Similar Prognosis Research Articles

FDG uptake patterns in isolated and systemic cardiac sarcoidosis

AimsWe aimed to investigate the pre-treatment characteristics and treatment responses of isolated and systemic cardiac sarcoidosis (ICS and SCS) from FDG-PET/CT studies and to compare the prognoses of the two groups. MethodsFDG-PET/CT images taken before and after treatment of 31 ICS and 91 SCS patients were analyzed retrospectively. Treatment response and recurrence were determined from the course of FDG-PET/CT. Treatment response and the incidence of both recurrence and major adverse cardiac events (MACE) were assessed in 16 ICS and 35 SCS patients who had been treated for more than 2 years. ResultsA focal uptake pattern was more often observed than a focal-on-diffuse uptake pattern in both the ICS (74.2%) and SCS (63.7%) groups. Right ventricular involvement was significantly more frequent in SCS than ICS (44.0% vs. 9.6%, p < .001). SUVmax, cardiac metabolic volume (CMV), and cardiac metabolic activity (CMA) were significantly higher in SCS than ICS (SUVmax, 9.1 ± 4.1 vs. 4.8 ± 2.1; CMV, 118.0 ± 111.3 ml vs. 68.3 ± 94.7 ml; CMA, 541.6 ± 578.7 MBq vs. 265.1 ± 396.0 MBq, p < .001). Treatment responses in the two groups were similar, and complete resolution of cardiac uptake after immunosuppressive treatment was obtained in 62.5% of ICS patients and 77.1% of SCS patients (not significantly different). Likewise, no significant difference was found in the incidence of recurrence (40.0% for ICS, 44.4% for SCS) or MACE (25.0% for ICS, 22.8% for SCS). ConclusionSCS patients had more active and extensive CS lesions than ICS patients before treatment, but the two groups showed similar treatment responses and prognoses.

CLINICAL OUTCOMES BY PROGRESSION OF DISEASE WITHIN 24 MONTHS (POD24) IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) FOLLICULAR LYMPHOMA (FL) TREATED WITH LINPERLISIB

Introduction: Linperlisib, a PI3Kδ inhibitor, has shown clinically efficacy and manageable safety profile as third- or further-line treatment in patients with R/R FL from a multicenter phase 2 trial (NCT04370405). We aimed to perform a subgroup analysis to evaluate the impact of POD24, a well-established indicator of poor survival, on the efficacy of linperlisib. Methods: This phase 2 study was conducted at 25 sites in China between April 2019 and September 2020. Linperlisib 80 mg was given orally once daily until disease progression, intolerable toxicity or withdrawal from the study. Response was assessed by an independent review committee according to the International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017). The primary endpoint was objective response rate (ORR). Results: The POD24 group had a lower median age (49 vs. 53 years) and lower proportion of patients with at least three lines of prior therapies (73.8% vs. 87.0%) than the non-POD24 group. All patients in both groups had received prior anti-CD20 antibody and alkylating agent. The ORR (77.1%, 47/61) in the POD24 group was numerically lower than that (87.0%, 20/23) in the non-POD24 group, but without statistical significance (p = 0.314). Both groups showed similar progression-free survival (13.7 months vs. 11.5 months). The most common grade ≥3 treatment-related adverse events were infectious pneumonia (19.7%), decreased neutrophil count (14.8%), and interstitial lung disease (4.9%) in the POD24 group, and decreased neutrophil count (17.4%) and infectious pneumonia (17.4%) in the non-POD24 group (Table). Conclusions: For R/R FL, patients with POD24 could also benefit from subsequent linperlisib treatment, with similar prognosis to those without POD24. Linperlisib could be an appropriate option for this difficult-to-treat population. The research was funded by: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2022-I2M-1-022) and Shanghai Yingli Pharmaceutical Co., Ltd. Keyword: molecular targeted therapies No conflicts of interests pertinent to the abstract.

Clinicopathological Characteristics and Prognosis of Mucinous Gastric Cancer.

