Worse Eastern Cooperative Oncology Group Research Articles

Wedge resection, segmentectomy, and lobectomy: oncologic outcomes based on extent of surgical resection for ≤2 cm stage IA non-small cell lung cancer.

Long-standing controversy has existed over whether sublobar resection is an adequate oncological procedure for clinical stage IA non-small cell lung cancer (NSCLC) ≤2 cm, despite the recent randomized trial reports of Japanese Clinical Oncology Group (JCOG) 0802 and Cancer and Leukemia Group B (CALGB) 140503 demonstrating non-inferior outcomes with sublobar resection compared to lobectomy. As practice patterns shift, we sought to compare oncologic outcomes in patients with these early-stage tumors after wedge resection, segmentectomy, or lobectomy in a contemporary, real-world, cohort. A retrospective review of a prospectively maintained database from a single institution was conducted from 2011 to 2020 to identify all patients with clinically staged IA1 or IA2 NSCLC (tumors ≤2 cm with no nodal involvement). The primary outcomes of interest were overall survival (OS) and disease-free survival (DFS), with secondary outcomes of lung cancer-specific survival (LCSS), recurrence patterns, and perioperative morbidity and mortality. A total of 480 patients were identified; 93 (19.4%) patients underwent wedge resection, 90 (18.7%) received segmentectomy, and 297 (61.9%) underwent lobectomy. Patients who underwent wedge resection had worse Eastern Cooperative Oncology Group (ECOG) performance status (23.7% ECOG 1 or 2 vs. 5.6% among segmentectomy and 5.4% among lobectomy, P<0.05). Both wedge resection and segmentectomy patients had lower preoperative mean percentage of predicted forced expiratory volume in one second (%FEV1) compared to the lobectomy group (81.8% and 82.6% vs. 89.6%, P=0.002), a higher proportion of patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), and a higher Charlson Comorbidity Index. There were no statistically significant differences in 5-year OS, DFS, or LCSS between groups: 90%, 61%, 78% for wedge resections compared with 85%, 75%, 86% for segmentectomy, and 87%, 77%, 87% for lobectomy, respectively. Recurrence was observed in 17 patients who underwent wedge resection (18.3%, 8 local, 9 distant), 12 patients who received segmentectomy (13.4%, 6 local, 6 distant), and 38 patients who underwent lobectomy (12.8%, 11 local, 27 distant), which was not significantly different (P=0.36). Patients with inferior performance status or lower baseline pulmonary function are more likely to receive wedge resection for clinical stage IA NSCLC ≤2 cm in size. For these small tumors, lobectomy, segmentectomy, and wedge resection provide comparable oncologic outcomes.

Longitudinal patient-reported outcomes in patients receiving chimeric antigen receptor T-cell therapy.

Chimeric antigen receptor T-cell therapy (CAR-T) has transformed the treatment for relapsed/refractory hematologic malignancies; however, data on patient-reported outcomes in CAR-T are limited. We conducted a longitudinal study of adults with hematologic malignancies receiving CAR-T. We assessed quality of life (QOL; functional assessment of cancer therapy-general), psychological distress (hospital anxiety and depression scale, patient health questionnaire-9, posttraumatic stress disorder [PTSD] checklist), and physical symptoms (Edmonton symptom assessment scale-revised) at baseline, 1week, 1, 3, and 6months after CAR-T. We used linear mixed models to identify factors associated with QOL trajectory. We enrolled 103 of 142 eligible patients (3 did not receive CAR-T). QOL (B= 1.96; P< .001) and depression (B=-0.32; P= .001) worsened by 1week and improved by 6months after CAR-T. At 6months, 18%, 22%, and 22% reported clinically significant depression, anxiety, and PTSD symptoms, respectively. At 1week, 52% reported severe physical symptoms, declining to 28% at 6months after CAR-T. In unadjusted linear mixed models, worse Eastern Cooperative Oncology Group performance status (B= 1.24; P= .042), receipt of tocilizumab (B= 1.54; P= .042), and receipt of corticosteroids for cytokine release syndrome and/or neurotoxicity (B= 2.05; P= .006) were associated with higher QOL trajectory. After CAR-T, QOL declined, and depression increased early, followed by improvements in QOL, psychological distress, and physical symptoms by6months after infusion. A significant minority of patients reported substantial psychological distress and physical symptoms longitudinally.

