Good Risk Group Research Articles

Scoring System to Personalize Management of Emphysematous Pyelonephritis.

Emphysematous pyelonephritis (EPN) is a life-threatening condition that requires prompt diagnosis and treatment. The prognosis of EPN is variable, and there is no single treatment that is universally effective. In this study, we developed a scoring system to predict the prognosis of EPN and to guide management. The scoring system was developed based on a retrospective analysis of 91 patients with EPN. Nineteen risk factors for emphysematous pyelonephritis were assessed with univariate and multivariate analysis. Seven factors were found significant on analysis. The scoring system was developed by including these 7 risk factors: renal stone disease, leukocytosis, raised creatinine, EPN grade, and septic shock. The score ranged from 1 to 18, with a higher score indicating a worse prognosis. The scoring system was able to stratify patients into three risk groups: good risk, intermediate risk, and poor risk. The scoring system can be used to personalize the management of EPN. Patients in the good-risk group may be managed with conservative treatment, while patients in the intermediate-risk and poor-risk groups may require intervention, such as DJ stenting, percutaneous nephrolithotomy or nephrectomy. The scoring system is a valuable tool for predicting the prognosis of EPN and guiding management. It can help clinicians to tailor treatment to the individual patient and to improve outcomes. The prognostic score helps identify patients who are at high risk. This score helps in the selection of appropriate management options.

CD302 predicts achievement of deep molecular response in patients with chronic myeloid leukemia treated with imatinib

AbstractAchieving a deep molecular response (DMR) is a prerequisite for treatment-free remission in chronic myeloid leukemia (CML) and a key milestone for patients with CML. This study identified patients unlikely to achieve a 5-year DMR through differential expression of cluster of differentiation (CD) genes, and clinical variables at diagnosis. Peripheral blood samples (n = 131) from patients treated with imatinib or nilotinib underwent transcriptomic microarray profiling. The decision-tree analysis delineated 2 distinct poor-risk (PR) cohorts, distinguished by high 3-month BCR::ABL1% (PR-1), or high CD302 expression (PR-2). The 5-years DMR achievement rate was significantly lower in both PR groups than in the good-risk (GR) group in patients treated frontline with imatinib (0% vs 27% vs 83%; P < .0001) or nilotinib (PR-2 vs GR, 17% vs 83%; P = .02). Gene-set enrichment analysis revealed reduced expression of cell cycle–related genes in PR-2, as well as increased metabolism and STAT3 pathway genes, which has previously been linked to leukemic cell persistence and resistance to tyrosine kinase inhibitors. Moreover, PR-2 had a higher frequency of CD34+CD302+ and CD14+CD302+ cells than GR samples. Strategies aimed at targeting STAT3 and/or metabolic pathways associated with high CD302 may provide novel therapeutic approaches that could help improve treatment outcomes and eradicate residual disease.

The outcome in pediatric acute myeloblastic leukemia; results of the first-line treatment and contribution of hematopoietic stem cell transplantation to survival of relapsed patients.

To analyze the long-term outcome of pediatric patients with acute myeloblastic leukemia. Data from 69 patients 0-18 years of age diagnosed between December 2001 and October 2019 were analyzed in April 2023. Patients received MRC-AML10 chemotherapy (2ADE+MACE+MidAC). No maintenance chemotherapy or preventive cranial radiotherapy was administered. Twelve patients with Down syndrome and 15 patients with promyelocytic leukemia were in the cohort. Patients with Down syndrome received reduced chemotherapy (cumulative anthracycline 420 mg/m2, cytarabine 3.4 g/m2, etoposide 1400 mg/m2). ATRA was added to chemotherapy in promyelocytic leukemia. Four patients (5.8%) died in the induction (two typhlitis, one intracranial hemorrhage, and one resistant disease). The complete remission rate of 66 patients was 87.8%. There was one death due to cardiotoxicity. Total infection-related deaths were 7.2%. Seven patients with high-risk criteria and one with resistant disease underwent hematopoietic stem cell transplantation (HSCT) following the first-line treatment. All seven patients in remission were alive and disease-free. The relapse rate was 34.4% (n = 21). Four patients developing marrow relapse were disease-free in the second remission after salvage and maintenance chemotherapy. Thirteen patients (18.84%) underwent HSCT in the second remission and 8 are alive and disease-free. The mean follow-up period of patients from diagnosis was 185 ± 13 months. Thirty-four patients (49.2%) were alive and disease-free in the first remission whereas another two patients in the first remission developed secondary malignancy. In good, standard, and poor risk groups, event-free survival (EFS) rates were 68.2%, 52.9%, and 10%, and overall survival (OS) rates were 86.4%, 79.4%, and 20%, respectively. Fifteen years of EFS and OS of the whole cohort were 49.3% and 69.6%, respectively. When compared with national data and multicenter studies of developed countries, survival rates were acceptable.

