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Authors: Maria Luisa Machado Heredia1,2 Alphi Kuriakose1,2 Huma Javaid1,3 Brian Menegaz 1,3 Alastair Thompson1,2,3 Bora Lim1,2 Affiliation 1Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030 2 Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030 3 Department of Surgery, Baylor College of Medicine, Houston, TX 77030 Background and Purpose Increasing research data support the existence of barriers and discrepancies to oncology interventional clinical trial enrollment rate based on patients’ social-economic status. However, few studies examined if such discrepancy exists in observational trials. We hypothesize the enrollment discrepancy remains the same in specimen collection only protocols, and several factors including health literacy and religious belief contribute to such discrepancy. Methods Data was collected from March 1st, 2022, to July 7th, 2022, as part of an ongoing pilot study examining circulating tumor DNA (ctDNA) from patients diagnosed with stage IV metastatic breast cancer starting a new line of therapy treatment (BCM protocol number H- 48751). This study was selected as specimen collected is part of normally scheduled standard of care clinical labs and beyond informed consent does not require any additional patient commitment for participation. This study was performed across both county and private practice sites:1) Smith Clinic-Harris Health System 2) Baylor Saint Luke’s Medical center (BSLMC); respectively. Correlations for independent variables potentially affecting enrollment were assessed to estimate the association between patient participation and socio-economic factors like religious affiliation and level of formal education received. Free-form text responses were collected from patients who declined study participation. Results Fourteen eligible candidates were asked to participate in the observational trial to determine whether serial changes in ctDNA ratio correlate with the results of first monitoring patients via imaging at three months. Out of 14 patients approached, 5 patients (36%) declined. Interestingly, all five patients who declined were from Smith Clinic- Harris Health System, while all BSLMC patients agreed to enroll. Based on the free-text response of why patients declined the ctDNA study, we identified a total of 4 different categories: Language barriers, low health literacy, religious objection, and disinterest in research. Using these four categories, we continue to collect data to improve our understanding of barriers in observational trial enrollment. Conclusion Low literacy and other socioeconomic factors serve as barriers to enrollment in observational trials for patients who suffer from stage IV breast cancers. In our preliminary data, we also noted that these barriers are only relevant for patients who are treated at the county hospital. An investigation to recognize low literacy and religious affiliation as barriers to poor trial accrual is ongoing. Reasons to declining participation in observational trial. Citation Format: Maria L. Machado Heredia, Alphi Kuriakose, Brian A. Menegaz, Alastair M. Thompson, Bora Lim, Huma Javaid. Barriers to enrolling in observational trials for patients with stage IV breast cancer. [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 P6-08-03.

Background/Purpose: Superparamagnetic iron oxide (SPIO)-based techniques like Magseed and Magtrace offer alternatives for breast lesion and sentinel lymph node (SNL) localization. Magseeds placed under ultrasound guidance offer logistical and safety advantages compared to traditional wire-localization or radioactive seed placement. Further, Magtrace injection is a viable SNL-localization alternative that overcomes radiation safety, skin necrosis, and allergic reactions associated with traditional 99mTc colloid and Methylene blue/Isosulfan blue dyes. To evaluate the effectiveness of these techniques in surgical practice, we report the implementation of Magseed and Magtrace at Baylor St. Luke’s Medical Center. Methods: We retrospectively reviewed prospectively collected data from the 128 female patients undergoing Magseed/Magtrace procedures from October 2019 to December 2020. Demographics and clinical characteristics were summarized, and surgical outcomes analyzed including margin status, re-excision rates, post-operative breast and axilla complications, successful localization and detection rates. Results: Patients presented with varied diagnoses including 98 (77%) with invasive carcinoma, 21 (16%) with DCIS, and 9 (7%) with fibroadenoma, papillary, or other lesions. 