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Background: The phase 3, randomised True North (TN) study demonstrated the efficacy and safety of ozanimod for up to 52 weeks in patients (pts) with moderately to severely active ulcerative colitis (UC). The ongoing TN open-label extension (OLE) aims to assess the long-term efficacy and safety of ozanimod in UC. This analysis evaluated the cumulative long-term safety of ozanimod in these studies, which included pts with up to ~3 years of treatment exposure. Method(s): In TN, pts were randomised to once-daily ozanimod 0.92 mg or placebo, or to open-label ozanimod for a 10-week induction period. Ozanimod clinical responders were rerandomised at Week 10 to ozanimod or placebo in the maintenance period through Week 52. TN pts were eligible to enrol in the OLE and receive ozanimod if they did not achieve clinical response at the end of induction (Week 10), lost response during maintenance, or completed maintenance at Week 52. This interim analysis of the TN OLE (data cutoff: 10 January 2022) included all pts who entered the OLE from TN (n=823). Safety was monitored from the first dose of ozanimod in TN and throughout the subsequent OLE. Exposureadjusted incidence rates per 100 patient-years (PY) were calculated. Result(s): The average age of TN OLE study participants was 41.7 years (+/-13.6), 41% were female, 62% had left-sided UC disease, and 35% had prior exposure to tumor necrosis factor inhibitors. Total PY exposure to ozanimod was 2219 years (mean [SD] exposure = 2.7 [1.6]). The most frequent treatment-emergent adverse events (TEAEs) reported through OLE Week 94 (up to 146 weeks of continuous treatment) are listed in the Table. Most TEAEs were nonserious;TEAEs leading to discontinuation were uncommon. Bradycardia was reported in 3 pts (0.4%;EAIR 0.1/100 PY;2 in TN and 1 in OLE;no pts were discontinued from treatment). Macular edema was reported in 2 (0.2%;EAIR 0.1/100 PY) pts. Reductions in ALC were common (470 [57.1%] had ALC < 500 cells/mm3), as previously described, but ALC reductions were not associated with the occurrence of TEAEs. Malignancies were uncommon (n=13 [1.6%];EAIR 0.6/100 PY), and included 6 basal cell carcinomas and 3 colorectal neoplasms. Two deaths were reported: 1 due to COVID-19 and 1 sudden death. Investigators deemed both to be unrelated to treatment. Ozanimod was not associated with an increased risk of ischemic heart disease or thromboembolic events. Conclusion(s): Long-term exposure to ozanimod for up to 3 years was well tolerated in pts with moderately to severely active UC. No new safety signals were observed with long-term ozanimod use in UC (2219 PY exposure). Safety findings are consistent with previous reports from the UC and multiple sclerosis development programs (>16,512 PY exposure). (Table Presented).
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Background: Colorectal cancer remains the fourth most common malignancy in Korea, and has been ranked as the third leading cause of cancer deaths in 2020. This study aims to describe the epidemiologic status of colorectal cancer in Korea, and provide basic data for effective primary and secondary prevention methods by summarizing risk factors and screening tools. Current Concepts: Although colorectal cancer incidence and mortality have decreased in recent years in Korea, it still poses a significant public health burden. From the early 1990s until the mid-2000s, the 5-year relative survival of patients with colorectal cancer in Korea continuously increased. This can be attributed to the successful introduction of the government-led screening program;development of improved surgical techniques, anticancer drugs, and adjuvant treatment;and advances medical resources and infrastructure along with economic growth. However, since the late 2000s, the improvement in survival has stagnated. The coronavirus disease 2019 outbreak has reduced hospital visits and screenings, which is assumed to cause delays in diagnosis, leading to a worse prognosis in the patients. To overcome these obstacles, it is essential to explore modifiable environmental risk factors and appropriate screening test methods in Korea. Discussion and Conclusion(s): Primary prevention through risk factor modification and secondary prevention using suitable screening programs can reduce the incidence and mortality rates of colorectal cancer.Copyright © Korean Medical Association.