Potential Predictive Biomarkers for the Development and Outcomes of Inhibitors in Hemophilia A Patients

Introduction Inhibitor development poses a significant challenge in the treatment of hemophilia A (HA). Approximately 30% of HA patients develop inhibitors in response to FVIII infusion therapy. While the risk is highest early in treatment days, patients are at risk throughout their lifetime. Regardless of certain known risk factors, the lack of biomarkers for inhibitor development hampers efforts to prevent their occurrence. Since inflammation is a well-known risk factor, one of our goals is to identify potential biomarkers among inflammatory cytokines. Another focus is glycosylation-related biomarkers, which has drawn great attention in biomarker discovery of various diseases including cancers. By analyzing the association of cytokines and plasma glycosylation with inhibitor formation, this research aims to provide valuable references for clinical care. Methods Plasma samples from 60 HA patients, and 23 healthy donors were analyzed to detect the levels of G-CSF, IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10, IL12p70, IP-10 and TNF. The HA samples were divided into inhibitor negative (InhNeg, BU &amp;lt; 0.6, n = 26) and inhibitor positive (InhPos, BU ≥ 0.6, n = 34) groups. A predictive model of inhibitor development was established using logistic regression analysis. To investigate the correlation between cytokine levels and high inhibitor titers, the inhibitor-positive samples were further categorized into good risk (&amp;lt; 10 BU, n = 14) and poor risk (≥ 10 BU, n = 20) groups based on immune tolerance induction therapy prognosis. Total plasma N-glycans were released, methylated, and analyzed by using MALDI-TOF MS/MS. A synthesized N-glycan was spiked in to quantify each glycoform. The study evaluated the correlation between HA sample groups and various glycosylation ratios, including for sialylation, core-fucosylation, galactosylation and galactose. The cut-off value of each glycosylation ratio was based on the median of the inhibitor-negative group. Results The adjusted odds ratio of inhibitor development for elevated G-CSF, IL-6 and decreased IL-10 were 2.84 (95% CI: 1.45-8.48; p = 0.021), 1.50 (95% CI: 1.14-2.42; p = 0.069), and 0.28 (95% CI: 0.10-0.61; p = 0.006), respectively in HA patients. Among InhPos HA patients, the levels of G-CSF, IL-2, IL-6, IL-8, and IL-10 in poor risk group were significantly higher than in good risk group (p-value &amp;lt; 0.05, ANOVA). Since aging also causes glycosylation changes, we analyzed adult (≥ 18 years old, n = 31) and pediatric (&amp;lt; 18 years old, n = 17) HA patients separately. Among analyzed glycan ratios, 80% of adult HA patients with inhibitors had a higher core-fucosylation ratio. All pediatric patients with inhibitors had significant lower sialylation and higher galactosylation ratios. Strikingly, pediatric patients with inhibitors exhibited around 2-fold higher core-fucosylation than those without inhibitor. Conclusion Our finding of elevated levels of G-CSF and IL-6 along with decreased levels of IL-10 associated with the presence of inhibitors, suggests the potential for prediction of inhibitor development. Moreover, high levels of G-CSF, IL-2, IL-6, IL-8 and IL-10 in patients with high inhibitor titers (≥ 10 BU, poor risk group) but not in good risk group imply they could be explored in future studies as prognostic factors in immune tolerance therapy. Glycan ratios can also hold promise as biomarkers including higher core-fucosylation in adult patients. Additionally, significant lower sialyation, higher galactosylation and core-fucosylation ratios indicate higher possibility of inhibitor development in pediatric patients.

Prognostic Impact of Blood Lipid Profile in Patients With Advanced Solid Tumors Treated With Immune Checkpoint Inhibitors: A Multicenter Cohort Study.

Specific components of lipid profile seem to differently impact on immune activity against cancer and unraveling their prognostic role in patients with solid cancer treated with immune checkpoint inhibitors (ICIs) is needed. We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile (total cholesterol [TC], triglycerides [TG], low-density lipoproteins [LDL], high-density lipoproteins [HDL]) of patients with consecutive solid cancer treated with ICIs, and we investigated their role in predicting clinical outcomes. At a median follow-up of 32.9 months, among 430 enrolled patients, those with TC ≥ 200 mg/dl showed longer median progression-free survival (mPFS; 6.6 vs. 4.7 months, P = .4), although not reaching statistical significance, and significantly longer median overall survival (mOS; 19.4 vs. 10.8 months, P = .02) compared to those with TC < 200 mg/dl. Conversely, patients with TG ≥150 mg/dl displayed shorter PFS (3.4 vs. 5.1 months, P = .02) and OS (7.1 vs. 12.9 months, P = .009) compared to those with TG <150 mg/dl. TC and TG were then combined in a "LIPID score" identifying three subgroups: good-risk (GR) (TC ≥200 mg/dl and TG <150 mg/dl), intermediate-risk (IR) (TC <200 mg/dl and TG <150 mg/dl or TC ≥200 mg/dl and TG ≥150 mg/dl) and poor-risk (PR) (TC <200 mg/dl and TG ≥150 mg/dl). The mPFS of GR, IR, and PR groups was 7.8, 4.3, and 2.5 months, respectively (P = .005); mOS of GR, IR, and PR was 20.4, 12.4, and 5.3 months, respectively (P < .001). At multivariable analysis, the PR profile represented an independent poor prognostic factor for both PFS and OS. We developed a lipid score that defined subgroups of patients with cancer who differently benefit from ICIs. Further mechanistic insights are warranted to clarify the prognostic and predictive role of lipid profile components in patients treated with ICIs.

