Citations

ObjectiveThe present study was undertaken to evaluate changes in knee magnetic resonance imaging (MRI) findings over the course of 18 months in subjects with osteoarthritic change and meniscal tear treated with arthroscopic partial meniscectomy (APM) or nonoperatively with physical therapy (PT).MethodsWe used 18‐month follow‐up data from the Meniscal Tear in Osteoarthritis Research Trial. MRI results were read with reference to the MRI Osteoarthritis Knee Score. We focused on 18‐month change in bone marrow lesions (BMLs), cartilage thickness, cartilage surface area, osteophyte size, effusion‐synovitis, and Hoffa‐synovitis. We used multinomial logistic regression to assess associations between MRI‐based changes in each feature and treatment type.ResultsA total of 351 subjects were randomized, and 225 had both baseline and 18‐month MRI results. In both treatment groups, patients experienced substantial changes in several MRI‐based markers. In 60% of the APM group, versus 33% of the PT group, cartilage surface area damage advanced in ≥2 subregions (adjusted odds ratio 4.2 [95% confidence interval 2.0–9.0). Patients who underwent APM also had greater advancement in scores for osteophytes and effusion‐synovitis. We did not find significant associations between treatment type and change in cartilage thickness, BMLs, or Hoffa‐synovitis.ConclusionThis cohort of patients with meniscal tear and osteoarthritis showed marked advancement in MRI‐based features over 18 months. Patients treated with APM showed more advancement in some features compared to those treated nonoperatively. The clinical relevance of these early findings is unknown and requires further study.

Level of Evidence : 5 Technical Efficacy : Stage 5 J. Magn. Reson. Imaging 2019.

627 Background: The SLI of the BEACON CRC phase 3 study assessed the safety and efficacy of the combination of the BRAF inhibitor encorafenib (ENCO) + MEK inhibitor binimetinib (BINI) + anti-EGFR antibody cetuximab (CETUX) in pts with BRAFV600E-mutant mCRC after 1 or 2 prior regimens. CEA and CA19-9 are tumor markers that are widely used to monitor the effectiveness of systemic therapies for mCRC; here we report on the association of CEA and CA19-9 changes while on treatment with clinical outcomes in pts from the SLI. Methods: Pts in the SLI received the triplet of ENCO 300 mg QD + BINI 45 mg BID + CETUX 400 mg/m2 (initial dose) then 250 mg/m2 QW in 28-day cycles. Pts were evaluated for safety, radiographic response, and change in tumor markers CEA and CA19-9. Results: 30 pts were treated. The triplet was generally well tolerated, and adverse events were consistent with known BRAF, MEK, and EGFR inhibitor toxicities. The rate of severe skin toxicities (grade 3/4) was lower than generally observed for CETUX in mCRC. Of the 29 pts with a BRAFV600E mutation, the median time on study treatment was 5.6 mo (range, 1.0–9.3 mo), and 22 (76%) remained on study treatment at the time of data cutoff. The confirmed overall response rate (ORR) was 41%, with 1 complete and 11 partial responses. In addition, 9 pts had prolonged stable disease (SD) up to 9.3 mo.CEA and CA19-9 were analyzed in 28 pts. CEA and CA19-9 decreased in 96% and 82% of these pts, respectively. Among 15 pts with treatment duration ≥5.6 mo, median/mean % decreases were 97%/79% for CEA and 92%/82% for CA19-9 in confirmed responders (n=6). Respective decreases in pts with prolonged SD (n=9) were similar: 84%/68% for CEA and 89%/68% for CA19-9. Updated safety, efficacy, and tumor marker results will be provided. Conclusions: ENCO + BINI + CETUX is generally well tolerated and has encouraging clinical activity in BRAFV 600E mCRC, with a confirmed ORR of 41%. In pts with study treatment duration ≥5.6 mo, the tumor markers CEA and CA19-9 decreased markedly and to the same degree in responders vs pts with prolonged SD, providing additional evidence of the meaningful clinical activity of this regimen. Clinical trial information: NCT02928224.

