Durable Response to Atezolizumab in Extensive-Stage Small-Cell Lung Cancer Leading to 60 Months Overall Survival: A Case Report
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors
This is a well-written case report. The discussion is interesting and complete. Here are my comments/questions/corrections:
You wrote twice highlights on line 24 and 25, you might want to change your choice of words.
Typos on line 69: results and confirmed
Typo on line 76: image
Line 90: you should say partial response instead of overall positive response
Line 94: what was included in the radiation field in the ‘thorax’? The largest lung nodule? Other lung nodules? Mediastinal nodules? Could you clarify?
Line 99: could you specify at which interval are the MRI surveillances performed for the patient?
Line 113: why were 6 cycles initially planned? Only 4 cycles of chemotherapy were given with immunotherapy in both Impower 133 and CASPIAN trials
Line 118: again, why 6 cycles?
Typo on line 139: atezolizumab. The sentence ‘There resolution of nodules seen in Septembre 2020 scan’ does not make sense.
Line 153: what was the CTCAE grade for transaminitis and how long the patient had to be on prednisone?
Line 164: what about brain MRIs?
Line 212: did you try liquid biopsy? Do you have access to it?
Author Response
Comment 1: You wrote twice highlights on line 24 and 25, you might want to change your choice of words.
Response 1: Thank you for pointing this out; wording on line 25 has been changed to “driving”.
Comment 2: Typos on line 69: results and confirmed
Typo on line 76: image
Response 2: These have been corrected.
Comment 3: Line 90: you should say partial response instead of overall positive response
Response 3: Thank you, this has been changed as per your suggestion.
Comment 4: Line 94: what was included in the radiation field in the ‘thorax’? The largest lung nodule? Other lung nodules? Mediastinal nodules? Could you clarify?
Response 4: Radiation was delivered to the left lower lobe pleural based lesion, the largest lesion at the time, as well as left-sided hilar and mediastinal nodes. This information has been added at lines 95-96.
Comment 5: Line 99: could you specify at which interval are the MRI surveillances performed for the patient?
Response 5: This is an excellent point. MR head surveillance was initially planned q.3 monthly for 1 year. However, the ongoing COVID-19 pandemic caused significant issues locally in obtaining MR imaging, and this was not able to be done at a 3-month interval after the 6 month mark. We obtained MR imaging as regularly as possible until it was determined that our patient was succeeding well beyond what guidelines assumed; at this point, with his agreement, he was transitioned to symptom-triggered screening. This information has been incorporated at lines 153-159.
Comment 6: Line 113: why were 6 cycles initially planned? Only 4 cycles of chemotherapy were given with immunotherapy in both Impower 133 and CASPIAN trials
Response 6: After re-reviewing the clinical notes in detail, we believe there was an error in documentation and that the plan was in fact initially for 4 cycles based on the chemotherapy orders. This has been corrected to reflect that the original plan for the first induction round was indeed 4 cycles. Thank you for facilitating this correction (see lines 114-116 in the edited manuscript where the reference to potential 6 cycles was removed).
Comment 7: Line 118: again, why 6 cycles?
Response 7: In the re-challenge setting, once the patient had received 4 cycles, it was determined to continue with an additional 2 cycles (therefore 6 total at re-challenge) as the patient was tolerating the chemotherapy well and treatment was desired to be as definitive as possible. This information has been added to lines 122-124 in the edited manuscript.
Comment 8: Typo on line 139: atezolizumab. The sentence ‘There resolution of nodules seen in Septembre 2020 scan’ does not make sense.
Response 8: Thank you for pointing this out. The sentence has been edited for clarification, which is now at line 145-146.
Comment 9: Line 153: what was the CTCAE grade for transaminitis and how long the patient had to be on prednisone?
Response 9: Our patient experienced CTCAE grade 3 elevation in GGT (elevations in other liver enzymes were grade 1). He completed a 6 week taper of prednisone and restarted atezolizumab with no recurrence of transaminitis. This information was added at lines 167-169.
Comment 10: Line 164: what about brain MRIs?
Response 10: this information is reflected in our edits at lines 153-159 and has been referenced in a short note at line 177, thank you for requesting clarification.
Comment 11: Line 212: did you try liquid biopsy? Do you have access to it?
Response 11: We appreciate you raising this point. We unfortunately do not have access to liquid biopsy as part of routine clinical management – it is not funded in our provincial healthcare system. We also did not have any trials at the time to facilitate liquid biopsy, and cost to the patient was prohibitive. This information has been incorporated into the manuscript at lines 227-229.
Reviewer 2 Report
Comments and Suggestions for Authors
The case report is very clear and well-written. It is impressive to see the tumor reduction and the patient outcome. I believe it can be accepted in the present form.
Author Response
Comment 1: The case report is very clear and well-written. It is impressive to see the tumor reduction and the patient outcome. I believe it can be accepted in the present form.
Response 1: Thank you for taking the time to review our manuscript. We appreciate your endorsement of our report and ideas.
