Citations

Reconstruction of facial trauma has seen a significant evolutionary leap in the last 100 years. The current surgical management of facial fractures was made possible by the efforts and creativity of pioneer surgeons, advances in anatomic understanding, and the continued development of biomaterials and imaging technologies. Virtual surgical planning (VSP) and 3-dimensional printing (3DP) are being incorporated into the management of acute facial trauma. The integration of this technology at the point of care is rapidly expanding globally. This article reviews the history of the management of craniomaxillofacial trauma, current practices, and future directions. The use of VSP and 3DP in facial trauma care is highlighted with a description of EPPOCRATIS, a rapid point-of-care process incorporating VSP and 3DP at the trauma center.

Abstract Background: Ovarian cancer ranks fifth in cancer deaths among women. The gold standard of care for advanced disease includes cytoreductive surgery along with adjuvant or neoadjuvant platinum/taxane-based chemotherapy. Although response to this treatment is high, chemotherapy-induced nausea and vomiting due to platinum agents and allergic reactions due to both agents are common. For nearly half a century, the glucocorticoid (GC) dexamethasone (DEX) has been administered as part of supportive care. However, there have periodically been questions about the possible deleterious effects of DEX on chemotherapy response, especially in solid tumors. Methods: Platinum-sensitive, glucocorticoid receptor (GRα) expressing ovarian cancer cells were exposed to DEX prior to chemotherapy and clonogenic survival was assessed. The effects of DEX on cell cycle and apoptosis were assessed by flow cytometry. Changes in the tumor cell transcriptome after acute DEX treatment were determined by RNA sequencing. Mice bearing orthotopic ovarian cancer patient-derived xenografts (PDXs) were treated with chemotherapy ± DEX to assess changes in chemotherapy response in vivo. Findings: DEX pre-treatment decreased platinum cytotoxicity in ovarian cancer cell lines in vitro and diminished platinum response in some PDXs analyzed for chemotherapy response ex vivo. RNA-seq analysis revealed changes in transcripts encoding proteins involved in platinum detoxification and TNFα pro-survival signaling. In ovarian cancer PDXs, DEX decreased platinum response in one model and had limited impact on both platinum and platinum/taxane chemotherapy in three distinct studies. Interpretation: DEX appears to modulate chemotherapy response in some settings in vitro and ex-vivo. The impact of DEX on chemotherapy response in vivo appears to be limited. However, further investigation of this question in vivo in non-immunosuppressed murine models appears warranted. Citation Format: Annapoorna Venkatachalam, Cristina Correia, Cordelia D. Mcgehee, Sarah Finstuen-Magro, Jamison VanBlaricom, Paula A. Schneider, Kevin L. Peterson, Ethan P. Heinzen, Melissa C. Larson, Xiaonon Hou, Ann L. Oberg, Saravut John Weroha, Scott H. Kaufmann. Impact of dexamethasone on chemotherapy response in ovarian cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5058.

Objective: To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS). Background: Liver resections for HCC on MS are associated with high perioperative morbidity and mortality. No data on the minimally invasive approach in this setting exist. Material and Methods: A multicenter study involving 24 institutions was conducted. Propensity scores were calculated, and inverse probability weighting was used to weight comparisons. Short-term and long-term outcomes were investigated. Results: A total of 996 patients were included: 580 in OLR and 416 in MILR. After weighing, groups were well matched. Blood loss was similar between groups (OLR 275.9±3.1 vs MILR 226±4.0, P=0.146). There were no significant differences in 90-day morbidity (38.9% vs 31.9% OLRs and MILRs, P=0.08) and mortality (2.4% vs 2.2% OLRs and MILRs, P=0.84). MILRs were associated with lower rates of major complications (9.3% vs 15.3%, P=0.015), posthepatectomy liver failure (0.6% vs 4.3%, P=0.008), and bile leaks (2.2% vs 6.4%, P=0.003); ascites was significantly lower at postoperative day 1 (2.7% vs 8.1%, P=0.002) and day 3 (3.1% vs 11.4%, P<0.001); hospital stay was significantly shorter (5.8±1.9 vs 7.5±1.7, P<0.001). There was no significant difference in overall survival and disease-free survival. Conclusions: MILR for HCC on MS is associated with equivalent perioperative and oncological outcomes to OLRs. Fewer major complications, posthepatectomy liver failures, ascites, and bile leaks can be obtained, with a shorter hospital stay. The combination of lower short-term severe morbidity and equivalent oncologic outcomes favor MILR for MS when feasible.

