Tumor-positive Margins Research Articles

Clinicopathological parameters associated with cervical lymph node metastases in differentiated thyroid cancer.

Lymph node metastasis (LNM) has an important role for the prognosis of diferentiated thyroid cancer (DTC). The aim of the study was to investigate the efect of clinicopathologic parameters on cervical LNM in DTC. The patients who underwent thyroidectomy along with neck dissection were analyzed retrospectively. Of the 150 patients diagnosed with DTC who underwent neck dissection, 1 had follicular thyroid carcinoma and 149 had papillary thyroid carcinoma (PTC). The median tumor size was 14.0 mm. The tumor diameter with the highest specificity and sensitivity for the detection of LNM was >11.5 mm. Extrathyroidal extension (ETE) was observed in 35.3% of the patients. The rate of multifocality in tumors with extrathyroidal spread was significantly higher than in tumors without ETE. LNM was observed in 60.0% of the patients. ETE was present in 28.9% of the tumors that had LNM. Lymphovascular invasion (LVI), perineural invasion (PNI), and positive surgical margin were observed in 13.3%, 2.7%, and 14% of the patients respectively. A significant positive correlation was found between LNM and tumor diameter, ETE, positive tumor margin and LVI (Pp=.006, P=.031, P = .002, and P=.014, respectively). In this study, ETE, LVI, positive tumor margin, and tumor diameter greater than 11.5 mm were significantly correlated with the presence of LNM. These findings may be useful in bringing to mind the possibility of lymph node metastases that have not been able to be detected before surgery and in monitoring these patients more closely.

Fluorescence-guided surgery using cetuximab-800CW in patients with penile carcinoma.

To investigate the feasibility of fluorescence molecular imaging (FMI), using cetuximab-800CW, as an intraoperative tool to determine surgical margins in penile squamous cell carcinoma (PSCC). A total of 11 patients with PSCC received 75 mg cetuximab followed by 15 mg cetuximab-800CW 2 days before surgery. FMI of the whole excision specimen and tissue slices was performed. Fluorescence visualisation was correlated to histopathology. Based on tumour and healthy tissue regions of interest, mean fluorescence intensity was calculated for each individual patient. Significant differences between tumour and healthy mean fluorescence intensity were found with tumour-to-background ratios of a median (IQR) of 1.51 (0.99) and a mean (SD) of 1.51 (0.32) in the excision specimen and tissue slices, respectively. One patient showed a high relative fluorescence intensity with a signal-to-background ratio of 1.79, corresponding to a tumour-positive margin on fresh frozen sectioning. In this Phase I study we showed that cetuximab-800CW seems suitable to discriminate PSCC from background tissue. The tracer was well tolerated, and no false positive spots were seen.

Recurrent dedifferentiated retroperitoneal liposarcoma complicating pregnancy

Retroperitoneal liposarcoma is an uncommon tumor both in the pregnant and nonpregnant state. Its exact incidence is unknown because of its rarity. Due to its propensity for local recurrence, prognosis depends on histologic subtype and negative margins of resection. Surgery remains the mainstay of treatment, and timing is critical in terms of finding a surgically resectable lesion while balancing fetal risks. This report describes tumor recurrence in a pregnancy with a prior history of surgery for an atypical lipomatous tumor presenting as a retroperitoneal mass. After discussion with the multidisciplinary team, as well as with the patient’s consent, the plan was to defer surgery until 34 weeks, followed by scheduled tumor removal 2 weeks postpartum. She delivered abdominally to a baby girl with a good outcome. Histopathology showed dedifferentiated liposarcoma with a positive tumor margin. The patient has survived at 6-month follow-up and completed four cycles of chemotherapy with doxorubicin, ifosfamide, and mesna. However, surveillance imaging again showed tumor recurrence.

A dual-camera hyperspectral laparoscopic imaging system.

