 

Revision: We agree that this could be better described. Information to help the readership determine the population under study and reasons for incompletion are available by interrogating table 1: Cancer site and in more detail in Table 1b: further provided information on whether pts were in hospital or outpatients, whether they lived in urban or rural areas (examining whether distance/access to RT may have been a factor), whether they had brain or liver mets, whether they were receiving concurrent chemotherapy, or were being  retreated. Most of these factors were not robust to influence completion rates as per table 2 multivariate analysis. RT site of treatment was not associated with RT incompletion and was not included in the univariate or multivariate analysis. We will add this to Table 1 and add a statement in the results  to further clarify this for the readership.

Reviewer 3 Report

Comments and Suggestions for Authors

Title is the manuscript: Factors Associated with Completion of Palliative Radiotherapy at the End of Life. This is a well-written, well-structured, and important work dealing with completion rate of end-of-life radiotherapy (RT); however, the final findings are not surprising for an experienced radiotherapy /clinical oncology expert. Nevertheless, the final messages important to the routine clinical practice, so the reviewer suggests considering the manuscript for the final approvement. The reviewer has some comments and recommendations to the authors:

1, The original number of the patient dataset was 2040, but finally the data of 367 patients were further analysed. Please clarify both in the Abstract and both in the Methods section that the final elaboration was carried in those patients who had all the clinical / RT / social etc. data.

2, There is no data about the indications of palliative RT. It is an important issue, since in case of vertebral or other bone metastases in a poor condition patient the single fraction RT is the every-day practice, however in case of mediastinal node enlargement or in case of multiple brain mets the single fraction RT is not recommended. Note that in case of multiple brain metastases it is not unusual ceasing RT because of neurological deterioration of the patient (15% of the pts had brain involvement). Please clarify it.

3, It is very interesting that 13% of the planned single fraction RT was not delivered. It means a poor estimation quality of the patient tolerance (and preference). Please comment it in the Discussion section.

4, There is no data in the manuscript about the causes of interruption of RT. Deterioration of the general condition? Patient refusal? The common decision of the family, the patient, and the physician? Logistic problems? It is an important issue. Maybe it is not possible to elaborate these data thoroughly, but it is recommended to debate this issue in the Discussion section.

5, It is an interesting finding the role of multiple cancer diseases in this context. The authors discussed it in the Discussion section; however, the reviewer is wondering about the role of the psychological state of the patients. Maybe a multiple cancer patient would rather refuse any kind of medical / oncology intervention.

6, The reviewer was wondering about the fact that the performance state had been not influenced the rate of incomplete RT. However, in the research the cut off value was 70 considering KPS. This cut off value is general in clinical trials with active oncotherapy, however in case of palliative care it would be recommended to choose another cut of value. Maybe still it is impossible to elaborate these alternative data, but the reviewer would like to suggest discussing this issue.

7, Please consider the modification of the title of the work with more messages to the readers.

Author Response

REVIEWER 3:

1, The original number of the patient dataset was 2040, but finally the data of 367 patients were further analysed. Please clarify both in the Abstract and both in the Methods section that the final elaboration was carried in those patients who had all the clinical / RT / social etc. data.

Response: Thank you for the suggestion. Clarified

2, There is no data about the indications of palliative RT. It is an important issue, since in case of vertebral or other bone metastases in a poor condition patient the single fraction RT is the every-day practice, however in case of mediastinal node enlargement or in case of multiple brain mets the single fraction RT is not recommended. Note that in case of multiple brain metastases it is not unusual ceasing RT because of neurological deterioration of the patient (15% of the pts had brain involvement). Please clarify it.

Response: We agree that this is an important issue. We will add this to the discussion.

3, It is very interesting that 13% of the planned single fraction RT was not delivered. It means a poor estimation quality of the patient tolerance (and preference). Please comment it in the Discussion section.

Response: Agree  - will add to discussion.

4, There is no data in the manuscript about the causes of interruption of RT. Deterioration of the general condition? Patient refusal? The common decision of the family, the patient, and the physician? Logistic problems? It is an important issue. Maybe it is not possible to elaborate these data thoroughly, but it is recommended to debate this issue in the Discussion section.

Response: Agree - added to point 2 in discussion.

5, It is an interesting finding the role of multiple cancer diseases in this context. The authors discussed it in the Discussion section; however, the reviewer is wondering about the role of the psychological state of the patients. Maybe a multiple cancer patient would rather refuse any kind of medical / oncology intervention.

Response: Agree that this is interesting and hypothesis generating. We added a comment on the psychological state of the patient as a factor to consider.

6, The reviewer was wondering about the fact that the performance state had been not influenced the rate of incomplete RT. However, in the research the cut off value was 70 considering KPS. This cut off value is general in clinical trials with active oncotherapy, however in case of palliative care it would be recommended to choose another cut of value. Maybe still it is impossible to elaborate these alternative data, but the reviewer would like to suggest discussing this issue.

Response: Will add a comment in the discussion.

7, Please consider the modification of the title of the work with more messages to the readers.

Response: Title modified to improve clarity

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have addressed the reviewer's comments and expanded on discussion and improved clarity.  

Reviewer 3 Report

Comments and Suggestions for Authors

I accept the answers and the corrections and I think that the content of the material has improved.