Clinical Effect of the C-Reactive Protein to Serum Albumin Ratio in Patients with Metastatic Gastric or Gastroesophageal Junction Cancer Treated with Trifluridine/Tipiracil.

Trifluridine/tipiracil (FTD/TPI) is an oral anticancer agent used as a third- or later-line treatment for patients with metastatic gastric cancer/gastroesophageal junction cancer (mGC/GEJC). The C-reactive protein-to-serum albumin ratio (CAR) is an inflammation-based prognostic marker in gastric cancer. This retrospective study evaluated CAR's clinical significance as a prognostic factor in 64 patients with mGC/GEJC administered FTD/TPI as a third- or later-line therapy. Patients were categorized into high- and low-CAR groups based on pre-treatment blood data. This study evaluated associations between CAR and overall survival (OS), progression-free survival (PFS), clinicopathological features, treatment efficacy, and adverse events. The high-CAR group had significantly worse Eastern Cooperative Oncology Group performance status, a higher prevalence of patients administered with a single course of FTD/TPI, and a higher rate of patients not administered chemotherapy after FTD/TPI therapy than the low-CAR group. Median OS and PFS were significantly poorer in the high-CAR group than in the low-CAR group (113 vs. 399 days; p < 0.001 and 39 vs. 112 days; p < 0.001, respectively). In multivariate analysis, high CAR was an independent prognostic factor for OS and PFS. The overall response rate was not significantly different between the high- and low-CAR groups. Regarding adverse events, the high-CAR group had a significantly lower incidence of neutropenia and a higher incidence of fatigue than the low-CAR group. Therefore, CAR may be a potentially useful prognostic factor for patients with mGC/GEJC treated with FTD/TPI as third- or later-line chemotherapy.

Real-World First-Line Use of Pertuzumab With Different Taxanes for Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: A Comparative Effectiveness Study Using US Electronic Health Records.

On the basis of the results from CLEOPATRA, pertuzumab plus trastuzumab and chemotherapy is the first-line standard of care for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). However, discrepancies have been reported between clinical trial and real-world outcomes. We report real-world outcomes for patients with HER2-positive MBC treated with first-line pertuzumab plus trastuzumab and a taxane in routine clinical practice in the United States. A retrospective analysis was conducted using electronic health record-derived deidentified data from the Flatiron Health database. Patients were grouped according to the first taxane received (paclitaxel/nab-paclitaxel or docetaxel). Median real-world progression-free survival (rwPFS) and overall survival (rwOS) was estimated using Kaplan-Meier methodology. Subgroup analyses were conducted in patients treated with docetaxel who met CLEOPATRA's key eligibility criteria. We included 1,065 patients; 313 patients received paclitaxel/nab-paclitaxel and 752 received docetaxel. Patients who received paclitaxel/nab-paclitaxel were older, had a worse Eastern Cooperative Oncology Group Performance Status, and had more recurrent metastatic disease compared with the docetaxel group. After adjustment for potential confounders, similar median rwPFS (inverse probability of treatment weighted average treatment effect for the treated [IPTW-ATT] hazard ratio [HR], 1.09; 95% CI, 0.9 to 1.3; P = .365) and rwOS (IPTW-ATT HR, 1.23; 95% CI, 0.96 to 1.58; P = .101) was observed between treatment groups. In the subgroup of CLEOPATRA-eligible patients, median rwPFS and rwOS were 16.9 months and 57.8 months, respectively. There was no statistically significant difference in real-world outcomes between patients treated with paclitaxel/nab-paclitaxel and those treated with docetaxel. Selecting patients using key CLEOPATRA eligibility criteria resulted in rwPFS and rwOS similar to those observed in CLEOPATRA, highlighting the importance of ensuring similar patient populations when comparing clinical trial and real-world data.

Follicular Helper T-Cell-derived Nodal Lymphomas: Study of Histomorphologic, Immunophenotypic, Clinical, and RHOA G17V Mutational Profile.