Abstract The recent pace, extent, and impact of paradigm-changing cancer prevention science has been remarkable. The American Association for Cancer Research (AACR) convened a 3-day summit, aligned with five research priorities: (i) Precancer Atlas (PCA). (ii) Cancer interception. (iii) Obesity-cancer linkage, a global epidemic of chronic low-grade inflammation. (iv) Implementation science. (v) Cancer disparities. Aligned with these priorities, AACR co-led the Lancet Commission to formally endorse and accelerate the NCI Cancer Moonshot program, facilitating new global collaborative efforts in cancer control. The expanding scope of creative impact is perhaps most startling—from NCI-funded built environments to AACR Team Science Awarded studies of Asian cancer genomes informing global primary prevention policies; cell-free epigenetic marks identifying incipient neoplastic site; practice-changing genomic subclasses in myeloproliferative neoplasia (including germline variant tightly linked to JAK2 V617F haplotype); universal germline genetic testing for pancreatic cancer; and repurposing drugs targeting immune- and stem-cell signals (e.g., IL-1β, PD-1, RANK-L) to cancer interception. Microbiota-driven IL-17 can induce stemness and transformation in pancreatic precursors (identifying another repurposing opportunity). Notable progress also includes hosting an obesity special conference (connecting epidemiologic and molecular perspectives to inform cancer research and prevention strategies), co-leading concerted national implementation efforts in HPV vaccination, and charting the future elimination of cancer disparities by integrating new science tools, discoveries and perspectives into community-engaged research, including targeted counter attacks on e-cigarette ad exploitation of children, Hispanics and Blacks. Following this summit, two unprecedented funding initiatives were catalyzed to drive cancer prevention research: the NCI Cancer Moonshot (e.g., PCA and disparities); and the AACR-Stand Up To Cancer bold “Cancer Interception” initiative.

Abstract Background Stenotrophomonas maltophilia is a hospital acquired infection that is associated with high morbidity and mortality. There has been a reported rise in S. maltophilia infections, presumed secondary to the increase in the population at risk. Methods We retrospectively reviewed all hospitalized adult patients in Mayo Clinic, MN with S. maltophilia bacteremia from January 2008 through January 2018. We analyzed patient population and described patients at risk, sources of infection, and changes in antimicrobial susceptibility profile. Results A total of 94 patients were analyzed, including 52 males, median age of 56 (46–65.75 IQR). The population included 60 infections in those with malignancies and 30 infections in transplant recipients. At presentation, 58 (61.7%) were febrile, while 54 (58.1%) presented with hemodynamic instability. Majority (70.2%) received broad-spectrum antimicrobials within 2 weeks of presentation. The most common source was catheter associated infection (n = 60), 15 cases were secondary to gastrointestinal, and 9 due to a pulmonary source. Almost half, 46 (48.9%) required ICU admission. Two patients were diagnosed with endocarditis. Most isolates, 61(64.9%), were resistant to ceftazidime, 2 (2.2%) resistant to TMP/SMX and 20 (21.5%) were resistant to levofloxacin. Exposure to a quinolone in the 30 days prior to presentation did not impact fluoroquinolone resistance. Five patients were exposed to Trimethoprim/Sulfamethoxazole (TMP/SMX) in the 30 days prior to presentation, which was associated with higher rate of TMP/SMX resistance compared with those without exposure (80% vs. 98.8%, P = 0.004). Treatment options commonly included combination therapy, and TMP/SMX was a primary agent used in the majority, 59 (62.8%). All-cause in-hospital mortality was 26.6%. All-cause mortality was lower for line associated infections (16.67%) vs. other sources (44.12%) with P = 0.0038. Conclusion S. maltophilia bacteremia should be considered in hospitalized patients with recent use of broad-spectrum antibiotics. Although TMP/SMX continues to have reliable activity, use of empiric ceftazidime pending susceptibility testing should be avoided as trend toward increasing resistance is noted. We noted a drop in TMP/SMX susceptibility in those with recent reported TMP/SMX use. Disclosures All authors: No reported disclosures.