Mucinous gastric carcinoma (MGC) has a poor prognosis. Due to the differences in clinicopathology factors between MGC and non-MGC (NMGC), it is difficult to compare them. In this study, we compared the clinicopathological characteristics and prognosis of MGC and NMGC patients. For gastric carcinoma (GC), 3,042 gastrectomy patients were included in the study and divided into the MGC (n=86) and NMGC (n=2,956) groups. The characteristics and prognoses of patients in both groups were compared before and after (both groups, n=86) propensity score matching. Significant differences were observed in the tumor location (upper) (MGC group: 28.0% vs. NMGC group: 24.7%, p=0.003), tumor diameter (median) [65 mm (8-200 mm) vs. 40 mm (2-75 mm), p<0.001], lymph node metastasis (70.9% vs. 37.3%, p<0.001), venous invasion (57.0% vs. 40.4%, p<0.001), and lymphatic invasion (62.8% vs. 34.9%, p<0.001) before propensity score matching. The 5-year overall survival (OS) (70.9% vs. 76.2%, p=0.006) and cancer-specific survival (CSS) (75.5% vs. 82.4%, p=0.014) rates were significantly lower in the MGC group. After propensity score matching, there were no significant differences in either the 5-year OS (70.9% vs. 73.7%, p=0.230) or CSS (75.5% vs. 75.7%, p=0.587) rates. In addition, no substantial difference was observed in either of the recurrence forms. MGC is rare and usually diagnosed at a more advanced stage. However, MGC and NMGC have similar prognoses.

Analysis of risk factors for postoperative mortality in acute type A aortic dissection patients under different critical levels

We built up a risk stratification model to divide acute type A aortic dissection (aTAAD) patients into low- and high-risk groups, further, to evaluate the risk factors for postoperative mortality. A total of 1364 patients from 2010 to 2020 in our center were retrospectively analyzed. More than twenty clinical variables were related with postoperative mortality. The postoperative mortality of the high-risk patients was doubled than the low-risk ones (21.8% vs 10.1%). The increased operation time, combined coronary artery bypass graft, cerebral complications, re-intubation, continuous renal replacement therapy and surgical infection were risk factors of postoperative mortality in low-risk patients. In addition, postoperative lower limbs or visceral malperfusion were risk factors, axillary artery cannulation and moderate hypothermia were protective factors in high-risk patients. A scoring system for quick decision-making is needed to select appropriate surgical strategy in aTAAD patients. For low-risk patients, different surgical treatments can be performed with similar clinical prognosis. Limited arch treatment and appropriate cannulation approach are crucial in high-risk aTAAD patients.

Evaluation of a New Aptamer-Based Array for Soluble Suppressor of Tumorgenicity (ST2) and N-terminal Pro-B-Type Natriuretic Peptide (NTproBNP) in Heart Failure Patients.

Recent advances in multi-marker platforms offer faster data generation, but the fidelity of these methods compared to the ELISA is not established. We tested the correlation and predictive performance of SOMAscan vs. ELISA methods for NTproBNP and ST2. Patients ≥ 18years with heart failure and ejection fraction < 50% were enrolled. We tested the correlation between SOMA and ELISA for each biomarker and their association with outcomes. There was good correlation of SOMA vs. ELISA for ST2 (ρ = 0.71) and excellent correlation for NTproBNP (ρ = 0.94). The two versions of both markers were not significantly different regarding survival association. The two ST2 assays and NTproBNP assays were similarly associated with all-cause mortality and cardiovascular mortality. These associations remained statistically significant when adjusted for MAGGIC risk score (all p < 0.05). SOMAscan quantifications of ST2 and NTproBNP correlate to ELISA versions and carry similar prognosis.

Public voices on tie-breaking criteria and underlying values in COVID-19 triage protocols to access critical care: a scoping review

BackgroundTo reduce the arbitrariness in the allocation of rare resources in intensive care units (ICU) in the context of the pandemic, tiebreakers were considered in some COVID-19 triage algorithms. They were also contemplated to facilitate the tragic decisions of healthcare workers when faced with two patients with similar prognosis and only one ICU bed available. Little is known about the public's perspective on tiebreakers.ObjectivesTo consolidate the available scientific literature on public consultations, particularly on tiebreakers and their underlying values. Also, to obtain an overview of the key arguments presented by the participating public and to identify potential gaps related to this topic.MethodsThe steps described by Arksey and O’Malley was the preferred method to our approach. Seven electronic databases were searched from January 2020 to April 2022, using keywords for each database: PubMed, Medline, EMBASE, Web of Science, PsycINFO, EBM reviews, CINAHL complete. We also searched in Google and Google Scholar, and in the references of the articles found. Our analysis was mainly qualitative. A thematic analysis was performed to consider the public’s perspectives on tiebreakers and their underlying values, according to these studies.ResultsOf 477 publications found, 20 were selected. They carried out public consultations through various methods: surveys (80%), interviews (20%), deliberative processes (15%) and others (5%) in various countries: Australia, Brazil, Canada, China, France, Germany, India, Iran, Italy, Japan, Korea, Netherlands, Portugal, Spain, Switzerland, Thailand, United Kingdom, and United States. Five themes emerged from our analysis. The public favored the life cycle (50%) and absolute age (45%) as a tiebreaker. Other values considered important were reciprocity, solidarity, equality, instrumental value, patient merit, efficiency, and stewardship. Among the new findings were a preference for patient nationality and those affected by COVID-19.ConclusionsThere is a preference for favoring younger patients over older patients when there is a tie between similar patients, with a slight tendency to favor intergenerational equity. Variability was found in the public’s perspectives on tiebreakers and their values. This variability was related to socio-cultural and religious factors. More studies are needed to understand the public's perspective on tiebreakers.