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Background: Colorectal cancer remains the fourth most common malignancy in Korea, and has been ranked as the third leading cause of cancer deaths in 2020. This study aims to describe the epidemiologic status of colorectal cancer in Korea, and provide basic data for effective primary and secondary prevention methods by summarizing risk factors and screening tools. Current Concepts: Although colorectal cancer incidence and mortality have decreased in recent years in Korea, it still poses a significant public health burden. From the early 1990s until the mid-2000s, the 5-year relative survival of patients with colorectal cancer in Korea continuously increased. This can be attributed to the successful introduction of the government-led screening program;development of improved surgical techniques, anticancer drugs, and adjuvant treatment;and advances medical resources and infrastructure along with economic growth. However, since the late 2000s, the improvement in survival has stagnated. The coronavirus disease 2019 outbreak has reduced hospital visits and screenings, which is assumed to cause delays in diagnosis, leading to a worse prognosis in the patients. To overcome these obstacles, it is essential to explore modifiable environmental risk factors and appropriate screening test methods in Korea. Discussion and Conclusion: Primary prevention through risk factor modification and secondary prevention using suitable screening programs can reduce the incidence and mortality rates of colorectal cancer.
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Aim: Routine endoscopic services were significantly reduced in response to the COVID-19 pandemic. As a response, two-week- wait referral for patients with rectal bleeding suspicious of colorectal cancer, incorporated qFIT as a tool to identify patients that may require further investigation. This study aimed to analyse the accuracy and sensitivity of qFIT as a tool to identity malignant colorectal neoplasia. Correlations between qFIT, anatomical site of neoplasia and haemoglobin status (Hb) was similarly considered. Method(s): Participants were included if they had confirmed colorectal adenocarcinoma or adenoma detected via the two-week- wait referral system alongside a qFIT score. A qFIT score of >=10mg/g was interpreted as positive. Exclusion criteria included anal cancers, neuroendocrine cancers, small bowel tumours and participants without a qFIT level. Participants with polyps and confirmed rectal, sigmoid and/or colonic cancer were included. Haemoglobin level at diagnosis, colonoscopy report and histological outcomes were analysed. Result(s): 3664 patients were referred in on the two-week- wait pathway in 2020. Of these 372 (10%) were coded as having a gastrointestinal tumour or polyp cancer diagnosis. 119 (32%) of participants fulfilled the criteria to be amenable for review. Of these 10 (8.4%) participants only had a polyp, while 109 (91.6%) participants had colorectal adenocarincoma +/-polyps. A total of 12 (11%) participants with colorectal adenocarcinoma had a qFIT level of <=10mg/g, with 2 (16%) of these having concurrent anaemia. There was no demonstratable level of qFIT that correlated with right versus left sided colonic tumours. Conclusion(s): Symptomatic patients with a qFIT of >=10mg/g should undergo further investigation for malignant colorectal neoplasia. This study found that qFIT did not reliably predict the site of neoplasia. A qFIT of <=10mg/g was present in 11% of participants with colorectal adenocarcinomas and is therefore not a sensitive tool in excluding colorectal neoplasia.
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Background: Despite the growing popularity of teleoncology in the context of the COVID-19 pandemic, there is great concern about the quality and accuracy of clinical encounters as there is virtually no physical examination (PE) provided. Objectives: To evaluate the primary sites and clinical variables that could predict a higher frequency of abnormal PE findings and a consequent change in conduct, thus allowing the selection of patients who are possibly ineligible for remote care. Methods: Observational and prospective study, conducted at the oncology center of two public hospitals in Brazil. A multiple- choice form, developed by the researchers, was filled in to collect the clinical variables of the patients, data regarding the service, and oncological conduct determined at the end of the consultation. Results: 368 clinical evaluations of patients with cancer were included in the study, with breast, colorectal, and prostate tumors being the most frequent. The physical examination was normal or with alterations already seen in previous consultations in 87% of the cases while 13% had new changes in the PE. Among patients with new changes in the PE, cancer treatment was maintained in 59% of cases. Thus, PE led to a change in antineoplastic therapy in 12 cases (3% of all patients being 1% only because of the PE findings and 2% after completion of a complimentary examination). Statistical analysis showed a significant association between the altered PE and the following variables: primary site breast (n=27;21%;p<0.01), head and neck (n=7;26%;p<0, 01) and ovary (n=2;17%;p<0.01), presence of symptoms (n=31;21%;p<0.01), and treatment with palliative intent (n=23;19%;p<0.01). However, only the presence of symptoms showed a positive association with the altered PE and consequent treatment change (p<0.01). Conclusions: Telemedicine seems to be a safe modality in the vast majority of cases, given the large percentage of asymptomatic patients with no changes in the PE during face-to-face care. Regarding symptomatic patients, we suggest priority to in-person care. In those with EC IV tumors undergoing palliative treatment or with breast, head and neck, and ovarian cancer, we recommend evaluating case by case and considering face-to-face care.
