Multicenter Cancer Research Articles

Feasibility of structuring electronic health record data to facilitate real-world data research: ICAREdata methods applied to multicenter cancer clinical trials.

The use of electronic health record (EHR) data for research is limited by a lack of structure and a standard data model. The objective of the ICAREdata (Integrating Clinical Trials and Real-World Endpoints Data) project was to structure key research data elements in EHRs using a minimal Common Oncology Data Elements (mCODE) data model to extract and transmit data. The ICAREdata project captured two EHR data elements essential to clinical trials: cancer disease status and treatment plan change. The project was implemented in clinical sites participating in Alliance for Clinical Trials in Oncology trials. Data were extracted from EHRs and sent by secure Fast Healthcare Interoperability Resource messaging (a standard for exchanging EHRs) to a database. Selected elements were compared with corresponding data from the trial's electronic data capture (EDC) system, Medidata Rave. By December 2023, data were extracted and transmitted from 10 sites for 35 patients, involving 367 clinical encounters across 15 clinical trials. Data through March 2023 demonstrated that concordance for the elements treatment plan change and cancer disease status was 79% and 34%, respectively. When disease evaluation was reported by both EHR and EDC (n=15), there was 87% agreement on cancer disease status. Documentation, extraction, and aggregation of structured data elements in EHRs using mCODE and ICAREdata methods is feasible in multi-institutional cancer clinical trials. EDC as a reference data setallowed assessment of the completeness of EHR data capture. Future initiatives will focus on elements with shared definitions in clinical and research environments and efficient workflows. Clinical trials use electronic case report forms to report data, and data must be manually entered on these forms, which is costly and time consuming. ICAREdata methods use structured, organized data from clinical trials that can be more easily shared instead having to enter free text into electronic health records.

The Cancer Clinical Library Database (CCLD) from the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) Project.

The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea's cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.

Long-Term Survival of Patients With Cancer, Sepsis, and Vasopressor Requirements Based on Lactate Levels.

A prospective cohort study was conducted to evaluate the 1-year survival of cancer patients with sepsis and vasopressor requirements. Eligible patients were admitted a Comprehensive Cancer Center's ICU and were compared based on their admission lactate levels. Of the 132 included patients, 87 (66%) had high lactate (HL; > 2.0 mmol/L), and 45 (34%) had normal lactate (NL; ≤ 2.0 mmol/L). The 1-year survival rates of the two groups were similar (HL 16% vs. NL 18%; p = 0.0921). After adjustment for ICU baseline characteristics, HL was not significantly associated with a 1-year survival (Hazards ratio, 1.39; 95% CI, 0.94-2.05). Critically ill cancer patients with sepsis and vasopressor requirements, regardless of the lactate level, had 1-year survival of less than 20%. Large multicenter cancer registries would enable to confirm our findings and better understand the long-term trajectories of sepsis in this vulnerable population.

Sex-specific Associations between Body Mass Index and Thyroid Cancer Incidence among Korean Adults.

The potential differences by sex in the association between body mass index (BMI) and thyroid cancer risk remain unconfirmed. Data from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS; 2002-2015; population size = 510,619) and the Korean Multi-center Cancer Cohort (KMCC) data (1993-2015; population size = 19,026) were used. We constructed Cox regression models, adjusted for potential confounders, to evaluate the association between BMI and thyroid cancer incidence in each cohort, and assessed the consistency of the results. In the NHIS-HEALS, 1,351 and 4,609 incident thyroid cancer cases occurred during the follow-up among men and women, respectively. Compared with BMI of 18.5-22.9 kg/m2, BMI of 23.0-24.9 [no. of cases = 410; HR, 1.25; 95% confidence interval (CI), 1.08-1.44], 25.0-29.9 (no. of cases = 522; HR, 1.32; 95% CI, 1.15-1.51), and ≥30.0 kg/m2 (no. of cases = 48; HR, 1.93; 95% CI, 1.42-2.61) were associated with an increased risk of incident thyroid cancer among males. Among females, BMI of 23.0-24.9 (no. of cases = 1,300; HR, 1.17; 95% CI, 1.09-1.26) and 25.0-29.9 (no. of cases = 1,406; HR, 1.20; 95% CI, 1.11-1.29) were associated with incident thyroid cancer. The analyses using the KMCC demonstrated results consistent with wider CIs. Sex differences in the associations between BMI and thyroid cancer incidence were observed in Korean cohorts. BMI <23 kg/m2 may help prevent incident thyroid cancer, especially among men.

