BackgroundCOVID‐19 infection delays therapy and in‐person evaluation for oncology patients, but clinic clearance criteria are not clearly defined.MethodsWe conducted a retrospective review of oncology patients with COVID‐19 at a tertiary care center during the Delta and Omicron waves and compared clearance strategies.ResultsMedian clearance by two consecutive negative tests was 32.0 days (Interquartile Range [IQR] 22.0–42.5, n = 153) and was prolonged in hematologic malignancy versus solid tumors (35.0 days for hematologic malignancy, 27.5 days for solid tumors, p = 0.01) and in patients receiving B‐cell depletion versus other therapies. Median clearance by single negative test was reduced to 23.0 days (IQR 16.0–33.0), with recurrent positive rate 25.4% in hematologic malignancy versus 10.6% in solid tumors (p = 0.02). Clearance by a predefined waiting period required 41 days until an 80% negative rate.ConclusionsCOVID‐19 clearance remains prolonged in oncology patients. Single‐negative test clearance can balance delays in care with risk of infection in patients with solid tumors.

Background Clostridioides difficile infection (CDI) immune response is influenced by the innate and adaptive (humoral) immune systems. Our prior research found attenuated humoral responses to C. difficile in immunocompromised hosts (ICHs) with CDI. We sought to evaluate whether the innate immune response to CDI was influenced by ICH status. Methods We conducted a prospective study of hospitalized adults with CDI (acute diarrhea, positive C. difficile stool nucleic acid amplification testing (NAAT), and decision to treat), with and without immunosuppression and measured a panel of cytokines (G-CSF, IL-10, IL-15, IL-1β, IL-4, IL-6, IL-8, and TNF-α) in blood and stool at CDI diagnosis. Results were compared with measurements from a cohort of asymptomatic carrier patients (ASC) (NAAT positive, without diarrhea) with and without immunocompromise. Results 123 subjects (42 ICHs, 50 non-ICHs, 31 ASCs) were included. Median values for blood and stool cytokines were similar in ICH versus non-ICH CDI subjects. In blood, G-CSF, IL-10, IL-15, IL-6 and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P <0.05). In stool, IL-1β and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P <0.05). Stool concentrations of IL-1β demonstrated significant differences between the groups (median: ICHs 10.97 pg/mL, non-ICH: 9.71 pg/mL and ASC 0.56 pg/mL) (P<0.0001). Conclusions In this small exploratory analysis, ICH status did not significantly impact blood and fecal patterns of cytokines in humans at the diagnosis of CDI, suggesting that the innate immune response to C. difficile may be conserved in immunocompromised patients.

516 Background: Combined hepatocellular intrahepatic cholangiocarcinoma (HCC CC) is a rare tumor defined by pathologic characteristics of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Immunohistochemical (IHC) and genetic profiles (GP) are used for diagnosis and therapeutic decisions, however often mixed tumors are treated as ICC given the presumption this subtype dominates response. Recent studies challenged this practice by demonstrating improved response with immune oncology (IO) therapy. Methods: We identified nine patients with biopsy-proven mixed HCC CC between September 2013 and March 2022. We classified IHC as related to either HCC (HepPar1, Glypican3, CD10, Glutamine Synthetase, CEA, AFP, Arginase1) or ICC (CK19, CK7, CK20, CDX2, Mucicarmine, CA9, MOC31). GP results were classified as HCC-related (TERT, CTNNB1, MYC) or ICC-related (ARID1A, FGFR2, IDH1). Treatment selection, duration of response, and survival were recorded. Results: All subjects had a mix of IHC markers, although six had a preponderance of HCC-related IHC. GP information was available for seven patients, of whom six demonstrated mutations relating only to HCC, and one demonstrated mutations relating only to ICC. All sequenced tumors were MSS, and six of the seven were TMB low. Four subjects used only liver directed therapy for small intrahepatic tumors. Four subjects underwent systemic therapy, a mix of HCC and ICC regimens, three of whom used IO agents. Median survival was 12 months. Conclusions: HCC CC tumor profiling by IHC and GP was more closely aligned with HCC than ICC. However, the median survival for these patients was lower than expected for liver-restricted HCC, more congruent with an ICC phenotype. Although liver-directed therapy was used, the duration of response was shorter than expected for HCC, even in HCC-like tumors. For those receiving systemic therapy, most subjects did not achieve median response with any regimen. Although a previous case series showed good response to IO agents, in our cohort we did not see this effect. In this series, mixed HCC CC was more aggressive than HCC, with largely poor response to both liver directed and systemic therapy. We have insufficient information to correlate systemic treatment response relative to IHC or GP.[Table: see text]

42 Background: COVID-19 presents a particular challenge in oncology, as in-person visits and treatments can be delayed during infection and patients are at risk for prolonged viral shedding. Our center uses two consecutive negative PCR tests for patients to return to clinic. As vaccination rates increase, we questioned the need for this strategy vs a time-based clearance approach. Methods: We identified cancer patients who tested positive for COVID-19 from 10/1/2021 to 3/31/2022 at a single tertiary care center and performed chart review under an IRB-approved protocol. Subgroups were compared using the Welch’s t-test and Welch’s ANOVA for 2 or > 2 groups, respectively. Results: 169 patients were identified. 153 had documented clearance defined as two consecutive negative PCR tests. The mean clearance time was 35.7 days (95% CI 32.3-39.0). There was a trend toward longer clearance time in patients with hematologic vs solid tumors (39.6 vs 33.2, p =.06) and a significant increase in patients treated with B cell depletion (58.0) vs chemo/targeted therapy (35.7, p =.01) or immunotherapy (29.0, p =.004). No significant difference was found by vaccination status or between the Delta and Omicron waves. If defined as one negative test, mean clearance time was 25.9 days (95% CI 23.6-28.1), and there was a significant difference in patients with hematologic vs solid tumors and in those treated with B cell depletion vs other therapies. However, 16.0% (27/169) of patients had a subsequent positive test after a first negative result, with increased incidence in patients with hematologic malignancy (26.2%, 16/61) and stem cell/adoptive cell transplant (46.2%, 6/13). Conclusions: COVID-19 is a significant barrier to oncologic care, and clearance times remain longer than reported for the general population. In this single center study, clearance time was > 1 month and further increased in patients with hematologic malignancy or on B cell depleting therapy. While adjusting clearance criteria to a single negative test or specific timeframe may be an attractive option to reduce delays, a large proportion of patients may have further positive PCR testing.[Table: see text]