Surveillance Group Research Articles

PB1770: REASONS FOR CHANGES OF BONE FORMATION PROCESSES IN CHILDREN WITH ALL LIVING IN RADIOACTIVELY CONTAMINATED TERRITORIES OF UKRAINE

Background: The state of bone structures, stromal microenvironment of the bone marrow and their hormonal regulation can be affected by iron metabolism. The mechanisms of increased bone density (IBD) in children with ALL deserve special attention. Aims: Identify the reasons of elevated bone density in children with ALL, who living in radiatioactively contaminated areas (RCA). Methods: 96 children aged 2 to 18 years with common-B ALL were examined after completion of maintenance therapy according to the protocol. The children lived at the RCA of Ukraine and were examined from 2012 to 2021. Data were studied in a comparative aspect in ALL children of 2 groups: Group I (n = 36) - with elevated IBD, above 100 units (117.4 ± 10.2 units), Group II (n = 60) - with standard IBD (100-85 units, 87.4 ± 9.1 units). Bone fractures in the anamnesis, dental caries, obesity, biochemical parameters of blood (amino acids in urine, serum ferritin (SF), serum alkaline phosphatase (AF), cholesterol, calcium, vitamin D, free thyroxine, thyroid-stimulating hormone, pituitary hormone, cortisol) as IBD were evaluated. The doses of bone marrow irradiation in patients according to their length of stay on RCA were calculated. Conducted statistical processing of materials (t-Student, Spearman’s correlation coefficient, U-Test). Results: The distribution of children by age in both groups did not differ. Boys (52 out of 60) predominated in Group I and in 30% of patients the levels of SF exceeded 500 ng / ml (728.8 ± 12.3 units). In children of both groups, a direct correlation was found between IBD and SF (p <0.001 and p <0.01, respectively). In children of Group I there was a direct relationship between IBD and fractures frequency (p <0,01). There were more children with low levels of total serum protein and glycine (p <0.01) in Group I, as number of children with high levels of alkaline phosphatase and cholesterol were less (p <0.05). IBD was inversely correlated with cortisol levels (rs = -0.73; p <0.001) and alkaline phosphatase activity (rs = -0.21; p <0.05). Dental caries in children in Group I was less frequent than in Group II (p <0.05). Survival of children was directly correlated with IBD (p <0.001). Irradiation doses in patients of Groups I and II ranged from 0.03 to 5.51 mSv (average 4.01 ± 0.17 mSv and 3.66 ± 0.18 mSv, respectively). In children, regardless of the surveillance group, there was a direct correlation between radiation dose, age of the child and the presence of obesity (p <0.001). Summary/Conclusion: The state of bone homeostasis in children with ALL depends on anabolic and catabolic metabolic processes that provide energy substrate for bone formation, the level of iron stores in the body and hormonal regulation.

Surgery or Surveillance for Esophageal Squamous Cell Carcinoma With Clinical Complete Response After Neoadjuvant Chemoradiotherapy

We aimed to evaluate the role of esophagectomy in patients with esophageal squamous cell carcinoma with clinically complete response (cCR) after neoadjuvant chemoradiotherapy. Data of patients with locally advanced esophageal squamous cell carcinoma who achieved cCR after neoadjuvant chemoradiotherapy between October 2008 and September 2018 were retrospectively reviewed. The criteria for cCR include: (1) tumor resolution on computed tomography, (2) maximum standardized uptake value decrement >35% on positron-emission tomography-computed tomography scan, and (3) a negative endoscopic biopsy result. Overall survival (OS) and disease-free survival (DFS) were compared between patients who received surveillance only (surveillance) and those who underwent surgery. A total of 154 patients with cCR, including 54 in the surveillance group and 100 in the surgery group, were included. The 5-year OS rates in the surveillance and surgery groups were 47.9% and 36.9 %, respectively (P= 0.210). The 5-year DFS rates were 38.1% and 28.2%, respectively (P = 0.203). Surgery was not a prognostic factor in the multivariable analysis (OS: HR: 1.26, 95% CI: 0.69-2.33, P = 0.453; DFS: HR: 1.08, 95% CI: 0.60-1.96, P=0.795). In the surgery group, ypT0N0, ypT+Nany, and ypT0N+ were noted in 54%, 37%, and 9% of patients, respectively. The 5-year OS rates were 55.8%, 22.2%, and 12.4%, respectively (P=0.001). No survival differences were noted between the surveillance and surgery groups. However, 46% of cCR patients in the surgery group did not have pathological complete response, and their outcomes were poor. Esophagectomy may be the only way to identify patients with residual disease.

Impact of nationwide hepatocellular carcinoma surveillance on the prognosis in patients with chronic liver disease.