Why Is End-of-Life Spending So High? Evidence from Cancer Patients

Abstract We study the sources of high end-of-life spending for cancer patients. Even among patients with similar initial prognoses, spending in the year postdiagnosis is over twice as high for those who die within the year than those who survive. Elevated spending on decedents is predominantly driven by higher inpatient spending, particularly low-intensity admissions. However, most such admissions do not result in death, making it difficult to target spending reductions. Furthermore, end-of-life spending is substantially more elevated for younger patients, compared to older patients with similar prognoses. Results highlight sources of high end-of-life spending without revealing any natural “remedies.”

Impact of Resolved Preformed, Persistent Preformed, and De Novo Anti-HLA Donor-Specific Antibodies in Kidney Transplant Recipients on Long-Term Renal Graft Outcomes.

The post-transplant evolution of antihuman leukocyte antigen donor-specific antibodies (anti-HLA DSAs) includes three clinical patterns: resolved preformed DSAs, persistent preformed DSAs, and de novo DSAs. The aim of this retrospective study was to analyze the impact of resolved preformed, persistent preformed, and de novo anti-HLA-A, -B, and -DR DSAs in kidney transplant recipients on long-term renal allograft outcomes. This is a post hoc analysis of the study conducted in our transplant center. One hundred eight kidney transplant recipients were included in the study. Patients were followed for a minimum of 24 months after allograft biopsy, which was performed 3 to 24 months after kidney transplantation. The identification of persistent preformed DSAs at the time of biopsy was the most significant predictor of the combined endpoint of the study (>30% decline in estimated glomerular filtration rate or death-censored graft loss; HR = 5.96, 95% CI 2.041-17.431, p = 0.0011), followed by the occurrence of de novo DSAs (HR = 4.48, 95% CI 1.483-13.520, p = 0.0079). No increased risk was observed in patients with resolved preformed DSAs (HR = 1.10, 95% CI 0.139-8.676, p = 0.9305). Patients with resolved preformed DSAs have similar graft prognoses as patients without DSAs, therefore, the persistence of preformed DSAs and development of de novo DSAs are associated with inferior long-term allograft outcomes.

LEFT CA MAMMAE WITH FEBRILE NEUTROPENIA : A CASE REPORT

Introduction: Breast cancer is the most common cancer diagnosed, especially in women, accounting for more than 1 in 10 new cancer diagnoses each year. Physical examination, imaging and biopsy must be done to diagnose breast cancer.1,2 Staging is performed to define prognosis and guide treatment recommendations for patients with a similar prognosis. Chemotherapy, hormone therapy, and targeted therapy are the systemic therapies used in breast cancer management. The therapies option are has an side effect, especially chemotherapy. Chemotherapy induced neutropenia is a common toxicity caused by the administration of anticancer drugs. This side effect are life-threatening infections and alter the chemotherapy schedule.&#x0D; Case presentation: A female 50-years-old patient with left breast cancer on chemotherapy. She already has 3 times chemotherapy session and now had a fever with leucocyte result is 520 mg/dl and neutrophilia is 1.9 mg/dl. The patient has a history of painless lump in left breast since 11 months ago and growing proggresive. From physical examination, the lump with an ulcer with size 6x7x3cms and palpable hard consistency lump size is 8x8x5cms with irreguler edges and immobile. Patient had a biopsy examination with result invasive carcinoma ; high grade. From chest xray and USG Abdomen no finding sign of metastatic. Patient had an neo adjuvant chemotherapy&#x0D; Conclusion: Breast cancer is cancer of the breast tissue. Risk factors for breast cancer are divided into two, namely risk factors that cannot be changed (gender, age, genetic factors, previous cancer history, race and ethnicity, menstrual history and history of chest radiation) and those that can be changed (history of contraception, history of pregnancy, hormone therapy after menopause, breastfeeding, alcohol consumption, and obesity). Therapy for breast cancer is divided into five, namely surgical therapy, radiotherapy, chemotherapy, biologic therapy, and hormonal therapy. The goal of breast cancer therapy is to increase the survival rate and quality of life of patients.

