ИММУНОЛОГИЧЕСКИЙ МОНИТОРИНГ БИОТЕРАПИИ ДИССЕМИНИРОВАННЫХ ФОРМ ПОЧЕЧНО-КЛЕТОЧНОГО РАКА

The Use of Combination PACE Regimens for Patients with Relapsed and Refractory Multiple Myeloma (MM) and Their Impact on Stem Cell Transplantation (SCT)

e16017 Background: Sarcomatoid-variant represents a spindle cell phenotype of RCC that can be present in any subtype, usually showing aggressive biological behavior. MSKCC experience was studied to provide data on outcome and survival to systemic therapy for metastatic, sarcomatoid-variant RCC. Methods: Clinical features, treatment outcome and survival were reviewed in 63 pts with sarcomatoid-variant metastatic RCC from a database of 650 pts treated at MSKCC with systemic therapy (cytokines, anti-angiogenesis targeted therapy and chemotherapy). Response to therapy, progression-free survival (PFS), and overall survival (OS) was determined for pts based on their first treatment at MSKCC. The percentage of sarcomatoid component in the tumors was assessed. Results: Histology subtypes with sarcomatoid-variant among the 63 pts included 46 clear cell, 5 papillary, 5 chromophobe, 1 collecting duct, and 6 unclassified. 60 pts had prior nephrectomy. MSKCC risk group distribution was 37% good risk, 59% intermediate risk, and 5% poor risk. 34 pts received targeted therapy (29 sunitinib, 3 sorafenib, 2 temsirolimus), 20 pts received cytokine therapy (19 interferon, 1 interleukin) and 9 received other therapies. 5/63 pts achieved an objective response: 1/19 to interferon and 4/29 to sunitinib. In 63 pts, median PFS was 3 months (95% CI 2–4) and median OS was 10 months (95% CI 8–14). Differences in PFS were observed based on therapy (sunitinib vs. all other) and histology (clear cell vs. non-clear cell). The median PFS for sunitinib therapy was 4.4 months (95% CI 2.2–6.7) versus 2 months (95% CI 1.7–2.7) for all other therapies (p = 0.02); and 3 months (95% CI 2.3–4.5) for clear cell versus 1.6 months (95% CI 1.0–2.1) for non-clear cell histology (p = 0.007). In a subset (n = 31) with available specimen, the median % sarcomatoid content was 20% (range 2%-100%). No difference in PFS or OS was observed according to % sarcomatoid content. Conclusions: Metastatic sarcomatoid-variant RCC is associated with a poor prognosis. Sunitinib resulted in a modest response rate and longer PFS versus other therapies. Studies to assess outcome, characterize tumor biology, and develop novel treatment strategies are warranted. [Table: see text]

ObjectivesTo evaluate the validity of Memorial Sloan‐Kettering Cancer Center (MSKCC) and International Extranodal Lymphoma Study Group (IELSG) prognostic scoring systems for Overall Survival (OS) in intracranial Primary CNS lymphoma (PCNSL) of all patients diagnosed at a single center.Material and MethodsPretreatment clinical factors including tumor characteristics and histology, treatment, and survival of PCNSL patients with diagnostic biopsies over a 12‐year period (2003–2014) were retrieved from a prospective database at Oslo University Hospital.ResultsSeventy‐nine patients with intracranial PCNSL were identified. The female:male ratio was 1:1.63 and the median age was 65.3 years [range 18.9–80.7]. Involvement of deep brain structures was shown in 63 patients. Six patients were MSKCC risk group 1, 35 patients were in risk group 2, and 38 patients were in risk group 3. International Extranodal Lymphoma Study Group scores were <2 in 17 patients (22%). After a median follow‐up of 70.5 months, 55 patients were dead. Median OS was 16.4 months [range 0.2–157.7]. Age, sLDH by recursive partitioning analysis (RPA), Eastern Cooperative Oncology Group score (ECOG), lesion size, involvement of deep brain structures, IELSG score, and MSKCC score were significant factors for OS in univariate analysis. Multivariate analysis confirmed the significance of age (p < .05), sLDH by RPA (p < .005), ECOG (p < .05), and deep brain structure involvement (p < .05) for OS. The six‐tiered IELSG scores had to be dichotomized according to RPA analysis into <2 and ≥2 in order to have prognostic value. In contrast, when using the three‐tiered MSKCC, three distinct risk groups were identified.ConclusionsOur study failed to verify the IELSG, but validated the use of MSKCC for prognostication of OS in intracranial PCNSL.

