Shape-Sensing Robotic Bronchoscopy with Integrated Mobile Cone-Beam CT Guidance for Intraoperative Localization of Lung Tumors Using Indocyanine Green

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This article presents a clinical study that utilizes a shape-sensing robotic bronchoscope (SS-RAB) combined with mobile cone-beam CT (mCBCT) for intraoperative positioning of pulmonary nodules by injecting indocyanine green (ICG), and proposes a simplified surgical procedure strategy.My comments are as follows:

1. The manuscript only mentions "retrospectively reviewed patients", but does not specify whether it was a continuous inclusion process, or if there were any excluded cases (such as those with severe emphysema, inability to tolerate one-lung ventilation, or cases where mCBCT guidance failed and alternative positioning methods were used).
2. The definition of "success" in the article is "as assessed by the operating surgeon", which means it relies on the subjective judgment of the surgeon (grossly adequate). This lacks objective validation. It is recommended to add:

• Has there been postoperative pathology to confirm the correspondence between the ICG deposition location and the lesion?
• Has intraoperative mCBCT or postoperative specimen CT confirmed the location of the dye?
• If no supplementary data can be provided, at least it should be clearly stated in the Limitations section that this is an important limitation of this study.

3. The ICG dosage range (0.5 - 1 mL) spans by a factor of two and is not specified: Is the dosage selection adjusted based on the size, depth or density of the nodule? Injection speed, how long to wait after injection before starting the surgery? Do you need to recheck the position of the needle?
4. Table 3 reports the reference air kerma and kerma-area product, which should be compared with the following reference values: the radiation dose for conventional percutaneous CT-guided puncture positioning. The dose of simple diagnostic CBCT or intraoperative CBCT;
5. It is necessary to discuss the impact of the learning curve -》 Analyze the success rate and operation time either in chronological order (such as the first 10 cases vs. the last 18 cases) or based on the cumulative number of cases;
6. The reference list is in a disorganized format.
7. Currently, only "pneumothorax, persistent air leak, new oxygen requirement" are listed, without any severity grading.
8. The SS-RAB (Ion system) combined with mCBCT (Cios 3D Spin) is an expensive equipment combination that requires the presence of a multidisciplinary team (interventional pulmonology, thoracic surgery, anesthesia) at the same time. Currently, the discussion has not covered:

• The cost difference compared to percutaneous hook-wire/microcoil or traditional ENB;
• The actual impact on the hospital's surgical scheduling efficiency (does it occupy more OR time?) ；

Author Response

Comment 1

The manuscript only mentions "retrospectively reviewed patients", but does not specify whether it was a continuous inclusion process, or if there were any excluded cases (such as those with severe emphysema, inability to tolerate one-lung ventilation, or cases where mCBCT guidance failed and alternative positioning methods were used).

Response 1

Thank you for your comment. The inclusion was continuous; no patients were excluded in that period. We have added this important point to the manuscript. (line 82)

 

Comment 2

The definition of "success" in the article is "as assessed by the operating surgeon", which means it relies on the subjective judgment of the surgeon (grossly adequate). This lacks objective validation. It is recommended to add:

Has there been postoperative pathology to confirm the correspondence between the ICG deposition location and the lesion?

Has intraoperative mCBCT or postoperative specimen CT confirmed the location of the dye?

If no supplementary data can be provided, at least it should be clearly stated in the Limitations section that this is an important limitation of this study.

Response 2

Thanks for highlighting this. Unfortunately, it is a limitation common to almost all prior studies on the same topic. The definition of success is always subjective based on the surgeons ability to locate the ICG and the pathologists to locate the lesion in the surgical specimen with adequate margins.

Since this was not a prospective protocol, the pathologists were not asked to look for ICG in their specimens.

Although we did not perform a repeat cone beam CT spin after injection (once we had the needle in the target area per CBCT we injected and proceeded with surgery), such a small amount of ICG (0.5cc) may also not be detected by Cone Beam CT.

 

We have then followed your advice and added a statement on this being a major limitation of the study. See lines 335-336.