Laparoscopic versus open surgery for gallbladder carcinoma: safety, feasibility, and oncological outcomes

BackgroundGallbladder carcinoma (GC) is a rare malignant tumor. Laparoscopic technology has revolutionized the reality of surgery. However, whether laparoscopic surgery is suitable for GC has not been clarified. We aimed to analyze the safety, feasibility, and oncological outcomes of laparoscopic surgery in GC.MethodsThe medical records of patients with GC treated at our hospital between January 2016 and December 2021 were retrospectively reviewed. Patients who underwent laparoscopic and open surgery were compared. Propensity score matched analysis was performed to balance the basic characteristics of the two groups. Kaplan–Meier curves were used to describe and compare the overall and disease-free survival rates between the groups.ResultsA total of 163 patients with GC were included. Cholelithiasis was detected in 64 (39.3%) patients. Seventy patients were matched after propensity score matching. The laparoscopic group was significantly better than the open group in terms of operation time (p < 0.001), blood loss (p = 0.002), drain time (p = 0.001), and hospital stay (p < 0.001). After a median follow-up time of 19 (12, 35) months, there was no significant difference in the cumulative overall (p = 0.650) and disease-free (p = 0.663) survival rates between the laparoscopic and open groups according to Kaplan–Meier curves.ConclusionLaparoscopic surgery can reduce the operation time and blood loss, and shorten drain time and hospital stay without increasing the incidence of complications. Patients undergoing laparoscopic and open surgery have a similar prognosis. Laparoscopic surgery is worth promoting in patients with GC.

Nationwide experience with transcarotid transcatheter aortic valve implantation: Insights from the POL-CAROTID registry.

The carotid artery is an alternative access route for transcatheter aortic valve implantation (TAVI), especially useful in patients unsuitable for traditional access routes including transfemoral (TF), subclavian, transapical, and aortic. To investigate the feasibility and safety of transcarotid (TC) access for TAVI in comparison to the TF approach in a multicenter setting. A total of 41 patients, treated between December 2014 and December 2018, were retrospectively reported to the Polish Registry of Common Carotid Artery Access for TAVI (POL-CAROTID). The median follow-up time was 619 (365-944) days, and Valve Academic Research Consortium-2 (VARC-2) definitions were applied. Clinical outcomes were compared with 41 propensity-matched TF-TAVI patients. The mean (standard deviation [SD]) patients' age was 78.0 (7.2) years, and 29 patients (70.7%) were men. Prohibitive iliofemoral anatomy and/or obesity (46.3%) and/or the presence of a stent graft in the abdominal aorta (31.7%) were the most common indications for TC-TAVI. Device success for TC-TAVI was comparable with the matched TF-TAVI group (90.2% vs. 95.3%, respectively, P = 0.396), and no periprocedural mortality was observed. Moreover, early safety was similar between the two groups (92.7% vs. 95.3%, respectively, log-rank P = 0.658) with only 1 case of non-disabling stroke during the first month after TC-TAVI. Consequently, no cerebrovascular events were observed in the mid-term, and the clinical efficacy of TC-TAVI corresponded well with TF-TAVI (90.2% vs. 92.7%, respectively, log-rank P = 0.716). A total of 4 (9.8%) deaths were noted in the TC-TAVI cohort in comparison to 3 (7.3%) in the TF-TAVI group. The results of the study indicated that the first cohort of Polish patients with implantations of second-generation transcarotid transcatheter heart valves had a similar prognosis to TF-TAVI with regard to safety and feasibility. TC access may be considered an optimal alternative for patients in whom the TF approach is precluded.