Minimally invasive surgery (MIS) has expanded broadly in the field of abdominal and pelvic surgery. However, there are still prevalent issues surrounding intracorporeal surgery, such as iatrogenic injury, anastomotic leakage, or the presence of positive tumor margins after resection. Current approaches to address these issues and advance laparoscopic imaging techniques often involve fluorescence imaging agents, such as indocyanine green (ICG), to improve visualization, but these have drawbacks. Hyperspectral imaging (HSI) is an emerging optical imaging modality that takes advantage of spectral characteristics of different tissues. Various applications include tissue classification and digital pathology. In this study, we developed a dual-camera system for high-speed hyperspectral imaging. This includes the development of a custom application interface and corresponding hardware setup. Characterization of the system was performed, including spectral accuracy and spatial resolution, showing little sacrifice in speed for the approximate doubling of the covered spectral range, with our system acquiring 29 spectral images from 460-850 nm. Reference color tiles with various reflectance profiles were imaged and a RMSE of 3.56 ± 1.36% was achieved. Sub-millimeter resolution was shown at 7 cm working distance for both hyperspectral cameras. Finally, we image ex vivo tissues, including porcine stomach, liver, intestine, and kidney with our system and use a high-resolution, radiometrically calibrated spectrometer for comparison and evaluation of spectral fidelity. The dual-camera hyperspectral laparoscopic imaging system can have immediate applications in various surgeries.

Hospital variation and outcomes after repeat hepatic resection for colorectal liver metastases: a nationwide cohort study

BackgroundApproximately 70% of patients with colorectal liver metastases (CRLM) experiences intrahepatic recurrence after initial liver resection. This study assessed outcomes and hospital variation in repeat liver resections (R-LR). MethodsThis population-based study included all patients who underwent liver resection for CRLM between 2014 and 2022 in the Netherlands. Overall survival (OS) was collected for patients operated on between 2014 and 2018 by linkage to the insurance database. ResultsData of 7479 liver resections (1391 (18.6%) repeat and 6088 (81.4%) primary) were analysed. Major morbidity and mortality were not different. Factors associated with major morbidity included ASA 3+, major liver resection, extrahepatic disease, and open surgery. Five-year OS after repeat versus primary liver resection was 42.3% versus 44.8%, P = 0.37. Factors associated with worse OS included largest CRLM >5 cm (aHR 1.58, 95% CI: 1.07–2.34, P = 0.023), >3 CRLM (aHR 1.33, 95% CI: 1.00–1.75, P = 0.046), extrahepatic disease (aHR 1.60, 95% CI: 1.25–2.04, P = 0.001), positive tumour margins (aHR 1.42, 95% CI: 1.09–1.85, P = 0.009). Significant hospital variation in performance of R-LR was observed, median 18.9% (8.2% to 33.3%). ConclusionSignificant hospital variation was observed in performance of R-LR in the Netherlands reflecting different treatment decisions upon recurrence. On a population-based level R-LR leads to satisfactory survival.

Time-resolved fluorescence and diffuse reflectance for lung squamous carcinoma margin detection.

A major challenge in non-small cell lung cancer surgery is the occurrence of positive tumor margins. This may lead to the need for additional surgeries and has been linked to poor patient prognosis. This study aims to develop an in vivo surgical tool that can differentiate cancerous from noncancerous lung tissue at the margin. A time-resolved fluorescence and diffuse reflectance bimodal device was used to measure the lifetime, spectra, and intensities of endogenous fluorophores as well as optical properties of lung tissue. The tumor and fibrotic tissue data, each containing 36 samples, was obtained from patients who underwent surgical removal of lung tissue after being diagnosed with squamous carcinoma but before any other treatment was administered. The normal lung tissue data were obtained from nine normal tissue samples. The results show a statistically significant difference between cancerous and noncancerous tissue. The results also show a difference in metabolic related optical properties between fibrotic and normal lung tissue samples. This work demonstrates the feasibility of a device that can differentiate cancerous and noncancerous lung tissue for patients diagnosed with squamous cell carcinoma.

A color-based tumor segmentation method for clinical ex vivo breast tissue assessment utilizing a multi-contrast brightfield imaging strategy.

We demonstrate an automated two-step tumor segmentation method leveraging color information from brightfield images of fresh core needle biopsies of breast tissue. Three different color spaces (HSV, CIELAB, YCbCr) were explored for the segmentation task. By leveraging white-light and green-light images, we identified two different types of color transformations that could separate adipose from benign and tumor or cancerous tissue. We leveraged these two distinct color transformation methods in a two-step process where adipose tissue segmentation was followed by benign tissue segmentation thereby isolating the malignant region of the biopsy. Our tumor segmentation algorithm and imaging probe could highlight suspicious regions on unprocessed biopsy tissue to guide selection of areas most similar to malignant tissues for tissue pathology whether it be formalin fixed or frozen sections, expedite tissue selection for molecular testing, detect positive tumor margins, or serve an alternative to tissue pathology, in countries where these services are lacking.

