Tumor-positive Margins Research Articles

Salvage Surgery in Recurrent Oral Squamous Cell Carcinoma.

More than half of patients with oral cancer recur even after multimodality treatment and recurrent oral cancers carry a poorer prognosis when compared to other sites of head and neck. The best survival outcome in a recurrent setting is achieved by salvage surgery; however, objective criteria to select an ideal candidate for salvage surgery is difficult to frame, as the outcome depends on various treatment-, tumor-, and patient-related factors. The following is summarizes various tumor- and treatment-related factors that guide our decision-making to optimize oncologic and functional outcomes in surgical salvage for recurrent oral cancers. Short disease-free interval, advanced tumor stage (recurrent and primary), extracapsular spread and positive tumor margins in a recurrent tumor, regional recurrence, and multimodality treatment of primary tumor all portend worse outcomes after surgical salvage. Quality of life after surgical intervention has shown improvement over 1 year with a drastic drop in pain scores. Various trials are underway evaluating the combination of immunotherapy and surgical salvage in recurrent head and neck tumors, including oral cavity, which may widen our indications for salvage surgery with improved survival and preserved organ function.

Vertical tumor margin of endoscopic resection for T1 colorectal carcinoma affects the prognosis of patients undergoing additional surgery.

Vertical tumor margin-negative T1 colorectal carcinoma (CRC) is an absolute curative condition following complete endoscopic resection (ER). However, the influence on prognosis in relation to vertical tumor margin is unclear. Therefore, we evaluated the influence of the distance from vertical tumor margin to resected specimen edge (vertical margin distance) of ER for T1b (submucosal invasion depth > 1000μm) CRC on the prognosis of patients undergoing additional surgery after ER. In total, 215 consecutive patients with T1b CRC who underwent additional surgery after ER at Hiroshima University Hospital between February 1992 and June 2019 were enrolled. We assessed 191 patients without lymph node metastases at the additional surgery. The specimens resected by ER were classified into three groups based on the vertical margin distance: patients with a vertical margin distance of ≥ 500μm (Group A); patients with a vertical margin distance of < 500μm (Group B); and patients with a positive vertical tumor margin (Group C). Subsequently, we evaluated the prognosis of the patients in relation to the clinicopathological characteristics among the three groups. There were no significant differences in clinicopathological characteristics among the three groups. Group A had a significantly higher recurrence-free 5-year survival rate than Groups B and C (100%, 84.5%, and 81.8%, respectively). Similarly, Group A had a significantly higher disease-specific 5-year survival rate than Group C (100% vs. 95.5%). Complete en bloc resection with sufficient submucosal layer from the invasive front (vertical margin distance > 500μm) by ER for T1 CRC reduces the risk of metastatic recurrence after additional surgery.

The Margins' Challenge: Risk Factors of Residual Disease After Breast Conserving Surgery in Early-stage Breast Cancer.

Clinicopathological features of patients undergoing margin enlargement after lumpectomy for early breast cancer with positive/close excision margins were analyzed in order to define whether a re-operative procedure could have been avoided. Furthermore, a standardized protocol of specimen orientation was adopted in order to optimize both the widening procedure as well as the oncologic outcome. A retrospective analysis was performed including pre-, peri-, and post-operative parameters, and a predictive score by means of a multivariate model was developed using all clinically and statistically significant variables associated with residual disease (RD). RD was significantly related to positive tumor margins, hormone receptor negative, HER2-positive, and tumors with high Ki67 proliferation index (p<0.001); the corresponding contribution to the prognostic score was as follows: close margins, 3 points; hormone receptor positive disease, 2 points; low Ki67, 2 points; HER2 negativity, 1 point. In 102 patients with a score >3, only 2 patients (2.0%) had RD, while in 81 patients with a score ≤3, 55 patients (67.9%) had RD (p<0.001). This predictive model might aid in clinical-decision making of patients with positive margins who actually require a widening procedure after intraoperative and/or definitive histology.

Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy.