The study was designed to review the demographic, clinical, and pathologic characteristics of follicular helper T cells (TFH)-derived nodal PTCL in India including angioimmunoblastic T-cell lymphoma (AITL), peripheral T-cell lymphoma (PTCL) with follicular helper T cell phenotype (P-TFH), and follicular T-cell lymphoma with additional immunohistochemistry (IHC) and RHOAG17V mutational analysis, as well as their impact on survival. This retrospective study included 88 cases of PTCL that were reclassified using IHC for TFH markers (PD1, ICOS, BCL6, and CD10) and dendritic-meshwork markers (CD21, CD23). Cases of TFH cell origin were evaluated for RHOAG17V mutation using Sanger sequencing and amplification-refractory mutation system-polymerase chain reaction (PCR) (validated using cloning and quantitative PCR) with detailed clinicopathologic correlation. Extensive re-evaluation with added IHC panel resulted in a total of 19 cases being reclassified, and the final subtypes were AITL (37 cases, 42%), PTCL-not otherwise specified (44, 50%), P-TFH (6, 7%), and follicular T-cell lymphoma (1, 1%). The presence of at least 2 TFH markers (>20% immunopositivity) determined the TFH origin. AITL patients tended to be male and showed increased presence of B-symptoms and hepatosplenomegaly. Histomorphology revealed that 92% of AITL cases had pattern 3 involvement. Sanger sequencing with conventional PCR did not yield any mutation, while RHOAG17V was detected by amplification-refractory mutation system-PCR in AITL (51%, P =0.027) and P-TFH (17%), which was validated with cloning followed by sequencing. Cases of RHOAG17V-mutant AITL had a worse Eastern Cooperative Oncology Group performance status initially but fared better in terms of overall outcome ( P =0.029). Although not specific for AITL, RHOAG17V mutation shows an association with diagnosis and requires sensitive methods for detection due to low-tumor burden. The mutant status of AITL could have prognostic implications and translational relevance.

A cross-sectional study evaluating health-related quality of life of Chinese pediatric patients with hematological malignancies using EQ-5D-Y.

The study aimed to assess health-related quality of life (HRQoL) and to estimate the health utility of pediatric patients with hematological malignancies (HMs) in China. A cross-sectional study recruited a series of pediatric inpatients diagnosed with HM from November 2018 to May 2019 in the Shanghai Children's Medical Center. Subjects were interviewed to collect sociodemographic information about themselves and their guardians. The EQ-5D-Y was completed by each patient to rate their own HRQoL, which later derived the health utility. The health status was also assessed by clinicians following the Eastern Cooperative Oncology Group (ECOG) system. Upon the descriptive analysis and univariate analysis, multivariate generalized linear models were built to explore the associations of risk factors with HRQoL measures of utility, Visual Analog Scale (VAS) score, and the five EQ-5D-Y domains. The 96 subjects had a mean age of 10.5 years and included 62 (64.4%) boys. There were 46 (47.9%) and 25 (26.0%) children diagnosed with acute lymphoblastic leukemia and non-Hodgkin's lymphoma, respectively. The means (SD) of utility and EQ-VAS scores were 0.88 (0.10) and 85.8 (15.1), respectively. Twenty-six (27.1%) patients were graded poor health by the ECOG standard (score 2/3). Both univariate and multivariate analyses found strong correlations between ECOG and HRQoL. After adjusting for covariates, poor ECOG score was significantly associated with an impaired utility and VAS of -0.103 and -8.65, respectively. With regard to individual HRQoL domains, worse ECOG was more likely to report health problems with an increased risk of 2.94 to 12.50; residence, income, guardians' education, and disease duration were also found to be significantly related to either the utility or certain health domains. The HRQoL of Chinese pediatric patients with HM is considered relatively poor and of great concern to healthcare. With the strong correlations between EQ-5D-Y-related HRQoL measures and the traditional clinical index ECOG, the EQ-5D-Y is able to provide valuable evidence for clinical decision-making at the individual level. At the same time, its health utility can inform resource allocation at a macro level.

Sorafenib versus nivolumab after lenvatinib treatment failure in patients with advanced hepatocellular carcinoma.