Breast surgery after neoadjuvant chemotherapy in patients with lobular carcinoma: surgical and oncologic outcome.

Breast cancer patients with invasive lobular carcinoma (ILC) have an increased risk of positive margins after surgery and often show little response to neoadjuvant chemotherapy (NAC). We aimed to investigate surgical outcomes in patients with ILC treated with NAC. In this retrospective cohort study, all breast cancer patients with ILC treated with NAC who underwent surgery at the Netherlands Cancer Institute from 2010 to 2019 were selected. Patients with mixed type ILC in pre-NAC biopsies were excluded if the lobular component was not confirmed in the surgical specimen. Main outcomes were tumor-positive margins and re-excision rate. Associations between baseline characteristics and tumor-positive margins were assessed, as were complications, locoregional recurrence rate (LRR), recurrence-free survival (RFS), and overall survival (OS). We included 191 patients. After NAC, 107 (56%) patients had breast conserving surgery (BCS) and 84 (44%) patients underwent mastectomy. Tumor-positive margins were observed in 67 (35%) patients. Fifty five (51%) had BCS and 12 (14%) underwent mastectomy (p value < 0.001). Re-excision was performed in 35 (33%) patients with BCS and in 4 (5%) patients with mastectomy. Definitive surgery was mastectomy in 107 (56%) patients and BCS in 84 (44%) patients. Tumor-positive margins were associated with cT ≥ 3 status (OR 4.62, 95% CI 1.26-16.98, p value 0.021) in the BCS group. Five-year LRR (4.7%), RFS (81%), and OS (93%) were not affected by type of surgery after NAC. Although 33% of ILC breast cancer patients undergoing BCS after NAC required re-excision for positive resection margins, it is considered safe given that five-year RFS remained excellent and LRR and OS did not differ by extent of surgery.

Santeon’s Lessons from a Decade of Implementing Value-Based Health Care

Summary Despite growing global support for value-based health care (VBHC), there is no consensus on the best approach for the identification of improvement potential nor on the selection and implementation of improvement initiatives. In addition, varying frames of reference shape how individuals interpret the concept of value and how they implement VBHC. As a result, it is often implemented in various and fragmented ways. Santeon, a nonprofit formal alliance of seven Dutch teaching hospitals, has been working on VBHC since 2012. In this article, intended to address gaps in the literature regarding the implementation of VBHC, the authors use the new strategic agenda for value transformation to share more than 10 years of Santeon’s VBHC implementation experience. The authors provide an overview of Santeon’s implementation methods; describe challenges and lessons learned; and demonstrate how value transformation was achieved with tangible examples from birth care, chronic kidney disease care, and breast cancer care. In breast cancer care, for example, system-wide improvement initiatives resulted in an increase in breast-conserving surgeries on an outpatient basis (from 391 in 2014 and 2015 to 458 in 2016), and a reduction in reoperation rates owing to positive tumor margins (from 39 in 2014 and 2015 to 33 in 2016). These results were subsequently used to negotiate a collective value-based reimbursement model with insurance companies.

Development of an augmented reality guidance system for head and neck cancer resection.

The use of head-mounted augmented reality (AR) for surgeries has grown rapidly in recent years. AR aids in intraoperative surgical navigation through overlaying three-dimensional (3D) holographic reconstructions of medical data. However, performing AR surgeries on complex areas such as the head and neck region poses challenges in terms of accuracy and speed. This study explores the feasibility of an AR guidance system for resections of positive tumour margins in a cadaveric specimen. The authors present an intraoperative solution that enables surgeons to upload and visualize holographic reconstructions of resected cadaver tissues. The solution involves using a 3D scanner to capture detailed scans of the resected tissue, which are subsequently uploaded into our software. The software converts the scans of resected tissues into specimen holograms that are viewable through a head-mounted AR display. By re-aligning these holograms with cadavers with gestures or voice commands, surgeons can navigate the head and neck tumour site. This workflow can run concurrently with frozen section analysis. On average, the authors achieve an uploading time of 2.98min, visualization time of 1.05min, and re-alignment time of 4.39min, compared to the 20 to 30min typical for frozen section analysis. The authors achieve a mean re-alignment error of 3.1mm. The authors' software provides a foundation for new research and product development for using AR to navigate complex 3D anatomy in surgery.