Simple SummaryPatients diagnosed with pancreatic cancer have a poor prognosis at time of diagnosis, with a 5-year survival rate of merely 10%. The only treatment with curative intent is surgical resection of the tumor and adjacent tumor-containing lymph nodes. To improve surgical outcome and survival, additional (imaging) tools are needed that support complete surgical tumor resection. Firstly, more accurate monitoring of tumor response to neoadjuvant treatment and subsequent determination of resectability is needed. Secondly, an imaging tool is needed for intraoperative guidance allowing accurate identification, delineation, and complete resection of the tumor and suspected lymph nodes. Therefore, both tumor-targeted PET/CT before surgery and real time fluorescence-guidance during surgery could be helpful to improve patient outcome. This review focusses on literature considering tumor-targeted PET/CT and near-infrared fluorescence (NIRF) imaging. Several tumor-targeted agents are under clinical evaluation, and several other promising agents are currently tested preclinically, both with promising results. Their additional diagnostic value and feasibility for future implementation in standard clinical care of PDAC has yet to be established in phase III clinical trials.Background: Despite recent advances in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC), overall survival remains poor with a 5-year cumulative survival of approximately 10%. Neoadjuvant (chemo- and/or radio-) therapy is increasingly incorporated in treatment strategies for patients with (borderline) resectable and locally advanced disease. Neoadjuvant therapy aims to improve radical resection rates by reducing tumor mass and (partial) encasement of important vascular structures, as well as eradicating occult micrometastases. Results from recent multicenter clinical trials evaluating this approach demonstrate prolonged survival and increased complete surgical resection rates (R0). Currently, tumor response to neoadjuvant therapy is monitored using computed tomography (CT) following the RECIST 1.1 criteria. Accurate assessment of neoadjuvant treatment response and tumor resectability is considered a major challenge, as current conventional imaging modalities provide limited accuracy and specificity for discrimination between necrosis, fibrosis, and remaining vital tumor tissue. As a consequence, resections with tumor-positive margins and subsequent early locoregional tumor recurrences are observed in a substantial number of patients following surgical resection with curative intent. Of these patients, up to 80% are diagnosed with recurrent disease after a median disease-free interval of merely 8 months. These numbers underline the urgent need to improve imaging modalities for more accurate assessment of therapy response and subsequent re-staging of disease, thereby aiming to optimize individual patient’s treatment strategy. In cases of curative intent resection, additional intra-operative real-time guidance could aid surgeons during complex procedures and potentially reduce the rate of incomplete resections and early (locoregional) tumor recurrences. In recent years intraoperative imaging in cancer has made a shift towards tumor-specific molecular targeting. Several important molecular targets have been identified that show overexpression in PDAC, for example: CA19.9, CEA, EGFR, VEGFR/VEGF-A, uPA/uPAR, and various integrins. Tumor-targeted PET/CT combined with intraoperative fluorescence imaging, could provide valuable information for tumor detection and staging, therapy response evaluation with re-staging of disease and intraoperative guidance during surgical resection of PDAC. Methods: A literature search in the PubMed database and (inter)national trial registers was conducted, focusing on studies published over the last 15 years. Data and information of eligible articles regarding PET/CT as well as fluorescence imaging in PDAC were reviewed. Areas covered: This review covers the current strategies, obstacles, challenges, and developments in targeted tumor imaging, focusing on the feasibility and value of PET/CT and fluorescence imaging for integration in the work-up and treatment of PDAC. An overview is given of identified targets and their characteristics, as well as the available literature of conducted and ongoing clinical and preclinical trials evaluating PDAC-targeted nuclear and fluorescent tracers.

Outcomes and Prognostic Factors in Patients with Malignant Peripheral Nerve Sheath Tumor

Objective: To investigate and report the clinical profiles, treatment patterns, and oncologic outcomes in MPNST patients, and to identify the prognostic factors that significantly affect survival.Materials and Methods: Patients diagnosed with and treated for histologically confirmed MPNST at our institute during the January 1997 to June 2018 study period were included. Patient medical records and surgical specimens were reviewed, and study-related data was extracted and analyzed.Results: There were 27 males and 32 females with a mean age of 44 years. Most patients presented with mass and most patients were AJCC stage III. Twenty-nine percent of patients had MPNST that was associated with NF-1. At a median follow-up time, 18 patients (30.51%) suffered from local disease recurrence. Two-year and 5-year overall survival was 72% and 46%, respectively. In univariate analysis, chemotherapy treatment and positive tumor margin were adverse prognostic factors for disease-free survival. In multivariate analysis, chemotherapy treatment (hazard ratio (HR): 3.415, 95% CI: 1.367-16.021; p=0.013) and positive tumor margin (HR: 4.680, 95% CI 1.828-10.314; p=0.014) were found to be independent prognostic factors for disease-free.Conclusion: Chemotherapy treatment and positive tumor margin were identified as independent adverse prognostic factors for disease-free and overall survival, respectively. Accordingly, early detection and appropriate treatment are essential for improved patient outcome.