An optimal sequential anti-hepatocellular carcinoma (HCC) agent that can be used after failed lenvatinib treatment has not been established. Here, we compared the outcomes of sorafenib and nivolumab as second-line agents after failed lenvatinib treatment in patients with advanced HCC. Patients with advanced HCC who had received sorafenib or nivolumab as second-line agents after failed lenvatinib treatment were recruited from two Korean tertiary institutions between November 2018 and June 2020. The median age of the 60 participants (52 treated with sorafenib and eight treated with nivolumab) at baseline was 56.8 years. The demographic, laboratory and tumor variables, as well as lenvatinib treatment duration, were similar between the two groups. The median durations of sorafenib and nivolumab treatment were 1.2 and 2.6 months, respectively ( P = 0.164). Twenty-four (40.0%) patients died during the follow-up period (median, 15.8 months). The median overall survival (OS) of the study population was 5.8 months. The median OS of patients treated with sorafenib was significantly longer than the median OS of patients treated with nivolumab (8.7 vs. 3.0 months; P = 0.046). Sorafenib treatment (vs. nivolumab) was independently associated with a lower risk of mortality (hazard ratio = 0.194; 95% confidence interval, 0.053-0.708; P = 0.013). Worse Eastern Cooperative Oncology Group performance status, larger maximal tumor size, lymph node metastases and higher total bilirubin levels were independently associated with increased mortality risk (all P < 0.05). Lenvatinib-sorafenib sequential treatment resulted in significantly better survival did than lenvatinib-nivolumab sequential treatment in patients with advanced HCC. Larger studies are needed to validate our results.

Are there differences in the characteristics of patients who respond to gemcitabine plus cisplatin chemotherapy and those who respond to pembrolizumab therapy for metastatic urothelial carcinoma? Multicenter retrospective study.

To evaluate factors to predict overall survival of metastatic urothelial carcinoma patients treated with gemcitabine plus cisplatin chemotherapy or pembrolizumab therapy. We retrospectively evaluated two metastatic urothelial carcinoma cohorts treated with (i) gemcitabine plus cisplatin or (ii) pembrolizumab. The gemcitabine plus cisplatin cohort was treated from December 2005 through December 2014 while the pembrolizumab cohort was treated from January 2018 through December 2020. Using multivariate analyses, we evaluated the risk factors for overall survival in each cohort and compared them. None of the gemcitabine plus cisplatin cohort patients were treated with pembrolizumab. All patients in the pembrolizumab cohort were treated with prior platinum-based chemotherapy. There were 184 patients in the gemcitabine plus cisplatin cohort and 91 in the pembrolizumab cohort. The mean follow-up periods were 714 and 284 days, respectively. In multivariate analysis, the risk factors for overall survival in the gemcitabine plus cisplatin cohort were liver metastasis, worse Eastern Cooperative Oncology Group performance status (1 or more), no primary site resection, and a high prognostic index (1 or more). In the pembrolizumab cohort, liver metastasis, bone metastasis, and worse Eastern Cooperative Oncology Group-performance status (1 or more), and high prognostic index (1 or more) were the risk factors for overall survival. In the pembrolizumab cohort, patients with a complete response or partial response during prior platinum-based chemotherapy had better overall survival with the following pembrolizumab treatment than those with stable or progressive disease (P = 0.004). Considering the similarity of these risk factors in two sequential treatments, it may be possible to predict the response to pembrolizumab according to the response to prior chemotherapy.

Pathologic and clinical outcomes after neoadjuvant modified FOLFIRINOX and gemcitabine and NAB-paclitaxel for pancreatic cancer.

e16236 Background: Surgical resection is the only potentially curative option for pancreatic cancer (PC). Unfortunately, just 15-20% of patients (pts) have resectable disease at the time of diagnosis. Recently, for a variety of reasons, neoadjuvant chemotherapy (NAC) has been widely adopted in both borderline resectable and resectable tumors. Most guidelines recommend either modified FOLFIRINOX (mFOLFIRINOX) or gemcitabine and NAB-paclitaxel (GnP) in this setting. This is largely based on phase II trials and extrapolations from trials in the metastatic setting. Here we investigate the difference in tumor regression score (TRS) and clinical outcomes between these regimens. Methods: We retrospectively collected data from pts who underwent resection of PC after NAC at Ochsner Health between July 2012 and July 2021. Primary objective was TRS on operative pathology as assessed by the reading pathologist. Secondary objectives were progression free survival (PFS) from the date of surgery and overall survival (OS) from the date of diagnosis. TRSs were dichotomized as complete (0)/moderate (1) responses versus (vs) minimal (2)/poor (3) responses. The dichotomized score was assessed using log-binomial regression. Kaplan-Meier survival analysis was utilized to estimate PFS and OS. Survival curves were compared by the log-rank test. Results: We identified 96 pts with PC who had NAC followed by surgical resection. Mean age at diagnosis was 65.7. 55% had borderline resectable and 45% had clearly resectable disease at diagnosis. 74 pts received mFOLFIRINOX and 22 pts received GnP. Pts receiving GnP were more likely to be older (71 vs 64, P = 0.001) and have a worse Eastern Cooperative Oncology Group performance status (PS) (P = 0.019). TRSs were similar between the 2 groups with 58.1% and 59.1% in each group achieving a TRS of 2. 7 pts in the mFOLFIRINOX group had TRS of 0 (CR) while 0 pts in the GnP group had a TRS of 0. When controlling for age and PS, risk ratio for a lower TRS (0/1 vs 2/3) with mFOLFIRINOX vs GnP was 1.22 (0.27 - 5.47). 40% and 36.4% had disease recurrence after mFOLFIRINOX and GnP, respectively. Median PFS and OS were 15.6 and 23.4 months (m) in the mFOLFIRINOX group and 18.9 and 27.6 m in the GnP group (P = 0.996, P = 0.933, respectively). On multivariate analysis, controlling for age and PS, hazard ratios for OS and PFS with mFOLFIRINOX vs GnP were 0.86 (95% CI 0.38–2.18) and 1.17 (95% CI 0.53–2.84), respectively. Conclusions: Our study showed no difference in TRS between mFOLFIRINOX or GnP as NAC, although the small number of pts who received GnP precluded statistical inference. Differences in survival outcomes between the two NAC regimens were not significantly different, and outcomes were comparable to those reported in the phase II SWOG S1505 trial. Large prospective trials comparing these two regimens in terms of efficacy and toxicity will be required to better answer these questions.