Echocardiographic findings in cardiogenic shock due to acute myocardial infarction versus heart failure

BackgroundAcute myocardial infarction (AMI) is the prototypical cause of cardiogenic shock (CS), yet CS due to heart failure (HF-CS) is increasingly common. Little is known regarding cardiac function in AMI-CS versus HF-CS. We compared transthoracic echocardiography (TTE) findings in AMI-CS versus HF-CS and identified predictors of mortality in AMI-CS patients. MethodsWe performed a single-center, retrospective analysis of CS admissions between 2007 and 2018. We compared baseline demographic and TTE parameters in patients with AMI-CS and HF-CS as well as ST elevation myocardial infarction (STEMI)-CS versus non-ST elevation myocardial infarction (NSTEMI)-CS. ResultsWe included 893 unique patients, including 581 (65%) with AMI-CS. AMI-CS patients were older but had lower illness severity and non-cardiac comorbidity burden. AMI-CS patients had better left ventricular function (LVEF 35% versus 28%), lower biventricular filling pressures, and higher stroke volume versus those with HF-CS. Among TTE measurements, myocardial contraction fraction had the highest discrimination for mortality in AMI-CS (AUC: 0.64); AUC values for LVEF and SOFA score were 0.61 and 0.65, respectively. Differences in TTE findings between STEMI-CS versus NSTEMI-CS were modest. There were no significant differences in unadjusted or adjusted in-hospital mortality between AMI-CS and HF-CS (31% versus 35%) or STEMI-CS and NSTEMI-CS (31% versus 30%) groups (all p > 0.05). ConclusionsPatients with HF-CS and AMI-CS differ in terms of clinical and TTE variables yet have similar prognoses. TTE is useful in determining prognosis of patients admitted with AMI-CS and may allow for early triage and directed therapy.

Sublobar resection versus lobectomy in the treatment of synchronous multiple primary lung cancer

ObjectiveAlthough synchronous multiple primary lung cancers (sMPLCs) are common in clinical practice, the choice of surgical modalities for the main lesion is still at the stage of exploration. This study is designed to analyze the prognosis of sMPLCs and single primary lung cancers with similar tumor stages and to explore whether sublobar resection has a similar prognosis as lobectomy for sMPLCs.MethodsOne-hundred forty-one cases of sMPLCs were selected, including the following: 65 cases underwent lobectomy for main lesions, and 76 cases underwent sublobar resection for main lesions. One thousand one hundred forty-four cases of single primary lung cancer were matched at 1:1 by propensity score matching. Then, the patients with sMPLCs were divided into a lobectomy group and a sublobar group according to the first tumor stage. Ninety-eight cases of patients with sMPLCs were matched. The short-term perioperative effect, 5-year disease-free survival (DFS) rate, and 5-year overall survival (OS) rate between the two groups were compared.ResultsThere was no significant difference in OS between sMPLCs and single primary lung cancer after lobectomy (77.1% vs. 77.2%, P = 0.157) and sublobar resection (98.7% vs. 90.7%, P = 0.309). There was no significant difference in OS (86.7% vs. 83.9%, P = 0.482) or DFS (67.6 vs. 87.7%, P = 0.324) between the lobectomy group and sublobar group with sMPLCs. The sublobar resection group obtained a lower incidence of postoperative complications (40.8% vs. 16.3%, P = 0.007) and shorter postoperative hospital stay (11.22 vs. 9.27, P = 0.049).ConclusionThe prognosis of patients with sMPLCs generally depends on the main tumor state, which has no statistical difference regardless of sublobar resection or lobectomy, and the perioperative period of sublobar resection is safer than that of lobectomy.

Metabolic syndrome is associated with similar long-term prognosis in those living with and without obesity: an analysis of 45 615 patients from the nationwide LIPIDOGRAM 2004-2015 studies.

We aimed to evaluate the association between metabolic syndrome (MetS) and long-term all-cause mortality. The LIPIDOGRAM studies were carried out in the primary care in Poland in 2004, 2006, and 2015. MetS was diagnosed based on the National Cholesterol Education Program, Adult Treatment Panel III (NCEP/ATP III), and Joint Interim Statement (JIS) criteria. The cohort was divided into four groups: non-obese patients without MetS, obese patients without MetS, non-obese patients with MetS, and obese patients with MetS. Differences in all-cause mortality were analysed using Kaplan-Meier and Cox regression analyses. A total of 45 615 participants were enrolled (mean age 56.3, standard deviation: 11.8 years; 61.7% female). MetS was diagnosed in 14 202 (31%) by NCEP/ATP III criteria and 17 216 (37.7%) by JIS criteria. Follow-up was available for 44 620 (97.8%, median duration 15.3 years) patients. MetS was associated with increased mortality risk among the obese {hazard ratio, HR: 1.88 [95% confidence interval (CI) 1.79-1.99] and HR: 1.93 [95% CI 1.82-2.04], according to NCEP/ATP III and JIS criteria, respectively} and non-obese individuals [HR: 2.11 (95% CI 1.85-2.40) and 1.7 (95% CI 1.56-1.85) according to NCEP/ATP III and JIS criteria, respectively]. Obese patients without MetS had a higher mortality risk than non-obese patients without MetS [HR: 1.16 (95% CI 1.10-1.23) and HR: 1.22 (95% CI 1.15-1.30), respectively in subgroups with NCEP/ATP III and JIS criteria applied]. MetS is associated with increased all-cause mortality risk in non-obese and obese patients. In patients without MetS, obesity remains significantly associated with mortality. The concept of metabolically healthy obesity should be revised.