This study aimed to investigate the effect of hepatocellular carcinoma (HCC) surveillance using the Korea National Liver Cancer Screening Program on the receipt of curative treatment for HCC and mortality in patients with chronic liver disease. This population-based cohort study from the Korean National Health Insurance Service included 2003 to 2015 claims data collected from 1,209,825 patients aged ≥40 years with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis. Patients were divided according to HCC surveillance using ultrasonography and serum alpha-fetoprotein every 6-12 months. The study outcomes were the receipt of curative treatment (surgical resection, radiofrequency ablation, or liver transplantation) and all-cause mortality. The study population consisted of 1,209,825 patients with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis (median age, 52.0 years; interquartile range, 46-55 years; 683,902 men [56.5%]). The proportion of participants who underwent HCC surveillance was 52.7% (n=657,889). During 10,522,940 person-years of follow-up, 74,433 HCC cases developed, including 36,006 patients who underwent curative treatment. The surveillance group had a significantly higher proportion of curative treatment for HCC than the non-surveillance group after adjusting for confounding factors (adjusted hazard ratio [HR], 5.64; 95% confidence interval [CI], 5.48-5.81). The surveillance group had a significantly lower mortality rate than the non-surveillance group (adjusted HR, 0.56; 95% CI, 0.55-0.56). HCC surveillance using the national screening program in patients with chronic viral hepatitis or liver cirrhosis provides better opportunity for curative treatment for HCC and improves overall survival.

Effect of more versus less frequent abdominopelvic computed tomography follow-up testing on overall survival in patients with stage II or III colon cancer.

3604 Background: Patients with colon cancer undergo an abdominopelvic computed tomography (AP-CT) scan surveillance every 6-12 months for five years after surgery. However, evidence of survival benefit from more intensive AP-CT patients in stage II and III colon cancer is still elusive. Methods: A total of 2,137 patients with stage II-III colon cancer who received curative aim surgery were analyzed in the Yonsei Cancer Registry Database between Jan 1, 2005, to Dec 31, 2015. The surveillance start date was defined as 90 days after curative resection or one day after adjuvant chemotherapy. All patients had at least one AP-CT for two years after the surveillance period. The average interval of AP-CT per patient was calculated as the postoperative surveillance duration divided by the number of AP-CT examinations. Patients who underwent AP-CT with an average interval of 6 months and 12 months were assigned to the high-frequent and low-frequent surveillance groups. Association of AP-CT frequency and demographic factors with overall survival (OS) were evaluated. Univariate and multivariate analyses were conducted. Results: Among 2,137 patients who underwent curative aim surgery, the median intervals of AP-CT scan were 6.1 months in high-frequent surveillance and 10.8 months in the less-frequent surveillance group, respectively. The 5-year overall survival (OS) was not significantly different in both groups; however, OS was significantly longer in the high-frequent surveillance group of patients who harvested lymph nodes less than 12 in curative resection ( P = 0.015) or measured postoperative serum carcinoembryonic antigen (CEA) level higher than 5 ng/ml ( P = 0.023). Of note, high-frequent surveillance group detected liver metastasis earlier (6.7 months) than the low-frequent group, leading to more curative aim metastasectomy (28.0% vs 4.3%, P = 0.020), and significantly longer 5-year OS (62.2% vs 34.8%, P = 0.017). Multivariate analysis showed that harvesting lymph nodes less than 12 (HR = 4.37, P = 0.004) and postoperative CEA level higher than 5 ng/ml (HR = 7.39, P &lt; 0.001) were prognostic factors for overall survival. Conclusions: The average interval of AP-CT in patients with stage II-III colon cancer is not associated with improved OS. However, a high-frequent AP-CT enabled early detection of liver metastases, leading to the improved OS in high-risk patients, including the number of harvested lymph nodes less than 12 or postoperative CEA level is higher than 5 ng/ml. The risk-stratified approach is warranted to guide postoperative colon cancer surveillance.

P-138 Real-world delivery, toxicity and outcomes of perioperative FLOT chemotherapy in resectable gastric/gastroesophageal adenocarcinoma: A population-based study

Perioperative docetaxel, oxaliplatin and fluorouracil/leucovorin (FLOT) has become the new standard of care for resectable gastric/ gastroesophageal adenocarcinoma since publication of the FLOT-AIO clinical trial. However, delivery, toxicity, and outcomes of this regimen in routine practice have not been widely studied. Data from Surveillance and Reporting group of Cancer Control Alberta was used to obtain data of all patients with resectable gastric and GEJ adenocarcinoma, who were treated with perioperative FLOT chemotherapy in the province of Alberta, Canada between August 1, 2017 and August 1, 2020. Charts were retrospectively reviewed for baseline demographics, cumulative doses and number of cycles received, chemotherapy-related toxicities and hospitalizations, extent of surgical resection achieved and disease-free and overall survival. Toxicities were graded using CTCAE v5 criteria. In total, 48 patients met inclusion criteria. Median age of patients was 60 and 54% (26/48) were male. Of those with reported pre-treatment ECOG and clinical stage, 94% (30/32) were ECOG ≤1 and 57% (21/37) clinical stage ≤2. Ninety-six percent (46/48) of patients completed 4 cycles of pre-operative FLOT and 94% (45/48) proceeded to surgery, while only 50% (24/48) completed 4 cycles of post-operative FLOT. Twenty-nine percent (14/48) of patients required hospitalization with a chemotherapy-related toxicity, most commonly from a gastrointestinal bleed (6/14) or infection (6/14). Pathological complete response was observed in 8.3% of patients (4/48). Fifty percent of patients (24/48) experienced a grade ≥3 chemotherapy-related toxicity. There were no treatment-related fatalities. Median overall survival and disease-free survival were 26.2 and 16.5 months respectively. In this real-world study, perioperative FLOT chemotherapy was feasible. Rates of treatment completion of all cycles, grade ≥3 toxicities and hospitalizations secondary to chemotherapy were high, but similar to those seen in the randomized trial. Median overall survival was considerably less than in the randomized trial, but this is likely due to short follow-up time. Further study is required to understand factors associated with completion of chemotherapy and overall survival in routine practice.

