Deterioration of Performance Status during Palliative Radiotherapy Suggests a Significant Short Survival Duration: Indicating the Necessities for Considering Radiotherapy Discontinuation
, Kazuaki Kushi 3, Isoko Owan 4, Takuro Ariga 2,5, Joichi Heianna 2 and Akihiro Nishie 2
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors
The paper does address an interesting topic with limited literature-reported data.
The paper is well written, aims, results and discussion are clear and well presented.
There is only one weakness: the analyzed population is limited in size.
However, authors clearly state such weakness. Such issue can not be improved.
Author Response
Response to Reviewer 1:
The paper does address an interesting topic with limited literature-reported data.
The paper is well written, aims, results and discussion are clear and well presented.
There is only one weakness: the analyzed population is limited in size.
However, authors clearly state such weakness. Such issue can not be improved.
Response: Thank you for your positive evaluation of our work. As you pointed out, this study has a weakness: the limited sample size. This weakness is formally recognized within the manuscript. We express gratitude for the allocation of your precious time to assess our manuscript.
Reviewer 2 Report
Comments and Suggestions for Authors
Very interesting study looking at palliative radiotherapy. Limitations well described in the discussion. Suggestions:
1 - In Introduction (lines 50-56) consider including the decision making from the perspective of both the palliative care physician and the radiation oncologist rather than the palliative care physician alone. Discuss the importance of joint decision making with palliative care, RO and the patient.
2 - In Methods, need to better explain how/when PS was measured during RT. Was it reported every day?
3 - In Methods - statistical analysis (line 94) unclear what is meant by 'final course'. Does this mean the longest course or the last course to finish?
4 - Table 1 should be revised to better present the different RT regimens. Also the note at the end is unclear. Seems to suggest that this patient was not included in the study at all, rather than not included in the analysis of multiple metastases only. Did the review capture if patients had previous RT to the current target? May be helpful to include if available.
5 - In Results (lines 122-132) the description of the dose/fractionation by primary site is not very informative. Consider reporting it by target site.
6 - In Results (lines 150-154) unclear where 117 days came from, why is this different than the 125 days for the 'stable group'
7 - In Results (line 159) was this patient with treatment stopped early included in the analysis? Please clarify
8 - In Discussion (line 227) unclear why patients would be prescribed longer course with lower dose overall. Did they have previous radiation?
Comments on the Quality of English Language
Please check the grammar/clarity of the following lines
#58
#123
#217-218
#257-258 - Error - take this out
Author Response
Response to Reviewer 2:
Very interesting study looking at palliative radiotherapy. Limitations well described in the discussion.
Response: Thank you for devoting your valuable time to improving our manuscript.
Suggestions:
1 - In Introduction (lines 50-56) consider including the decision making from the perspective of both the palliative care physician and the radiation oncologist rather than the palliative care physician alone. Discuss the importance of joint decision making with palliative care, RO and the patient.
Response: Thank you for your advice. We have added the following text with references in the Introduction.
‘Ideally, decisions regarding palliative care, including discontinuation of palliative radiotherapy, should be achieved collaboratively through comprehensive discussions involving patients, family caregivers, palliative care physicians [36,37], and radiation oncologists. Nonetheless, realizing this ideal within a clinical setting can pose challenges. Substantial disparities in knowledge may exist between patients and medical practitioners. Communication between palliative care physicians and radiation oncologists may be constrained, for example, due to their limited overlap in their work schedules at the facility’.
2 - In Methods, need to better explain how/when PS was measured during RT. Was it reported every day?
Response: Thank you for your question. We have added the following text to 2.2. Patients of Materials and Methods.
‘Palliative care nurses and physicians kept sufficient medical records daily, facilitating retrospective assessment of PS. In addition, radiation oncologists documented PS directly in the medical records at initial consultations and weekly during the course of palliative radiotherapy’.
3 - In Methods - statistical analysis (line 94) unclear what is meant by 'final course'. Does this mean the longest course or the last course to finish?