PELVIC LYMPH NODE DISSECTION CAN BE CURATIVE IN PATIENTS WITH NODE POSITIVE BLADDER CANCER

Low serum interleukin-6 levels as a predictive marker of recurrence in patients with hepatitis B virus related hepatocellular carcinoma who underwent curative treatment

Prognostic significance of early tumor shrinkage following treatment with tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC) has not been fully elucidated. The aim of this study was to assess the impact of early tumor shrinkage induced by first-line TKIs on overall survival (OS) in mRCC patients. This study retrospectively included 185 consecutive Japanese patients with mRCC treated with either sunitinib or sorafenib for at least 3months as first-line molecular-targeted therapy between April 2011 and December 2014 at Kobe University Hospital and its affiliated institutions. Median OS in the 185 patients was 33.6months. At 12weeks after the introduction of TKIs, 9 patients had achieved tumor shrinkage from -100 to -50%, 43 from -49 to -25%, 61 from -24 to 0%, and the remaining 72 patients showed an increase in tumor size. The median OS stratified according to tumor shrinkage as shown above was 59.2, 39.1, 31.4, and 16.1months, respectively. Univariate analysis identified prior nephrectomy, Memorial Sloan Kettering Cancer Center (MSKCC) risk classification, C-reactive protein (CRP) level, liver metastasis, number of metastatic organs, histological subtype, sarcomatoid feature, and early tumor shrinkage as significant predictors of OS. Of these significant factors, only the MSKCC classification, CRP level, liver metastasis, and early tumor shrinkage were shown to be independently associated with OS on multivariate analysis. Early tumor shrinkage could be a useful predictor of OS in mRCC patients receiving TKIs as a first-line molecular-targeted agent.

Treatments, Outcomes, and Validity of Prognostic Scores in Patients With Sarcomatoid Renal Cell Carcinoma: A 20-Year Single-Institution Experience.

The identification of prognostic factors for pancreatic cancer patients could provide insightful information for their management in the clinic. A total of 302 pancreatic cancer patients were enrolled in this study. The clinicopathological characteristics, treatment selection and laboratory test data were retrospectively retrieved from the medical records and follow-up data were obtained via telephone interview. Cox survival analysis was used to assess the potential prognostic factors, and survival curves were obtained by Kaplan-Meier analyses. The mortality rate of the patients was 83.4% (252/302) and the median survival of these patients was 6.1 months, with 1-, 2- and 3-year survival rates of 30.1 (91/302), 10.6 (32/302) and 2.6% (8/302), respectively. The most influential factors for the survival of these patients were the site of primary cancer, tumor stage, treatment selection, serum levels of glutamic-pyruvic transaminase, albumin, lactate dehydrogenase and hemoglobin, and white blood cell counts (P<0.05). The median survival of patients who did not receive any treatment or just received supportive treatment was 1.3 months, while the median overall survival of patients who underwent surgery, chemotherapy, biliary drainage therapy, arterial interventional chemotherapy and comprehensive treatment was 11.0, 7.3, 3.5, 9.0 and 11.0 months, respectively (P<0.05). Furthermore, single-drug chemotherapy was not statistically associated with patient survival in those who received the multi-drug regimen (P>0.05). However, the mortality risk of patients who received platinum chemotherapy was decreased [hazard ratio (HR)=0.56, 95% CI 0.35-0.88, P=0.011] compared to the patients who did not receive this treatment (P<0.05). Tumor stage, treatment selection, serum albumin levels, urea nitrogen, CA19-9, white blood cell and platelet counts were independent prognostic factors for the prediction of survival in pancreatic cancer. Future studies are required in order to verify these data. Chemotherapy with platinum regimens could improve overall survival in patients with pancreatic cancer.

Altered overnight levels of pro-inflammatory cytokines in men and women with posttraumatic stress disorder

Schizophrenia, a multisystem disorder with an unknown etiology, is associated with several immune dysfunctions, including abnormal levels of circulating cytokines. In this review, we investigated the changes of cytokines in schizophrenic patients, their connection with behavioral symptoms severity and their potential clinical implications. We also assessed the possible causative role of abnormal cytokine levels in schizophrenia pathogenesis. Based on meta-analyses, we categorized cytokines according to their changes in schizophrenic patients into four groups: (1) increased cytokines, including interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β, IL-12, and transforming growth factor (TGF)-β, (2) non-altered cytokines, including IL-2, IL-4, and IL-17, (3) increased or non-altered cytokines, including IL-8 and interferon (IFN)-γ, and (4) IL-10 with increased, decreased, and non-altered levels. Notably, alterations in cytokines may be variable in four different categories of SP, including first-episode and drug-naïve, first-episode and non-drug-naïve, stable chronic, and chronic in acute relapse. Furthermore, disease duration, symptoms severity, incidence of aggression, and cognitive abilities are correlated with levels of certain cytokines. Clinical implications of investigating the levels of cytokine in schizophrenic patients include early diagnosis, novel therapeutic targets development, patient stratification for choosing the best therapeutic protocol, and predicting the prognosis and treatment response. The levels of IL-6, IL-8, IFN-γ, IL-2 are related to the treatment response. The available evidence shows a potential causative role for cytokines in schizophrenia development. There is a substantial need for studies investigating the levels of cytokines before disease development and delineating the therapeutic implications of the disrupted cytokine levels in schizophrenia.