Real-world progression-free and overall survival for patients with advanced ovarian cancer utilizing PARP inhibitor second-line maintenance therapy vs active surveillance.

e18812 Background: Ovarian cancer (OC) is the fifth leading cause of cancer death among women. Poly(ADP-ribose) polymerase inhibitors (PARPis) are recommended following response to second-line (2L) chemotherapy as 2L maintenance treatment by the National Comprehensive Cancer Network for OC patients (pts), based on results from clinical trials demonstrating their ability to extend progression-free survival (PFS), the time between chemotherapy and relapse, in this patient population. We present recent estimates of real-world PFS and overall survival (OS) for pts on 2L PARPi maintenance therapy vs active surveillance. Methods: From the iKnowMed electronic health record database and a review of patient charts within the US Oncology Network, which includes 1200 physicians operating in over 470 sites of care in the US, adult females were included if they were diagnosed with advanced OC, had received a 2L platinum-containing regimen for advanced OC, and had ≥2 visits within the database between 1 Jan 2016 and 1 Dec 2020. Among these, a subset of charts were reviewed to confirm eligibility and to assess PFS. Patients were followed longitudinally until 31 March 2021, the last pt record, or date of death, whichever occurred earliest. Kaplan-Meier survival methods and log-rank tests were used to estimate and compare the OS as well as PFS of the groups to 24 months. Results: A total of 1154 pts met study inclusion criteria for advanced OC and either a PARPi or active surveillance for the 2L maintenance period. Of these, 142 patient charts were further manually reviewed to assess real-world PFS: 84 received a PARPi, and 58 received active surveillance. Median age at the start of 2L maintenance was 65.7 years and was not significantly different between groups. There was a significant difference in the distribution of the ECOG PS category between groups (ECOG PS 0: 22.6% vs 1.7%, ECOG PS 1: 39.3% vs 50.0%, for PARPi vs active surveillance, respectively; P&lt; 0.0001). Median follow-up time from discontinuation of 2L platinum chemotherapy until the end of observation was significantly longer in the active surveillance group (41.5 vs 23.5 months; P&lt; 0.0001). PFS probability from the beginning of 2L maintenance was higher in the PARPi group vs active surveillance (24% vs 10% at 24 months; P= 0.0003). OS probability was also significantly higher in the PARPi group vs active surveillance (78% vs 55% at 24 months; P= 0.0272). Conclusions: This study of PARPi therapy vs active surveillance confirms the efficacy benefits that have been demonstrated in randomized clinical trials of PARPis vs placebo, and it provides further evidence of the real-world effectiveness of PARPi maintenance therapy to improve survival in a population with advanced OC.

The effect and therapeutic compliance of adjuvant therapy in patients with cholangiocarcinoma after R0 resection: a retrospective study.

This study aimed to compare clinical outcomes between surveillance and adjuvant therapy (AT) groups after R0 resection for cholangiocarcinoma (CCA). A total of 154 patients who underwent R0 resection for CCA at the Daegu Catholic University Medical Center between January 2010 and December 2019 were included. Overall survival (OS) and progression-free survival (PFS) were analyzed. The median follow-up duration was 899 days. There were 109 patients in the AT group and 45 patients in the surveillance group. The patients in the AT group were younger (67 years vs. 74 years, p<0.001) and included more males (64.2% vs. 46.7%, p=0.044). The proportion of patients with stage III CCA was larger in the AT group than in the surveillance group (13.8% vs. 2.2%, p=0.005). In addition, AT did not improve OS (5-year OS rate, 69.3% in the AT group vs. 64.2% in the surveillance group, p=0.806) or PFS (5-year PFS rate, 42.6% in the AT group vs. 48.9% in the surveillance group, p=0.113). In multivariate analysis using the Cox proportional hazards model, stage III CCA (hazard ratio [HR], 10.81; 95% confidence interval [CI], 2.92-40.00; p<0.001) was a significant predictor of OS. American Society of Anesthesiologists classification II (HR, 0.50; 95% CI, 0.31-0.81; p=0.005), and American Joint Committee on Cancer stages II (HR, 3.14; 95% CI, 1.25-7.89; p=0.015) and III (HR, 8.08; 95% CI, 2.80-23.32; p<0.001) were independent predictors of PFS. AT after R0 resection for CCA did not improve OS or PFS.

Survival after active surveillance versus upfront surgery for incidental small pancreatic neuroendocrine tumours.

The safety of observing small non-functioning pancreatic neuroendocrine tumours (NF-Pan-NETs) remains under debate. This was a multicentre retrospective study of patients with small incidental NF-Pan-NETs. Survival of patients who underwent upfront surgery versus active surveillance was compared. The risk of death was matched with that in the healthy population. The excess hazard rate and probability of a normal lifespan (NLP) were calculated. Propensity score matching (PSM) with a 1 : 1 ratio was used to minimize the risk of selection bias. Some 222 patients (43.7 per cent) underwent upfront surgery and 285 (56.3 per cent) were observed. The excess hazard rate for the entire cohort was quantifiable as 0.04 (95 per cent c.i. 0 to 0.08) deaths per 1000 persons per year, and the NLP was 99.7 per cent. Patients in the active surveillance group were older (median age 65 versus 58 years; P < 0.001), and more often had co-morbidity (45.3 versus 24.8 per cent; P = 0.001), and smaller tumours (median 12 versus 13 mm; P < 0.001), less frequently located in the pancreatic body-tail (59.5 versus 69.6 per cent; P = 0.008, 59.3 versus 73.9 per cent; P = 0.001). Median follow-up was longer for patients who underwent upfront surgery (5.6 versus 2.7 years; P < 0.001). After PSM, 118 patients per group were included. The excess hazard rates were 0.2 and 0.9 deaths per 1000 persons per year (P = 0.020) for patients in the active surveillance and upfront surgery groups respectively. Corresponding NLPs were 99.9 and 99.5 per cent respectively (P = 0.011). Active surveillance of small incidental NF-Pan-NETs is a reasonable alternative to resection.