50 patients (39%) underwent neoadjuvant therapy. Mean BMI at surgery was 27.33 kg/m2 (range, 17.80-48.65) and mean age was 57.26 years (range, 27-86). Breast density varied, 5 (4%) categorized as almost entirely fatty, 69 (54%) as heterogeneously dense, 12 (9%) as extremely dense, and 39 (30%) with fibroglandular density. For breast size there were 2 (2%) A cups, 13 (10%) B cups, 16 (13%) C cups, 10 (8%) D cups, 8 (6%) DD cups, 2 (2%) DDD cups, 1 (.8%) F cup, and 12 (9%) with in between breast size (A-DDD). 108 patients (84%) had on-table Magtrace injection and 52 (41%) had Magseed localization. 18 (14%) patients had Methylene blue/Isosulfan blue dye or Technetium-99 used with Magseed and/or Magtrace. There was a 100% (52/52) success rate of lesion localization using Magseed and a 94% (101/108) success rate of SLN detection using Magtrace. Magtrace brown skin staining occurred in 12/108 patients (11%). Breast complications occurred in 43 patients (34%), with bruising/hematoma in 30/43 (70%), seroma in 7/43 (16%), and infection in 4/43 (9%). Axilla complications occurred in 11 patients (9%): 5/11 (45%) had bruising/hematoma, 6/11 (55%) had seroma, and 1/11 (9%) had infection. Positive margins were seen in 11 (9%) patients with re-excision performed in 8 women (6%). Conclusions: Magseed and Magtrace are comparable to standard practices in terms of practicality, surgical implementation, and risk of surgical complications and re-excision, providing a rationale for the adoption of SPIO-based techniques. By putting these surgical techniques into practice and evaluating their success in excising a wide range of lesions and monitoring complications, there is possibility of introducing new, innovative techniques into a standardized clinical setting within surgical oncology. Magseed/Magtrace Procedures at BSLMCRaw NumberPercentageTechniquesMagtrace Only6047%Magseed Only1915%Magtrace + Magseed3124%Isotope1713%Blue Dye11%Skin Staining Post-Op.1211%Breast Complication4334%Wound Complication921%Infection49%Bruising/Hematoma3070%Seroma716%Patients with >1 complication49%Axilla Complication119%Wound Complication00%Infection19%Bruising/Hematoma545%Seroma655%Patients with >1 complication19%Re-excision Rate86%Histological TypesER+, HER2-7055%ER+10078%HER2+2016%TNB1310% Citation Format: Jessica Montalvan, Logan Healy, Huma Javaid, Ivan Marin, Brian Menegaz, Cary Hsu, Eric Silberfein, Elizabeth Bonefas, Stacey Carter, Alastair Thompson. Magseed/magtrace-guided surgery in breast cancer- an institutional perspective [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-20-06.

Background: Ensuring negative margins at the time of breast conserving surgery for invasive breast cancer or ductal carcinoma in situ is necessary to minimize the chance of local recurrence and avoid re-excisions that cause patient concern and may delay adjuvant therapy. However, about 25% of women who have lumpectomy have a second surgery to remove residual disease, suggesting an ongoing need for improved methods of intraoperative margin assessment. This study aimed to perform a contemporary review of methods of intraoperative margin assessment during breast conservation surgery. Methods: A review of the scientific literature from 2009 to 2021 comprising 62 manuscripts of the current and proposed. intraoperative techniques for breast margin assessment during breast conservation surgery was conducted via PubMed and Google Scholar. The methods assessed were grouped into 10 categories based on the technology employed: bioimpedance/radiofrequency, high-resolution imaging, optical imaging, mass spectrometry, magnetic-resonance imaging, 2D/3D specimen CT, X-ray, multimodal optical microscopy, pharmacologic