The relationship between a priori defined prognostic risk groups and and overall survival (OS) in men with metastatic hormone sensitive prostate cancer (mHSPC).

5073 Background: Prior analyses have shown that men who present with high volume (HV) disease and de novo metastases have shorter OS compared with other mHSPC subgroups. The objective of this analysis was to determine the prognostic relationship between a-priori defined 4-prognostic groups and OS in men with mHSPC and in a subset of trials in patients treated with androgen deprivation therapy (ADT) +docetaxel. This hypothesis was investigated by the STOPCAP M1 collaborators. Methods: We obtained individual patient data (IPD) from 13 randomized trials comparing treatment regimens (ADT or ADT + docetaxel in the control or research arms) in mHSPC. OS was defined as the time between date of randomization and date of death/or last follow-up. Patients (pts) were classified into 4 mutually exclusive groups. Poor prognostic risk-group was defined as HV (presence of visceral metastases, and/or &gt; 4 bone metastases or presence of bone metastases beyond pelvic or vertebral bones) plus synchronous diagnosis (SYN); whereas intermediate risk groups were patients with HV and metachronous (MET; intermediate A) or low volume plus SYN (intermediate B); and lastly good risk group had LV plus MET. The proportional hazards model was used to estimate the hazard ratio (HR) and assess the prognostic significance of risk groups in predicting OS adjusting for treatment. Results: Of 6041 pts included in this analysis, 60% (3622 pts) had died. Median follow-up time=5-years. Overall 11%, 8%, 47% and 34% were in the good, intermediate A, intermediate B and poor risk groups, respectively and for trials including docetaxel (n=2627 pts) 9%, 5%, 39% and 47% respectively. HRs for risk groups are shown in the table. Conclusions: Differences in OS across the risk groups were observed. Further work is needed to investigate if more precise prognostic groups can be defined such as better characterization of patients' groupings of extent of bone metastases and visceral metastases. Clinical trial information: NCT00309985 ; NCT00268476 ; NCT00104715 ; NCT00079001 ; NCT00002651 ; NCT00685646 . [Table: see text]

The new prognostic index of advanced gastric cancer using the data from JCOG1013.

342 Background: We previously reported that performance status (PS) ≥1, no prior gastrectomy, number of metastatic sites ≥2, and high serum ALP level are poor prognosis factors and proposed a JCOG prognostic index by analyzing the data of advanced gastric cancer (AGC) patients enrolled in JCOG9912 (Takahari D et al. Oncologist 2014). Recently, Neutrocyte/ Lymphocyte Ratio (NLR) and diffuse type of cancer have also been reported to be prognostic factors of AGC. Methods: Prognostic factors were assessed in patients with AGC who enrolled in JCOG1013, the phase III study comparing docetaxel, cisplatin, and S-1 (DCS) versus cisplatin and S-1 (CS) in first-line treatment (Yamada Y et al. Lancet Gastroenterol Hepatol. 2019) was retrospectively evaluated using a Cox proportional regression model. The overall adequacy of risk prediction in the modified JCOG prognostic index and the original index were assessed by C-statistics. Results: Among 741 patients, 730 with all data for this analysis were selected. The median overall survival (OS) was 14.9 months (95% confidence interval [CI], 14.1–15.8). The median OS of the good (n=233), moderate (n=444), and poor (n=53) risk groups by the original JCOG index was 19.0, 14.2, and 9.1 months, respectively. The HRs compared with the good group were 1.59 [95% CI, 1.33–1.89; p &lt; 0.0001] in the moderate group, and 2.47 [95% CI, 1.81–3.38; p &lt; 0.0001] in the poor group with C-statistics of 0.572. In the multivariable analysis of 7 factors which showed p&lt;0.1 in univariable analysis, PS ≥1 (hazard ratio [HR], 1.490; 95% CI, 1.264–1.755; p &lt; 0.0001), diffuse type (HR, 1.337; 95% CI, 1.122–1.594; p = 0.012), number of metastatic sites ≥2 (HR, 1.256; 95% CI, 1.058–1.492; p = 0.0093), and NLR≥3.1 (HR, 1.539; 95% CI, 1.309–1.809; p &lt; 0.0001) were significantly associated with worse prognosis, whereas no prior gastrectomy, peritoneal metastasis, and high serum ALP level were not. As the modified JCOG prognostic index, patients were classified into three groups according to the number of these four newly identified prognostic risk factors: good (no), moderate (1 or 2), and poor (3 or 4). Median OS of the good (n=221), moderate (n=441), and poor (n=68) risk groups was 20.6, 13.7, and 9.4 months, respectively. The HRs compared with the good group were 1.70 [95% CI, 1.42–2.03; p &lt; 0.0001] in the moderate group, and 3.11 [95% CI, 2.33–4.14; p &lt; 0.0001] in the poor group with C-statistics of 0.591. Three groups by the modified JCOG prognostic index also showed clear separation of OS in either subgroup of DCS or CS. Conclusions: Modified JCOG prognostic index, including NLR ≥3.1 and diffuse type instead of no prior gastrectomy and high serum ALP level, showed clear stratification of OS in JCOG1013.