Association between intensity of imaging surveillance and clinical outcomes in patients with hepatocellular carcinoma

BackgroundThe role of computed tomography (CT)/magnetic resonance imaging (MRI) surveillance for hepatocellular carcinoma (HCC) is unclear. We aimed to determine whether the intensity of imaging surveillance using CT and MRI is associated with tumor stage at diagnosis or survival in patients with HCC. MethodsThis retrospective cohort study included 529 patients with newly diagnosed HCC under regular surveillance (twice a year testing) at a tertiary academic center. All patients were divided into a standard surveillance group (n = 62; ultrasonography [US] with alpha-fetoprotein) and an intensive imaging surveillance group (US and CT/MRI with alpha-fetoprotein); the latter was divided into a low- (n = 232) and high-intensive (n = 235) imaging surveillance group based on the median percentage of CT/MRI investigations (cut-off, 27%). Relationship between surveillance imaging, stage of HCC at diagnosis, and overall survival (OS) were analyzed. ResultsThe low- and high-intensive imaging surveillance groups (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.20–0.95; p = 0.034 and OR, 0.40; 95% CI, 0.19–0.86; p = 0.014, respectively) had better performances than the standard surveillance group to detect very early-stage HCC. OS was associated with albumin-bilirubin grade (hazard ratio [HR], 1.98; 95% CI, 1.28–3.07; p < 0.001 for grade 2 and HR, 3.03; 95% CI, 1.11–8.30; p = 0.027 for grade 3) and the applicability of curative treatment (HR, 2.34; 95% CI, 1.63–3.36; p < 0.001). However, surveillance intensity did not affect OS (p > 0.05). ConclusionsImaging surveillance for HCC using alternative CT/MRI in addition to US compared to standard practice of US only facilitates the diagnosis of very early-stage HCC but may not improve OS.

Early stage ovarian immature teratoma, surveillance or chemotherapy after surgery? A propensity score matched analysis

ObjectiveTo compare the survival outcomes between surveillance and adjuvant chemotherapy in patients with stage I ovarian immature teratomas (ITs) who underwent fertility sparing surgery. MethodsIn this retrospective cohort analysis, patients with stage IA Grade 2–3, stage IB and IC ovarian ITs who underwent surveillance after surgery between 2016 and 2021 from Peking Union Medical College Hospital were identified. A 1:1 propensity score matching was performed in patients who had adjuvant chemotherapy by age, stage, and grade. ResultsA total of 16 patients without adjuvant chemotherapy were identified. There were 3 stage IA and 13 stage IC patients. The median age at diagnosis was 14.5 years old (range 3–30). There were 6 patients who had grade 1 tumor, 5 grade 2, 5 grade 3. After a mean follow-up period of 27.4 months, a patient with stage IA grade 2 IT who underwent ovarian cystectomy had recurrence in the same ovary. 16 patients who received adjuvant chemotherapy were screened as controls. The tumor stage and grade were similar in two groups. The median age was older in the chemotherapy group. Of the 16 matched patients there was one recurrence. There was no statistical difference in 3-year disease-free survival (DFS) between surveillance group and chemotherapy group (p = 0.808). ConclusionWe did not observe survival differences or recurrence rates between patients who underwent adjuvant chemotherapy or those who did not with stage I ovarian ITs. Our study suggests surveillance may be safe and preferable in early-stage IT patients who underwent complete tumor resection.

Investigation of urinary volatile organic compounds as novel diagnostic and surveillance biomarkers of bladder cancer

BackgroundThe diagnosis and surveillance of urothelial bladder cancer (UBC) require cystoscopy. There is a need for biomarkers to reduce the frequency of cystoscopy in surveillance; urinary volatile organic compound (VOC) analysis could fulfil this role. This cross-sectional study compared the VOC profiles of patients with and without UBC, to investigate metabolomic signatures as biomarkers.MethodsUrine samples were collected from haematuria clinic patients undergoing diagnostic cystoscopy and UBC patients undergoing surveillance. Urinary headspace sampling utilised solid-phase microextraction and VOC analysis applied gas chromatography-mass spectrometry; the output underwent metabolomic analysis.ResultsThe median participant age was 70 years, 66.2% were male. Of the haematuria patients, 21 had a new UBC diagnosis, 125 had no cancer. In the surveillance group, 75 had recurrent UBC, 84 were recurrence-free. A distinctive VOC profile was observed in UBC patients compared with controls. Ten VOCs had statistically significant abundances useful to classify patients (false discovery rate range 1.9 × 10−7–2.8 × 10−2). Two prediction models were evaluated using internal validation. An eight-VOC diagnostic biomarker panel achieved AUROC 0.77 (sensitivity 0.71, specificity 0.72). A six-VOC surveillance biomarker panel obtained AUROC 0.80 (sensitivity 0.71 and specificity 0.80).ConclusionsUrinary VOC analysis could aid the diagnosis and surveillance of UBC.