Evaluating the impact of performance status criteria on minority eligibility for oncology clinical trials.

e18701 Background: Restrictive criteria contribute to low enrollment in clinical trials. These criteria can also amplify health disparities by reducing the racial and ethnic diversity of the cohort. Many studies show that minority patients exhibit worse Eastern Cooperative Oncology Group (ECOG) performance status than white patients. Based on clinical trial data, some researchers have hypothesized that relaxing the ECOG criterion in clinical trial criteria could improve the diversity of the cohort. However, little research exists to measure ECOG’s impact on minority eligibility. Using Real-World Data (RWD), we evaluate whether relaxing the ECOG criterion monotonically increases the racial diversity of the cohort in oncology clinical trials. Methods: We used ConcertAI’s database of US oncology Electronic Medical Record (EMR) data, which includes clinical data from CancerLinQ Discovery™. We conducted sensitivity analyses for the inclusion criteria of 16 different clinical trials across multiple cancer indications. For each trial, we created five cohorts based on five different ECOG score upper limits. For example, the first cohort only included patients who had an ECOG of 0, the second cohort included patients with an ECOG of 0 or 1, etc. We then recorded the percentage of non-white patients for the resulting cohorts. We ran simple linear regressions to measure whether the change in the percentage of non-white patients was statistically significant. Results: Relaxation in ECOG status led to no uniform change in the racial diversity of patients across the 16 trials. The limited changes we did observe were not statistically significant. Conclusions: Our findings suggest that improving diversity will require more than just relaxing ECOG restrictions, and a multi-faceted approach may be needed. Future research exploring the relationship between ECOG and diversity should control for potential confounders like age, gender, and comorbidities using multivariable models. Such research needs to also account for patients with unknown race and ECOG, which represented large parts of our study population. Such research could elucidate whether the phenomenon observed in the general population—that minority patients tend to have worse performance status than whites—holds true in the sub-population of oncology patients.[Table: see text]

Validity of a single-item indicator of treatment side effect bother in a diverse sample of cancer patients

PurposeWith higher efficacy of cancer therapies, the numbers and types of side effects experienced by patients have also increased, evidencing a need for brief assessments of side effect bother. The Functional Assessment of Cancer Therapy-General (FACT-G) includes the item “I am bothered by side effects of treatment” (GP5). This study aimed to confirm GP5’s validity in a large, diverse, real-world patient sample.MethodsReal-world data were drawn from 10 Adelphi Disease Specific Programmes (DSP™) conducted between 2015 and 2019 in France, Germany, Italy, Spain, the UK and the USA, covering 10 cancer sites. We examined correlations between GP5 responses and varied measures of patient-reported global health and the number of side effects experienced. We explored whether more advanced patients and those with worse Eastern Cooperative Oncology Group Performance Status Rating (ECOG PSR) reported greater side effect bother. Finally, we conducted differential item functioning (DIF) assessment using the Mantel–Haenszel approach.ResultsThe sample included 6755 advanced cancer patients. GP5 responses were distributed similarly across most cancer sites. A moderate, negative correlation (rpolyserial = − 0.43) between GP5 responses and global health evidenced convergent validity. Known groups validity was evidenced by dichotomised distributions of GP5, showing expected results between cancer stage 2 vs. 3 and 4 and with ECOG PSR (p < 0.001). Little evidence of DIF was found.ConclusionGP5 exhibited evidence of validity across cancer sites and countries and appeared to measure the same construct across these countries. GP5 has significant promise as a summary indicator of side effect bother.