and pathological margin assessment. All technologies were reviewed for overall effectiveness in lowering re-excision rates derived from their respective advantages, limitations, sensitivity, and specificity. Results: Overall, 8 current and 7 technologies under development were assessed (Table 1). Frozen section and cytology yielded the highest diagnostic accuracy; however, these can be time-consuming, resource-intensive, and have limited sampling points. Conversely, 2D specimen CT provides rapid results but is limited by relatively low sensitivity. Future technologies such as optical coherence tomography showed promising results in demonstrating higher diagnostic accuracy for lumpectomy and margin shaves, but remain to be proven in clinical practice. Conclusion: Intraoperative margin assessments can lower final positive margins and subsequent re-excisions rates. A number of current and upcoming technologies that assess margin status range in their respective efficacies and limitations. There remains demand for improved margin assessment at the time of breast conserving surgery, but which technologies will become standard of care remains, at present, unclear. Table 1.Methods of intraoperative margin assessmentMethod:Brand:Sensitivity:Specificity:Source:Bioimpedence• ClearEdge™87.3%75.6%Dixon et al. 2016• MarginProbe75.2%70-87%Schanabel et al., 2014Cytology:• Imprint72%97%Esbona & Zhanhai 2012; Qui et al., 2018Frozen Section–83%95%Schmidt et al, 2020; Schwarz & Schmidt, 2020Mass Spectrometry• iKnife93.4-94.7%94.7-96.2%St. John et al., 2017• MasSpec Pen83-95%95-100%Garza et al., 2020Multimodal optical microscopy• fluorescence imaging combination withRCM/OCT subsystemTBDTBDScimone et al., 2021MRI• ClearSight™93%92%Moshe et al., 2016Optical Coherence Tomography (OCT)• OTIS™96%92%Mojahed et al., 2020; Schmidt et al. 2020Pharmacology• Bevacizumab98%79%Koch et al., 2017• Lumicell2-3D specimen CT• Mozart®93%78%Black et al., [poster]• Faxitron78.6-85.6%100%Emmadi & Wiley 2012; Bathla et al. 2011• MicroCT56%100%Qiu et al. 2018X-ray• XPCI83%83%Massimi et al. 2021 Citation Format: Huma Javaid, Ivan Marin, Jessica Montalvan, Logan Healy, Brian Menegaz, Cary Hsu, Eric Silberfein, Elizabeth Bonefas, Stacey A. Carter, Alastair M. Thompson. Current options and future perspectives for breast margin assessment in clinical practice [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-10.

Endoscopic necrosectomy has emerged as the preferred treatment modality for walled-off pancreatic necrosis. This study was designed to evaluate the safety and efficacy of direct endoscopic necrosectomy with and without hydrogen peroxide (H2O2) lavage.Retrospective chart reviews were performed for all patients undergoing endoscopic transmural management of walled-off pancreatic necrosis at 9 major medical centers from November 2011 to August 2018. Clinical success was defined as the resolution of the collection by imaging within 6 months, without requiring non-endoscopic procedures or surgery.Of 293 patients, 204 met the inclusion criteria. Technical and clinical success rates were 100% (204/204) and 81% (166/189), respectively. For patients, 122 (59.8%) patients had at least one H2O2 necrosectomy (H2O2 group) and 82 (40.2%) patients had standard endoscopic necrosectomy. Clinical success was higher in the H2O2 group: 106/113 (93.8%) vs 60/76 (78.9%), P = 0.002. On a multivariate analysis, the use of H2O2 was associated with higher clinical success rate (odds ratio 3.30, P = 0.033) and earlier resolution (odds ratio 2.27, P0.001). During a mean follow-up of 274 days, 27 complications occurred. Comparing procedures performed with and without H2O2 (n = 250 vs 183), there was no difference in post-procedure bleeding (7 vs 9, P = 0.25), perforation (2 vs 3, P = 0.66), infection (1 vs 2, P = 0.58), or overall complication rate (n = 13 [5.2%] vs 14 [7.7%], P = 0.30).H2O2-assisted endoscopic necrosectomy had a higher clinical success rate and a shorter time to resolution with equivalent complication rates relative to standard necrosectomy.See the visual abstract at http://links.lww.com/AJG/B714.(Equation is included in full-text article.).