Introduction Pregnancy in patients with chronic intestinal failure (CIF) is a relatively rare occurrence but is an important contemporary topic given both the increasing use of home parenteral nutrition (HPN) and the demographics of patients with CIF. Method An opinion-based survey was produced in a multidisciplinary manner, which was then distributed internationally, via the European Society for Clinical Nutrition and Metabolism network, using a web-based survey tool for healthcare professionals with a specialist interest in the management of CIF. Results Seventy specialists from 11 countries completed the survey. Fifty-four per cent of the respondents reported some experience of managing pregnancy in patients with CIF. However, 60% stated that they did not feel that it was their role to discuss the topic of pregnancy with their patients, with fewer than 10% stating that they routinely did so. Respondents felt that an individualised approach was required when considering alterations to parenteral support prior to conception, during pregnancy and in the postnatal period. Most respondents also felt there was no increased risk of catheter-related blood stream infections, while catheter-related thrombosis was deemed to be the most significant HPN-related complication for pregnant women. Conclusion This study reports a variable experience, knowledge and confidence of healthcare professionals when considering pregnancy in patients with CIF. The risk of HPN-related complication was felt to be greater during pregnancy, with an individualised approach being the preferred route for most aspects of care. The findings support the need for an international registry and subsequent consensus guidelines for the management of pregnancy in CIF.

We conducted a retrospective/prospective worldwide study on patients with neuroendocrine neoplasms (NENs) and a molecularly proven SARS-CoV-2 positivity. Preliminary results regarding 85 patients of the INTENSIVE study have been published in 2021. Now we are reporting the 2-year analysis.Here, we are reporting data from consecutive patients enrolled between 1 June 2020, and 31 May 2022. Among the 118 contacted centers, 25 were active to enroll and 19 actively recruiting at the time of data cut-off for a total of 280 patients enrolled. SARS-CoV-2 positivity occurred in 47.5% of patients in 2020, 35.1% in 2021, and 17.4% in 2022. The median age for COVID-19 diagnosis was 60 years. Well-differentiated tumors, non-functioning, metastatic stage, and gastroenteropancreatic (GEP) primary sites represented most of the NENs. COVID-19-related pneumonia occurred in 22.8% of the total, with 61.3% of them requiring hospitalization; 11 patients (3.9%) needed sub-intensive or intensive care unit therapies and 14 patients died (5%), in 11 cases (3.9%) directly related to COVID-19. Diabetes mellitus and age at COVID-19 diagnosis > 70 years were significantly associated with COVID-19 mortality, whereas thoracic primary site with COVID-19 morbidity. A significant decrease in both hospitalization and pneumonia occurred in 2022 vs 2020. In our largest series of NEN patients with COVID-19, the NEN population is similar to the general population of patients with NEN regardless of COVID-19. However, older age, non-GEP primary sites and diabetes mellitus should be carefully considered for increased COVID-19 morbidity and mortality. Relevant information could be derived by integrating our results with NENs patients included in other cancer patients with COVID-19 registries.

684 Background: In the COSMIC-021 phase 1b study (NCT03170960) evaluating cabozantinib plus atezolizumab in advanced solid tumors, this combination therapy demonstrated encouraging clinical activity in patients with advanced non-clear cell renal cell carcinoma (nccRCC) with a median follow-up of 13 mo (Pal. JCO 2021). Results after extended follow-up in nccRCC are presented. Methods: Patients with advanced nccRCC and ECOG PS 0/1 who had ≤1 prior VEGFR-targeting tyrosine kinase inhibitor (TKI) were eligible. Prior treatment with TKIs targeting MET or immune checkpoint inhibitors was not allowed. Patients received cabozantinib 40 mg PO QD plus atezolizumab 1200 mg IV Q3W until unacceptable toxicity or progression; dose reductions of cabozantinib (40 mg QD to 20 mg QD, then to 20 mg QOD) were permitted to manage adverse events. The primary endpoint was objective response rate (ORR) per RECIST v1.1 by the investigator; other endpoints included safety, duration of response (DOR), PFS, and OS. Results: The study enrolled 32 patients with nccRCC (2 from dose escalation phase, and 30 from expansion phase of the study): median age, 62 y; male, 81%; ECOG PS 0/1, 75%/25%; histology, papillary/chromophobe/clear cell/other, 47%/28%/3%/22%; sarcomatoid feature, 13%; IMDC risk favorable/intermediate/poor, 50%/41%/9%; ≥3 tumor sites, 56%; tumor sites, lung/kidney/bone/liver, 50%/25%/16%/16%; prior nephrectomy, 63%; prior VEGFR TKI, 22%; 0/1 lines of prior therapy (locally advanced/metastatic setting), 81%/19%. As of July 21, 2022, median follow-up was 37.2 mo (range 32.1–58.5) with 5 (16%) patients remaining on study treatment. ORR by investigator was 31% (all PRs) and disease control rate was 94% (Table); median DOR was 8.1 mo. Median PFS was 9.3 mo (95% CI 5.5–12.3), and median OS was not reached (95% CI 23.0–NE). PFS and OS estimates at 12 mo were 34% and 84%, respectively; 24-mo estimates were 6% and 70%. Treatment-related AEs occurred in 97% (grade 3/4, 53%); the most common AEs included diarrhea (69%), palmar-plantar erythrodysesthesia (50%), fatigue (44%), dysgeusia (41%), hypertension (31%) and nausea (31%). One grade 5 treatment-related AE of pulmonary hemorrhage occurred. Treatment-related AEs leading to discontinuation of both study treatments occurred in 13% of patients. Conclusions: Extended 3-year follow-up reinforces the encouraging clinical activity of cabozantinib plus atezolizumab in advanced nccRCC with a manageable safety profile. Clinical trial information: NCT03170960 . [Table: see text]