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium

BackgroundPatients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.Patients and methodsPatients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients).ResultsA total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality.ConclusionsClinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies.Clinical trial identifierNCT04354701

High fibrinogen-albumin ratio index predicts poor prognosis for lung adenocarcinoma patients undergoing epidermal growth factor receptor-tyrosine kinase inhibitor treatments.

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) have become the preferred therapy as first-line treatment of non-small cell lung cancer patients harboring sensitizing EGFR mutations. However, the prognostic indicators are limited. The present study aimed to assess the prognostic value of immune-inflammation factors, fibrinogen-albumin ratio index (FARI), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) in EGFR-Mutant lung adenocarcinoma patients receiving first-generation EGFR-TKIs treatment.194 patients were included in this retrospective analysis. FARI was calculated as fibrinogen / albumin. Receiver operating characteristic curve was used to evaluate the optimal cut-off value for FARI, NLR, and PLR to progression free survival (PFS). Univariate and multivariate survival analysis were performed to identify factors correlated with PFS and overall survival (OS).Applying cut-offs of ≥0.08 (FARI), ≥3.28 (NLR), and ≥273.85 (PLR), higher FARI or NLR was associated with worse Eastern Cooperative Oncology Group performance status (ECOG PS) (P = .018, .002, respectively), and there were more males in high NLR group (P = .043). In univariate analysis, ECOG PS status, NLR, PLR, and FARI were significantly associated with PFS (P = .017, .004, <.001, .001, respectively) as well as OS (P < .001, = .001, .002, .023, respectively). In multivariate analysis, PLR (hazard ratios [HR] 1.692; 95% CI 1.054–2.715; P = .029) and FARI (HR 1.496; 95% CI 1.031–2.172; P = .034) were independent prognostic factors for PFS. While only ECOG PS status (HR 2.052; 95% CI 1.272–3.310; P = .003) was independently correlated with OS.FARI is independently associated with PFS in EGFR-Mutant lung adenocarcinoma patients receiving first-line EGFR-TKIs treatment.

Outcomes By Cardiac Stage in Newly Diagnosed AL Amyloidosis: Results from Andromeda

Outcomes By Cardiac Stage in Newly Diagnosed AL Amyloidosis: Results from Andromeda

Neutrophil to lymphocyte ratio predicts prognosis in unresectable pancreatic cancer

Inflammation-based prognostic indicators have been developed to predict the prognosis in patients with pancreatic cancer. However, prognostic indices have not been established in patients with unresectable pancreatic cancer, including those without indication for chemotherapy at diagnosis. This study aimed to identify the predictors in all patients with unresectable pancreatic cancer. We retrospectively analyzed data of 119 patients with unresectable pancreatic cancer from June 2006 to September 2018. The following laboratory parameters were evaluated: the Glasgow Prognostic Score (GPS), modified GPS, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein albumin (CRP/Alb) ratio, and prognostic nutritional index (PNI). We performed time-dependent receiver operating characteristic analysis, overall survival (OS) analysis, and univariate and multivariate analyses to determine the prognostic factors in patients with unresectable pancreatic cancer. The cut-off value for NLR was determined to be 3.74. The 6-month OS rates in low and high NLR groups were 75.5% and 18.8% (P < 0.001). In the univariate analysis, advanced age (P = 0.003), metastatic pancreatic cancer (P = 0.037), no treatment (P < 0.001), worse Eastern Cooperative Oncology Group Performance Status (ECOG-PS) (P < 0.001), high GPS (P < 0.001), high modified GPS (P < 0.001), high NLR (P < 0.001), high PLR (P = 0.002), high CRP/Alb ratio (P < 0.001), and low PNI (P < 0.001) were identified as the prognostic factors. The multivariate analysis revealed that metastatic pancreatic cancer (P = 0.046), no treatment (P < 0.001), worse ECOG-PS (P = 0.002), and high NLR (P < 0.001) were independently associated with OS. We revealed that the high NLR could be an independent indicator of poor prognosis in patients with unresectable pancreatic cancer.

