Surgical excision is the primary treatment for solid tumors in oral squamous cell carcinomas, where achieving a healthy tissue margin of >5 mm is the goal. However, current clinical methods of assessing surgical margins cannot provide assessment of the whole margins intraoperatively (while the patient is still on the operating table) and while recent intraoperative fluorescence-guided surgery approaches have shown promise for detected “positive” inadequate margins (<1 mm), they have had limited success in the detection of “close” inadequate margins (1-5 mm), in patients injected with cetuximab-IRDye 800CW prior to surgery. Here, a dual aperture fluorescence ratio (dAFR) approach presented previously by our group is expanded upon, where herein we present a version of the analysis where the measurements are normalized by a background signal. We compare this additional approach directly against a single aperture view fluorescence (sAF) and pathology measurements of margin thickness in specimens from five patients and a total 14 margin locations (1 positive, 7 close, and 6 clear margins). The area under the curve of the receiver operating characteristic, representing the ability to detect close compared to clear margins was found to be 1.0 and 0.6 using dAFR and sAF, respectively, with the improvements in dAFR being statistically significant (p < 0.01). We demonstrate that the addition of a background normalization can account for noise and low signal in narrow aperture images.
In the United States, the annual incidence of oral squamous cell carcinoma (OSCC) exceeds 50,000 cases. Primary tumor resection remains the first line of treatment in these patients yet follow up neck dissection and chemoradiation treatment may be indicated if cancer has spread to tumor draining lymph nodes. There is a push to minimize morbidity from neck dissection by sentinel lymph node biopsy, where only the first lymph node(s) draining the primary tumor are excised and evaluated for cancer spread. However, with current pathology methods, results are not available to surgeons until patients have been sent home. In response, we are developing a method to rapidly stain and image whole excised lymph nodes in less than 30 min, so surgeons can react to positive cases while patients are still on the operating table. Here we present a human head and neck cancer spheroid model implanted in porcine lymph nodes as a means evaluating the potential for our staining and imaging protocols to rapidly identify cancer burden in lymph nodes.
SignificanceSurgical excision is the main treatment for solid tumors in oral squamous cell carcinomas, where wide local excision (achieving a healthy tissue margin of >5 mm around the excised tumor) is the goal as it results in reduced local recurrence rates and improved overall survival.AimNo clinical methods are available to assess the complete surgical margin intraoperatively while the patient is still on the operating table; and while recent intraoperative back-bench fluorescence-guided surgery approaches have shown promise for detecting “positive” inadequate margins (<1 mm), they have had limited success in the detection of “close” inadequate margins (1 to 5 mm). Here, a dual aperture fluorescence ratio (dAFR) approach was evaluated as a means of improving detection of close margins.ApproachThe approach was evaluated on surgical specimens from patients who were administered a tumor-specific fluorescent imaging agent (cetuximab-800CW) prior to surgery. The dAFR approach was compared directly against standard wide-field fluorescence imaging and pathology measurements of margin thickness in specimens from three patients and a total of 12 margin locations (1 positive, 5 close, and 6 clear margins).ResultsThe area under the receiver operating characteristic curve, representing the ability to detect close compared to clear margins (>5 mm) was found to be 1.0 and 0.57 for dAFR and sAF, respectively. Improvements in dAFR were found to be statistically significant (p<0.02).ConclusionsThese results provide evidence that the dAFR approach potentially improves detection of close surgical margins.
An increasing number of cancer surgery protocols are including sentinel lymph node biopsies on the day of resection to stage for non-palpable spread of cancer through tumor draining lymph nodes. The challenge is that often a tumor-positive node will make it necessary to perform an enhanced resection of the lymphatic network, and if lymph node processing is not completed within the timeframe of surgery, then patients may have to be called back for additional surgery or have to undergo amplified chemo or radiation therapy. Our group is working on a rapid lymph node staining and fluorescence tomography system that we call ADEPT to provide surgeons with lymph node biopsy results within 15 min. The aim is to minimize the number of callback surgery or amplified therapy procedures to minimize stress to patients and reduce health care costs. This work predicts, using Monte Carlo photon propagation modeling simulations, that ADEPT has the potential to yield greater than 95% accuracy in detecting the smallest amount of cancer considered clinically relevant withing 15 min of tissue processing and imaging.
Post-operative assessment of resected tumor margins is critical to ensure the entirety of malignant tissue has been removed from a patient. Microscopic assessment of tissue post-excision is the current gold standard, however the long wait times for proper specimen evaluation limit a surgeon’s ability to be certain they obtained clear margins. To address this need, fluorescence-guided surgery approaches are under development that can yield molecular contrast between healthy and malignant tissues intraoperatively. In head and neck cancer specifically, heterogenous optical properties lead to poor identification in margins greater than 1 mm thick when viewed with single projections. Thus, we demonstrate the use of variable aperture approach to decrease the effects of local optical property variations in the imaged specimen. Here we use Monte Carlo simulations to verify the utility of the idea in a homogenous medium as well in a medium with heterogenous properties. We demonstrate that a ratio metric approach can provide near identical depth discrimination as a single projection in a homogenous medium and is further capable of reducing pixel variability due to local optical properties in a heterogenous medium than a single projection alone.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.