Targeted Intraoperative Molecular Imaging for Localizing Nonpalpable Tumors and Quantifying Resection Margin Distances

Complete (R0) resection is the dominant prognostic factor for survival across solid tumor types. Achieving adequate tumor clearance with appropriate margins is particularly difficult in nonpalpable tumors or in situ disease. Previous methods to address this problem have proven time consumptive, impractical, or ineffective. To assess the capability of intraoperative molecular imaging (IMI), a novel technology using a fluorescent tracer targeted to malignant cells, to localize visually occult, nonpalpable tumors and quantify margin distances during resection. This nonrandomized open-label trial of IMI using a folate receptor-targeted fluorescent tracer enrolled patients between May 2017 and June 2020 at a single referral center. Eligible patients included those with a small (T1) lung lesion suspicious for malignant neoplasms and with radiographic features suggestive of a nonpalpable lesion. Patients were preoperatively infused with a folate receptor-targeted near-infrared tracer. Intraoperatively, surgeons used thoracoscopic visualization and palpation to identify lesions. IMI was performed to detect the lesion in situ, and lesions were imaged ex vivo. Margins were assessed by IMI before comparison with those reported on final histopathologic analysis. The main outcomes were whether IMI could (1) localize nonpalpable lung lesions in situ and (2) quantify margin distance with comparison with final pathology as the criterion standard. Patient demographic information and lesion characteristics were prospectively recorded. Of 40 patients, 26 (65%) were female, and the median (interquartile range) age was 66.5 (62-72) years. Conventional surgical methods localized 22 of 40 lesions (55%), while IMI localized 36 of 40 (90%). Of 18 nonpalpable lesions, 15 (83.3%) were identified by IMI. Both palpable and nonpalpable lesions demonstrated mean signal-to-background ratio more than 2. An IMI margin was able to be calculated for 39 of 40 patients (95%). IMI margins were nearly identical to margins reported on final pathology (R2 = 0.9593), with median (interquartile range) difference of 1.3 (0.7-2.0) mm. IMI detected 2 margins in nonpalpable tumors that were clinically unacceptable and would have had a high probability of recurrence. To our knowledge, this study presents the first clinical use of IMI for nonpalpable tumors and provides proof of principle for the utility of IMI across the field of surgical oncology in identifying occult disease and tumor-positive margins.

The application of Wood's lamp combined with 5-aminolevulinic acid for defining tumor margins in patients with extramammary Paget's disease

Objective: To evaluate the value of Wood's lamp examination combined with 5-aminolevulinic acid (5-ALA) photodynamic therapy (PDT) to determine positive tumor margins in patients with extramammary Paget's disease (EMPD) before surgery. Methods: We admitted 36 patients with EMPD from January 2016 to June 2019. The experimental group was the 5-ALA-PDT group, and the control group was the wide local excision (WLE) group. In the 5-ALA-PDT group, Wood's lamp examination combined with 5-ALA-PDT was used to trace the fluorescence range, and multipoint biopsy was performed according to the pathology to determine the final excision scope. We applied the standard partial expansion excision method for the WLE group, while frozen pathology assessment was applied to confirm the excision range. We measured the overall resection area of the WLE group and 5-ALA-PDT group. We analyzed the overall duration of surgery, the number of frozen pathology sections, patient satisfaction with appearance and function, the rate of functional sequelae, and the recurrence rate for both groups. Results: The results suggested that the difference in final resection margin between the WLE group and the 5-ALA-PDT group was significant. The number of frozen pathology sections, overall surgery time, and recurrence rate were significantly lower in the experimental group than in the control group (p<0.05). The occurrence rate of functional sequelae in the experimental group was lower, and patient satisfaction with appearance and function was significantly higher than that of the control group (p<0.05). Conclusion: Wood's lamp examination combined with 5-ALA-PDT may predict tumor margins in EMPD.