MicroRNA-199b Deregulation Shows a Strong SET-Independent Prognostic Value in Early-Stage Colorectal Cancer.

The endogenous PP2A inhibitor SET Nuclear Proto-Oncogene (SET) has been reported to play oncogenic roles and determines poor outcomes in colorectal cancer (CRC). Our group previously showed that miR-199b is deregulated in metastatic CRC, and reduced the cell viability and enhanced the sensitivity of CRC cells to standard induction chemotherapy drugs, mainly through direct negative SET regulation. Clinically, miR-199b downregulation was identified as the molecular mechanism responsible for SET overexpression in around half of metastatic CRC patients. However, the potential clinical value of miR-199b in early-stage CRC remains totally unknown. Thus, here we explored the expression levels of this microRNA in a cohort of 171 early-stage CRC patients using real-time polymerase chain reactions. MiR-199b downregulation was found in 21.6% of cases (37 out of 171) and was significantly associated with those patients with a worse Eastern Cooperative Oncology Group (ECOG) status (p = 0.045). Moreover, miR-199b downregulation predicted shorter overall (p < 0.001) and progression-free survival (p = 0.015). As expected, we next immunohistochemically analyzed SET, observing that it was significantly associated with miR-199b in our cohort. However, multivariate analyses showed that miR-199b was an independent biomarker of poor outcomes in early-stage CRC with a predictive value stronger than SET. In conclusion, our results highlight the potential clinical usefulness of miR-199b and suggest that it could represent a novel molecular target in this disease.

Pemetrexed-Based Chemotherapy Is Inferior to Pemetrexed-Free Regimens in Thyroid Transcription Factor 1 (TTF-1)-Negative, EGFR/ALK-Negative Lung Adenocarcinoma: A Propensity Score Matched Pairs Analysis

IntroductionThyroid transcription factor 1 (TTF-1) is a prognostic biomarker in lung adenocarcinoma; however, TTF-1–positive patients also display more favorable factors like actionable target mutations. In contrast, TTF-1–negative cancer is a poorly described entity. We performed a retrospective study to characterize a TTF-1–negative phenotype and to evaluate outcome depending on the chemotherapy regimen applied in the EGFR/ALK-negative population. Patients and MethodsPhenotypic traits were analyzed in 741 patients with evaluable TTF-1 expression status, among them 529 patients with platinum-based first-line chemotherapy, with disease diagnosed between 2009 and 2016 at a tertiary referral university hospital. The influence of TTF-1 and several cofactors on progression-free survival and overall survival (OS) were analyzed using a 1:1 propensity score matching model, depending on the platinum doublet chemotherapy’s incorporating pemetrexed or not, with subsequent Cox regression. ResultsTTF-1 negativity implied a distinct cancer phenotype with the predominance of male sex, worse Eastern Cooperative Oncology Group performance status, greater metastatic burden at primary diagnosis, and more adrenal gland metastases. These patients had improved progression-free survival (hazard ratio, 0.42; P = .001) and OS (hazard ratio, 0.40; P < .001) when gemcitabine-, taxane-, or vinorelbine-based regimens were provided instead of pemetrexed. None of the regimens was superior in TTF-1–positive patients with regard to OS. Overall, TTF-1 expression was strongly prognostic with a substantial increase in progression-free survival (hazard ratio, 0.54; P < .001) and OS (hazard ratio, 0.53; P < .001). ConclusionTTF-1 negativity is associated with a distinct cancer phenotype. Incorporation of this biomarker may be helpful when choosing an appropriate therapy regimen.

Cause of mortality in patients with lung cancer and brain metastasis.