Response: Based on your suggestion, we replaced ‘final’ with ‘last’.
4 - Table 1 should be revised to better present the different RT regimens. Also the note at the end is unclear. Seems to suggest that this patient was not included in the study at all, rather than not included in the analysis of multiple metastases only. Did the review capture if patients had previous RT to the current target? May be helpful to include if available.
Response: Thank you for your feedback. We have revised Table 1 and the accompanying note for enhanced clarity. This study included only one case of re-irradiation. In response to your suggestion outlined in point 8, we have incorporated the following addition into the manuscript.
‘The reasons for the five cases in which biologically effective dose was less than 30 Gy/10 fr were as follows: The lesions in each case of pelvic region and lung metastasis exhibited considerable size, prompting concerns regarding potential adverse events. The dose was reduced akin to standard fractionation for one patient each in the pelvic region and head and neck, as further radiation therapy was under consideration, although no additional radiotherapy was actually performed. Additionally, in one case of re-irradiation for head and neck, the dose was reduced. Among the 35 patients in this study, only one was a case of re-irradiation. The last course was included in the study as described within the Materials and Methods section for the case of re-irradiation.’.
5 - In Results (lines 122-132) the description of the dose/fractionation by primary site is not very informative. Consider reporting it by target site.
Response: Thank you for your suggestion. We have revised the manuscript as follows.
‘The treatment regimens, excluding 30 Gy/10 fr, and their corresponding target site were as follows: 21.6 Gy/12 fr (n = 2) for pelvic lesions, 25 Gy/10 fr (n = 1) for lung metastasis, 30 Gy/15 fr (n = 2) for head and neck and breast tumors, 36 Gy/12 fr (n = 1) for soft tissue sarcoma, 39 Gy/13 fr (n = 3) for soft tissue sarcoma and head and neck tumor, and bone metastasis, 40 Gy/20 fr (n = 2) for bone metastases, 42 Gy/14 fr (n = 1) for breast tumor, 45 Gy/15 fr (n = 1) and 50 Gy/25 fr (n = 1) for head and neck tumors.
6 - In Results (lines 150-154) unclear where 117 days came from, why is this different than the 125 days for the 'stable group'
Response: Thank you for your question. You may be confusing two different analysis results. We decided to change ‘stable group’ to ‘remaining 31 patients’ in the latter analysis to avoid confusion.
7 - In Results (line 159) was this patient with treatment stopped early included in the analysis? Please clarify
Response: Thank you for your advice. We added the following sentence to clarify: ‘This patient was also included in the analyses.
8 - In Discussion (line 227) unclear why patients would be prescribed longer course with lower dose overall. Did they have previous radiation?
Response: Thank you for your valuable inquiry. We have included the reason in the results section as presented in the answer to your fourth question, and have modified the discussion as follows.
’The prognosis was significantly reduced in cases where the irradiated dose was less than 30 Gy/10 fr in terms of biologically effective dose (the median survival, 21 vs. 114 days, p = 0.036). The reason behind the shorter prognosis was understandable, as the cases receiving the lower dose included the cases of exceedingly large tumors, the cases where additional irradiation was considered but not actually performed, and the case where re-irradiation was performed’.
Please check the grammar/clarity of the following lines
#58
#123
#217-218
#257-258 - Error - take this out
Response: Thank you for informing us. We have reviewed the manuscript and made the necessary corrections.
Reviewer 3 Report
Comments and Suggestions for Authors
I read with great notice the interesting manuscript by Hitoshi Maemoto et al. entitled: "Deterioration of performance status during palliative radiotherapy suggests a significant short survival duration: Indicating the necessities for considering radiotherapy discontinuation.".
Although it is a small retrospective study, there is a clear message concerning the fact that deterioration in ECOG PS during palliative radiotherapy signifies a markedly shorter survival duration.