A feasibility randomized controlled trial testing the use of indocyanine green fluorescence image-guidance in liver surgery compared to standard liver surgery alone in reducing microscopic positive tumor margin resection rate with an embedded qualitative study: the I-FIGS study protocol

Abstract Indocyanine green fluorescence image-guidance (I-FIGS) is gaining global popularity in liver surgery for various applications. However, its true clinical value in reducing microscopic positive margins (R1-resection rate) remains uncertain. To address this, a multi-center randomized controlled trial (RCT) comparing I-FIGS with standard liver surgery is needed. However, due to a lack of essential information on potential R1 reduction rate, sample size, methodology, intervention delivery and patient experience, a feasibility RCT protocol has been developed to determine the viability of conducting a full-scale RCT. The aim of the study is to conduct a feasibility RCT (fRCT) with an embedded qualitative study to gather all the necessary information for a full-scale RCT. Adult patients undergoing elective liver surgery for colorectal liver metastasis (CRLMs), hepatocellular carcinoma (HCC) or peripheral cholangiocarcinoma will be eligible for the study. Forty patients will be randomly assigned to either the control group (standard liver surgery) or the intervention group (standard liver surgery + I-FIGS). Patients in the I-FIGS group will receive intravenous injection of 0.03–0.05 mg/kg indocyanine green (ICG) dye 2–4 hours before the surgery. Data will be collected on demographics, screening, recruitment and retention rates, adherence to study methods, intraoperative details, postoperative histology, and experiences of both surgeons and patients. Interviews will be conducted with selected patients and surgeons to explore their experiences with the intervention. The protocol has been approved by the West-Midlands-Solihull Research Ethics Committee and registered with ClinicalTrials.gov (NCT05616039). The results will be disseminated through academic publications, congresses, newsletters and other platforms.

43843 Risk factors for terminating Mohs micrographic surgery with positive microscopic tumor margins

43843 Risk factors for terminating Mohs micrographic surgery with positive microscopic tumor margins

Predicting 18F-DCFPyL-PET/CT Scan Positivity in Prostate Cancer Patients with Biochemical Recurrence

To analyze variables that can predict the positivity of 18F-DCFPyL- positron emission tomography/computed tomography (PET/CT) and extent of disease in patients with biochemically recurrent (BCR) prostate cancer after primary local therapy with either radical prostatectomy or radiation therapy. This is a retrospective analysis of a prospective single institutional review board-approved study. We included 199 patients with biochemical recurrence and negative conventional imaging after primary local therapies (radical prostatectomy n=127, radiation therapy n=72). All patients underwent 18F-DCFPyL-PET/CT. Univariate and multivariate logistic regression analyses were used to determine predictors of a positive scan for both cohort of patients. Regression-based coefficients were used to develop nomograms predicting scan positivity and extra-pelvic disease. Decision curve analysis (DCA) was implemented to quantify nomogram's clinical benefit. Of the 127 (63%) post-radical prostatectomy patients, 91 patients had positive scans - 61 of those with intrapelvic lesions and 30 with extra-pelvic lesions (i.e., retroperitoneal or distant nodes and/or bone/organ lesions). Of the 72 post-radiation therapy patients, 65 patients had positive scans - 39 of them had intrapelvic lesions and 26 extra-pelvic lesions. In the radical prostatectomy cohort, multivariate regression analysis revealed original International Society of Urological Pathology category, prostate-specific antigen (PSA), prostate-specific antigen doubling time (PSAdt), and time from BCR (mo) to scan were predictors for scan positivity and presence of extra-pelvic disease, with an area under the curve of 80% and 78%, respectively. Positive versus negative tumor margin after radical prostatectomy was not related to scan positivity or to the presence of positive extra-pelvic foci. In the radiation therapy cohort, multivariate regression analysis revealed that PSA, PSAdt, and time to BCR (mo) were predictors of extra-pelvic disease, with area under the curve of 82%. Because only seven patients in the radiation therapy cohort had negative scans, a prediction model for scan positivity could not be analyzed and only the presence of extra-pelvic disease was evaluated. PSA and PSAdt are consistently significant predictors of 18F-DCFPyL PET/CT positivity and extra-pelvic disease in BCR prostate cancer patients. Stratifying the patient population into primary local treatment group enables the use of other variables as predictors, such as time since BCR. This nomogram may guide selection of the most suitable candidates for 18F-DCFPyL-PET/CT imaging.