Robust Validation of the UKALL High Hyperdiploid Risk Profile Using Individual Patient Data Collected By the Harmony Alliance

High hyperdiploidy (HeH) is the most prevalent genetic subtype in paediatric acute lymphoblastic leukaemia (ALL) and is associated with a favourable outcome. HeH karyotypes have an increased modal number of 51-67 chromosomes and chromosome gain is non-random. Even though the outcome of paediatric patients with HeH is better than other subgroups, in adults it is far less favourable. The prevalence of the subgroup means that it accounts for a significant proportion of relapses; hence identifying risk factors within HeH is important. We recently developed a novel risk profile for HeH. Patients with both +17 and +18 together or patients with either +17 or +18 coupled with an absence of +5 or +20 defined a good risk (GR) group with a relapse risk <5% [Lancet Haem. 2021;8(11):e828-e39]. The remaining patients with HeH [poor risk (PR) group] had a relapse risk ~15% (i.e. similar to patients with intermediate risk genetics). In our original publication, we were restricted to using a single UK based clinical trial, UKALL2003, to validate our novel risk profile developed on data from ALL97/99. However, a comprehensive assessment of a novel risk profile requires validation on multiple independent cohorts but such cohorts are rarely readily available. The HARMONY alliance (http://www.harmony-alliance.eu) is a European big data platform which has collected data on >115,000 patients with various haematological malignancies; including >10,000 patients with ALL. The aims of this project were to (a) determine if the UKALL-HeH risk profile can be validated in a large independent cohort comprising data from multiple clinical trials and from both childhood and adults patients; and (b) assess the added benefit of validating a risk profile using data from the HARMONY platform compared with a single a country-specific cohort. The ALL cohort within HARMONY comprised cases from multiple paediatric and adult ALL trials including UKALL2003. Only cases with karyotype written according to ISCN were eligible for this study. A search of the cohort revealed 1169 karyotypes with a modal number of 51-67 chromosomes. Karyotypes with t(9;22)(q34;q11) or chromosome patterns indicative of masked haploidy or low hypodiploidy were excluded. Using a custom built R function, we sorted karyotypes according to trisomic status of chromosomes 5, 17, 18 and 20 (fig1A). Karyotypes not assigned definitively to a risk group due to being incomplete or the presence of marker chromosomes were assigned to provisional groups but later combined with the definitive cases because their relapse rate was equivalent. A total of 865 (74%) karyotypes had a UKALL HeH GR profile whilst 304 (26%) had a PR profile. The proportion of patients with a PR profile was significantly higher among those aged over 25 years compared to those under 25 (63% v 25%, p<0.001). Overall, patients with a PR profile had a significantly higher relapse rate at 5 years compared with those with a GR profile 6% (4-7) v 19% (14-23), log rank p<0.001. The hazard ratio from a univariate Cox model was 3.52 (SE 0.20 p<0.001). This effect was independent of MRD - hazard ratio for relapse from multivariate model was 3.30 (SE 0.26 p<0.001). The prognostic impact of the UKALL HeH profile was similar across all age groups examined including adults aged over 25 years but was greater among patients that were MRD negative (<0.01%) at the end of induction compared with MRD positive (≥0.01%) cases (fig1B). Compared to using the UKALL2003 cohort alone for validation, HARMONY provided a validation cohort that was 60% larger with a broader age range: 1-24 vs. 1-70 years. In addition, the Cox model estimates were more accurate with smaller standard errors. The standard error for the hazard ratio for risk of relapse reduced from 1.11 to 0.20. Moreover, validation on cohorts of patients treated on protocols from other study groups provides additional evidence for the robustness of the risk profile. In conclusion, we have validated the UKALL HeH risk profile on a larger and more heterogeneous cohort of patients. We confirm that the profile defines both a low risk subgroup of HeH paediatric patients that could be considered for treatment reduction, as well as a subgroup of HeH that has a risk of relapse similar to patients with intermediate risk genetics. In addition, we have demonstrated how the HARMONY data platform, which provides access to a standardised disease-specific datasets, can rapidly facilitate biomarker research. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Risk Model for Patients with PSA-Only Recurrence (Biochemical Recurrence) Based on PSA and PSMA PET/CT: An Individual Patient Data Meta-Analysis.