Reviewer 3 Report
Comments and Suggestions for Authors
I have reviewed your manuscript titled "Durable Response to Atezolizumab in Extensive Stage Small Cell Lung Cancer Leading to 57 Months Overall Survival: A Case Report." The case report presents a compelling account of a patient achieving an exceptional response to atezolizumab, contributing valuable insights into the potential for long-term survival in ES-SCLC patients treated with immunotherapy.
Your detailed description of the treatment regimen, supported by imaging evidence, effectively illustrates the patient's positive response and sustained survival. The discussion on the need for further research into the factors underlying such durable responses is particularly pertinent and well-articulated.
However, I noted a few areas that could benefit from revision to enhance the clarity and impact of your report:
Comments:
1. Clarify and simplify some medical terms and measurements to ensure consistency.
2. Provide a more detailed account of the patient's quality of life throughout the treatment process.
Comments on the Quality of English Language
Throughout the manuscript, attention to grammatical consistency and clarity can enhance readability and comprehension. Here are some specific suggestions:
1. Line 17: "experienced mild progressive disease" - The term "mild progressive disease" could be simplified to "mild disease progression".
2. Line 59: "along with multiple other smaller pulmonary nodules ranging from 5-15mm" - "5-15mm" should have a space between the number and the unit, i.e., "5-15 mm".
3. Line 68: "lefted sided" - should be "left-sided".
4. Line 103: "apperance" - should be "appearance".
5. Line 135: "apperance" - should be "appearance".
6. Line 139: "Residual scarring is present." - should be rephrased for clarity, e.g., "Residual scarring was observed."
7. Line 141: "maintanence" - should be "maintenance".
8. Line 157: "age 63" - could be better phrased as "aged 63".
9. Line 172: "minimal symptoms" - might be better phrased as "few symptoms".
10. Line 207: "biomarkers been established" - should be "biomarkers have been established".
11. Line 211: "initial biopsy had insufficient tissue" - could be better phrased as "the initial biopsy sample was insufficient".
12. Line 250: "induction regimen was considered to be the best approach" - could be simplified to "induction regimen was deemed the best approach".
Author Response
Comment 1: I have reviewed your manuscript titled "Durable Response to Atezolizumab in Extensive Stage Small Cell Lung Cancer Leading to 57 Months Overall Survival: A Case Report." The case report presents a compelling account of a patient achieving an exceptional response to atezolizumab, contributing valuable insights into the potential for long-term survival in ES-SCLC patients treated with immunotherapy.
Your detailed description of the treatment regimen, supported by imaging evidence, effectively illustrates the patient's positive response and sustained survival. The discussion on the need for further research into the factors underlying such durable responses is particularly pertinent and well-articulated.
Response 1: Thank you for your review and comments on our report, we appreciate the time and thought.
Comment 2: However, I noted a few areas that could benefit from revision to enhance the clarity and impact of your report:
Comments:
- Clarify and simplify some medical terms and measurements to ensure consistency.
- Provide a more detailed account of the patient's quality of life throughout the treatment process.
Response 2:
- We appreciate you highlighting this. Your below suggestions have been implemented and the paper has been reviewed to catch any further instances.
- This is an excellent suggestion. We have added comments on his experiences of the initial induction regimen (lines 88-89), radiation (lines 100-101), time before rechallenge (lines 110-112), and re-challenge (lines 127-128). Lines 148-149 contain a summary of his experience of maintenance atezolizumab.
Comment 3: Throughout the manuscript, attention to grammatical consistency and clarity can enhance readability and comprehension. Here are some specific suggestions:
Response 3: Thank you for your time with these suggestions. They have been implemented with further comments below.
- Line 17: "experienced mild progressive disease" - The term "mild progressive disease" could be simplified to "mild disease progression".
Response: This has been rephrased, thank you.
- Line 59: "along with multiple other smaller pulmonary nodules ranging from 5-15mm" - "5-15mm" should have a space between the number and the unit, i.e., "5-15 mm".
Response: Units have been reviewed for spacing.
- Line 68: "lefted sided" - should be "left-sided".
- Line 103: "apperance" - should be "appearance".
- Line 135: "apperance" - should be "appearance".
Response: These above three typos have all been corrected, thank you.
- Line 139: "Residual scarring is present." - should be rephrased for clarity, e.g., "Residual scarring was observed."
Response: This has been changed, thank you.
- Line 141: "maintanence" - should be "maintenance".
Response: Corrected, thank you.
- Line 157: "age 63" - could be better phrased as "aged 63".
- Line 172: "minimal symptoms" - might be better phrased as "few symptoms".
- Line 207: "biomarkers been established" - should be "biomarkers have been established".
- Line 211: "initial biopsy had insufficient tissue" - could be better phrased as "the initial biopsy sample was insufficient".
Response: The four above phrasing suggestions have been implemented, thank you.
- Line 250: "induction regimen was considered to be the best approach" - could be simplified to "induction regimen was deemed the best approach".
Response: This seems to be at line 119 and is an excellent point; it has been corrected.