Small Choroidal Melanoma: Outcomes After Surveillance Versus Immediate Treatment

To quantify potential loss (loss of vision) and gain (freedom from metastasis) in patients with small choroidal melanoma treated after a period of surveillance to document growth. A total of 167 patients with small choroidal melanoma (size: 5.0-16.0 mm in largest basal diameter and 1.0-2.5 mm in height) were identified: 42 treated after surveillance (documented growth) and 125 treated immediately. A prediction model was applied to each patient in the immediate treatment group to obtain the predicted risk of melanoma (high risk vs low risk). Potential loss (loss of vision) and gain (freedom from metastasis) were compared between the low-risk immediate treatment group and those treated after surveillance. By using the optimal cut point (0.60; 95% confidence interval: 0.37-0.61) of predicted risk for small choroidal melanoma (sensitivity: 0.74, specificity: 0.95), we identified 94 (75%) patients as high risk (score: ≥0.6) and the remaining 31 (25%) as having low-risk melanoma (score: <0.6). Over a median follow-up of 34.6 months, 5 developed metastasis (high risk=4, low risk=1) compared with 1 patient in the surveillance group. Initial visual acuity and loss of <15-letter visual acuity were not significantly different at 36 months between the low-risk patients immediately treated and those treated after surveillance (81% vs 83%), respectively. Low-risk choroidal melanoma identified by the prediction model can be labeled as an indeterminate melanocytic tumor. Such patients can be managed by surveillance to document growth before receiving vision-threatening treatment without increased risk of metastatic death. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

162 Comparative study of previous pregnant women of COVID-19 care at the intensive care unit in a west hospital in the Western Amazon, In the years 2020/2021

Introduction: Novocoronavirus contamination in Brazil has been increasing significantly.In December/2020 there was an increase in deaths and new infections, with the appearance of the P1 variant in the city of Manaus-Amazonas.This new variant, when compared with the hospitalization and evolution of pregnant women and women of the previous year, seems to be associated with greater virulence and the development of a clinical picture even more severe than the strain that circulated in the first wave in Western Amazonia. Objective: To report the cases of pregnant women with COVID-19 attended in the ICU in the first three months of 2021 compared to the year 2020. Method: Comparative study of data from the intensive care unit of a hospital in the western Amazon. Results: In the period from March to December 2020, 14 patients were treated at the ICU: 08 pregnant women and 06 puerperal women, of whom 07(50,0%) evolved with the need for orotracheal intubation and 03(21,42%) died. In the period from January to March 2021, there were 27 hospitalizations:10 pregnant women,17 puerperal women with COVID-19,of these 22(81,4%) orotracheal intubation,09(33,3%) died,11(40,0%) they were discharged,07(25,9%) are still hospitalized with severe conditions. Conclusion: The increase in the severe condition in pregnant women and women who have recently given birth with COVID-19 may be related to a greater virulence of new strains and / or variants of the strain that circulated in the first wave in 2020. It is important to consider that further studies should be carried out in this group of patients and greater genomic surveillance of the virus, in order to identify the infection as early as possible, and to establish protocols for adequate clinical management

Masking Adherence in K-12 Schools and SARS-CoV-2 Secondary Transmission.

Masking is an essential coronavirus 2019 mitigation tool assisting in the safe return of kindergarten through 12th grade children and staff to in-person instruction; however, masking adherence, compliance evaluation methods, and potential consequences of surveillance are currently unknown. We describe 2 school districts' approaches to promote in-school masking and the consequent impact on severe acute respiratory syndrome coronavirus 2 secondary transmission. Two North Carolina school districts developed surveillance programs with daily versus weekly interventions to monitor in-school masking adherence. Safety teams recorded the proportion of students and staff appropriately wearing masks and provided real-time education after observation of improper masking. Primary infections, within-school transmission, and county-level severe acute respiratory syndrome coronavirus 2 infection rates were assessed. Proper mask use was high in both intervention groups and districts. There were variations by grade level, with lower rates in elementary schools, and proper adherence being higher in the weekly surveillance group. Rates of secondary transmission were low in both districts with surveillance programs, regardless of intervention frequency. Masking surveillance interventions are effective at ensuring appropriate masking at all school levels. Creating a culture of safety within schools led by local leadership is important and a feasible opportunity for school districts with return to in-person school. In our study of schools with high masking adherence, secondary transmission was low.

Mobile-CEA - A Novel Surveillance Method for Patients with Colorectal Cancer.

ObjectiveThe follow-up of the increasing number of cancer survivors threatens to overload the health care system. While short message system (SMS)–based communication is widely used in other areas of the health care system, there are no studies of its appliance in cancer surveillance. The aim of the current study was to analyze the acceptability, convenience and impact of a novel mobile phone messaging -based system (Mobile-CEA) on health personnel contacts in patients with colorectal cancer (CRC) during 2 years of follow-up.MethodsThe follow-up data of 52 curatively treated patients with CRC (22 Mobile-CEA-, 30 standard surveillance) was collected retrospectively from the electronic archives. Mobile-CEA patient satisfaction was measured by a tailored non-validated questionnaire. Health personnel satisfaction was assessed by personal interviews.ResultsMobile-CEA surveillance group had less health personnel contacts than the standard surveillance group: median 3 (min 0–max 7) vs 5 (min 4–max 7) and 77.2% of the Mobile-CEA group had less than 4 contacts (minimum with the standard surveillance) to health personnel. There were no recurrences in either group. Mobile-CEA patients were satisfied with this novel follow-up method. Health personnel considered it as a practical and safe tool in CRC surveillance.ConclusionMobile-CEA surveillance seems to be a promising and effective follow-up method for curatively treated patients with CRC. Further studies and experiences are needed.