An individual patient meta-analysis followed 1216 patients with PSA-only recurrence (biochemical recurrence, BCR) restaged with [68Ga]Ga-PSMA-11 PET/CT before the salvage treatment for median 3.5 years and analyzed the overall survival (OS). A new risk model included a good risk group with a prescan PSA &lt; 0.5 ng/mL (26%), an intermediate risk group with a prescan PSA &gt; 0.5 ng/mL and a PSMA PET/CT with 1 to 5 positive sites (65%), and a poor risk group with a prescan PSA &gt; 0.5 ng/mL and a PSA PET/CT with &gt; 5 positive sites (9%) (p &lt; 0.0001, log rank test). The poor risk group had a five-year OS &gt; 60%. Adding a BCR risk score by the European Association of Urology did not significantly improve the prediction of OS (p = 0.64). In conclusion, the restaging PSMA PET/CT markedly predicted the 5-year OS. The new risk model for patients with PSA-only relapse requires a restaging PSMA PET/CT for patients with a prescan PSA &gt; 0.5 ng/mL and has a potential use in new trials aiming to improve the outcome for patients with PSA-only recurrence who have polysites prostate cancer detected on PSMA PET/CT.

Patterns of Relapse and Risk Reduction Following Tumor Debulking by Bridging Radiotherapy prior to Chimeric Antigen Receptor T Cell Therapy in Non-Hodgkin Lymphoma

Patterns of Relapse and Risk Reduction Following Tumor Debulking by Bridging Radiotherapy prior to Chimeric Antigen Receptor T Cell Therapy in Non-Hodgkin Lymphoma

Clinical Characteristics and Prognostic Factors in Primary Breast Diffuse Large B-Cell Lymphoma.

BackgroundPrimary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare subtype of non-Hodgkin lymphoma (NHL) with limited data on the clinical features and prognostic factors.Patients and MethodsA consecutive cohort of patients with PB-DLBCL was retrospectively analyzed in our hospital from February 1997 through July 2018. The primary endpoint is overall survival (OS) contributing to any cause.ResultsA total of 76 patients were diagnosed with PB-DLBCL. The median age at diagnosis was 51 years (range: 25–80 years), with female prevalence (98.7%). Forty (52.6%) patients had right-sided breast involvement but no bilateral breast involvement at diagnosis. Overall, disease stages IE and IIE were seen in 55 (72.4%) and 21 (27.6%) patients, respectively. According to the stage-modified International Prognostic Index (IPI), 37 (48.7%) patients were classified in the very good risk group (IPI 0). Of the 72 patients available, the non-germinal center B-cell (non-GCB) subtype of DLBCL was observed in 66 (91.6%) patients. All patients received anthracycline-based chemotherapy, 56 (73.7%) with rituximab, 31 (40.8%) also with additional radiation therapy, and 14 (18.4%) patients received a prophylactic intrathecal injection. Seven (9.2%) patients had refractory disease. With a median follow-up of 6.8 years (range 0.4–25.0 years), 10 (13.2%) patients had a relapse in the central nervous system (CNS) site. The 5-year and 10-year OS of all the patients was 97.2% (95% CI: 99.3–89.5) and 84.8% (95% CI: 70.0–93.5), respectively. The median OS was not reached. The median progression-free survival (PFS) was 10.3 years for patients with PB-DLBCL. The 5-year PFS of all the patients was 76.3% (95% CI: 64.6–84.6). Univariate analysis revealed several prognostic factors, including stage-modified IPI, breast surgery, refractory disease, and CNS relapse. Multivariate analyses produced two independent prognostic factors for patients with PB-DLBCL, including stage-modified IPI score (2–3 versus 0) (hazard ratio: 19.114, 95% CI 1.841 to 198.451, p=0.013) and CNS relapse (hazard ratio: 5.522, 95% CI 1.059 to 28.788, p=0.043).ConclusionIn our cohort, PB-DLBCL clinical features are similar to prior literature reports. Stage-modified IPI score and CNS relapse were associated with overall survival.

Antibiotic-dependent effect of probiotics in patients with non-small cell lung cancer treated with PD-1 checkpoint blockade

BackgroundWe previously validated in European patients with NSCLC treated with programmed death-1 (PD-1) checkpoint inhibitors the cumulative detrimental effect of concomitant medications. Materials and methodsWe evaluated the prognostic ability of a “drug score” computed on the basis of baseline corticosteroids, proton pump inhibitors, and antibiotics, in an independent cohort of Japanese patients with advanced NSCLC treated with PD-1 monotherapy. Subsequently, we assessed the impact of baseline probiotics on the score's diagnostic ability and their interaction with antibiotics in influencing survival. ResultsAmong the 293 eligible patients, good (19.5 months), intermediate (13.4 months), and poor (3.7 months) risk groups displayed a significantly different overall survival (OS) (log-rank test for trend: p = 0.016), but with a limited diagnostic ability (C-index: 0.57, 95%CI: 0.53–0.61), while no significant impact on progression-free survival (PFS) was reported (log-rank test for trend: p = 0.080; C-index: 0.55, 95%CI: 0.52–0.58). Considering the impact of the probiotics∗antibiotics interaction (p-value 0.0510) on OS, we implemented the drug score by assigning 0 points to concomitant antibiotics and probiotics. With the adapted drug score good, intermediate, and poor risk patients achieved a median OS of 19.6 months, 13.1 months, and 3.7 months, respectively, with a similar diagnostic ability (log-rank test for trend: p = 0.006; C-index: 0.58, 95%CI: 0.54–0.61). However, the diagnostic ability for PFS of the adapted score was improved (log-rank test for trend: p = 0.034; C-index: 0.62, 95%CI: 0.54–0.69). ConclusionsAlthough we failed to validate the drug score in this independent Japanese cohort, we showed that probiotics may have an antibiotic-dependent impact on its prognostic value. Further investigation looking at the effect of concomitant medications and probiotics across cohorts of different ethnicities is warranted.