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Background and Aims: The COVID-19 pandemic profoundly impacted clinical services globally, including colorectal cancer (CRC) testing such as fecal immunochemical test (FIT) screening and colonoscopy. We investigated the impact of the pandemic on FIT and colonoscopy utilization, and colorectal neoplasia detection in a large community-based population in the United States. Methods: We performed a retrospective cohort study of patients ages 18-89 years undergoing FIT screening or colonoscopy in 2019 and 2020 within Kaiser Permanente Northern California (KPNC), a large integrated healthcare organization. We calculated percentage changes in FIT kits mailed, FITs completed, positive FITs, colonoscopies performed overall and by indication, and colorectal neoplasia detection (advanced adenoma and CRC) in 2020 compared to 2019. Results: FIT kit mailings ceased in mid- March through April 2020 but rebounded thereafter leading to an 8.7% increase in total FIT kits mailed in 2020 compared to 2019. However, with the later mailing of FIT kits, there were 9.0% fewer FITs completed and 10.1% fewer positive tests in 2020 compared to 2019. Colonoscopy volumes nadired in April 2020, with a 79.4% reduction compared with April 2019, but recovered to near pre-pandemic monthly volumes in September through December 2020. However, overall, there was a 26.9% decline in colonoscopies performed in 2020 compared to 2019. Declines of 41.5%, 38,3%, 19.9%, and 20.0% were seen for screening, surveillance, diagnostic, and FIT positive colonoscopies, respectively, in 2020 compared to 2019. With the gradual recovery of colonoscopy volumes after the initial pandemic lockdown, by November and December 2020 the numbers of patients with advanced adenomas or CRC detected by colonoscopy were comparable to those same months in 2019. However, the total number of patients with advanced adenomas or CRC detected by colonoscopy declined by 26.9% and 8.7%, respectively, in 2020 compared to 2019. Conclusions: The COVID-19 pandemic led to fewer FIT screenings and colonoscopies performed in 2020 compared with 2019. However, after the lifting of regional lockdowns, FIT screenings exceeded, and colonoscopy volumes nearly reached numbers from those same months in 2019. Overall, the pandemic led to 27% and 9% reductions in advanced adenoma and CRC detection, respectively, in 2020 compared to 2019, validating concerns about the potential for stage progression for cancers that went undetected due to the pandemic. Strategies to identify high-risk patients for expedited colonoscopy procedure scheduling and resolve remaining colonoscopy procedure backlogs are needed to mitigate this risk.(Figure Presented)Figure 1. Number of FIT kits mailed, completed, and positive in 2019 and 2020(Figure Presented)Figure 2. Number of colonoscopies and advanced adenomas and colorectal cancers detected by colonoscopy in 2019 and 2020
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(Background) Endoscopic procedures are interventions that have been defined as carrying a high-risk of infection with COVID-19. Most endoscopy units restrict their activity based on pre-endoscopic diagnosis. (Objective) To determine the consequences of endoscopic restrictions as a result of the COVID-19 pandemic and their impact on digestive cancer diagnosis. (Design) A comparison of upper digestive endoscopies and colonoscopies with gastrointestinal cancers diagnosed between three endoscopic centers, two of which restricted their procedures and one that did not but performed the procedures under a strict protocol. (Setting) A retrospective analysis was performed collecting data between 15 March 2019 and 15 August 2020. Two-factor ANOVA and a Tukey's a posteriori test were used as statistical tests. (Main outcome measures) There was variation in gastrointestinal cancer diagnosis between 2019 and 2020, considering the endoscopic procedures performed each year. (Result) There was a significant decrease in the total endoscopic procedures performed between 2019 and 2020 (p < 0.001), the result of reduced testing at the two centers (p < 0.001) with pre-endoscopic restrictions, which was not compensated for by a slight increase in procedures at the center without restrictions (p = 0.139). Regarding the total cancers diagnosed, while a significant decrease was observed for the two centers with pre-endoscopic restrictions (p = 0.007), a significant increase was registered in the center that maintained its endoscopic productivity (p < 0.001). After 851 procedures (537 upper digestive endoscopies and 314 colonoscopies) there was no evidence of COVID-19 infection in the endoscopic staff. (Conclusion) Endoscopic restrictions based on preendoscopic diagnosis should be reassessed in consideration of local pandemic situations, and a balance should be sought between COVID-19 infection risk and the detrimental delay of potential cancer diagnosis.
