Acute Metastatic Spinal Cord Compression: Urgent Surgery versus Radiotherapy and Treatment Result Prediction versus Actual Results

Round 1

Reviewer 1 Report

The manuscript by Hershkovich et al aims at supporting the beneficial use of urgent-surgery  compared to radiotherapy alone in treating acute metastatic spinal cord compression. Although the subject is of great interest, overall the study design and the manuscript itself do not meet the requirements to be published.

As this pathology is extremely common, the number of involved patients in this retrospective analysis (54) is well beyond the number required to draw any significant conclusion
The radiation group is significantly different compared to the surgery grop in terms of other osseous metastases as well as the time from tumor diagnosis to AMSCC. This could have a major role in the overall outcome difference that is observed by the authors between the two groups
The use of 30Gy in 10 fractions has been shown not to have a major benefit compared to lower fractionations in the palliative setting, with the added benefit of having less side effects to the organs at risk. Moreover, the type of radiotherapy technique used is not mentioned (3D vs VMAT) which could have major implications in the outcome observed by the authors.

The introduction has elements of discussion and methodology which do not fit this section. These should be moved to their respective sections.

Author Response

September 2022

COVER LETTER

 

I am enclosing a manuscript entitled "Acute Metastatic Spinal Cord Compression – Urgent Surgery versus Radiotherapy, Treatment result prediction versus actual results" submitted to the "Current Oncology" journal after extensive revision based on your reviewers' comments and remarks for possible evaluation.

With the submission of this manuscript, I would like to undertake that the abovementioned manuscript has not been published elsewhere, accepted for publication elsewhere, or under editorial review for publication elsewhere.

Type of Submitted manuscript:

• Original Article

 

I want to share the following information with Editor-in-Chief:

 

"The role of Radiotherapy versus surgery in treating acute metastatic spinal cord compression (AMSCC) has changed over the years. Our study evaluates neurological and functional outcomes following urgent surgery and Radiotherapy (USFR) versus urgent Radiotherapy alone in treating AMSCC.

We held a retrospective cohort of 54 patients with AMSCC with variable neurological deficits. Thirty-two patients were treated with USFR, and 22 received Radiotherapy alone.

Our study's main findings showed that despite similar neurological status at AMSCC presentation between cohorts regarding Asia and Frankel scores, continence and ambulation, and Kranofsky's functional score, following USFR, 59.3% of the patients had a motor strength improvement, 31.3% regained sphincter function, and 34.4% regained ambulation. In comparison, 90% of the patients treated with Radiotherapy showed no improvement. One patient under Radiotherapy lost sphincter function. The treatment received did not affect the patient's survival. A subanalysis of patients with a short life expectancy, by Tomita and Tokuhashi scores,  showed missed prediction in 29.4%.

 The study supports the beneficial effect of UFSR compared to urgent Radiotherapy alone in treating AMSCC in all subgroups. Early surgery improved function, motor strength, sphincter control and ambulation without affecting life span. Prognostic scores failed to predict life span in almost a third of the patients, requiring further investigation."

The significant findings presented in this work are essential evidence to further support recent literature on surgical treatment for patients with AMSCC and the need better to understand the role of the available prognostic scales.

As such, we would like it to be published in the journal.

 

On behalf of all the authors,

 

The corresponding author

 

 

Dear Reviewers, 

We appreciate your efforts in making our paper better and suitable for publication in the Journal of Clinical Medicine. 

 

Please find our point-to-point replies to your queries. 

All changes in the text are underlined and bolded.  

 

Article

Acute Metastatic Spinal Cord Compression – Urgent Surgery versus Radiotherapy,

Treatment result prediction versus actual results

 

Reviewer 1:

The manuscript by Hershkovich et al aims at supporting the beneficial use of urgent-surgery  compared to Radiotherapy alone in treating acute metastatic spinal cord compression. Although the subject is of great interest, overall the study design and the manuscript itself do not meet the requirements to be published.