Impact of margin status on outcomes after endoscopic resection of well-differentiated duodenal neuroendocrine tumors

Duodenal neuroendocrine tumors (DNETs) are known to have low metastatic potential and follow an indolent course. Although DNETs<1 cm in size are amenable to endoscopic resection, little is known about the long-term outcomes and recurrence rates of this approach. Sixty-three patients with DNETs from 3 centers were retrospectively studied from 2003 to 2018. We analyzed their resection modality (EMR, snare polypectomy, or forceps polypectomy), margin status, risk factors for recurrence, recurrence rate, and endoscopic surveillance patterns. Of the 63 patients who underwent endoscopic resection, 13 (20.6%) had recurrence. The presence of R1 margins was found to be a statistically significant risk factor for recurrence (P= .048). Mean surveillance time for all DNETs was 2.8 ± 2.6 years. Ninety-two percent of recurrences were detected within 3 years of resection. Our data suggest that the main predictor of recurrence in low-grade DNETs<1.0 cm is the presence of positive tumor margins at the initial endoscopic resection. More frequent, earlier surveillance after resection than that currently recommended by European Neuroendocrine Tumor Society guidelines may be warranted to promptly capture DNET recurrences. Additionally, no recurrences occurred in our cohort after 4 years of surveillance.

A single institution experience with papillary thyroid cancer: Are outcomes better at comprehensive cancer centers?

IntroductionPapillary thyroid cancer (PTC) is the most common form of thyroid cancer. Although the survival rate is excellent, recurrence is as high as 20%. The mainstay of therapy is thyroidectomy and lymph node dissection based on risk factors. Data from other cancers suggest that surgical outcomes are most optimal at comprehensive cancer centers. We hypothesize that patients with PTC who had their initial operation at a comprehensive cancer center would have a better oncologic outcome. MethodsWe utilized an IRB-approved cancer care registry database of patients with thyroid cancer who were seen at our institution between 2000 and 2018. Patient records were updated with cancer-specific outcomes including recurrence and need for re-intervention. Clinical and surgical outcomes were then compared between patients who had their initial operation at a comprehensive cancer center (CCC group, n = 503) versus those who did not (non-CCC group, n = 72). ResultsMean patient age was 49 ± 16 years and 70% were female. Average tumor size was 1.6 ± 1.6 cm. There was no difference in tumor size, age, gender or race between groups. Pre-operative ultrasound was more frequently performed at the CCC (89%) than at non-CCC’s (51%, p < 0.001). CCC patients were more likely to undergo initial total thyroidectomies compared to non-CCC patients (76% vs. 21%, p < 0.001). Positive surgical margins were more frequently found in patients at non-CCC’s (19%) than at the CCC (9.7%, p = 0.016). Finally, CCC patients had a significantly lower cancer recurrence rate (5.0% vs. 37.5%, p < 0.001). Therefore, the need for additional cancer operations was much greater in patients who had initial thyroid surgery at non-CCC (31.9% vs. 1.4%, p < 0.001). ConclusionsPatients with PTC who have their initial thyroidectomy at non-CCC have higher recurrence rates, higher rates of positive tumor margins on pathology, and increased need for additional operations. These data suggest that patients who have their initial procedure at a CCC for PTC have better long-term outcomes.

Abstract PS1-21: 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 and a surrounding rim of normal tissue, while preserving as much of the normal breast tissue as possible. Incomplete resections are associated with higher rates of surgical re-excision. 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 critical for successful outcome. Breast cancer tissue produces significantly higher amounts of VEGF-A than healthy tissue. VEGF-A stimulates tumor angiogenesis and is therefore an excellent target for molecular imaging techniques. The fluorescence imaging agent bevacizumab-IRDye800CW (Beva800) is a conjugate of bevacizumab (a humanized antibody targeting human VEGF) and IRDye800CW (a near-infrared fluorescence dye) which binds specifically to VEGF-A. Beva800 provides a potentially highly efficacious approach to imaging specimen and cavity margins during BCS. Herein we present 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 compared to intraoperative assessment with 4.5 mg Beva800 and fluorescence imaging with the SurgVision Explorer Air camera. Patients undergoing neoadjuvant chemotherapy were excluded. All patients received a single intra-venous 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). This wavelength window typically has very low tissue auto-fluorescence (filtering out background noise) and greater tissue penetration depth due to reduced haemoglobin absorption. Standard of care 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. The results per patient were divided into two clusters: results after standard of care BCS and results after fluorescence guided surgery, according to their margin status at pathology. The need for re-operation because of involved margins within 30 days after the first BCS and the safety of 4.5 mg Beva800 was assessed.Results:The recruitment goal of 40 patients in 5 centers has almost been reached and results of the final analysis will be presented at the meeting.Conclusion:Molecular fluorescence-guided surgery using Beva800 has the potential to change the practice of breast conserving surgery by avoiding unnecessary re-operations. This would lead to fewer interventions, a reduced burden on patients through repeat surgery and reduced delay of adjuvant therapies. 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 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-21.