183. Decrease in Invasive Pneumococcal Disease in 7 United States Children’s Hospitals during the COVID-19 Pandemic

BackgroundDuring the 2020 SARS-CoV-2 pandemic, physical distancing and mask use guidelines were implemented resulting in a decline in the number of infections caused by influenza, respiratory syncytial virus and otitis media. A surveillance analysis from England and Taiwan showed a decline in invasive pneumococcal disease (IPD) (Clin Infect Dis. 2021;72: e65-75 and J Infect. 2021;82:296-297). We hypothesized that COVID mitigation efforts resulted in a decrease in incidence of pediatric IPD within the U.S. during 2020 compared to previous years.MethodsWe reviewed all cases of IPD among 7 children’s hospitals from the U.S. Pediatric Multicenter Pneumococcal Surveillance Group from 2017-2020. IPD was defined by the isolation of Streptococcus pneumoniae from normally sterile sites (eg. blood, cerebrospinal, pleural, synovial or peritoneal fluid). Pneumococcal pneumonia was defined as an abnormal chest radiograph in the presence of a positive blood, pleural fluid or lung culture. Mastoiditis was identified by positive middle ear, subperiosteal abscess or mastoid bone culture. Serotypes were determined by the capsular swelling method. Hospital admission numbers were obtained for incidence calculations. Statistical analyses were performed using STATA11. A p< 0.05 was considered significant.ResultsA total of 410 IPD cases were identified. The cumulative incidence of IPD (0-22 years of age) decreased from 99.2/100,000 admissions in 2017-2019 to 53.8/100,000 admissions in 2020 (risk ratio 0.54, CI: 0.40-0.72, p< 0.00001). Pneumococcal bacteremia and pneumonia decreased significantly in 2020 (p< 0.05), and although not statistically significant, there were fewer cases of meningitis and mastoiditis when compared to previous years (p=0.08) (Figure 1). Sex, race, age or presence of comorbidities were not significantly different between groups. Most common serotypes in 2020 were 35B, 3 and 15B/C (Figure 2). ConclusionThe observed decline in IPD cases during the first year of the SARS-CoV-2 pandemic is likely associated with mask use and physical distancing limiting transmission of S. pneumoniae via droplets and viral infections frequently preceding IPD. These precautions might be useful in the future to decrease IPD, especially in high-risk patients.Disclosures Sheldon L. Kaplan, MD, Pfizer (Research Grant or Support) Tina Q. Tan, MD, GSK (Individual(s) Involved: Self): Advisor or Review Panel member, Grant/Research Support; ILiAD (Individual(s) Involved: Self): Advisor or Review Panel member; Merck (Individual(s) Involved: Self): Advisor or Review Panel member, Grant/Research Support; Moderna (Individual(s) Involved: Self): Advisor or Review Panel member; Pfizer (Individual(s) Involved: Self): Advisor or Review Panel member Pia S. Pannaraj, MD, MPH, Pfizer (Grant/Research Support)Sanofi-Pasteur (Advisor or Review Panel member)Seqirus (Advisor or Review Panel member) Larry Givner, MD, AstraZeneca (Advisor or Review Panel member) Kristina G. Hulten, PhD, Pfizer (Research Grant or Support)

Multiinstitutional Validation Study of Cyst Fluid Protein Biomarkers in Patients With Cystic Lesions of the Pancreas.

Prospective evaluation of 2 clinical-molecular models in patients with unknown pathology who underwent endoscopic ultrasound with fine-needle aspiration (EUS-FNA) for a cystic lesion of the pancreas. Preoperative prediction of histologic subtype (mucinous vs nonmucinous) and grade of dysplasia in patients with pancreatic cystic neoplasms is challenging. Our group has previously published 2 clinical-molecular nomograms for intraductal papillary mucinous neoplasms (IPMN) that incorporated both clinical/radiographic features and cyst fluid protein markers (sFASL, CA72-4, MMP9, IL-4). This multiinstitutional study enrolled patients who underwent EUS-FNA for a cystic lesion of the pancreas. Treatment recommendations regarding resection were based on standard clinical, radiographic, and endoscopic features. Predicted probabilities of high-risk IPMN (high-grade dysplasia/invasive cancer) were calculated using the previously developed clinical-molecular nomograms. Cyst fluid was obtained from 100 patients who underwent diagnostic EUS-FNA. Within this group there were 35 patients who underwent resection, and 65 were monitored radiographically. Within the group that underwent resection, 26 had low-risk IPMN or benign non-IPMN lesions, and 9 had high-risk IPMN. Within the surveillance group, no patient progressed to resection or developed cancer after a median follow-up of 12months (range: 0.5-38). Using the clinical/radiographic nomogram alone, 2 out of 9 patients with high-risk IPMN had a predicted probability >0.5. In the clinical-molecular models, 6 of 9 patients in model 1, and 6 of 9 in model 2, had scores >0.5. This prospective study of patients with unknown cyst pathology further demonstrates the importance of cyst fluid protein analysis in the preoperative identification of patients with high-risk IPMN. Longer follow-up is necessary to determine if this model will be useful in clinical practice.