 

Comment 3

The ICG dosage range (0.5 - 1 mL) spans by a factor of two and is not specified: Is the dosage selection adjusted based on the size, depth or density of the nodule? Injection speed, how long to wait after injection before starting the surgery? Do you need to recheck the position of the needle?

Response 3

Thanks for your comments. Unfortunately, this is a retrospective study, and the dosage was selected by the bronchoscopists based on prior literature. There was no specific adjustment based on lesion characteristics. The speed of injection, which we can characterize as a slow push, was not measured. As we described in methods, we check the position of the needle with mCBCT immediately before injection, if adequate, we inject, if not, we repositioned the needle and checked again with a new mCBCT spin (lines 136-141).

 

Comment 4

Table 3 reports the reference air kerma and kerma-area product, which should be compared with the following reference values: the radiation dose for conventional percutaneous CT-guided puncture positioning. The dose of simple diagnostic CBCT or intraoperative CBCT;

Response 4

Thanks for your comment.

During CT-guided percutaneous procedures radiation exposure is typically quantified using Dose-Length Product (measured in mGy-cm) rather than Kerma Area Product (measured in mGy or Gy-cm²). Thus, it is difficult to compare our data with percutaneous CT guided procedures. However, the Dose or Kerma Area Product of a standard chest CT is known, and it is 30-40 Gy-cm². We changed the units we had reported in Table 3 from mGy-cm² to Gy-cm², so we can show how the Dose/Kerma area product in our cohort was roughly a tenth of the radiation associated with a standard diagnostic chest CT.  We also compare favorably with a diagnostic bronchoscopy with CBCT guidance where the dose area product reported ranges between 20 and 70 Gy-cm². Our radiation exposure was minimal.

See Lines 328-3333.

 

Comment 5

It is necessary to discuss the impact of the learning curve -》 Analyze the success rate and operation time either in chronological order (such as the first 10 cases vs. the last 18 cases) or based on the cumulative number of cases;

Response 5

Thanks for your comment.

ICG marking was only unsuccessful in 2 out of 30 lesions, one was the 3^rd case and one was the second to last case, unrelated to the learning curve.  Respectfully, further analysis of the learning curve is not within the scope of our study.

 

Comment 6

The reference list is in a disorganized format.

Response 6

All we could find was a missing “et al”. The format is not disorganized and Endnotes was utilized following instructions for authors.

 

Comment 7

Currently, only "pneumothorax, persistent air leak, new oxygen requirement" are listed, without any severity grading.

Response 7

Thanks for your comment. All these were explained in detail in the original submission between lines 191-197. Please see lines 193-194 where the degree and repercussion of the pneumothorax was explained.  The specific case of a new home O2 requirement was described as well in lines 197-199.  The definition utilized for the persistent air-leak is included in line 196.

Comment 8

The SS-RAB (Ion system) combined with mCBCT (Cios 3D Spin) is an expensive equipment combination that requires the presence of a multidisciplinary team (interventional pulmonology, thoracic surgery, anesthesia) at the same time. Currently, the discussion has not covered:

The cost difference compared to percutaneous hook-wire/microcoil or traditional ENB;

The actual impact on the hospital's surgical scheduling efficiency (does it occupy more OR time?) ；

Response 8

Thanks for your comment. You are correct about the high cost of the robotic bronchoscopy and CBCT equipment. But of course, these expensive pieces of equipment would not be purchased specifically for ICG marking. When available, and the number of centers is growing exponentially in the US, it can be utilized for ICG marking, in addition to diagnostic bronchoscopy (its main purpose). Anesthesia and thoracic surgery are always needed for sublobar resections. It is a question of involving either interventional radiology or interventional pulmonology for tumor localization. Moreover, a growing number of thoracic surgeons are performing ICG marking with these technologies on their own.

A cost-effectiveness analysis and comparison with other techniques would be complex and would render different results based on the geographical location, healthcare system, as well as the institution, and it is beyond the scope of this small retrospective study. But this issue is now mentioned in the discussion.

The impact on OR efficiency would probably have to be analyzed in a randomized prospective trial. ICG marking may add 20-30 min to the procedure, but then again if the lesion can be localized sooner this way, it may still make the overall OR time the same or even shorter. That question cannot be answered with our study.