Clinical and inflammation marker features of cancer patients with COVID-19: data of Istanbul, Turkey multicenter cancer patients (2020–2022)

Objective We aimed to identify a rapid, accurate, and accessible biomarker in the early stages of COVID-19 that can determine the prognosis of the disease in cancer patients. Methods A total number of 241 patients with solid cancers who had a COVID-19 diagnosis between March 2020 and February 2022 were included in the study. Factors and ten different markers of inflammation were analyzed by year of diagnosis of COVID-19 and grouped by severity of infection. Results Hospitalization, referral to the intensive care unit (ICU), mechanical ventilation, and death were more frequent in 2020 than in 2021 and 2022 (mortality rates, respectively, were 18.8%, 3.8%, and 2.5%). Bilateral lung involvement and chronic lung disease were independent risk factors for severe disease in 2020. In 2021–2022, only bilateral lung involvement was found as an independent risk factor for severe disease. The neutrophil-to-lymphocyte platelet ratio (NLPR) with the highest area under the curve (AUC) value in 2020 had a sensitivity of 71.4% and specificity of 73.3% in detecting severe disease (cut-off > 0.0241, Area Under the Curve (AUC) = 0.842, p <.001). In 2021–2022, the sensitivity of the C-reactive protein-to-lymphocyte ratio (CRP/L) with the highest AUC value was 70.0%, and the specificity was 73.3% (cut-off > 36.7, AUC = 0.829, p = .001). Conclusions This is the first study to investigate the distribution and characteristics of cancer patients, with a focus on the years of their COVID-19 diagnosis. Based on the data from our study, bilateral lung involvement is an independent factor for severe disease, and the CRP/L inflammation index appears to be the most reliable prognostic marker.

Impact of radiation therapy on fatigue at 1 year in breast cancer survivors in the prospective multicentre CANcer TOxicity cohort

BackgroundFatigue is a common and disabling symptom after breast cancer (BC) treatment, significantly impacting patients' quality of life. We aimed to assess the impact of radiation therapy (RT) modalities on fatigue one year after treatment among patients with early-stage BC. MethodsWe used CANTO-RT, a subcohort of CANcer TOxicity (CANTO; NCT01993498), a multicentric nationwide prospective cohort of stages I–III BC treated from 2012 to 2017. Our primary outcome was severe global fatigue 1 year after RT completion (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 score ≥40/100). The secondary outcomes included severe physical, emotional and cognitive fatigue (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-FA12). RT-related variables were used as independent variables. Multivariable logistic regression models assessed associations between RT-related variables and fatigue. ResultsThe final analytic cohort included 3295 patients. The prevalence of severe global fatigue 1 year after treatment was 33.3%. Internal mammary chain RT (adjusted odds ratio [OR] 1.48 [95% confidence interval [CI] 1.03–2.13; p = 0.0355]) and normofractionated RT (adjusted OR 1.88 [95% CI 1.06–3.31; p = 0.0298]) were associated with increased odds of severe global fatigue. In addition, there was a significant association between normofractionated RT (adjusted OR 1.849 [95% CI 1.04–3.3; p = 0.0354]) and an increased likelihood of severe physical fatigue. ConclusionWe found a significant association between internal mammary chain RT (versus No), normofractionated RT (versus hypofractionated RT) and increased likelihood of persistent severe global fatigue. Our data add to the current understanding of treatment-related factors affecting fatigue after BC and could lead to personalised interventions to improve the prevention and management of this disabling symptom.

A comparison of Chinese multicenter breast cancer database and SEER database

There are different characteristics of BC in developing countries and developed countries. We intended to study the factors which influence the survival and prognosis of BC between southern China and the United States. (a) To study the two groups BC patients in southern China from 2001 to 2016 and SEER database from 1975 to 2016. (b) To register, collect and analyze the clinicopathological features and treatment information. Our study found that there are significant differences in tumor size, positive lymph node status and KI-67 between southern China and SEER cohort (P < 0.000). The positive lymph node status may be one of the causes of difference of morbidity and mortality of BC patients in China. Furthermore, the differences in treatment methods may also account for the differences between China and seer databases.

The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival.