The prognostic nomogram for PSA-incongruent low-risk prostate cancer treated by radical prostatectomy.

To establish a prognostic nomogram for PSA-incongruent low-risk prostate cancer (PCa) patients (Gleason score 6 and clinical stage T2a) at diagnosis and treated with radical prostatectomy (RP), based on clinical and pathological metrics. In total, 217 patients diagnosed with PCa were included in this study. All patients had a Gleason score of 6 (GS6) in biopsy, had clinical T2a before surgery and were treated with RP. Biochemical progression-free survival (bPFS) was analyzed using the Kaplan-Meier method. Univariate and multivariate analyses were used to determine prognostic factors related to bPFS. A prognostic nomogram was established based on factors that were significant in the multivariate analyses. The median bPFS had a significant difference in the subgroup of PSA at diagnosis (' < 10ng/mL': 71.698 [67.549-75.847] vs '10-20ng/mL': 71.038 [66.220-75.857] vs ' ≥ 20ng/mL': 26.746 [12.384-41.108] months [Log Rank P < 0.001]), the subgroup of T stage upgrade (Negative: 70.016 [65.846-74.187] vs 'T2b/c': 69.183 [63.544-74.822] vs 'T3/4': 32.235 [11.877-52.593] months [Log Rank P < 0.001]) and the subgroup of Gleason score upgrade (Negative: 72.63 [69.096-76.163] vs '3 + 4': 68.393 [62.243-74.543] vs '4 + 3': 41.427 [27.517-55.336] vs ' ≥ 8': 28.291 [7.527-49.055] [Log Rank P < 0.001]). PSA at diagnoses (Hazard Ratio (HR) 1.027, 95% CI 1.015-1.039, P < 0.001), T stage upgrade (HR 2.116, 95% CI 1.083-4.133, P = 0.028), and Gleason score upgrade (HR 2.831, 95% CI 1.892-4.237, P < 0.001) were identified as independent predictors with significance in multivariable Cox regression analysis. A nomogram was established based on these three factors. Our study indicated that PSA-incongruent low-risk PCa patients (PSA with 10-20ng/mL) had a similar prognosis to those with real low-risk PCa (PSA < 10ng/mL) in the D' Amico criteria. We also established a nomogram based on three significant prognostic factors, including PSA at diagnosis, T stage upgrade, and Gleason score upgrade, which were associated with clinical outcomes in prostate cancer patients with GS6 and T2a after surgery.

Abstract 924: The prognostic impact of the KRAS G12C-mutation in non-small cell lung cancer (NSCLC): a real-world analysis