As this pathology is extremely common, the number of involved patients in this retrospective analysis (54) is well beyond the number required to draw any significant conclusion
The radiation group is significantly different compared to the surgery grop in terms of other osseous metastases as well as the time from tumor diagnosis to AMSCC. This could have a major role in the overall outcome difference that is observed by the authors between the two groups

The use of 30Gy in 10 fractions has been shown not to have a major benefit compared to lower fractionations in the palliative setting, with the added benefit of having less side effects to the organs at risk. Moreover, the type of radiotherapy technique used is not mentioned (3D vs VMAT) which could have major implications in the outcome observed by the authors.

The introduction has elements of discussion and methodology which do not fit this section. These should be moved to their respective sections.

We appreciate the effort in reviewing our paper.

Although our cohort is limited, the differences between the treatment outcomes in the two groups were statistically significant. Although a larger cohort is desirable, we have discussed the cohort characteristics and limitations thoroughly in the discussion and were still able to reach statistically significant conclusions. The pre-intervention characteristics in our study were similar in both groups. The differences that reached statistical significance, such as the Tomita score, are without clinical significance (1.1 score difference).  

Studies not reaching statistical significance would require a larger cohort.

We have discussed our study limitations in the text –

"The study cohorts were not randomized, and a selection bias exists regarding time with a  diagnosed malignancy (p = 0.005) and the number of extra-spinal osseous metastases (p = 0.004), favouring Radiotherapy. However, the cohorts did not significantly differ between functional and prognostic scores, probably reducing the impact of additional osseous metastatic involvement on patient survival." 

The radiation therapy protocol we reported was our oncological\radiation therapy institutional protocol. The protocol was 30GY in 10 3D fractions. This vital information was embedded in the text – please see bolded and underlined.

We have rearranged the introduction and discussion accordingly – please see underlined and bolded.

 

Thank you for your efforts and input. 

We have answered all your points as explained above.

 

Thank you for your kind words. 

We hope this revised version can now be published in Current Oncolgy journal. 

 

BW

The corresponding author

Author Response File: Author Response.docx

Reviewer 2 Report

The authors present their series on 54 patients with AMSCC which were managed initially by urgent surgery vs those managed by radiation. They found statistically significant differences in neurological function preservation/rebound in the surgical group. The groups did not differ in overall survival.

The authors contend that this issue is still a matter of debate and refer to literature in the introduction to support this claim. Overall we do not find this to be a contentious area but do believe that other areas are more contentious. Ie what to do in cases of high disease burden or low KPS and outcomes by management option. It would be worthwhile to do a subgroup analysis of these populations in the two arms to see if any differences exist. 

 

Also, what was the timing to RS? Is it worthwhile to split these groups into two? Did any patients receive surgery after 48 hours? Answers to these questions would strengthen the concluding arguments of " beneficial effect of urgent surgical intervention compared to 263 Radiotherapy alone in treating AMSCC in all subgroups"

Author Response

September 2022

COVER LETTER

 

I am enclosing a manuscript entitled "Acute Metastatic Spinal Cord Compression – Urgent Surgery versus Radiotherapy, Treatment result prediction versus actual results" submitted to the "Current Oncology" journal after extensive revision based on your reviewers' comments and remarks for possible evaluation.

With the submission of this manuscript, I would like to undertake that the abovementioned manuscript has not been published elsewhere, accepted for publication elsewhere, or under editorial review for publication elsewhere.

Type of Submitted manuscript:

• Original Article

 

I want to share the following information with Editor-in-Chief:

 

"The role of Radiotherapy versus surgery in treating acute metastatic spinal cord compression (AMSCC) has changed over the years. Our study evaluates neurological and functional outcomes following urgent surgery and Radiotherapy (USFR) versus urgent Radiotherapy alone in treating AMSCC.

We held a retrospective cohort of 54 patients with AMSCC with variable neurological deficits. Thirty-two patients were treated with USFR, and 22 received Radiotherapy alone.