PURPOSETo report pancreas surveillance outcomes of high-risk individuals within the multicenter Cancer of Pancreas Screening-5 (CAPS5) study and to update outcomes of patients enrolled in prior CAPS studies.METHODSIndividuals recommended for pancreas surveillance were prospectively enrolled into one of eight CAPS5 study centers between 2014 and 2021. The primary end point was the stage distribution of pancreatic ductal adenocarcinoma (PDAC) detected (stage I v higher-stage). Overall survival was determined using the Kaplan-Meier method.RESULTSOf 1,461 high-risk individuals enrolled into CAPS5, 48.5% had a pathogenic variant in a PDAC-susceptibility gene. Ten patients were diagnosed with PDAC, one of whom was diagnosed with metastatic PDAC 4 years after dropping out of surveillance. Of the remaining nine, seven (77.8%) had a stage I PDAC (by surgical pathology) detected during surveillance; one had stage II, and one had stage III disease. Seven of these nine patients with PDAC were alive after a median follow-up of 2.6 years. Eight additional patients underwent surgical resection for worrisome lesions; three had high-grade and five had low-grade dysplasia in their resected specimens. In the entire CAPS cohort (CAPS1-5 studies, 1,731 patients), 26 PDAC cases have been diagnosed, 19 within surveillance, 57.9% of whom had stage I and 5.2% had stage IV disease. By contrast, six of the seven PDACs (85.7%) detected outside surveillance were stage IV. Five-year survival to date of the patients with a screen-detected PDAC is 73.3%, and median overall survival is 9.8 years, compared with 1.5 years for patients diagnosed with PDAC outside surveillance (hazard ratio [95% CI]; 0.13 [0.03 to 0.50], P = .003).CONCLUSIONMost pancreatic cancers diagnosed within the CAPS high-risk cohort in the recent years have had stage I disease with long-term survival.

Verification of the association of the cycle threshold (Ct) values from HPV testing on Cobas4800 with the histologic grades of cervical lesions using data from two population-based cervical cancer screening trials

ObjectiveTo verify the association of high-risk human papillomavirus (hrHPV) viral load reflected by cycle threshold (Ct) values from HPV testing on Cobas4800 assay with the histologic grades of cervical lesions via analysis on the combined data from two cervical cancer screening trials and to explore the referability of Ct values in management of the abnormalities from cervical cancer primary screening.MethodsWe analyzed the data from Chinese Multi-Center Screening Trial (CHMUST) and BUJI Cervical Cancer Screening Study Project (BUJI Study). All data to be analyzed in this paper were related to provider-collected samples. One-way ANOVA was performed to compare the Ct values among different histological groups, and Kendall’s tau-b correlation was applied to examine the association between Ct values and cervical lesion grades. The stepwise incidence of CIN2+ and CIN3+ in every 100 HPV positive individuals were calculated according to the descending of the genotype specific Ct values. The highest Ct values related to CIN3+ incidence rate 4% (or 25%) were used as the cutoffs to distinguish low-Ct value cases from the high-Ct value ones.ResultsA total of 1376 women in CHUMUST and BUJI Study who were aged 30–59 and positive of hrHPV for provider-collected samples on Cobas4800 with complete data in terms of the relevant Ct values (CtV) and the histological diagnosis were included for analysis. Our data showed significant difference among different histological grades of cervical lesions in the CtV of hrHPV, HPV16-plus (positive of HPV16 only or HPV16 plus 18 and/or pooled 12-HPV), and pooled 12-HPV (P < 0.05). No significant difference was found among different grades of lesions in term of correlated CtV of HPV18-plus (positive of HPV18 only or HPV18 plus pooled 12-HPV) (P > 0.05). The CIN2+ or CIN3+ incidence per 100 positives significantly increased corresponding to the descending of the CtV of hrHPV, HPV16-plus and pooled 12-HPV. Compared with high-CtV groups (CtV > 33.2 for hrHPV, CtV > 29.6 for pooled 12-HPV), the relevant risks (RRs) of CIN2+ for hrHPV and pooled 12-HPV positive groups with low-CtV (CtV ≤ 33.2 and ≤ 29.6, respectively) were 3.2 (95%CI 2.18–4.80) and 2.3 (95%CI 1.50–3.45). Similarly, the RRs of CIN3+ for hrHPV and pooled 12-HPV positive groups with low-CtV were 6.5 (95%CI 2.83–14.80) and 2.7 (95%CI 1.15–6.39), respectively. The RRs of CIN2+ for medium- (30.3 < CtV ≤ 37.4) and low- (≤ 30.3) CtV HPV16-plus positives were 5.1 (95%CI 0.68–38.38) and 20.6 (95%CI 2.96–143.92) related to high-CtV (> 37.4) groups, and the CIN3+ incidence in low-CtV value group was nine-fold higher of that in medium-CtV ones [RRs, 9.0 (95%CI 2.89–28.10)]. In comparing with the algorithms of “HPV16-plus/18-plus + cytology ≥ ASCUS for pooled 12-HPV”, triage algorithm “HPV16-plus/18-plus + Ct value ≤ 33.2 for pooled 12-HPV” could achieve a comparable sensitivity of 93.2%.ConclusionHPV viral loads reflected by Ct values for hrHPV, HPV16-plus and pooled 12-HPV from Cobas4800 HPV testing were directly associated with the severity of cervical lesions. A lower HPV genotype-specific Ct value prompted a significantly high CIN3+ risk of 4% or higher in women positive of hrHPV, HPV16-plus or pooled 12-HPV, indicating that HPV viral load reflected by Ct values on Cobas4800 may be a promising risk indicator in management of abnormalities from primary cervical cancer screening.