Abstract Background: KRAS mutations occur in ~30% of NSCLC; KRAS G12C is the most common subtype (~40%). Limited data exist on the prognostic impact of KRAS G12C in NSCLC. Methods: This retrospective study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine Clinico-Genomic Database (FH-FMI CGDB; January 1, 2011-March 31, 2022). De-identified data originated from ~280 US cancer clinics (~800 sites of care). Patients (pts) were aged ≥18 years; had advanced (adv)/metastatic NSCLC; and had received 1L treatment (tx) initiated on or after October 1, 2016. Pts with EGFR, ALK, ROS1, BRAF, MET, or NTRK alterations were excluded. Key endpoints were overall survival (OS) and real-world progression-free survival (rwPFS). Propensity score matching and a multivariate Cox hazard model were used. Results: Analyses included pts with KRAS G12C (n=847) and KRAS wild-type (WT; n=2679) NSCLC. In comparison to WT, pts with KRAS G12C were more likely to be female (56% vs 40%), former/current smokers (97% vs 93%), have non-squamous disease (91% vs 52%), have Stage IV disease at initial diagnosis (64% vs 56%), have brain metastases (22% vs 16%), have low (&amp;lt;10 mut/Mb) tumor mutational burden (59% vs 51%), and have high (≥50%) PD-L1 expression (43% vs 23%). Overall, 39% of KRAS G12C, and 33% of WT received chemo (CT) + immunotherapy (IO) as 1L tx. More pts with KRAS G12C vs WT did not receive 2L tx (61% vs 54%). No significant differences were seen in rwPFS and OS between KRAS G12C and WT (Table 1). In pts receiving 1L CT + IO (n=1218), pts with KRAS G12C had shorter rwPFS compared with pts with WT (adjusted hazard ratio: 1.22; p=0.04). In pts with KEAP1 or STK11 mutations, co-mutation with KRAS G12C was associated with shorter OS. Conclusions: Pts with KRAS G12C and WT had similar overall prognosis; however, those with KRAS G12C had worse rwPFS with CT + IO tx, as opposed to a trend in the opposite direction for pts treated with IO mono. KRAS G12C imposed worse prognosis vs WT in pts with STK11 or KEAP1 mutations. Table 1. OS and rwPFS in the overall population and subgroups PSM-based comparisona KRAS G12C KRAS WT OS N 847b 1318b Median, months (95% Cl) 11.8 (10.2-14.1) 12.5 (11.6-14.0) HR (95% CI); p value 1.05 (0.91-1.21); 0.47 rwPFS N 846b,c 1317b,c Median, months (95% Cl) 5.5 (4.9-6.2) 5.6 (5.2-5.9) HR (95% CI); p value 1.06 (0.94-1.20); 0.33 Multivariate Cox proportional hazard modela Multivariate HRd (95% CI), KRAS G12C vs KRAS WT; p value OS All pts (N=3526) 1.05 (0.92-1.10); 0.47 KEAP1 mutation (n=506) 1.64 (1.17-2.00); &amp;lt;0.01 STK11 mutation (n=523) 1.38 (1.02-1.86); 0.04 IO monotherapy in 1L (n=752) 0.86 (0.64-1.15); 0.32 CT + IO in 1L (n=1218) 1.15 (0.92-1.44); 0.22 rwPFS All pts (N=3526) 1.06 (0.94-1.20); 0.35 KEAP1 mutation (n=506) 1.51 (1.11-2.05); &amp;lt;0.01 STK11 mutation (n=523) 1.25 (0.97-1.61); 0.09 IO monotherapy in 1L (n=752) 0.91 (0.71-1.17); 0.46 CT + IO in 1L (n=1218) 1.22 (1.01-1.49); 0.04 aRisk factors included in PSM and the multivariate Cox model: age, gender, race, ECOG performance status, smoking status, histology, stage at initial diagnosis, presence of brain metastases, PD-L1 expression category, and 1L treatment; bAll pts in KRAS G12C and WT populations in PSM (1 to up to 2 match); cAll patients with atleast 1 progression assessment; dMultivariate Cox model HR was based on complete case analyses, i.e., pts with non-missing data. CI, confidence interval; HR, hazard ratio; PSM, propensity score matching. Citation Format: Lova Sun, Julia Kim, Shetal A. Patel, Yehrim Kang, Vincent Pretre, Nydia Caro, Stefanie Knoll, Rafael Caparica, Fen Ye, Karen L. Reckamp. The prognostic impact of the KRAS G12C-mutation in non-small cell lung cancer (NSCLC): a real-world analysis [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 924.

Constructing metabolism-protein interaction relationship to identify glioma prognosis using deep learning

Glioma is heterogeneous disease that requires classification into subtypes with similar clinical phenotypes, prognosis or treatment responses. Metabolic-protein interaction (MPI) can provide meaningful insights into cancer heterogeneity. Moreover, the potential of lipids and lactate for identifying prognostic subtypes of glioma remains relatively unexplored. Therefore, we proposed a method to construct an MPI relationship matrix (MPIRM) based on a triple-layer network (Tri-MPN) combined with mRNA expression, and processed the MPIRM by deep learning to identify glioma prognostic subtypes. These Subtypes with significant differences in prognosis were detected in glioma (p-value < 2e-16, 95% CI). These subtypes had a strong correlation in immune infiltration, mutational signatures and pathway signatures. This study demonstrated the effectiveness of node interaction from MPI networks in understanding the heterogeneity of glioma prognosis.