DCIS is traditionally viewed as a surgical problem managed in a comparable way to invasive breast cancer, by breast conservation or mastectomy, to prevent the evolution of intraductal to invasive disease. The need for surgery has been challenged by retrospective case series demonstrating that progression from DCIS to invasive disease is variable, increases with time, but may be modified by endocrine therapy. This data has led to the innovative trials currently under way of active monitoring compared with surgery – the “if” of whether surgery is needed. What surgery to perform requires pathology confirmation of the diagnosis, awareness of the heterogeneity of DCIS (and the potential for sampling to miss invasive disease) together with imaging by mammography, ultrasound and/or MRI. Clinical impressions, imaging and pathology findings direct treatment options. Surgery comprises lumpectomy versus simple, skin sparing or nipple sparing mastectomy (with consideration for reconstruction) potentially partnered with axillary node surgery, at least for those undergoing mastectomy. When (and how) to perform surgical and allied techniques is undergoing change. The required surgical margins of 2mm (for pure DCIS) at the time of conservation to reduce local recurrence remains challenging, with technologies such as optical coherence tomography demonstrating promise for intraoperative determination of adequate margins. Rather than routine sentinel lymph node biopsy, with the attendant risks of lymphedema, iron oxide/dextran coated particles injected prior to surgery, rapidly migrate to and lodge in the axillary nodes and provide an option for delayed axillary surgery if invasive disease is identified. Neoadjuvant approaches to DCIS, targeting the estrogen receptor or HER2, to downstage the extent of surgery are less favored than for invasive breast cancers, but DCIS may be the residue left after neoadjuvant treatment for invasive disease. However, adjuvant endocrine therapy and adjuvant radiotherapy may each have an impact on reducing the chance of re-occurrence of DCIS or development of invasive cancer. Currently, surgery remains the primary treatment for DCIS. If surgery is performed, what is done and when surgery takes place varies with the nature, the extent of the DCIS and is influenced by patient preference. Citation Format: Alastair M. Thompson, Elizabeth Bonefas, Stacey Carter, Ivan marin, Huma Javaid, Jessica Montalvan. Surgery for DCIS: If, what and when [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA019.

Ductal carcinoma in situ (DCIS) is early-stage non-malignant breast cancer that tumor cells are confined to the lumens of ducts. Over 50,000 DCIS patients are diagnosed each year in the United States, however, less than half of DCIS will develop into invasive breast cancer (IBC), suggesting a risk of overtreatment for some DCIS patients. A comprehensive investigation of the molecular mechanisms of DCIS initiation and progression is urgently needed that can facilitate us stratifying the risk of DCIS invasion and design better intervention approaches. In this study, we conducted single-cell RNA-seq and spatial transcriptomics (ST) on DCIS and IBC samples (most estrogen receptor positive). We first inferred copy number aberrations (CNA) in these samples and found that DCIS and IBC shared the most copy number events while only marginal differences were identified. Tumor CNA subclones colocalized in different ductal regions from the ST data. Further, we applied a sample-wise non-negative matrix factorization (NMF) to identify robust gene expression metaprograms across tumor samples. On the ST data, we found these metaprograms also displayed distinct spatial patterns. For non-tumor cells in the TME, we sub-clustering them into cell states and identified that some cell states showed a gradual change along breast cancer initiation and progression. To recapitulate the tumor ecosystems, we also conducted an ecotype analysis in DCIS samples and identified that some ecotypes showed an increasing/decreasing trend in IBC patients. Further, tumor and TME ecotypes also showed spatially colocalizations based on our ST data. In summary, these results demonstrated that genomic signatures could hardly predict the DCIS progression while tumor metaprograms and TME ecotypes might serve as a potential risk stratification approach for DCIS patients. Citation Format: Runmin Wei, Siyuan He, Shanshan Bai, Emi Sei, Min Hu, Chandandeep Nagi, Brian Menegaz, Huma Javaid, Jelle Wesseling, Andrew Futreal, Alastair Thompson, Savitri Krishnamurthy, Nicholas Navin. A single-cell and spatial investigation of tumor and TME for DCIS [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA013.