Usefulness of serum CCL2 as prognostic biomarker in prostate cancer: a long-term follow-up study

Prostate-specific antigen is considered the most useful biomarker for prostate cancer, but not in all cases. In a previous study, we have shown that a risk classification combining prostate-specific antigen ≥100ng/mL and chemokine (CC motif) ligand 2≥320pg/mL can predict survivals. We investigated the long-term usefulness of serum chemokine (CC motif) ligand 2 as a complementary biomarker to prostate-specific antigen and developed a novel risk classification system. Serum samples were collected from 379 patients who underwent prostate biopsy at Kanazawa University Hospital between 2007 and 2013, and 255 patients with histologically diagnosed prostate cancer were included in this study. We retrospectively examined the efficacy of serum chemokine (CC motif) ligand 2 as a prognostic biomarker. Patients with chemokine (CC motif) ligand 2≥320pg/mL exhibited a significantly shorter overall survival, prostate cancer-specific survival and castration-resistant prostate cancer-free survival than those with chemokine (CC motif) ligand 2<320pg/mL. Multivariate analysis was performed to determine whether chemokine (CC motif) ligand 2 was a useful prognostic factor. Independent significant predictors of worse overall survival were prostate-specific antigen≥100ng/mL, Gleason score≥8 and chemokine (CC motif) ligand 2≥320pg/dL. Prognostic predictors of prostate cancer-specific survival or cancer-free survival in multivariate analysis were prostate-specific antigen≥100ng/mL and Gleason score≥8. A novel risk classification system was created to predict overall survival in patients based on the number of risk factors present (chemokine (CC motif) ligand 2≥320pg/mL, prostate-specific antigen≥100ng/mL, Gleason score≥8). Scores 2 or 3, 1 and 0 indicated Poor, Intermediate and Good risk groups, respectively. This study demonstrated the utility of serum chemokine (CC motif) ligand 2 level as a predictive biomarker of long-term overall survival in prostate cancer. A novel risk classification system that predicts long-term overall survival based on the combined indications of chemokine (CC motif) ligand 2 level, prostate-specific antigen level and Gleason score may be a useful prognostic tool for prostate cancer.

Cancer of unknown primary with gastrointestinal profiles: A favorable CUP subset.

e16225 Background: Cancer of unknown primary (CUP) with a “gastrointestinal (GI) profile” appears to be a clinically distinct subset, based on immunophenotyping, specifically staining with cytokeratins 20 (CK20) and 7 (CK7), a type I and II keratin, respectively and caudal type homeobox 2 (CDX2) protein, a transcription factor expressed in nuclei of intestinal epithelial cells. However, only a limited clinicomolecular account of this entity exists. Comprehensive profiling is needed to impact personalized therapeutics and improve prognosis. Methods: We identified 497 pts using a retrospective/prospectively managed CUP database and tumor registry of pts evaluated at MD Anderson Cancer Center from 2012-2016. Pts were classified into 3 cohorts based on immunohistochemistry: lower GI profile CUP (LGI-CUP) [CK20+/CK7- or CK20+/CK7+/CDX2+], upper GI profile CUP (UGI-CUP) [CK20-/CDX2+ or CK7+/CK20+/CDX2-] and remaining were treated as a non-GI CUP (NGI-CUP) control group [CK20-/CDX2-]. Clinical and pathological data including molecular profiling, therapy and survival were logged. Fisher-exact test was used. Kaplan-Meier method was used to estimate overall survival (OS) and compared with log-rank test. Results: Among 497 pts, 316 (63.6%) had adequate immunostaining for analysis. Of these, 76 (24.1%), 75 (23.7%) and 165 (52.2%) were classified as LGI-CUP, UGI-CUP, and NGI-CUP, respectively. Median age at diagnosis for the 3 cohorts was 59, 62 and 60 years, respectively. Key baseline clinicopathological characteristics were balanced between groups except histology and Culine risk stratification. LGI-CUP were enriched for adenocarcinoma (89% v 54% v 57%, P = 0.009) and good risk group (65% v 46% v 43%, P &lt; 0.001) compared to UGI-CUP and NGI-CUP, respectively. Median OS for the 3 cohorts were: 18.5 months (95%CI: 10.8–26.2) for LGI-CUP compared to 12.3 months (95%CI: 6.3–18.3) for UGI-CUP (P = 0.06) and 13.5 months (95%CI: 10.6–16.6) for NGI-CUP (P = 0.040). On multivariate analyses, LGI-CUP subtype emerged as an independent prognostic factor for better overall survival (HR 0.69, 95%CI: 0.5–0.9, P = 0.046) in addition to histology and Culine risk group. Among LGI-CUP, 39 pts with complete treatment data, 29 (74%) received frontline colorectal cancer specific chemotherapy (5-FU/Capecitabine-based) therapy. Median time to treatment failure was 3.6 months compared 1.8 months for those who received non-colorectal therapy (P = 0.19). For LGI-CUP, most common genomic alterations were TP53 (22%), ERBB2 (12%), KRAS (10%). For UGI-CUP, most common genomic alterations were KRAS (11%), and TP53 (9%). Conclusions: CUP pts with lower GI profile have improved overall survival compared to those with an upper GI or a non-GI immunophenotype. Identifying these CUP subsets and rational use of immunotherapy and targeted therapy may provide benefit to CUP pts, particularly as these treatments evolve for the management of known GI cancers.