Objectives: The development and evaluation of percutaneous thrombectomy devices for pulmonary embolism (PE) pose a need for standardized large in vivo models with representative anatomical and physiological conditions and clots analogs. In this study, we present a swine model of PE model employing human-derived clot analogs. Material and Methods: Baseline angiographic and physiological pressure measurements were obtained in six adult Yorkshire pigs (45–65 kg) and results were benchmarked for interspecies comparison with published human data using fluoroscopic examinations, intra-arterial pressure measurements, and histologic studies. Then, clot analogs were created ex vivo employing banked human blood and a subset incubated in iodinated contrast for fluoroscopic visualization. Clot analogs were then embolized via a femoral venous access and angiographic/physiological consequences were evaluated. Results: The main, right, and left pulmonary artery diameters were 24 ± 1.1 mm, 16.5 ± 0.8 mm, and 12.6 ± 1.2 mm, respectively. The angle between the main pulmonary artery at the bifurcation point was approximately 90–95°. The clot analogs were heterogeneous and had increased fibrin content along the clot length. The overall composition was 96.63% red blood cell (RBC)/3.37% fibrin in the initial section, 48.85% RBC/51.15% fibrin in the intermediate section, and 3.44% RBC/96.56% fibrin in the final section. Embolization of the clot analogs resulted in distal occlusion of the right and left pulmonary arteries. Conclusions: This swine model coupled with clot analog is able to accurately mimic human anatomical and physiological conditions in PE making it feasible for the evaluation of pulmonary thrombectomy devices.

Background: Despite the well-established potent benefit of mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke, access to MT has not been studied globally. We conducted a worldwide survey of countries on 6 continents to define MT access (MTA), the disparities in MTA, and its determinants on a global scale. Methods: Our survey was conducted in 75 countries through the Mission Thrombectomy 2020+ global network between November 22, 2020, and February 28, 2021. The primary end points were the current annual MTA, MT operator availability, and MT center availability. MTA was defined as the estimated proportion of patients with LVO receiving MT in a given region annually. The availability metrics were defined as ([current MT operators×50/current annual number of estimated thrombectomy-eligible LVOs]×100 = MT operator availability) and ([current MT centers×150/current annual number of estimated thrombectomy-eligible LVOs]×100= MT center availability). The metrics used optimal MT volume per operator as 50 and an optimal MT volume per center as 150. Multivariable-adjusted generalized linear models were used to evaluate factors associated with MTA. Results: We received 887 responses from 67 countries. The median global MTA was 2.79% (interquartile range, 0.70–11.74). MTA was <1.0% for 18 (27%) countries and 0 for 7 (10%) countries. There was a 460-fold disparity between the highest and lowest nonzero MTA regions and low-income countries had 88% lower MTA compared with high-income countries. The global MT operator availability was 16.5% of optimal and the MT center availability was 20.8% of optimal. On multivariable regression, country income level (low or lower–middle versus high: odds ratio, 0.08 [95% CI, 0.04–0.12]), MT operator availability (odds ratio, 3.35 [95% CI, 2.07–5.42]), MT center availability (odds ratio, 2.86 [95% CI, 1.84–4.48]), and presence of prehospital acute stroke bypass protocol (odds ratio, 4.00 [95% CI, 1.70–9.42]) were significantly associated with increased odds of MTA. Conclusions: Access to MT on a global level is extremely low, with enormous disparities between countries by income level. The significant determinants of MT access are the country’s per capita gross national income, prehospital LVO triage policy, and MT operator and center availability.