Role of immunotherapy for lymph node positive vulvar melanoma: utilization and outcomes

ObjectiveTo investigate the utilization and outcomes of adjuvant immunotherapy for patients with vulvar melanoma and inguinal lymph node metastases.MethodsThe National Cancer Database was accessed and patients with vulvar melanoma diagnosed...

EGFR-targeted fluorescence molecular imaging for intraoperative margin assessment in oral cancer patients: a phase II trial

Inadequate surgical margins occur frequently in oral squamous cell carcinoma surgery. Fluorescence molecular imaging (FMI) has been explored for intraoperative margin assessment, but data are limited to phase-I studies. In this single-arm phase-II study (NCT03134846), our primary endpoints were to determine the sensitivity, specificity and positive predictive value of cetuximab-800CW for tumor-positive margins detection. Secondary endpoints were safety, close margin detection rate and intrinsic cetuximab-800CW fluorescence. In 65 patients with 66 tumors, cetuximab-800CW was well-tolerated. Fluorescent spots identified in the surgical margin with signal-to-background ratios (SBR) of ≥2 identify tumor-positive margins with 100% sensitivity, 85.9% specificity, 58.3% positive predictive value, and 100% negative predictive value. An SBR of ≥1.5 identifies close margins with 70.3% sensitivity, 76.1% specificity, 60.5% positive predictive value, and 83.1% negative predictive value. Performing frozen section analysis aimed at the fluorescent spots with an SBR of ≥1.5 enables safe, intraoperative adjustment of surgical margins.

Three-dimensional histological electrophoresis enables fast automatic distinguishment of cancer margins and lymph node metastases.

Tissue diagnosis is important during surgical excision of solid tumors for margin evaluation. Conventional histopathologic methods rely heavily on image-based visual diagnosis by specialized pathologists, which can be time-consuming and subjective. We report a three-dimensional (3D) histological electrophoresis system for rapid labeling and separation of the proteins within tissue sections, providing a more precise assessment of tumor-positive margin in surgically resected tissues. The 3D histological electrophoresis system uses a tumor-seeking dye labeling strategy to visualize the distribution of tumor-specific proteins within sections and a tumor finder that automatically predicts the tumor contour. We successfully demonstrated the system's capability to predict the tumor contours from five murine xenograft models and distinguish the tumor-invaded region of sentinel lymph nodes. Specifically, we used the system to accurately assess tumor-positive margins from 14 patients with cancer. Our 3D histological electrophoresis system serves as an intraoperative tissue assessment technology for more accurate and automatic pathologic diagnosis.

Paired-agent imaging as a rapid en face margin screening method in Mohs micrographic surgery.

Mohs micrographic surgery is a procedure used for non-melanoma skin cancers that has 97-99% cure rates largely owing to 100% margin analysis enabled by en face sectioning with real-time, iterative histologic assessment. However, the technique is limited to small and aggressive tumors in high-risk areas because the histopathological preparation and assessment is very time intensive. To address this, paired-agent imaging (PAI) can be used to rapidly screen excised specimens and identify tumor positive margins for guided and more efficient microscopic evaluation. A mouse xenograft model of human squamous cell carcinoma (n = 8 mice, 13 tumors) underwent PAI. Targeted (ABY-029, anti-epidermal growth factor receptor (EGFR) affibody molecule) and untargeted (IRDye 680LT carboxylate) imaging agents were simultaneously injected 3-4h prior to surgical tumor resection. Fluorescence imaging was performed on main, unprocessed excised specimens and en face margins (tissue sections tangential to the deep margin surface). Binding potential (BP) - a quantity proportional to receptor concentration - and targeted fluorescence signal were measured for each, and respective mean and maximum values were analyzed to compare diagnostic ability and contrast. The BP and targeted fluorescence of the main specimen and margin samples were also correlated with EGFR immunohistochemistry (IHC). PAI consistently outperformed targeted fluorescence alone in terms of diagnostic ability and contrast-to-variance ratio (CVR). Mean and maximum measures of BP resulted in 100% accuracy, while mean and maximum targeted fluorescence signal offered 97% and 98% accuracy, respectively. Moreover, maximum BP had the greatest average CVR for both main specimen and margin samples (average 1.7 ± 0.4 times improvement over other measures). Fresh tissue margin imaging improved similarity with EGFR IHC volume estimates compared to main specimen imaging in line profile analysis; and margin BP specifically had the strongest concordance (average 3.6 ± 2.2 times improvement over other measures). PAI was able to reliably distinguish tumor from normal tissue in fresh en face margin samples using the single metric of maximum BP. This demonstrated the potential for PAI to act as a highly sensitive screening tool to eliminate the extra time wasted on real-time pathological assessment of low-risk margins.