Intraoperative Radiation Mitigates the Effect of Microscopically Positive Tumor Margins on Survival Among Pancreatic Adenocarcinoma Patients Treated with Neoadjuvant FOLFIRINOX and Chemoradiation.

Microscopically positive margins (R1) negatively impact survival in pancreatic ductal adenocarcinoma (PDAC). For patients with close/positive margins, intraoperative radiotherapy (IORT) can improve local control. The prognostic impact of an R1 resection in patients who receive total neoadjuvant therapy (TNT; FOLFIRINOX with chemoradiation) and IORT is unknown. Clinicopathologic data were retrospectively collected for borderline/locally advanced (BR/LA) PDAC patients who received TNT and underwent resection between 2011 and 2019. Disease-free (DFS) and overall survival (OS) measured from time of diagnosis were compared between groups. Two hundred one patients received TNT and were resected, with a median DFS and OS of 24months and 47months, respectively. Eighty-eight patients (44%) received IORT; of these, 69 (78%) underwent an R0 and 19 (22%) an R1 resection. There was no significant difference in clinicopathologic factors between the IORT and no-IORT groups, except for resectability status (LA: IORT 69%, no-IORT 53%, p = 0.021) and surgeons' concern for a positive/close margin. R1 resection was associated with worse DFS and OS in the no-IORT population. However, among patients who received IORT, there was no difference in DFS (R0: 29months, IQR 14-47 vs R1: 20months, IQR 15-28; p = 0.114) or OS (R0: 48months, IQR 25-not reached vs R1: 37months, IQR 30-47; p = 0.307) between patients who underwent R0 vs R1 resection. In multivariate analysis, within the IORT group, R1 resection was not associated with DFS or OS. IORT may mitigate the adverse effect of an R1 resection on DFS and OS in BR/LA PDAC patients receiving TNT.

Implantation of a neoantigen-targeted hydrogel vaccine prevents recurrence of pancreatic adenocarcinoma after incomplete resection

ABSTRACT Tumor involvement of major vascular structures limits surgical options in pancreatic adenocarcinoma (PDAC), which in turn limits opportunities for cure. Despite advances in locoregional approaches, there is currently no role for incomplete resection. This study evaluated a gelatinized neoantigen-targeted vaccine applied to a grossly positive resection margin in preventing local recurrence. Incomplete surgical resection was performed in mice bearing syngeneic flank Panc02 tumors, leaving a 1 mm rim adherent to the muscle bed. A previously validated vaccine consisting of neoantigen peptides, a stimulator of interferon genes (STING) agonist and AddaVaxTM (termed PancVax) was embedded in a hyaluronic acid hydrogel and applied to the tumor bed. Tumor remnants, regional lymph nodes, and spleens were analyzed using histology, flow cytometry, gene expression profiling, and ELISPOT assays. The immune microenvironment at the tumor margin after surgery alone was characterized by a transient influx of myeloid-derived suppressor cells (MDSCs), prolonged neutrophil influx, and near complete loss of cytotoxic T cells. Application of PancVax gel was associated with enhanced T cell activation in the draining lymph node and expansion of neoantigen-specific T cells in the spleen. Mice implanted with PancVax gel demonstrated no evidence of residual tumor at two weeks postoperatively and healed incisions at two months postoperatively without local recurrence. In summary, application of PancVax gel at a grossly positive tumor margin led to systemic expansion of neoantigen-specific T cells and effectively prevented local recurrence. These findings support further work into locoregional adjuncts to immune modulation in PDAC.