The manuscript disserves publication after revision. The authors should take into account the following:
1. Either in introduction or in the discussion the authors should comment on the fractionation, especially by referring to the paper of Jackson Sai-Yiu Wu et al. entitled “Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases” (Int J Radiat Oncol Biol Phys 2003 Mar 1;55(3):594-605).
2. The authors should be clear about the RT technique and the treatment planning used.
3. I would like to see data concerning the palliation between the two groups of patients. At least a visual analogue score and a comparison between them..
4. The authors beyond the limitation of the study should state about the necessity of a larger prospective randomized study.
5. In the discussion the phrase “For patients with multiple metastases not scheduled for systemic therapy, planning non-short course of palliative radiotherapy (≥10 fractions) may not be optimal.” needs clarification and commenting.
6. The conclusion needs improvement. The last phrase “his section is not mandatory but can be added to the manuscript if the discussion is unusually long or complex.” has no meaning.
7. The English of the manuscript need improvement. I propose to the authors to review the text by using someone whose native language is English.
Comments on the Quality of English Language
Quality of English needs improvemnt.
Author Response
Response to Reviewer 3:
I read with great notice the interesting manuscript by Hitoshi Maemoto et al. entitled: "Deterioration of performance status during palliative radiotherapy suggests a significant short survival duration: Indicating the necessities for considering radiotherapy discontinuation".
Although it is a small retrospective study, there is a clear message concerning the fact that deterioration in ECOG PS during palliative radiotherapy signifies a markedly shorter survival duration.
The manuscript disserves publication after revision. The authors should take into account the following:
Response: We would like to thank you for your favorable evaluation and the many meaningful suggestions for improving our manuscript.
- Either in introduction or in the discussion the authors should comment on the fractionation, especially by referring to the paper of Jackson Sai-Yiu Wu et al. entitled “Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases” (Int J Radiat Oncol Biol Phys 2003 Mar 1;55(3):594-605).
Response: Thank you for your suggestion. We have reviewed the suggested paper and included it in the references to enrich the section of Introduction.
- The authors should be clear about the RT technique and the treatment planning used.
Response: Thank you for your advice. We have revised the manuscript to include ‘The treatment planning was conducted utilizing Xio (Elekta, Stockholm, Sweden). Radiotherapy was performed with a three-dimensional conformal technique in all cases’.
- I would like to see data concerning the palliation between the two groups of patients. At least a visual analogue score and a comparison between them.
Response: Thank you for your interest in our research. We were also interested in the therapeutic effects. However, we have reached the conclusion that the evaluation of palliation was difficult, given the heterogeneity of the population in terms of symptoms, primary site, treatment target, and treatment regimen. In addition, the retrospective nature of the study and the inclusion of many cases with insufficient assessment of local symptom relief resulted in the evaluation of therapeutic effects challenging.
We have added the limitation that we have not analyzed the therapeutic effects.
- The authors beyond the limitation of the study should state about the necessity of a larger prospective randomized study.
Response: Thank you for your advice. We have added the text as follows.
‘To address these limitations, large-scale prospective studies would be necessary’.
- In the discussion the phrase “For patients with multiple metastases not scheduled for systemic therapy, planning non-short course of palliative radiotherapy (≥10 fractions) may not be optimal.” needs clarification and commenting.
Response: Thank you for your suggestion. We have revised the manuscript for clarification as follows.
‘For patients with multiple metastases not scheduled for systemic therapy, planning non-short course of palliative radiotherapy (≥10 fractions) may not be optimal, as their prognosis is expected to be relatively short’.
- The conclusion needs improvement. The last phrase “his section is not mandatory but can be added to the manuscript if the discussion is unusually long or complex.” has no meaning.
Response: Thank you for the information. We have removed the phrase.
- The English of the manuscript need improvement. I propose to the authors to review the text by using someone whose native language is English.
Response: We appreciate your feedback. Actually, this manuscript had already undergone professional English proofreading services. We will take your comment into account for future decisions regarding English proofreading services.
Round 2
Reviewer 3 Report
Comments and Suggestions for Authors
The manuscript has been improved. I suggest publication in its current form.