Any Postoperative Surveillance Improves Survival after Endovascular Repair of Ruptured Abdominal Aortic Aneurysms

Endovascular aortic repair (EVAR) has advanced the care of patients with ruptured abdominal aortic aneurysms (rAAA) with improved early postoperative morbidity and mortality. However, this comes at the cost of a rigorous postoperative surveillance schedule to monitor for further aneurysmal degeneration. Adherence to surveillance recommendations is known to be poor in the elective setting, but has yet to be studied in the ruptured population. The aim of this study is to investigate predictors of incomplete surveillance after EVAR for rAAA (rEVAR) and examine how adherence impacts outcomes. This was a retrospective case control study of patients undergoing rEVAR at a multiple hospital single healthcare center (2003-2020). Patients were excluded if they underwent open conversion during their index hospitalization or died within 60 days of surgery. Follow-up was broadly categorized as complete surveillance (60-day postoperative visit and annually thereafter) or incomplete surveillance, comprising both patients with less than recommended surveillance (minimal surveillance) and completely lost to follow-up (LTF). Any follow-up was defined as patients with complete or minimal surveillance. We investigated predictors of complete versus incomplete surveillance by multivariate logistic regression. Secondary outcomes included overall survival and cumulative incidence of reintervention controlling for the competing risk of mortality, generating hazard ratios (HR) and subdistribution hazard ratios (SHR). One-hundred and sixty patients (mean age 74 ± 10.1 years, 81.2% male) out of 673 total rAAA met study inclusion criteria. Complete surveillance was seen in 41.3% of our cohort, with the remainder with minimal surveillance (29.4%) or LTF (29.4%). Incomplete surveillance was associated with male sex (odds ratio [OR] 2.56; 95% CI 1.02-6.43), lack of a primary care provider (PCP; OR 0.20; 95% CI 0.04-0.99), and longer driving distance from home to treating hospital (OR 2.37; 95% CI 1.08-5.20). Survival was not different between complete and incomplete surveillance groups, however any follow-up conferred improved survival over LTF (HR 0.57; 95% CI 0.331-0.997; P=0.049). Reintervention was associated with incomplete surveillance (SHR 0.29; 95% CI 0.11-0.75), and discharge to a facility (SHR 0.25; 95% CI 0.067-0.94). Incomplete surveillance was observed in over 50% of patients who underwent rEVAR and was associated with male sex, lack of PCP, and longer driving distance. Any follow-up conferred a survival benefit, yet incomplete surveillance was associated with a lower risk of reintervention. Targeted strategies to prevent LTF, and less stringent, personalized follow-up plans that may confer similar survival benefit with better patient adherence should be investigated.

Post-exposure Lopinavir-Ritonavir Prophylaxis versus Surveillance for Individuals Exposed to SARS-CoV-2: The COPEP Pragmatic Open-Label, Cluster Randomized Trial.

BackgroundSince the beginning of the COVID-19 pandemic, no direct antiviral treatment is effective as post-exposure prophylaxis (PEP). Lopinavir/ritonavir (LPV/r) was repurposed as a potential PEP agent against COVID-19.MethodsWe conducted a pragmatic open-label, parallel, cluster-randomised superiority trial in four sites in Switzerland and Brazil between March 2020 to March 2021. Clusters were randomised to receive LPV/r PEP (400/100 mg) twice daily for 5 days or no PEP (surveillance). Exposure to SARS-CoV-2 was defined as a close contact of >15 minutes in <2 metres distance or having shared a closed space for ≥2 hours with a person with confirmed SARS-CoV-2 infection. The primary outcome is the occurrence of COVID-19 defined by a SARS-CoV-2 infection (positive oropharyngeal SARS-CoV-2 PCR and/or a seroconversion) and ≥1 compatible symptom within 21 days post-enrolment. ClinicalTrials.gov (Identifier: NCT04364022); Swiss National Clinical Trial Portal: SNCTP 000003732.FindingsOf 318 participants, 157 (49.4%) were women; median age was 39 (interquartile range, 28-50) years. A total of 209 (179 clusters) participants were randomised to LPV/r PEP and 109 (95 clusters) to surveillance. Baseline characteristics were similar, with the exception of baseline SARS-CoV-2 PCR positivity, which was 3-fold more frequent in the LPV/r arm (34/209 [16.3%] vs 6/109 [5.5%], respectively). During 21-day follow-up, 48/318 (15.1%) participants developed COVID-19: 35/209 (16.7%) in the LPV/r group and 13/109 (11.9%) in the surveillance group (unadjusted hazard ratio 1.44; 95% CI, 0.76-2.73). In the primary endpoint analysis, which was adjuted for baseline imbalance, the hazard ratio for developing COVID-19 in the LPV/r group vs surveillance was 0.60 (95% CI, 0.29-1.26; p =0.18).InterpretationThe role of LPV/r as PEP for COVID-19 remains unanswered. Although LPV/r over 5 days did not significantly reduce the incidence of COVID-19 in exposed individuals, we observed a change in the directionality of the effect in favour of LPV/r after adjusting for baseline imbalance. LPV/r for this indication merits further testing against SARS-CoV-2 in clinical trials.FundingSwiss National Science Foundation (project no.: 33IC30_166819) and the Private Foundation of Geneva University Hospitals (Edmond Rothschild (Suisse) SA, Union Bancaire Privée and the Fondation pour la recherche et le traitement médical).