Perioperative morbidity of Vulval cancer

Introduction: The present study is a retrospective analysis of vulval cancer patients who had been treated with surgery as primary mode. The cases studied were in tertiary care hospital south India of March 2008 to February 2013. Total number of patients was 11. Materials and Methods: The medical records of all patients studied retrospectively with reference to stage of the disease, surgery performed, prophylactic antibiotics, intra-operative and postoperative complications. Results: Among 11 patients 9 were postmenopausal. Ten patients histopathology showed stage 1b cancer for whom simple vulvectomy was performed, one patient had co-existing HGSIL( High Grade Squamous Intraepithelial Lesion) and positive right inguinal nodes, requiring TAH+ BSO+ right groin dissection and posterior colporrhaphy was done in one patient with rectocele. One patient presented with stage 2 disease for which radical vulvectomy with bilateral groin lymph node dissection was carried out. Postoperative radiotherapy was given for 8 patients with tumor positive margins. Conclusion: Even though many modifications in surgical methods of vulval cancer still morbidity is high. Particularly surgical complication of wound infection. This delay will further add up for delay in starting adjuvant treatment. Hence there is a need of further modifications of surgical treatments like minimally invasive approach. A team of oncology surgeons, medical oncologists, radiotherapists is needed to manage this rare cancer. With multidisciplinary approach Surgery for early stage vulval cancer has acceptable morbidity. Keywords: Carcinoma vulva, Saphenous vein, Vulval cancer.

Real-time surgical margin assessment using ICG-fluorescence during laparoscopic and robot-assisted resections of colorectal liver metastases.

BackgroundAlmost a third of the resections in patients with colorectal liver metastases (CRLM) undergoing curative surgery, end up being tumor-margin positive (≤1 mm margin). Near-infrared fluorescent (NIRF) imaging using the fluorescent contrast agent indocyanine green (ICG) has been studied for many different applications. When administered in a relatively low dose (10 mg) 24 hours prior to surgery, ICG accumulated in hepatocytes surrounding the CRLM. This results in the formation of a characteristic fluorescent ‘rim’ surrounding CRLM when located at the periphery of the liver. By resecting the metastasis with the entire surrounding fluorescent rim, in real-time guided by NIRF imaging, the surgeon can effectively acquire margin-negative (>1 mm) resections. This pilot study aims to describe the surgical technique for using near-infrared fluorescence imaging to assess tumor-margins in vivo in patients with CRLM undergoing laparoscopic or robot-assisted resections.MethodsOut of our institutional database we selected 16 CRLM based on margin-status (R0; n=8, R1; n=8), which were resected by a minimally-invasive approach using ICG-fluorescence. NIRF images acquired during surgery, from both the resection specimen and the wound bed, were analysed for fluorescent signal. We hypothesized that a protruding fluorescent rim at the parenchymal side of the resection specimen could indicate a too close proximity to the tumor and could be predictive for a tumor-positive surgical margin. NIRF images were correlated to final histopathological assessment of the resection margin.ResultsAll lesions with a NIRF positive resection plane in vivo were reported as having a tumor-positive margin. Lesions that showcased no protruding rim in the wound bed in vivo were diagnosed as having a tumor-negative margin in 88% of cases. A 5-step surgical workflow is described to document the NIRF signal was used assess the resection margin in vivo for future clinical studies.ConclusionsThe pilot study shows that image-guided surgery using real-time ICG-fluorescence has the potential to aid surgeons in achieving a tumor-negative margin in minimally invasive liver metastasectomies. The national multi-centre MIMIC-Trial will prospectively study the effect of this technique on surgical tumor-margins (Dutch Trial Register number NL7674).

S0101 Clinical and Demographic Predictors of Rapidly Progressive Disease in Patients Undergoing Surgery for Pancreatic Ductal Adenocarcinoma: Risk Profiling From the National Cancer Database

INTRODUCTION: Pancreatic cancer is the third most common cause of cancer-related mortality and survival times after surgery vary widely. There are limited studies that have evaluated clinical and demographic predictors of patients who survive less than one year following surgery. METHODS: We queried 380,524 participants diagnosed with pancreatic cancer between 2004 and 2016 from the National Cancer Data Base (NCDB) Participant User Files. We identified 51,345 patients with histologically-confirmed pancreatic adenocarcinoma and reported postoperative survival times. Patients were categorized into with rapidly progressive (RP) disease (3 months–1 year survival, n = 16,234) and those with non-rapidly progressive(nRP) disease (>1 year survival, n = 35,111). We conducted descriptive analysis and calculated risk using Cox regression models. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed after adjusting for patient, tumor, hospitalization, and treatment characteristics to assess for characteristics associated with RP compared with nRP. RESULTS: The median age of the NCDB cohort was 66 years, with a median survival time of 0.64 years (IQR: 0.45–0.81) for the RP group compared to 2.16 years (IQR: 1.48–3.55) for the nRP group. Notably, 56.6% were ≥65 years old, 13.1% were non-white, and 52.5% were on Medicare insurance. Several clinical and demographic characteristics were independent predictors of having RP versus NRP disease (Table 1). Patients with RP disease are more likely to have longer hospital stays, unplanned 30-day readmission, and worse tumor characteristics at time of surgery. Additionally, those lower income, as well as those with Medicaid and Medicare insurance were at higher risk for RP disease. Additionally, patients with a higher comorbidity score, tumor stage and grade, lymph node involvement, and positive tumor margins were at greater risk of RP. CONCLUSION: Pancreatic adenocarcinoma is highly lethal, and though surgery is reserved for patients without locally advanced disease, survival times after definitive treatment vary widely. More is needed to understand the demographic and clinical difference between RP and nRP disease so that follow-up care can potentially target those with higher risk demographics, more complicated hospital courses, and worse tumor characteristics.Table 1.: Multivariate Analysis for Predictors of Rapidly Progressive Disease (RP) Risk Among 51,345 NCDB Pancreatic Adenocarcinoma Surgical Patients with Reported Survival Times >90 Days from Surgery Date