Development of a postoperative nomogram to predict disease-specific mortality in gastric cancer: A competing risk analysis using variables the AJCC recommends be collected and registered.

e16099 Background: The American Joint Committee on Cancer (AJCC) has increasingly recognized the need for individual risk prediction model for the era of tailored therapy. In several reports, gastric cancer postoperative nomograms for predicting overall or disease-specific survival have been described. The AJCC Precision Medicine Core introduced the attractiveness of disease-specific mortality (DSM) as an endpoint of risk model. This study aimed to develop the first pretreatment gastric cancer postoperative nomogram for predicting DSM that considers competing risks (CRs). Methods: The nomogram was developed using data of 2,501 patients with primary gastric cancer who are potential candidate for adjuvant chemotherapy based on NCCN guideline, and it was created with a multivariable Fine and Gray subdistribution proportional hazard regression model. Fifteen pathological or non-tumor-related variables (age, sex tumor location, tumor size, macroscopic type, histology, depth (pT), number of positive nodes (pN), number of negative nodes, location of positive nodes, lymphovascular invasion, lavage cytology (CY), tumor margin, serum CEA and serum CA19-9) were collected. They are recommended to collect and register by the AJCC. The model was validated internally using measures of discrimination (Harrell’s C-index), calibration and decision curve analysis. Results: In the development procedure, multivariable analysis for DSM selected 12 variables (age, tumor location, macroscopic type, histology, pT, pN, number of negative nodes, location of positive nodes, lymphovascular invasion, CY, tumor margin and serum CEA) for constructing the nomogram. The developed nomogram showed good discrimination, with a C-index of 0.802(0.786-0.817) that of the American Joint Committee on Cancer (AJCC) pathological stage was 0.714 (0.697-0.734). The calibration appeared to be accurate for the 5-year prediction. Compared with scenarios in which no prediction model was used for postoperative treatment decision making (i.e., assume all or assume none), the nomograms had a favorable net benefit across a wide range of decision threshold probabilities between 5-year DSM probabilities of approximately 5 and 95%. Conclusions: This new postoperative risk model accurately predicts DSM in gastric cancer and can be used for patient counseling in clinical practice.

Factors associated with positive margins in major salivary gland cancer: An NCDB analysis.

e18093 Background: Major salivary gland cancer includes malignancies of the parotid, sublingual, and submandibular glands which represent a diverse spectrum of disease. Surgical resection is often the primary treatment. Positive tumor margins after resection have been associated with disease recurrence and worsened prognosis. This study investigates various factors and their influence on margin status. Methods: 41,705 patients with surgically treated major salivary gland cancer between 2004 and 2020 were identified in the National Cancer Database (NCDB). Factors including facility type, facility volume, surgical approach, primary site, Charlson-Deyo score, age, sex, race, Hispanic origin, income, and high school attainment were compared in patients based on margin status. Both macroscopic and microscopic positive margins were considered. Multivariate binary logistic regression analysis was performed in SPSS version 28 with a significance level of p &lt; 0.05. Results: Patients treated at an Academic/Research facility were 19% less likely to have positive margins than patients treated at a Community Cancer Program. Patients treated at facilities with case volume within the top 10% were 37% less likely to have positive margins. No significant difference was found in the margin status between different surgical approaches including open, endoscopic, and robotic. Patients with non-parotid major salivary gland cancer were 15% more likely to have positive margins than parotid cancers. Patients were more likely to have positive margins with an increasing Charlson-Deyo score and an increasing age. Female and Black patients were both 9% less likely to have positive margins than their counterparts. Other racial categories, ethnicity, income, and high school attainment did not significantly impact margin status. Conclusions: Factors associated with a lower likelihood of positive margins include treatment at an Academic/Research facility, higher volume center, parotid malignancies, lower Charlson-Deyo score, younger age, female sex, and Black race. The surgical approach and other demographic factors did not demonstrate any relationship with margin status. Identifying these associations can lead to a better understanding of prognostic factors and disparities in order to improve future care. [Table: see text]