Proteogenomic Profiling of High-Grade B-Cell Lymphoma With 11q Aberrations and Burkitt Lymphoma Reveals Lymphoid Enhancer Binding Factor 1 as a Novel Biomarker

High-grade B-cell lymphomas with 11q aberrations (HGBL-11q) represent a World Health Organization-defined group of lymphomas that harbor recurrent chromosome 11q aberrations involving proximal gains and telomeric losses. Although a limited number of HGBL-11q cases evaluated thus far appear to show a similar course and prognosis as Burkitt lymphoma (BL), many molecular differences have been appreciated, most notably the absence of MYC rearrangement. Despite biological differences between BL and HGBL-11q, histomorphologic and immunophenotypic distinction remains challenging. Here, we provide a comparative whole proteomic profile of BL- and HGBL-11q-derived cell lines, identifying numerous shared and differentially expressed proteins. Transcriptome profiling performed on paraffin-embedded tissue samples from primary BL and HGBL-11q lymphomas was additionally performed to provide further molecular characterization. Overlap of proteomic and transcriptomic data sets identified several potential novel biomarkers of HGBL-11q, including diminished lymphoid enhancer-binding factor 1 expression, which was validated by immunohistochemistry staining in a cohort of 23 cases. Altogether, these findings provide a comprehensive multimodal and comparative molecular profiling of BL and HGBL-11q and suggest the use of enhancer-binding factor 1 as an immunohistochemistry target to distinguish between these aggressive lymphomas.

Percutaneous versus surgical revascularization of unprotected left main coronary artery: Data from the Portuguese Registry of Acute Coronary Syndromes (ProACS)

BackgroundIn acute coronary syndromes (ACS), the optimal revascularization strategy for unprotected left main coronary artery (ULMCA) culprit lesion has been under-investigated. Therefore, we compared clinical characteristics and short- and medium-term outcomes of percutaneous and surgical revascularization in ACS. Methods and resultsOf 31886 patients enrolled in a multicenter, national, prospective registry study between October 2010 and December 2020, 246 (0.8%) had ULMCA as a culprit lesion and underwent percutaneous coronary intervention (PCI) alone (n=133, 54%) or coronary artery bypass grafting (CABG) alone (n=113, 46%). Patients undergoing PCI presented more frequently ongoing chest pain (68% versus 41%, p<0.001) and cardiogenic shock (25% versus 1%, p<0.001). Time from admission to revascularization was higher in surgical group with a median time to CABG of 4.5 days compared to 0 days to PCI (p<0.001). Angiographic success rate was 93.2% in patients who underwent PCI. Primary endpoint (all-cause death, non-fatal reinfarction and/or non-fatal stroke during hospitalization) occurred in 15.9% of patients and was more frequent in the PCI group (p<0.001). After adjustment, surgical revascularization was associated with better in-hospital prognosis (odds ratio (OR) 0.164; 95% confidence interval (CI), 0.04–0.64; p=0.009). Similar results were achieved after propensity score matching. No difference was found at one-year all-cause death. ConclusionPercutaneous coronary intervention was the most common revascularization strategy in the ACS with ULMCA culprit lesion. PCI was preferred in unstable patients and presented a high angiographic success. CABG was often delayed and preferred in low-risk patients. At one-year follow-up, PCI and CABG conferred a similar prognosis. The two approaches appear complementary in this high risk cohort.

Histone H3-wild type diffuse midline gliomas with H3K27me3 loss are a distinct entity with exclusive EGFR or ACVR1 mutation and differential methylation of homeobox genes

Diffuse midline gliomas (DMG) harbouring H3K27M mutation are paediatric tumours with a dismal outcome. Recently, a new subtype of midline gliomas has been described with similar features to DMG, including loss of H3K27 trimethylation, but lacking the canonical H3K27M mutation (H3-WT). Here, we report a cohort of five H3-WT tumours profiled by whole-genome sequencing, RNA sequencing and DNA methylation profiling and combine their analysis with previously published cases. We show that these tumours have recurrent and mutually exclusive mutations in either ACVR1 or EGFR and are characterised by high expression of EZHIP associated to its promoter hypomethylation. Affected patients share a similar poor prognosis as patients with H3K27M DMG. Global molecular analysis of H3-WT and H3K27M DMG reveal distinct transcriptome and methylome profiles including differential methylation of homeobox genes involved in development and cellular differentiation. Patients have distinct clinical features, with a trend demonstrating ACVR1 mutations occurring in H3-WT tumours at an older age. This in-depth exploration of H3-WT tumours further characterises this novel DMG, H3K27-altered sub-group, characterised by a specific immunohistochemistry profile with H3K27me3 loss, wild-type H3K27M and positive EZHIP. It also gives new insights into the possible mechanism and pathway regulation in these tumours, potentially opening new therapeutic avenues for these tumours which have no known effective treatment.This study has been retrospectively registered on clinicaltrial.gov on 8 November 2017 under the registration number NCT03336931 (https://clinicaltrials.gov/ct2/show/NCT03336931).