Prognostic Nutritional Index Predicts Early Mortality in Diffuse Large B-cell Lymphoma

Objective:The international prognostic index (IPI) and the revised IPI (R-IPI) are used to determine the prognosis in diffuse large B-cell lymphoma (DLBCL). However, these scoring systems are insufficient to identify very high-risk patients. Recently, the prognostic nutritional index (PNI) -calculated with lymphocyte count and albumin- has been used to determine the prognosis in DLBCL. This study aimed to evaluate the effect of PNI score on prognosis and survival in patients with high-risk DLBCL.Methods:Patients diagnosed with DLBCL and treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone were included. Pre-treatment IPI, R-IPI, and PNI scores and progression-free survival (PFS) and overall survival (OS) times were calculated. The cutoff value for PNI according to OS was determined by using the X-Tile program.Results:One hundred and ten patients were included, the median age was 63 years and the median follow-up period was 25 months. According to R-IPI, the median OS could not be reached for the very good risk group, and the median OS values were 83 and 17 months in the good and poor-risk groups, respectively (p=0.001). The cohort was divided into three groups according to the cut-off value for the PNI: patients with PNI <33 were classified as high-risk, 33-42 intermediate-risk, and ≥42 as low-risk. According to PNI, the median durations of PFS and OS were 2 months and 3 months in the high-risk group, 9 months and 19 months in the intermediate-risk group respectively, and in the low-risk group the median duration for PFS and OS could not be reached (p=0.001).Conclusions:The R-IPI is widely used to estimate the prognosis in DLBCL. But in our cohort, in the poor-risk patient group, the OS was 17 months according to R-IPI, while this period was 3 months according to PNI. This finding demonstrated that PNI might predict early mortality in DLBCL.

New prognostic model for patients with advanced gastric cancer: Fluoropyrimidine/platinum doublet for first-line chemotherapy.

BACKGROUNDNew prognostic factors have been reported in patients with metastatic or recurrent gastric cancer (MRGC), necessitating modifications to the previous prognostic model.AIMTo develop a new model, MRGC patients who received fluoropyrimidines/ platinum doublet chemotherapy between 2008 and 2015 were analyzed.METHODSA total of 1883 patients was divided into a training set (n = 937) and an independent validation set (n = 946).RESULTSMultivariate analysis showed that the following six factors were associated with poor overall survival (OS) in the training set: Eastern Cooperative Oncology Group performance score ≥ 2 and bone metastasis (2 points each), peritoneal metastasis, high alkaline phosphatase level, low albumin level, and high neutrophil-lymphocyte ratio (1 point each). A prognostic model was developed by stratifying patients into good (0-1 point), moderate (2-3 points), and poor (≥ 4 points) risk groups. In the validation set, the median OS of the three risk groups was 15.8, 10.1, and 5.7 mo, respectively, and those differences were significant (P < 0.001).CONCLUSIONWe identified six factors readily measured in clinical practice that are predictive of poor prognosis in patients with MRGC. The new model is simpler than the old and more easily predicts OS.

Brentuximab Vedotin Plus ESHAP (BRESHAP) Versus ESHAP As Salvage Strategy for Patients with Primary Refractory or Relapsed Classical Hodgkin's Lymphoma. Preliminary Results from the Breselibet Prospective Clinical Trial

Brentuximab Vedotin Plus ESHAP (BRESHAP) Versus ESHAP As Salvage Strategy for Patients with Primary Refractory or Relapsed Classical Hodgkin's Lymphoma. Preliminary Results from the Breselibet Prospective Clinical Trial

Combined immune score predicts the prognosis of newly diagnosed multiple myeloma patients in the bortezomib-based therapy era.