Phase I/II Multicenter Trial of a Novel Therapeutic Cancer Vaccine, HepaVac-101, for Hepatocellular Carcinoma

Abstract Purpose: Immunotherapy for hepatocellular carcinoma (HCC) shows considerable promise in improving clinical outcomes. HepaVac-101 represents a single-arm, first-in-human phase I/II multicenter cancer vaccine trial for HCC (NCT03203005). It combines multipeptide antigens (IMA970A) with the TLR7/8/RIG I agonist CV8102. IMA970A includes 5 HLA-A*24 and 7 HLA-A*02 as well as 4 HLA-DR restricted peptides selected after mass spectrometric identification in human HCC tissues or cell lines. CV8102 is an RNA-based immunostimulator inducing a balanced Th1/Th2 immune response. Patients and Methods: A total of 82 patients with very early- to intermediate-stage HCCs were enrolled and screened for suitable HLA haplotypes and 22 put on study treatment. This consisted in a single infusion of low-dose cyclophosphamide followed by nine intradermal coadministrations of IMA970A and CV8102. Only patients with no disease relapse after standard-of-care treatments were vaccinated. The primary endpoints of the HepaVac-101 clinical trial were safety, tolerability, and antigen-specific T-cell responses. Secondary or exploratory endpoints included additional immunologic parameters and survival endpoints. Results: The vaccination showed a good safety profile. Transient mild-to-moderate injection-site reactions were the most frequent IMA970A/CV8102-related side effects. Immune responses against ≥1 vaccinated HLA class I tumor-associated peptide (TAA) and ≥1 vaccinated HLA class II TAA were respectively induced in 37% and 53% of the vaccinees. Conclusions: Immunotherapy may provide a great improvement in treatment options for HCC. HepaVac-101 is a first-in-human clinical vaccine trial with multiple novel HLA class I– and class II–restricted TAAs against HCC. The results are initial evidence for the safety and immunogenicity of the vaccine. Further clinical evaluations are warranted.

Decision aids for localized prostate cancer in diverse minority men: Primary outcome results from a multicenter cancer care delivery trial (Alliance A191402CD)

Decision aids for localized prostate cancer in diverse minority men: Primary outcome results from a multicenter cancer care delivery trial (Alliance A191402CD)

Decision aids for localized prostate cancer in diverse minority men: Primary outcome results from a multicenter cancer care delivery trial (Alliance A191402CD).

Decision aids (DAs) can improve knowledge for prostate cancer treatment. However, the relative effects of DAs delivered within the clinical encounter and in more diverse patient populations are unknown. A multicenter cluster randomized controlled trial with a 2×2 factorial design was performed to test the effectiveness of within-visit and previsit DAs for localized prostate cancer, and minority men were oversampled. The interventions were delivered in urology practices affiliated with the NCI Community Oncology Research Program Alliance Research Base. The primary outcome was prostate cancer knowledge (percent correct on a 12-item measure) assessed immediately after a urology consultation. Four sites administered the previsit DA (39 patients), 4 sites administered the within-visit DA (44 patients), 3 sites administered both previsit and within-visit DAs (25 patients), and 4 sites provided usual care (50 patients). The median percent correct in prostate cancer knowledge, based on the postvisit knowledge assessment after the intervention delivery, was as follows: 75% for the pre+within-visit DA study arm, 67% for the previsit DA only arm, 58% for the within-visit DA only arm, and 58% for the usual-care arm. Neither the previsit DA nor the within-visit DA had a significant impact on patient knowledge of prostate cancer treatments at the prespecified 2.5% significance level (P = .132 and P = .977, respectively). DAs for localized prostate cancer treatment provided at 2 different points in the care continuum in a trial that oversampled minority men did not confer measurable gains in prostate cancer knowledge.