Hemophilia Natural History Study (ATHN 7): Safety of Current Therapies for People with Hemophilia A or B

INTRODUCTION: The recent introduction of new therapies for people with hemophilia A and B (HA and HB) mandates careful monitoring of the safety of these treatments. The primary aim of ATHN 7: A Natural History Study of the Safety, Effectiveness, and Practice of Treatment for People with Hemophilia (NCT03619863) is to monitor the safety of current hemophilia therapies.METHODS: ATHN 7 is a longitudinal, prospective cohort study being conducted at 26 American Thrombosis and Hemostasis Network (ATHN)-affiliated sites. The study is approved by central and local institutional review boards. Any person with a diagnosis of congenital hemophilia A or B (factor VIII or IX activity < 50%) who receives care at a participating site is eligible for inclusion. Participants and/or a parent/guardian sign informed consent and assent prior to participation. Adverse events, including those events designated by the European Haemophilia Safety Surveillance group as well as other adverse events of special interest, are recorded and monitored. Demographic and clinical information are collected at baseline and at least quarterly through participant interview and medical record review. Descriptive statistics of medical history and demographic data as well as longitudinal data are used to characterize the study population.RESULTS: As of June 2021, a total of 391 participants had enrolled in ATHN 7. The median age of participants was 22.5 ± 17.8 years. Males represented 97.7% (382/391) of participants. Eighty-five percent (333/391) were not Hispanic. White participants comprised 82.6% (323/391) of the study population, while 7.9% (31/391) were Black/African American, 3.8% (15/391) were Asian, 1.8% (7/391) were of mixed race, and 3.8% (15/391) were of other or unknown race. The primary diagnosis of participants included 70.1% (274/391) with severe HA, 15.3% (60/391) with moderate HA, 7.2% (28/391) with mild HA, 4.1% (16/391) with severe HB, 2.0% (8/391) with moderate HB, and 1.0% (4/391) with mild HB. Nineteen percent (71/391) of participants had a documented history of an inhibitor at the time of enrollment with a mean peak inhibitor titer of 96.7 ± 214.3 Bethesda Units. Substitution therapy with a non-factor molecule was the primary medication for 43.4% (162/391) participants, while 4.3% (16/391) utilized a plasma-derived clotting factor concentrate, 28.4% (196/391) utilized a standard half-life, recombinant factor concentrate, 18.3% (126/391) utilized an extended half-life recombinant factor concentrate, 4.1% (28/391) utilized a bypassing agent, and 19.3% (133/391) utilized some other hemostatic agent. Continuous prophylaxis was the primary regimen for 79.1% (295/391) participants. The remaining 19.6% (73/391) of participants were on episodic therapy. Within the cohort of 391 participants, a total of 14 adverse events have been reported in 8 participants. No adverse events of special interest were reported. Redness or rash at injection site accounted for 64.2% (9/14) of the reported adverse events, all in participants receiving emicizumab. Two participants experienced bruising or bleeding while on emicizumab. Two participants on emicizumab were diagnosed with malignancy, neither found to be attributed to their therapy. One participant developed an allergic reaction to their standard half-life recombinant factor concentrate.DISCUSSION: Open to enrollment in January 2019, ATHN 7 has now collected 18 months of longitudinal safety data for therapies used to treat HA and HB in 391 participants, an addition of 12 months and 24 participants since our last report. As the study was designed to enhance representation of those utilizing substitution therapy, almost half of the participants were on emicizumab for prophylaxis of bleeding. Adverse events attributable to hemophilia therapy was limited to minor skin reactions. As previously reported, a single participant experienced delayed bleeding after closed head trauma (despite factor replacement and normal intracranial imaging at the time of the event), providing potentially important information on the risk of delayed bleeding from significant trauma in those receiving emicizumab. Over the coming year, participants in ATHN 7 will be transitioned to ATHN's new longitudinal natural history study, ATHN TRANSCENDS (NCT04398628). DisclosuresBuckner: Pfizer: Honoraria; Takeda: Honoraria; Bayer: Honoraria; Sanofi: Honoraria; Spark: Honoraria; Genetech: Honoraria; CSL Behring: Honoraria; Novo Nordisk: Honoraria; Tremeau Pharmaceuticals: Consultancy, Honoraria; BioMarin: Consultancy, Honoraria; uniQure: Consultancy, Honoraria; American Thrombosis: Membership on an entity's Board of Directors or advisory committees; Hemostasis Network: Membership on an entity's Board of Directors or advisory committees. Carpenter: Hemophilia and Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees; Kedrion Pharmaceuticals: Honoraria; Genentech: Honoraria; Novo Nordisk: Honoraria. Raffini: Genentech: Consultancy; CSL Behring: Consultancy; HEMA Biologics: Consultancy; XaTek: Consultancy; Bayer: Consultancy. Zia: Takeda: Consultancy; Hemophilia and Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees. Recht: Hema Biologics: Consultancy; Kedrion: Consultancy; Novo Nordisk: Consultancy; Octapharma: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; uniQure: Consultancy; Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment; Genentech: Consultancy; CSL Behring: Consultancy; Catalyst Biosciences: Consultancy.