Our study's main findings showed that despite similar neurological status at AMSCC presentation between cohorts regarding Asia and Frankel scores, continence and ambulation, and Kranofsky's functional score, following USFR, 59.3% of the patients had a motor strength improvement, 31.3% regained sphincter function, and 34.4% regained ambulation. In comparison, 90% of the patients treated with Radiotherapy showed no improvement. One patient under Radiotherapy lost sphincter function. The treatment received did not affect the patient's survival. A subanalysis of patients with a short life expectancy, by Tomita and Tokuhashi scores,  showed missed prediction in 29.4%.

 The study supports the beneficial effect of UFSR compared to urgent Radiotherapy alone in treating AMSCC in all subgroups. Early surgery improved function, motor strength, sphincter control and ambulation without affecting life span. Prognostic scores failed to predict life span in almost a third of the patients, requiring further investigation."

The significant findings presented in this work are essential evidence to further support recent literature on surgical treatment for patients with AMSCC and the need better to understand the role of the available prognostic scales.

As such, we would like it to be published in the journal.

 

On behalf of all the authors,

 

Dr Oded Hershkovich

 

The corresponding author

Dear Reviewers, 

We appreciate your efforts in making our paper better and suitable for publication in the Journal of Clinical Medicine. 

 

Please find our point-to-point replies to your queries. 

All changes in the text are underlined and bolded.  

 

Article

Acute Metastatic Spinal Cord Compression – Urgent Surgery versus Radiotherapy,

Treatment result prediction versus actual results

 

Reviewer 2:

The authors present their series on 54 patients with AMSCC which were managed initially by urgent surgery vs those managed by radiation. They found statistically significant differences in neurological function preservation/rebound in the surgical group. The groups did not differ in overall survival.

The authors contend that this issue is still a matter of debate and refer to literature in the introduction to support this claim. Overall we do not find this to be a contentious area but do believe that other areas are more contentious. Ie what to do in cases of high disease burden or low KPS and outcomes by management option. It would be worthwhile to do a subgroup analysis of these populations in the two arms to see if any differences exist. 

We want to apriecate reviewer remarks.

We did appreciate the ongoing change in prognostic scales accuracy in the text. Our study showed that almost 30% of the short life expectancy subgroup survived longer than anticipated. However, the sub-group was too small for statistical analysis.

Also, what was the timing to RS? Is it worthwhile to split these groups into two? Did any patients receive surgery after 48 hours? Answers to these questions would strengthen the concluding arguments of " beneficial effect of urgent surgical intervention compared to 263 Radiotherapy alone in treating AMSCC in all subgroups"

The Radiotherapy alone group received the first treatment within 72h from presentation. There was no late radiation therapy group.

This was added to the methods section, underlined and bolded.

We compared early surgery with early radiation treatment. No subgroup was performed due to cohort size.

 

 

 

Thank you for your efforts and input. 

We have answered all your points as explained above.

 

Thank you for your kind words. 

We hope this revised version can now be published in Current Oncolgy journal. 

 

BW

The corresponding author

 

 

Round 2

Reviewer 1 Report

I thank the authors for their replies and appreciate the effort in editing the manuscript. However, in my opinion, the overall study limitation, albeit discussed in the text, is a major limitation in its relevance and thus it does not make this manuscript fit to be published on Current Oncology. 

Author Response

Dear Reviewer,
Thank you for your time and effort in evaluating our study. 
We understand the concerns presented, regarding the re-evaluation of surgery versus Radiotherapy alone in the treatment of acute metastatic cord compression patients, especially as compared to the Patchell study.

The Patchel study included patients from 1992 to 2002; during the twenty to thirty years since this study, the oncology field has undergone significant evolution, with the introduction of new chemotherapy agents, immunotherapy, patient-specific treatments and improved Radiotherapy. Although surgery has been superior to Radiotherapy alone, the decision upon treatment still relies on old prognostic scales that do not account for current advances, thus potentially biasing results and possibly dooming patients who, with current treatment strategies, can survive longer than predicted.

Current data should be analyzed in light of these concerns, and our study's novelty is in showing that these claims are valid and need further evaluation.

Therefore we believe that this study is  valuable and should be published in Current Oncology

BW 

Corresponding Author