The Association between Plasma Concentration of Phytoestrogens and Hypertension within the Korean Multicenter Cancer Cohort.

In order to examine the association between plasma phytoestrogen concentration (genistein, daidzein, equol and enterolactone) and hypertension, we conducted a nested case–control study for 229 hypertension cases including 112 prehypertension and 159 healthy controls derived from the Korean Multi-center Cancer Cohort (KMCC). The concentration of plasma phytoestrogens was measured using time-resolved fluoroimmunoassay. We assessed the association between plasma phytoestrogens and hypertension using logistic regression models using odds ratio (OR) and 95% confidence interval (95%CI). The highest tertile of plasma equol and enterolactone concentration exhibited a significantly decreased risk of hypertension (equol, OR = 0.34, 95%CI 0.20–0.57; enterolactone, OR = 0.32, 95%CI 0.18–0.57), compared with the lowest tertile. Equol and enterolactone showed reduced ORs for prehypertension (the highest tertile relative to the lowest tertile, OR = 0.50, 95%CI 0.26–0.96; OR = 0.38, 95%CI 0.19–0.75, respectively) and hypertension (OR = 0.42, 95%CI 0.22–0.81; OR = 0.28, 95%CI 0.14–0.54, respectively). There was a stronger association in hypertension (the highest tertile relative to the lowest tertile in obesity vs. non-obesity; equol, OR = 0.06 vs. 0.63; enterolactone, OR = 0.07 vs. 0.46; both p-heterogeneity < 0.01). This study suggests that equol and enterolactone may contribute to prevent primarily prehypertension and hypertension, and control cardiovascular disease (CVD) based on the continuum of hypertension and CVD. Further study to assess hypertension risk based on useful biomarkers, including phytoestrogens, may contribute to primary prevention of hypertension.

Looking for a strategy in treating peritoneal gastric cancer carcinomatosis: an Italian multicenter Gastric Cancer Research group\u2019s analysis

BackgroundThe present study provides a snapshot of Italian patients with peritoneal metastasis from gastric cancer treated by surgery in Italian centers belonging to the Italian Research Group on Gastric Cancer. Prognostic factors affecting survival in such cohort of patients were evaluated with the final aim to identify patients who may benefit from radical intent surgery.MethodsIt is a multicentric retrospective study based on a prospectively collected database including demographics, clinical, surgical, pathological, and follow-up data of patients with gastric cancer and synchronous macroscopic peritoneal metastases. Patients were surgically treated from January 2005 to January 2017. We focused on patients with macroscopic peritoneal carcinomatosis (PC) treated with upfront surgery in order to provide homogeneous evidences.ResultsOur results show that patients with peritoneal carcinomatosis cannot be considered all lost. Strictly selected cases (R0/R1 and P1 patients) could benefit from an aggressive surgical approach performing an extended lymphadenectomy and HIPEC treatment.ConclusionThe main result of the study is that GC patients with limited peritoneal involvement can have a survival benefit from a surgery with “radical oncological intent”, that means extended lymphadenectomy and R0 resection. The retrospective nature of this study is an important bias, and for this reason, we have started a prospective multicentric study including Italian stage IV patients that hopefully will give us more answers.

Fasting blood glucose was linearly associated with colorectal cancer risk in the population without self-reported diabetes mellitus history.