Background Hypertriglyceridemia induced acute pancreatitis (HIAP) is the third common cause of acute pancreatitis. HIAP can result in recurrent attacks of severe AP with significant morbidity and mortality. Hypertriglyceridemia (HTG) could be primary or secondary. Although genetic causes of HTG are well studied, the prevalence of secondary causes of HTG in patients presenting with HIAP is not well characterized. This study aimed to identify the prevalence of risk factors for secondary hypertriglyceridemia among patients presenting with HIAP in a tertiary referral center in a large metropolitan area. Methods This is a retrospective analysis of all patients admitted with AP from August 2012–2017. A subgroup of patients with triglycerides >880 mg/dl were included for analysis. Secondary causes of HTG were identified. Secondary analysis evaluating the severity of pancreatitis was performed. Results There were 3,746 patients admitted for AP of which 57 patients had AP and HTG. Of these 57 patients, 70.2% had history of diabetes mellitus, 26.3% had history of heavy alcohol use, 22.8% had chronic kidney disease, 47.3% with obesity, and 21.1% with metabolic syndrome. Two patients were classified as unexplained HTG. Secondary analysis showed a total of 45.6% of patients requiring ICU admission. 26.3% of patients with severe inflammatory pancreatitis and 17.5% of patients with severe necrotizing pancreatitis. Conclusions In our cohort of HIAP, 55 out of 57 patients had secondary causes for HTG. Identifying secondary causes of HTG during acute hospitalization is important to tailor outpatient treatment in order to prevent future admissions with HIAP.

Background & Aims Endoscopic submucosal dissection (ESD) is a widely accepted treatment option for superficial gastric neoplasia in Asia, but there are few data on outcomes of gastric ESD from North America. We aimed to evaluate the safety and efficacy of gastric ESD in North America. Methods We analyzed data from 347 patients who underwent gastric ESD at 25 centers, from 2010 through 2019. We collected data on patient demographics, lesion characteristics, procedure details and related adverse events, treatment outcomes, local recurrence, and vital status at the last follow up. For the 277 patients with available follow-up data, the median interval between initial ESD and last clinical or endoscopic evaluation was 364 days. The primary endpoint was the rate of en bloc and R0 resection. Secondary outcomes included curative resection, rates of adverse events and recurrence, and gastric cancer-related death. Results Ninety patients (26%) had low-grade adenomas or dysplasia, 82 patients (24%) had high-grade dysplasia, 139 patients (40%) had early gastric cancer, and 36 patients (10%) had neuroendocrine tumors. Proportions of en bloc and R0 resection for all lesions were 92%/82%, for early gastric cancers were 94%/75%, for adenomas and low-grade dysplasia were 93%/ 92%, for high-grade dysplasia were 89%/ 87%, and for neuroendocrine tumors were 92%/75%. Intraprocedural perforation occurred in 6.6% of patients; 82% of these were treated successfully with endoscopic therapy. Delayed bleeding occurred in 2.6% of patients. No delayed perforation or procedure-related deaths were observed. There were local recurrences in 3.9% of cases; all occurred after non-curative ESD resection. Metachronous lesions were identified in 14 patients (6.9%). One of 277 patients with clinical follow up died of metachronous gastric cancer that occurred 2.5 years after the initial ESD. Conclusions ESD is a highly effective treatment for superficial gastric neoplasia and should be considered as a viable option for patients in North America. The risk of local recurrence is low and occurs exclusively after non-curative resection. Careful endoscopic surveillance is necessary to identify and treat metachronous lesions.