Abstract P2-14-01: MOLECULAR FLUORESCENCE-GUIDED SURGERY USING BEVA800 FOR THE ASSESSMENT OF TUMOR MARGINS DURING BREAST CONSERVING SURGERY OF PATIENTS WITH PRIMARY BREAST CANCER (MARGIN-II)

Abstract Introduction: The goal of breast conserving surgery (BCS) for early breast cancer (EBC) is to remove the tumor in toto and preserving as much of the normal breast tissue as possible. In 20-50% of cases a re-excision is necessary because of involved margins. Repeat surgeries are not only a burden to patients physically but also psychologically and can delay recommended adjuvant therapies. Accurate determination of tumor margins during surgery is therefore a critical need. Breast cancer tissue produces significantly higher amounts of VEGF-A than healthy tissue. VEGF-A stimulates tumor angiogenesis and is therefore a target for molecular imaging techniques. The fluorescence imaging agent bevacizumab-IRDye800CW (Beva800) is a conjugate of bevacizumab and IRDye800CW and binds specifically to VEGF-A. Beva800 provides a potentially efficacious approach to imaging specimen and cavity margins during BCS. We are presenting a phase II study that combined Beva800 with the SurgVision Explorer Air camera for intraoperative margin assessment during BCS for EBC. Methods: MARGIN II is a multicenter open-label single arm prospective clinical trial aimed at evaluating Beva800 for assessment of tumor margins in women with EBC scheduled for BCS. The study was a within-patient comparison of positive tumor margin rates using BCS standard of care margin assessment compared to intraoperative assessment with 4.5 mg Beva800 and fluorescence imaging with the SurgVision Explorer Air camera. All patients received an i.-v. bolus injection of 4.5 mg of Beva800 three days before surgery. The fluorescent signal was visualized during surgery using NIR fluorescence imaging (700–1000 nm). Standard of care margin assessment was defined as visual inspection, palpation and, in cases of pre-operative wire marking, specimen sonography or mammography. Beva800 efficacy was determined as the number of patients in which a pathology-confirmed positive margin was identified by fluorescence-guided surgery using Beva800 but not by standard of care BCS. Results: 49 patients were included in 5 centers. 4 training cases were only included in the safety analysis, 45 patients were evaluable for the efficacy analysis. 8 patients (17.8%) had involved margins after standard of care BCS, 4 of which were detected by molecular fluorescence intraoperatively resulting in the reduction of patients with positive margins by 50% (95% CI: 15.7%, 84.3%). 4 patients (8.9%; 95% CI: 2.5%, 21.1%) needed a re-excision because of involved margins. In 27 patients (60.0%) the additional molecular fluorescence guided cavity shaving did not change the resection status from positive to negative (false positive). Adverse events were reported by 16 of 49 patients (32.7%), but only 3 (6.1%) were related to Beva800 (syncope, hot flush, hypertensive crisis). One patient experienced a treatment related SAE (hypertensive crisis). No anti-Beva800 antibodies were detected. Conclusion: In our analysis the rate of necessary second operations was reduced by 50% using Beva800 and the SurgVision Explorer Air camera. The safety analysis confirmed the positive safety profile of Beva800 found in previous studies. Molecular fluorescence-guided surgery may have the potential to change the practice of breast conserving surgery by reducing unnecessary re-excisions. Future studies will have to address the high false positive rates. Citation Format: Hans-Christian Kolberg, Carmen Röhm, Angrit Stachs, Florian Schütz, Jens-Uwe Blohmer, Sarah Wetzig, Steffi Hartmann, Jörg Heil, Markus Hahn. MOLECULAR FLUORESCENCE-GUIDED SURGERY USING BEVA800 FOR THE ASSESSMENT OF TUMOR MARGINS DURING BREAST CONSERVING SURGERY OF PATIENTS WITH PRIMARY BREAST CANCER (MARGIN-II) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-14-01.