Fasting plasma glucose level was linearly associated with colorectal cancer (CRC) risk. However, the dose–response relationship between fasting blood glucose (FBG) and CRC risk was still uncertain.A total of 11,632 patients without self-reported diabetes mellitus and colorectal polyps’ history were identified in the Korean Multicenter Cancer Cohort (1993–2005). The nonlinear relationship was estimated through a restricted cubic spline regression, and a two-piece-wise Cox proportional hazards model was further performed to calculate the threshold effect. Multiple imputation was used to control the bias from missing data.Overall, 1.1% (n = 132) of participants were diagnosed with CRC in the follow-up duration. With a median follow-up duration of 12.0 years, participants with FBG ≥126 mg/dL were associated with higher CRC risk (adjusted hazard ratio [HR], 1.67; 95% confidence interval [CI]: 1.01, 2.76). Landmark analyses limited to long-term survivors demonstrated increased CRC risk with FBG ≥ 126 mg/dL in all subsets (≥3years: HR,1.93 (95% CI: 1.13–3.29); ≥5years: HR, 2.04 (95% CI: 1.–3.63); ≥10years: HR, 2.50 (95% CI: 1.19–5.25)). With FBG smoothly increasing before, the latter increased dramatically after the turning point (P for nonlinearity = 0.283). When FBG was increasing per mmol/L, HR was 1.07(95% CI: 0.90, 1.29) for FBG < 126 mg/dL and 1.27 (95% CI: 1.06, 1.53) for FBG ≥ 126 mg/dL. Besides, HR was 1.09 (95% CI: 1.02, 1.16) for the CRC risk.In the population without self-reported diabetes mellitus and colorectal polyps’ history. FBG was linearly associated with CRC risk, especially for FBG over 126 mg/dL.

OC-0509 10-year outcome of ultrahypofractionated stereotactic RT from two multicenter prostate cancer trials

OC-0509 10-year outcome of ultrahypofractionated stereotactic RT from two multicenter prostate cancer trials

One-Year Mortality in Patients with Cancer Cachexia: Association with Albumin and Total Protein.

PurposeSerum albumin can indicate the onset of cancer cachexia, provide information about a patient’s nutritional status, and serve as a biomarker for the prognosis of patients with cancer cachexia. However, the relationship between serum albumin levels and mortality in patients with cancer cachexia remains unclear. We aimed to examine the association of albumin and total protein with 1-year mortality in patients with cancer cachexia.Patients and MethodsWe conducted a nested case–control study using data from a multicenter cancer clinical survey from 2013 to 2018. In total, 266 patients with cancer cachexia who survived for <1 year and 266 patients who survived for ≥1 year were included in this study. The participants were matched by age, sex, tumor type, tumor stage, and hospital site. The crude and adjusted risks of 1-year survival were estimated using odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression, with or without adjustment for covariates.ResultsLogistic regression analysis revealed a significantly negative linear association between albumin level and 1-year mortality in patients with cancer cachexia (p < 0.001). An L-shaped relationship existed between total protein and 1-year mortality, with a turning point at 70.4 g/L. When albumin was divided into quartiles, Q3 (OR: 0.40; 95% CI: 0.24, 0.68; p < 0.001) and Q4 (OR: 0.33; 95% CI: 0.19, 0.55; p < 0.001) were associated with higher 1-year survival than Q1 among patients with cancer cachexia. When total protein was divided into quartiles, Q2 (OR: 0.38; 95% CI: 0.23, 0.64; p < 0.001), Q3 (OR: 0.57; 95% CI: 0.33, 0.96; p = 0.035), and Q4 (OR: 0.43; 95% CI: 0.25, 0.72; p = 0.002) were associated with higher 1-year survival than Q1 among patients with cancer cachexia.ConclusionSerum albumin and total protein may predict 1-year survival. Future clinical studies should lead to a more comprehensive understanding of the effects of serum protein levels in patients with cancer cachexia.

P0939 - The role of psa density in decision making to perform transperineal prostate biopsy in men with multi-parametric MRI Likert 2 or 3 scores: A retrospective analysis from a multi-centre cancer network study

P0939 - The role of psa density in decision making to perform transperineal prostate biopsy in men with multi-parametric MRI Likert 2 or 3 scores: A retrospective analysis from a multi-centre cancer network study

Laboratory cross-comparison of homologous recombination repair mutation analysis in tumor in a multicenter epithelial ovarian cancer series: The BORNEO GEICO 60-0 study.