Please see added discussions in lines 340-346 (limitations).

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for the oportunity to review this article on an interesting topic, which introduces an innovative method for localization of lung tumors using Robotic Assisted Brochoscopy augmented with Cone-Beam CT and using Indocyanine Green for marking the lesions.

The article describes the current state in diagnosis and localization of lung tumors and the advantages of the aforementioned method, such as higher accuracy in localization and lower risk of complications.

The article is well written and easy to read. The conclusions indicate a major impact of the aforementioned method in the field of diagnosis and localization of lung tumors.

Although the present data are intriguing, there are some moments that need clarification:

1. What exclusion criteria were used in the study?
2. In Table 1, there are indicated 14 cases of primary lung cancer, but the staging is indicated only for 11 cases of primary lung cancer. Which stage do the other 3 cases belong to?
3. please add how this technique will change real life clinical practice and may be current guidelines

Author Response

COMMENT 1.

1. What exclusion criteria were used in the study?

RESPONSE 1

None, consecutive cases were included, and a statement was added in Methods section.

See Line 82.

COMMENT 2.

In Table 1, there are indicated 14 cases of primary lung cancer, but the staging is indicated only for 11 cases of primary lung cancer. Which stage do the other 3 cases belong to?

RESPONSE 2

Thanks so much for catching this error. The table was corrected, there were 13 cases in Stage I and 1 in stage II.

COMMENT 3. 

Please add how this technique will change real life clinical practice and may be current guidelines

RESPONSE 3

Thanks again.  Since the technologies that we utilized in this study are costly, we can only infer that it will change practice in centers where these pieces of equipment are available (growing number of centers in the US). (see Line 349)

 We humbly believe that our study is too small to make a statement with regard to a change in clinical guidelines.

Reviewer 3 Report

Comments and Suggestions for Authors

Peer Review Report

Manuscript Title: Shape-Sensing Robotic Bronchoscopy with Integrated Mobile Cone-Beam CT Guidance for Intraoperative Localization of Lung Tumors Using Indocyanine Green
Journal: Diagnostics
Manuscript ID: 4338361

Summary of the Study

The authors present a retrospective evaluation of 28 patients (30 lesions) undergoing shape-sensing robotic-assisted bronchoscopy (SS-RAB) with integrated mobile cone-beam CT (mCBCT) for intraoperative localization of lung tumors using indocyanine green (ICG). They also introduce a single-intubation, single-positioning (lateral decubitus) workflow for bronchoscopy and surgery. The study aims to assess the efficacy, safety, and procedural feasibility of this approach. Key findings include:

• ICG localization success: 28/30 lesions (93%)
• Median lesion size: 10.5 mm (IQR 8.7–14.6 mm)
• Median anesthesia time: 203 min (IQR 176–238 min)
• Low complication rates: one intraoperative pneumothorax (3.6%), two persistent air leaks (7%), no 30-day mortality
• Feasibility of single-intubation DL-ETT approach in 68% of patients

The study concludes that SS-RAB with integrated mCBCT and ICG marking is safe, effective, and potentially improves workflow efficiency, particularly with the single-intubation, lateral decubitus technique.

 

Major Comments

1. The manuscript addresses a timely clinical problem: precise intraoperative localization of small or subsolid lung nodules during minimally invasive surgery. The integration of SS-RAB with mCBCT and ICG marking, combined with a single-intubation approach, represents a notable contribution to thoracic surgical workflow optimization.
2. The retrospective, single-center design is acknowledged by the authors as a limitation.
3. The sample size is small (28 patients), which limits the statistical power, especially for comparisons such as single vs. two-intubation times.
4. No control group is included (e.g., traditional ENB or percutaneous ICG marking), making direct efficacy comparisons challenging.
5. The procedural workflow is described in detail, including DL-ETT use, lateral decubitus positioning, and mCBCT integration (pages 3–6, Figures 1–2).
6. Figures effectively illustrate equipment setup and ICG localization.
7. Statistical analysis is basic (median, IQR), which is acceptable for a small retrospective study but limits hypothesis testing.
8. The localization success rate (93%) and negative surgical margins are encouraging.
9. Safety outcomes are well-documented, with minimal complications.
10. Tables 1–3 provide clear demographic, lesion, procedural, and outcome data.
11. The discussion contextualizes the results against previous studies using SS-RAB and ENB (pages 10–12), which strengthens the scientific argument.

