Intraoperative Tumor Margin Identification With ICG Dye Imaging

Study Overview
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Brief Summary
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In this research study we want to learn more about the use of indocyanine green (ICG) during bone or soft tissue mass resections. Indocyanine green (ICG) is a type of dye that is used in medical diagnostics. We want to determine if ICG-guided tumor resection is more effective in obtaining negative margins. Lastly, we want to assess traditional oncologic outcomes of local recurrence, time to metastatic disease, and overall and disease specific survival.

Detailed Description
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If you are present for a preoperative clinic visit the day before your surgery, ICG may be administered via injection. Otherwise, ICG will be administered in the preoperative unit via IV injection at the time of presentation approximately 4 hours before your surgery. You will be monitored during and after ICG dosing. During surgery ICG fluorescence using a near-infrared imager will be performed at the time of and immediately following primary tumor resection. The imager will evaluate the primary tumor to ensure appropriate tumor fluorescence. Once the primary resection is complete and the surgeon believes that he/she has achieved negative or planned positive margins, fluorescence measurements of the tumor bed will be performed. If areas of positive signal remain, these areas will be resected if possible and sent to pathology for histologic evaluation. It will be recorded if the surgeon perceived negative margins but the device detected positive margins. Tumor specimens and residual fluorescence positive samples will be evaluated using fresh frozen and permanent histology. Permanent samples will be evaluated for tumor and local fluorescence using confocal microscopy with an ICG cube. Positive fluorescence signal and its correspondence with neoplasm will be noted, a will tumor that does not fluoresce. Tissue being removed is 1-2 mm from non-structurally important tissue that either has or does not have signal positivity for additional pathologic assessment. It should have no impact on patient outcome, does not represent intervention on sensitive areas (such as neurovascular structures), and can further be used as potential margin around the tumor.

Official Title
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Evaluation of Intraoperative Tumor Margin Identification With Fluorescent Dye Imaging

Conditions
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Benign Neoplasm, Malignant Neoplasm

Intervention / Treatment
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* Drug: Indocyanine green
* Device: SPY-PHI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients 18 years of age or older who present to Massachusetts General Hospital Department of Orthopaedic Surgery with a benign or malignant bone or soft tissue mass that is consented for surgery during the study period. Exclusion Criteria: Pregnant or nursing patients Patients with previously known anaphylaxis to IV contrast or iodine (other allergies may be considered on a case-by-case basis) Patients in renal failure who are not cleared for ICG administration by their primary physician or oncologist

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: ICG Dye and use of SPY-PHI Imaging<br>ICG will be administered in the pre-operative unit via IV injection at the time that they present to the pre-operative unit, which is approximately 4 hours before surgery. ICG Angiography (SPY PHI) will be performed to detect any residual signal | Drug: Indocyanine green<br>* The SPY PHI and its dye Indocyanine Green dye (ICG) is a non-invasive device that is connected to a light source tower that is already available in the hospital in the operating room under Gynecology and Obstetrics Equipment. This is a special light source lamp that allows to test for vascularity in the soft tissues intraoperatively. Previous research in animal models proved the concept that the increased vascularity in tumors can be used to use this device to improve intraoperative assessment of tumor margins during resection. Our study will help to establish a correlation between activity with the dye and histological findings. This information has the potential to help sarcoma patients by avoiding staged surgeries, decreasing hospitalization times, and decreasing the likelihood of local recurrence by improving margin quality.<br>Device: SPY-PHI<br>* The SPY PHI and its dye Indocyanine Green dye (ICG) is a non-invasive device that is connected to a light source tower that is already available in the hospital in the operating room under Gynecology and Obstetrics Equipment. This is a special light source lamp that allows to test for vascularity in the soft tissues intraoperatively. Previous research in animal models proved the concept that the increased vascularity in tumors can be used to use this device to improve intraoperative assessment of tumor margins during resection. Our study will help to establish a correlation between activity with the dye and histological findings. This information has the potential to help sarcoma patients by avoiding staged surgeries, decreasing hospitalization times, and decreasing the likelihood of local recurrence by improving margin quality.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| image-guided prediction of local recurrence | The primary outcome of this work is image-guided prediction of local recurrence, defined as pathologically confirmed return of the resected tumor local to the prior excision bed within 2 years of the primary surgery. | 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distant recurrence (metastatic disease) | If a participant develops metastatic disease after surgery with ICG and SPY-PHI. | 2 Years | 
| physician-perceived vs. device measured negative margins | physician-perceived vs. device measured negative margins (compared using pathologic specimens), which will be measured against formal margin analysis performed by a pathologist during the routine standard of care. | 14 days |