e17550 Background: In epithelial ovarian cancer (EOC), the identification of mutations in homologous recombination repair (HRR) genes on tumor is prognostic, predictive of response to PARP inhibitors, and a tool to identify individuals at genetic cancer risk. The aim of this study is to compare the concordance between two laboratories in identifying and classifying genetic variants in HRR genes. Methods: In a multicentre ambispective series of unselected, non mucinous EOC of all stages formalin-fixed and paraffin embedded tumors were collected. These samples underwent the same mutational analysis of 15 HRR genes ( ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, RAD54L) in two different Laboratories (Lab1, Lab2) that used their own validated multi-gene NGS panels. Variant allele frequency (VAF) threshold was 5% for single nucleotide polymorphism and 10% for indels. Large rearrangements were not analyzed. Variants were classified into three categories based on ACMG criteria: non-mutated (class 1-2), Variants of Uncertain Significance (VUS: class 3) and likely pathogenic/pathogenic (class 4-5). Results: A total of 81 cases were sent for the analysis. One had low DNA quality and therefore 80 cases were finally studied (85% high grade serous and 74% FIGO stage III-IV). Results reported by Lab1 and Lab2 (lab1/Lab2) were the following: 21/19 (26%/24%) cases had BRCA1/2 mutations, 7/8 (8.7%/10%) mutations on other HRR genes including two in ATM and RAD51D, one in CHEK1, CHEK2, and FANCL and one RAD51C reported in Lab2 only while the rest were either VUS 23/27 (29%/34%) or non-mutated 29/26 (36%/33%). Concordance between laboratories in classifying patients was 93.75% (kappa coefficient 0.86). Discrepancies (DC) on variants were classified into arbitrary categories, namely 0= complete concordance, category 1 meaning DC in detection assumed to be due to tumor heterogeneity (VAF nearby the threshold) or technique (1A), or caused by laboratories performance and avoidable (1B) and the category 2 identified DC in interpretation without clinical relevance (2A) or clinically relevant (2B), the results of total number of variants are shown in table. Overall, regarding clinically relevant DC in HRR genes, 9 DC in variants were observed including six 2B, two 1A and one 1B and they affect 5 (6.3%) patients since some were overlapping. Conclusions: In our EOC series the concordance of two Laboratories in the identification of clinically relevant HRR mutations on tumor is high but discrepancies in interpretation remain a challenge that needs further harmonization.[Table: see text]

Tumor PD-L1 expression and gene panel mutational profile as outcome predictors of PD-1-based checkpoint inhibition therapy in metastatic melanoma: A prospective multicenter DeCOG study.

9568 Background: PD-1 checkpoint inhibition (CPI) has recently advanced to one of the most effective treatment strategies in melanoma. However, since a considerable proportion of patients shows upfront therapy resistance, baseline predictive biomarkers of therapy outcome are needed. Methods: This prospective multicenter study included metastatic melanoma patients whose formalin-fixed paraffin-embedded tumor tissue samples taken prior to the start of a systemic non-adjuvant therapy of any line were analyzed for PD-L1 expression on tumor cells by immunohistochemistry (clone 28-8, DAKO) and for COSMIC-annotated oncogenic mutations by 29-gene panel sequencing (MiSeq, Illumina). Clinical baseline and follow-up data were collected within the DeCOG multicenter skin cancer registry ADOREG. Results: From 09/2015 until 10/2020, 706 enrolled patients from 15 centers were evaluable for the endpoints best overall response (BOR), progression-free (PFS) and overall survival (OS). Thereof, 540 patients received PD-1-based CPI as first systemic treatment after tumor tissue analysis. 197/540 patients tested positive for PD-L1 (cut-off = 5%) in pre-treatment tumors, and revealed a favourable BOR (objective response 34.4% versus 19.1%; p &lt; 0.0001), PFS (median 10.4 versus 4.2 months; p &lt; 0.0001) and OS (median 45.1 versus 18.8 months; p = 0.001) compared to patients with PD-L1 negative tumors. 47/540 patients presented oncogenic mutations of three or more genes in pre-treatment tumors, and revealed a favourable BOR (objective response 46.8% versus 32.1%; p = 0.041), PFS (median 15.1 versus 6.1 months; p = 0.008) and OS (median not reached versus 25.2 months; p = 0.027) compared to patients whose tumors showed mutations in two or less genes. Multivariable Cox regression including sex, primary site, non-adjuvant systemic pre-treatment, serum LDH, and ECOG performance state demonstrated tumor PD-L1 expression and gene panel mutational profile as independent predictors of survival upon treatment with PD-1-based CPI. In contrast, in 106/706 patients treated with BRAF/MEK inhibitors as first systemic treatment after tumor tissue analysis, no association was found between tumor PD-L1 expression or gene panel mutational profile and therapy outcome. Conclusions: PD-L1 expression quantification and gene panel mutational profiling provide useful outcome predictors of PD-1-based CPI therapy in metastatic melanoma patients.