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Background: Prevailing methods for patient recruitment in large prospective studies can be time consuming, expensive, and introduce selection bias against patients with low health literacy or reduced access to healthcare. Previous clinical trials have reported low recruitment of women, minorities, and individuals who face socioeconomic barriers;a concern which has been exacerbated by the COVID-19 pandemic. Here we describe a novel recruitment strategy that helps to address healthcare disparities. This study will support a pre-market approval application to the FDA for a multi-factor RNA-FIT assay for detection of colorectal neoplasia in average-risk individuals between the ages of 45-75. Methods: A decentralized clinical trial (CRC-PREVENT) was launched through a digital campaign (https://www.colonscreeningstudy.com/;NCT04739722) after the RNA-FIT test system entered design-lock. Online advertisements were published on multiple social media sites and engagement with materials directed patients to an online screener. Participants who completed the screener were considered eligible for enrollment if they met CRC-PREVENT inclusion/ exclusion criteria and were willing to complete all components of the clinical trial, including providing a stool sample prior to an optical colonoscopy. Results: After 3 months of active enrollment, 51,588 individuals have engaged with digital advertisements and completed pre-screener surveys to determine eligibility. In total, 35,280 individuals were deemed eligible based on survey response, and 13,294 eligible individuals also expressed interest in the CRC-PREVENT clinical trial. Of these individuals, 48% were female and 34% were over the age of 60 years old. Regarding race, interested individuals directly represented the intended use population: 17% were Black or African American, 2.7% were Asian, and 1.3% were Native Hawaiian, Pacific Islander, American Indian, or Alaskan Native. With respect to ethnicity, 8.4% identified as Hispanic or Latinx. The decentralized approach also permitted access to individuals with socioeconomic healthcare inequities: 27% had income under $29,999 and 14% were on Medicaid. Individuals were derived from all 48 continental United States, and of those who reported their residential location, approximately 3% were from rural areas. Conclusions: Use of a decentralized recruitment strategy permitted highly successful enrollment in the face of challenges associated with COVID-19. With respect to race, ethnicity, socioeconomic status, and geography, all metrics represented significantly more diverse populations than observed in traditional clinical studies. Decentralized enrollment mitigated selection bias, and will result in data more reflective of the intended use population.
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Background: The USPSTF recently recommended colorectal cancer (CRC) screening for adults aged 45 to 49 years in addition to those aged 50 to 75 years. This guideline update, which increases the number of screen-eligible individuals by∼19 million, is similar to the recommendation in 2018 by the American Cancer Society (ACS) and is based on the modeling studies that reflect rising CRC incidence rates in younger adults. Currently, only 67% of average-risk individuals over the age of 50 years are up-to-date on CRC screening, and adherence to screening is lower in younger individuals (e.g., 50-54 years). Despite the non-invasive nature of existing stool-based CRC tests, barriers remain to adoption, including a dislike for manipulating stool and a requirement for substantial navigational support. Blood tests may overcome these barriers through ease of sample collection and integration into routine blood work. Methods: Here we describe our prospective, multi-center registrational study for validating a blood-based multiomics test for average-risk CRC screening: PREEMPT CRC. Eligible participants include those aged 45-85 with no known history of CRC or colorectal adenomas who are undergoing CRC screening by colonoscopy. The target enrollment is 25,000 participants, and primary outcome measures are sensitivity for CRC and specificity for advanced colorectal neoplasia, which includes CRC and advanced adenomas. Secondary outcome measures include positive predictive value for CRC, negative predictive value for advanced colorectal neoplasia, and sensitivity for advanced adenomas. Novel recruitment methods have been implemented by combining traditional, site-based recruitment and virtual recruitment using an online web portal, coupled with mobile phlebotomy, to make participation broadly accessible, especially during the COVID19 pandemic. Participants have been enrolled from 40 states as of August 2021, and virtual recruitment has enabled widespread participation, potentially from any zip code in the continental US. To ensure adequate representation of the intended use population, community organizations, federally qualified health centers (FQHCs), and universities have been engaged to reach underserved and minority patient populations. The study was initiated in May 2020 and to our knowledge will be the largest prospective, multi-center registrational validation study of an averagerisk CRC screening test to date.