e21743 Background: Lung cancer is the most common cause of cancer-related mortality and most deaths are associated with metastatic disease, with brain being a common site. Historically, whole brain radiation therapy was the treatment of choice and resulted in median survivals in the range of 6 months. There is no consensus in management of patients who have brain metastasis with systemic disease.We aim to evaluate patients with brain metastasis from lung cancer for cause of death, to investigate whether patients died from central nervous system (CNS) progression or systemic disease or other/undetermined causes. Our hypothesis is that most deaths in contemporary patients with brain metastasis in lung cancer are due to systemic disease, and less commonly due to CNS progression. Methods: In this retrospective observational study, we did a chart review of all adult patients with non-small cell lung cancer and brain metastasis or leptomeningeal disease, who received treatment at Maimonides Cancer Center between 2010 and 2017. Patients with unavailable or incomplete medical records were excluded. Baseline characteristics, pathological factors of the tumor and cause of death was collected from the chart. The cause of death was categorized into systemic and brain causes, and difference in characteristics of patients and tumor were studied. Results: A total of 132 patients were included and their charts were reviewed. Out of 132, 96 could have a clear cause of death categorized into systemic or brain causes, the rest were either mixed or uncategorized. We found that 33% patients died of brain metastasis, and related causes, whereas 67% died of systemic disease progression. There were no different in the two groups in terms of gender, smoking status, histology, size of lung lesion, or number and size of brain lesion. The patients who died of brain metastasis had a significantly higher age, and worse Eastern Cooperative Oncology Group status. Interestingly, the patients who died of systemic causes more commonly had adrenal metastasis (12 vs 0) which was statistically significant, and liver (14 vs 3) metastasis which was not statistically significant. Conclusions: Two-thirds of patients with brain metastases died of systemic disease rather than CNS progression. This may reflect improvements in systemic and local therapies to forestall cancer progression in the CNS. This finding suggests that delaying systemic therapy for CNS treatment may negatively impact overall cancer control. More research needs to be done to answer this question with certainty, including prospective clinical trials.

Validation of Hyponatremia as a Prognostic Predictor in Multiregional Upper Tract Urothelial Carcinoma.

Hyponatremia has been shown to be associated with prognosis in various cancers, but its role in upper tract urothelial carcinoma (UTUC) is largely unidentified. We created an international multiregional cohort of UTUC, consisting of 524 and 213 patients from Taiwan and the U.S., to validate the significance of hyponatremia. Clinicopathologic characteristics were compared according to the presence of hyponatremia. Univariate and multivariate Cox regression models were used to investigate the association of hyponatremia with disease progression and survival. The impact of hyponatremia in patients from distinct regions was also analyzed. Hyponatremia was found in 143 (19.4%) patients. Hyponatremic patients had significantly worse Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.00001) and higher pT stage (p = 0.002). In multivariate analysis, hyponatremia was an independent prognostic factor for progression (HR 1.585, 95% CI 1.115–2.253, p = 0.010), cancer-specific death (HR 2.225, 95% CI 1.457–3.397, p = 0.0002), and overall mortality (HR 1.819, 95% CI 1.299–2.545, p = 0.0005). Kaplan–Meier analysis showed the consistent adverse effect of hyponatremia on all outcomes in patients from Taiwan and the U.S. (all p < 0.05). Hyponatremia is commonly accessible and can serve as a negative marker for both the general health condition and disease severity of UTUC patients. A similar implication of hyponatremia in progression and survival despite patients’ region of presentation suggests its general applicability across different ethnicities.

Shared decision making with oncologists and palliative care specialists effectively increases the documentation of the preferences for do not resuscitate and artificial nutrition and hydration in patients with advanced cancer: a model testing study

BackgroundCommunication in do not resuscitate (DNR) and artificial nutrition and hydration (ANH) at the end of life is a key component of advance care planning (ACP) which is essential for patients with advanced cancer to have cares concordant with their wishes. The SOP model (Shared decision making with Oncologists and Palliative care specialists) aimed to increase the rate of documentation on the preferences for DNR and ANH in patients with advanced cancer.MethodsThe SOP model was implemented in a national cancer treatment center in Taiwan from September 2016 to August 2018 for patients with advanced cancer visiting the oncology outpatient clinic. The framework was based on the model of shared decision making as “choice talk” initiated by oncologists with “option talk” and “decision talk” conducted by palliative care specialists.ResultsAmong 375 eligible patients, 255 patients (68%) participated in the model testing with the mean age of 68.5 ± 14.7 years (mean ± SD). Comparing to 52.3% of DNR documentation among patients with advanced cancer who died in our hospital, the rate increased to 80.9% (206/255) after the decision talk in our model. Only 6.67% (n = 17) of the participants documented their preferences on ANH after the model. A worse Eastern Cooperative Oncology Group Performance Status was the only statistically significant associating factor with a higher rate of DNR documentation in the multiple logistic regression model.ConclusionsThe SOP model significantly increased the rate of DNR documentation in patients with advanced cancer in this pilot study. Dissemination of the model could help the patients to receive care that is concordant with their wishes and be useful for the countries having laws on ACP.