 

Minor Comments

1. Abstract:
• Clearly summarizes objectives, methods, results, and conclusions.
• Could briefly mention sample size and single-center nature for transparency.
2. Figures:
• Figure 1 and 2 are informative; consider increasing contrast for clarity of endoscopic views in Figure 2C-D.
• Label all images consistently with letters and legends for easier reference.
3. Tables:
• Tables are readable; consider highlighting key outcome metrics (e.g., success rates, complications) for rapid assessment.
4. References:
• Current and relevant. Include both recent SS-RAB and ENB studies for context (pages 13–14).
• Minor typographical corrections in references (e.g., “Goerĵen” → “Gorjen”) may be required.
5. Language and Style:
• Generally clear and concise.
• Occasional minor grammatical inconsistencies (e.g., “beĴer identify nodules” on page 2) should be corrected.
6. Ethical Statement:
• IRB approval and waiver of informed consent are appropriately reported (page 12).

Author Response

Major Comments

1. The manuscript addresses a timely clinical problem: precise intraoperative localization of small or subsolid lung nodules during minimally invasive surgery. The integration of SS-RAB with mCBCT and ICG marking, combined with a single-intubation approach, represents a notable contribution to thoracic surgical workflow optimization.
2. The retrospective, single-center design is acknowledged by the authors as a limitation.
3. The sample size is small (28 patients), which limits the statistical power, especially for comparisons such as single vs. two-intubation times.
4. No control group is included (e.g., traditional ENB or percutaneous ICG marking), making direct efficacy comparisons challenging.
5. The procedural workflow is described in detail, including DL-ETT use, lateral decubitus positioning, and mCBCT integration (pages 3–6, Figures 1–2).
6. Figures effectively illustrate equipment setup and ICG localization.
7. Statistical analysis is basic (median, IQR), which is acceptable for a small retrospective study but limits hypothesis testing.
8. The localization success rate (93%) and negative surgical margins are encouraging.
9. Safety outcomes are well-documented, with minimal complications.
10. Tables 1–3 provide clear demographic, lesion, procedural, and outcome data.
11. The discussion contextualizes the results against previous studies using SS-RAB and ENB (pages 10–12), which strengthens the scientific argument.

 

RESPONSE 1-11:

Thanks for all these positive comments.

 

Minor Comments

1. Abstract:
• Clearly summarizes objectives, methods, results, and conclusions.
• Could briefly mention sample size and single-center nature for transparency.

 

RESPONSE:

Thanks. See lines 25 and 26 where we added the fact that it was a single center study after describing the sample size..

1. Figures:
• Figure 1 and 2 are informative; consider increasing contrast for clarity of endoscopic views in Figure 2C-D.
• Label all images consistently with letters and legends for easier reference.

RESPONSE:

Thanks for your comment. We have increased the contrast in Figures 2C-D as suggested. Images are labeled 1 (AB) and 2 (ABCD).

 

1. Tables:
• Tables are readable; consider highlighting key outcome metrics (e.g., success rates, complications) for rapid assessment.

RESPONSE:

Thanks for your comment. Major outcomes were highlighted (bold/italics).

 

1. References:
• Current and relevant. Include both recent SS-RAB and ENB studies for context (pages 13–14).
• Minor typographical corrections in references (e.g., “Goerĵen” → “Gorjen”) may be required.

RESPONSE

        Thanks for your comment.  Goertzen is properly spelled.

 

 

1. Language and Style:
• Generally clear and concise.
• Occasional minor grammatical inconsistencies (e.g., “beĴer identify nodules” on page 2) should be corrected.

RESPONSE

   Thanks for your comment.  “better identify” was changed to accurately identify.

 

1. Ethical Statement:
• IRB approval and waiver of informed consent are appropriately reported (page 12).

THANKS AGAIN.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Most of my comments have been addressed

Reviewer 2 Report

Comments and Suggestions for Authors

accept as it