Molecular targets for diagnostic and intraoperative imaging of pancreatic ductal adenocarcinoma after neoadjuvant FOLFIRINOX treatment

Neoadjuvant systemic treatment is increasingly being integrated in the standard treatment of pancreatic ductal adenocarcinoma (PDAC) patients to improve oncological outcomes. Current available imaging techniques remain unreliable in assessing response to therapies, as they cannot distinguish between (vital) tumor tissue and therapy induced fibrosis (TIF). Consequently, resections with tumor positive margins and subsequent early post-operative recurrences occur and patients eligible for potential radical resection could be missed. To optimize patient selection and monitor results of neoadjuvant treatment, PDAC-specific diagnostic and intraoperative molecular imaging methods are required. This study aims to evaluate molecular imaging targets for PDAC after neoadjuvant FOLFIRINOX treatment. Expression of integrin αvβ6, carcinoembryonic antigen cell adhesion molecule 5 (CEACAM5), mesothelin, prostate-specific membrane antigen (PSMA), urokinase-type plasminogen activator receptor, fibroblast activating receptor, integrin α5 subunit and epidermal growth factor receptor was evaluated using immunohistochemistry. Immunoreactivity was determined using the semiquantitative H-score. Resection specimens from patients after neoadjuvant FOLFIRINOX treatment containing PDAC (n = 32), tumor associated pancreatitis (TAP) and TIF (n = 15), normal pancreas parenchyma (NPP) (n = 32) and tumor positive (n = 24) and negative (n = 56) lymph nodes were included. Integrin αvβ6, CEACAM5, mesothelin and PSMA stainings showed significantly higher expression in PDAC compared to TAP and NPP. No expression of αvβ6, CEACAM5 and mesothelin was observed in TIF. Integrin αvβ6 and CEACAM5 allow for accurate metastatic lymph node detection. Targeting integrin αvβ6, CEA, mesothelin and PSMA has the potential to distinguish vital PDAC from fibrotic tissue after neoadjuvant FOLFIRINOX treatment. Integrin αvβ6 and CEACAM5 detect primary tumors and tumor positive lymph nodes.

A Case Report of Primary Breast Angiosarcoma: Clinical Presentation and Outcome After Adjuvant Radiotherapy

Angiosarcomas of the breast are infrequent subtypes of sarcoma that are often diagnosed after radiation therapy for primary breast cancer. Primary angiosarcomas (PAS) are rare tumors that constitute 0.04% of all malignant breast tumors. We report a case of a 40-year-old woman with a lump in the right breast and diagnosed as angiosarcoma by pathological evaluation. She underwent simple mastectomy followed by adjuvant radiation. She is alive and disease-free for 66 months although tumor size was large and one surgical margin was tumor positive. Breast angiosarcoma is often in advanced stage at diagnosis and tends to recur locally. Although surgical methods constitute the primary treatment, we believe that a multidisciplinary treatment strategy should be used in high-risk patients with large primary tumors and tumor positive margins.

Relapse-free survival after adjuvant radioactive iodine therapy in patients with differentiated thyroid carcinoma with a microscopically positive tumor margin.