To investigate the effect of a combined immune score including the lymphocyte-to-monocyte ratio (LMR) and uninvolved immunoglobulin (u-Ig) levels on the prognosis of newly diagnosed multiple myeloma (NDMM) patients treated with bortezomib.Clinical data of 201 NDMM patients were retrospectively analyzed. Patients with LMR ≥ 3.6 and LMR < 3.6 were scored 0 and 1, respectively. Patients with preserved u-Ig levels, suppression of 1 u-Ig, and suppression of at least 2 u-Igs were scored 0, 1, and 2, respectively. The immune score, established from these individual scores, was used to separate patients into good (0–1 points), intermediate (2 points), and poor (3 points) risk groups. The baseline data, objective remission rate (ORR), whether receive maintenance treatment regularly and overall survival of patients before treatment were analyzed.The ORR of the good-risk group was significantly higher than that of the intermediate-risk group (75.6% vs 57.7%, P = .044) and the poor-risk group (75.6% vs 48.2%, P = .007). The multivariate analysis results showed that age ≥ 65 years, International Staging System stage III, platelet count ≤ 100 × 109/L, lactate dehydrogenase (LDH) > 250 U/L, serum calcium > 2.75 mmol/L, no receipt of regular maintenance treatment, LMR < 3.6, suppressed u-Igs = 1, suppressed u-Igs ≥ 2, intermediate-risk group and poor-risk group were independent predictors of poor overall survival.In the bortezomib era, the LMR, u-Ig levels, and the immune score play an important role in the prognosis of NDMM patients. Among them, the immune score showed the strongest prognostic value, and it could be a beneficial supplement for the early identification of high-risk patients.

A novel clinical prognostic index for patients with advanced gastric cancer: possible contribution to the continuum of care

BackgroundThe Japan Clinical Oncology Group (JCOG) prognostic index, consisting of performance status, primary tumor resected, number of metastases, and serum alkaline phosphatase, has been one of the robust prognostic indices for patients with advanced gastric cancer on the basis of which clinical trials have stratified prognosis. Only a few studies, however, have utilized the JCOG prognostic index in daily practice.MethodsWe conducted a retrospective study on patients with advanced gastric cancer who received first-line platinum-containing chemotherapy at a single institute between 2011 and 2017. Prognostic factors were evaluated using a Cox proportional regression model.ResultsA total of 608 patients were enrolled. Multivariate analysis showed that performance status ≥1, presence or absence of primary tumor, serum alkaline phosphatase, neutrophil-to-lymphocyte ratio ≥4, and diffuse-type histology were significantly associated with worse prognosis, whereas the number of metastases was not. Although the original prognostic index could not adequately stratify patients into three risk groups, the modified index (good: 0 and 1, moderate: 2 and 3, poor: 4-6), which was established by incorporating diffuse-type histology and high neutrophil-to-lymphocyte ratio, demonstrated excellent stratification. The median overall survival of the good (n = 315), moderate (n = 243), and poor (n = 54) risk groups was 20.5, 13.5, and 10.2 months, respectively. Hazard ratios (HRs) were 1.69 [95% confidence interval (CI), 1.40-2.04; good versus moderate] and 1.52 (95% CI, 1.11-2.08; moderate versus poor). This novel index also demonstrated a statistically significant stratification of survival after progression following first-line chemotherapy (good versus moderate: HR, 1.41; 95% CI, 1.16-1.70; moderate versus poor: HR, 2.00; 95% CI, 1.45-2.74).ConclusionsThe modified JCOG prognostic index showed excellent stratification of overall survival in real-world patients, which could also help determine the need for treatment changes throughout the continuum of chemotherapy.

Eosinophil counts as a relevant prognostic marker for response to nivolumab in the management of renal cell carcinoma: a retrospective study.

BackgroundDespite improvements in the management of renal cell carcinomas (RCC) with the advent of immunotherapy, only a few patients respond to these treatments. Predictors of response to nivolumab are currently being investigated but are still lacking.Aim of the studyTo evaluate eosinophil levels and their variations during treatment as an accurate biomarker for outcome in metastatic RCC treated with nivolumab.MethodsA retrospective analysis was carried out for patients with metastatic RCC treated with nivolumab. Absolute eosinophil counts, their variation, and relative change were evaluated at six weeks. Relative eosinophil change was categorized in three groups (≥10%‐decrease, no change, ≥10%‐increase). Univariable and multivariable analyses were performed to determine whether eosinophils and their variations were prognostic markers for response at the first scan evaluation, progression‐free survival, and overall survival.ResultsSixty‐five patients aged on average 66 years, 68% men, and 77% with good or intermediate International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group were included. The median follow‐up was 16.6 months. Median overall survival (OS) was not reached for good prognosis and was 22.5 and 6.5 months for intermediate and poor prognosis, respectively. An increase in eosinophils and relative eosinophil change at six weeks of nivolumab was associated with a good response to immunotherapy (p = 0.012 and p = 0.024 respectively). In the group of patients with a 10%‐decrease in relative change, PFS reduced significantly compared to the other groups (p = 0.0044 with the 10%‐increase group and p = 0.03 with the no‐change group). This relative increase was independent of IMDC risks factors for better OS (HR = 3.3 [1.45–7.4]; p = 0.004). The eosinophil baseline level was not associated with response to treatment.ConclusionEosinophil levels and relative eosinophil change at 6 weeks might be good prognostic markers for response to nivolumab for metastatic RCC, and were associated with better PFS and OS.