Abstract Background: Despite evidence of substantial breast cancer risk reduction, few high-risk women adopt chemopreventive medications such as selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs). Women with benign breast disease, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have an increased risk of developing breast cancer and derive a greater benefit from antiestrogens compared to other high-risk women. Reasons for low uptake of chemoprevention include insufficient patient and clinician knowledge about antiestrogens, time constraints during the clinical encounter, and concerns about side effects. To address these barriers, we have developed patient and provider web-based decision support tools to improve informed choice about breast cancer chemoprevention among women with AH or LCIS. Study design: We are conducting a cluster-randomized controlled trial of clinical decision support to improve chemoprevention informed choice among women with AH or LCIS and their treating providers. Twenty-six U.S. sites through the SWOG Cancer Research Network were randomly assigned 1:1 to standard educational materials alone or in combination with the patient-centered decision aid (RealRisks) and provider decision support tool (BNAV). A total of 415 patients and 200 healthcare providers will be recruited from these sites. RealRisks consists of interactive modules to calculate personalized breast cancer risk and elicit preferences on chemoprevention. The modules are available in English and Spanish. BNAV is comprised of self-directed case-based learning modules on breast cancer risk assessment and chemoprevention. Patients complete questionnaires at baseline, 6 and 12 months. Providers complete surveys at baseline and after their enrolled patient’s 6-month clinical encounter. The primary endpoint is chemoprevention informed choice at 6 months, using a measure combining knowledge, attitude, and intention scales. Secondary endpoints include perceived breast cancer risk/worry, chemoprevention knowledge/intention, decision conflict/regret, shared decision-making, and chemoprevention uptake. For patients who begin chemoprevention, adherence and reasons for discontinuation are assessed annually for up to 5 years. Barriers and facilitators to implementing RealRisks and BNAV into clinic workflow will be assessed by conducting patient and provider interviews at baseline and mid-implementation. Eligibility criteria: Eligible patients include women, age 35-74 years, with AH or LCIS, no history of breast cancer, no prior use of SERMs or AIs, no bilateral mastectomies, English or Spanish-speaking, and access to the internet. Eligible providers include breast surgeons, medical oncologists, primary care providers, and physician extenders who see patients with AH or LCIS. Statistical methods: We have 90% power to detect a 15% increase in the frequency of chemoprevention informed choice with a 1-sided 0.025 level test, assuming an intraclass correlation (ICC) of 0.02 to account for clustering, roughly equal accrual at each site, 10% loss to follow-up, and ≤10% event rate in the control arm. Current/target accrual: The trial was activated on 9/1/2020. As of 7/7/2022, all 26 sites have been randomized, 157/200 providers and 184/415 patients have been enrolled. Discussion: Our hybrid effectiveness/implementation study seeks to evaluate the effectiveness of a multi-level intervention in promoting informed decision-making about breast cancer chemoprevention. Study results will provide valuable insights on how the decision support tools are integrated in diverse clinical settings. Citation Format: Katherine D. Crew, Garnet Anderson, Kathryn Arnold, Andrew Stieb, Jacquelyn N. Amenta, Cynthia Law, Ana Sandoval-Leon, Sarah Colonna, Tari King, Debra Mangino, Sandhya Pruthi, Maria Grosse Perdekamp, Christa Braun-Inglis, Stacy Krisher, Lisa Yee, Danielle Bertoni, Samantha Seaward, Kari B. Wisinski, Justin Floyd, Corrine Zarwan, Tarah J. Ballinger, Lindi VanderWalde, Masey M. Ross, Preston Steen, Shelly Lo, Alison Conlin, Kathleen Yost, John Ellerton, Erin Lin, Holly J. Pederson, Sagar Sardesai, Cheryl Jernigan, Dawn Hershman, Marian L. Neuhouser, Banu K. Arun, Rita Kukafka. SWOG 1904: Cluster-randomized controlled trial of patient and provider decision support to increase chemoprevention informed choice among women with atypical hyperplasia or lobular carcinoma in situ (MiCHOICE) [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 OT1-15-01.