In patients with differentiated thyroid carcinoma (DTC) with a microscopically positive tumor margin, the optimal first dose of I-131 during adjuvant radioactive iodine (RAI) therapy to improve relapse-free survival (RFS) is unclear. Due to the limited number of hospital beds, 1110MBq of I-131 is administered to such patients in Japan. This study primarily aimed to retrospectively determine the difference in RFS between high-dose (3700MBq) and low-dose (1110MBq) adjuvant RAI therapies in DTC patients with a microscopically positive tumor margin. The secondary aim was to investigate the background factors affecting RFS. Forty-eight consecutive patients (15 men and 33 women) who underwent total thyroidectomy between April 2007 and December 2017 for DTC without gross residual tumors and distant metastasis, and who were diagnosed with a positive margin histopathologically, followed by RAI therapy, were enrolled. We retrospectively investigated initial I-131 dose, classifying it into high-dose and low-dose groups. The primary endpoint was RFS. Relapse was considered in the following cases: patients with visible recurrent tumor and/or metastasis on neck ultrasound and/or computed tomography, and patients without visible tumor, but with clearly increasing thyroglobulin levels on follow-up every 3-6months. RFS outcomes were analyzed using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test, and multivariate analysis was undertaken using the Cox proportional hazard model. There were nine cases of recurrence (52.9%) in the low-dose group and seven in the high-dose group (22.5%) during follow-up. The estimated median RFS was 69.4months in the low-dose group and 120.7months in the high-dose group. High-dose administration was associated with improved RFS, as demonstrated by Kaplan-Meier survival curves (log-rank test [P = 0.009]). Patient factors associated with worse RFS included low-dose administration (hazard ratio [HR] = 91.9; 95% confidence interval [CI] = 7.66-1102.79); P < 0.001), T4 stage (HR = 1.88; 95% CI = 0.44-8.10; P = 0.015), and presence of central lymph node metastases (HR = 190; 95% CI = 3.80-9496; P = 0.009). The most common type of recurrence was lymph node metastasis. Patients with microscopically positive tumor margins could benefit from RAI with high activities.

Variables Affecting Basal Cell Carcinoma and Melanoma In Situ Excision Clearance: A Multi-institutional Retrospective Study.

The primary endpoint for surgical excision of skin cancer is the positive margin status. Tumor characteristics may explain much of this risk, but other important factors can include physician specialty. To determine the variables affecting the success of a basal cell carcinoma (BCC) or melanoma in situ (MIS) excision. An 8-year, multicenter, retrospective study of 5,800 BCC or MIS excisions performed at 13 different Kaiser Permanente medical centers. The margin status was determined by searching final pathology diagnosis texts for phrases associated with positive margins. An incomplete excision rate was found in 23% of all specimens (BCC-22%, MIS-25%). Per specialty, the proportion of specimens with positive tumor margins was 24% for dermatology, 26% for plastic surgery, 28% for otolaryngology, and 12% for general surgery. General surgeons most often excised large tumors and tumors from truncal regions, 2 variables conferring lower odds of an incomplete excision. For non-Mohs procedures, dermatologists were no different than otolaryngologists or plastic surgeons in performing an incomplete BCC or MIS excision in all multivariate models (all p > .05). Intrinsic tumor characteristics may influence the success of achieving tumor-free resection margins more than the specialty of the provider.

Time trends and predictors of survival in surgically resected early-stage non-small cell lung cancer patients.

The improvement in the management of lung cancer have the potential to improve survival in patients undergoing resection for early-stage (stage I and II) non-small cell lung cancer (NSCLC), but few studies have evaluated time trends and identified predictors of overall survival (OS). We identified surgically resected early-stage NSCLC between 1998 and 2016. The 3-year OS (1998-2014) and 5-year OS (1998-2012) rates were calculated for each year. Joinpoint regression was used to calculate annual percentage changes (APC) and to test time trends in OS. Multivariable Cox regression was used to identify predictors of OS. There was a significant upward trend in the 3-year (1998, 56%; 2014, 83%; APC = 1.8) and 5-year (1998, 47%; 2012, 76%; APC = 3.1) OS. Older age; male sex; history of diabetes, coronary artery disease, and chronic obstructive pulmonary disease; high ASA score; smoking pack-years; high-grade tumor; pneumonectomy; thoracotomy; neoadjuvant therapy; nodal disease; and positive tumor margin were predictors of poor OS. The upward time trend in OS suggests that improved staging, patient selection, and management have conferred a survival benefit in early-stage NSCLC patients. The prediction model of OS could be used to refine selection criteria for resection and improve survival outcomes.