BackgroundThere are few molecular markers driving treatment selection in later lines of treatment for advanced colorectal cancer patients. The vast majority of patients who progress after first- and second-line therapy undergo chemotherapy regardless of molecular data.ObjectiveWe aimed to assess the prognostic and predictive effects of specific RAS mutations on overall survival of patients receiving regorafenib (rego), trifluridine/tipiracil (TFD/TPI), or both.Patients and methodsThis was a retrospective observational study based on data from a previous study of our research network, involving nine Italian institutions over a 10-year timeframe (2012–2022). Extended RAS analysis, involving KRAS exon 2–4 and NRAS exon 2–4, and BRAF were the main criteria for inclusion in this retrospective evaluation. Patients with BRAF mutation were excluded. Patients were classified according to treatment (rego- or TFD/TPI-treated) and RAS mutational status (wild-type [WT], KRAS codon 12 mutations, KRAS codon 13 mutations, KRAS rare mutations and NRAS mutations, KRAS G12C mutation and KRAS G12D mutation).ResultsOverall, 582 patients were included in the present analysis. Overall survival did not significantly differ in rego-treated patients according to RAS extended analysis, although a trend toward a better median survival in patients carrying G12D mutation (12.0 months), Codon 13 mutation (8.0 months), and Codon 12 mutation (7.0 months) has been observed, when compared with WT patients (6.0 months). Overall survival did not significantly differ in TFD/TPI-treated patients according to RAS extended analysis, although a trend toward a better median survival in WT patients had been observed (9.0 months) in comparison with the entire population (7.0 months). Patients receiving both drugs displayed a longer survival when compared with the population of patients receiving rego alone (p = 0.005) as well as the population receiving TFD/TPI alone (p < 0.001), suggesting a group enriched for favorable prognostic factors. However, when each group was analyzed separately, the addition of TFD/TPI therapy to the rego-treated group improved survival only in all-RAS WT patients (p = 0.003). Differently, the addition of rego therapy to TFD/TPI-treated patients significantly improved OS in the Codon 12 group (p = 0.0004), G12D group (p = 0.003), and the rare mutations group (p = 0.02), in addition to all-RAS WT patients (p = 0.002). The rego-TFD/TPI sequence, compared with the reverse sequence, significantly improved OS only in the KRAS codon 12 group (p = 0.003).ConclusionsOur data demonstrate that RAS mutations do not affect outcome in rego-treated patients as well as TFD/TPI-treated patients. Nevertheless, a trend toward a higher efficacy of rego in RAS-mutated (in particular codon 12, rare RAS mutations, and G12D) patients has been recorded. The rego-TFD/TPI sequence seems to be superior to the reverse sequence in patients carrying an RAS codon 12 mutation, although the impact of other factors as disease burden or performance status cannot be excluded.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11523-024-01050-3.

Objective To evaluate and compare the value of interleukin(IL)-6,IL-8,tumor necrosis factor(TNF)-α,and soluble form of triggering receptor expressed on myeloid cells (sTREM)-1 in neonatal infection and detect the relationship between them.Methods Eighty-five full-term newborns who were admitted to the neonatal ward of Shanghai Children's Hospital of Shanghai Jiaotong University were enrolled,according to the locations and severity of infection,the patients were divided into three groups:systemic infection group (n =27),local infection group(n =28),and non-infection group (n =30).The level of plasma sTREM-1 was measured by enzyme-linked immunosorbent assay,and the levels of IL-6,IL-8 and TNF-α were measured using cytometric bead array.Results (1) The levels of sTREM-1,IL-6,IL-8 and TNF-α were significantly higher in infants with systemic infection group than local infection group and non-infection group(P ＜0.05).(2) There were 17 survivors and 10 deaths in systemic infection group,and the level of sTREM-1 in the non-survivor [(121.64 ±49.31) pg/ml] was higher than the survivor[(73.13 ± 34.92) pg/ml,P =0.006].But the levels of IL-6,IL-8 and TNF-α were not statistically significant in the survivor and the death (P ＞ 0.05).(3) Based on the receiver operating characteristic analysis,cutoff values were identified for each variable that maximized both the sensitivity and specificity.These markers were considered positive if sTREM-1 ≥43.75 pg/ml,IL-6 ≥ 89.80 pg/ml,IL-8 ≥569.55 pg/ml and TNF-α ≥ 24.80 pg/ml.Among these indexes,the sensitivities were 85.5％,89.1％,70.1％ and 69.5％ respectively; the specificity were 80.0％,100％,100％ and 93.3％ respectively.Compared the area under curve(AUC) of them,IL-6(AUC =0.981)＞ sTREM-1 (AUC =0.868) ＞ TNF-α (AUC =0.864) ＞ IL-8 (AUC =0.852).sTREM-1 was correlated with IL-6,IL-8 and TNF-α(Spearman coefficient of rank r =0.532,P ＜0.01 ;r =0.420,P ＜0.01 ;r =0.531,P ＜0.01).Conclusion (1) The levels of plasma sTREM-1,IL-6,IL-8 and TNF-α were higher in neonatal infections;(2) sTREM-1 was associated with prognosis; (3) sTREM-1 was correlated with IL-6,IL-8 and TNF-α. Key words: Infection; Soluble form of triggering receptor expressed on myeloid cells-1 ; Interleukin-6; Interleukin-8 ; Tumor necrosis factor-α; Infant,newborn

Effect of glandular metastases on overall survival of patients with metastatic clear cell renal cell carcinoma in the antiangiogenic therapy era

Clinical outcome in patients receiving systemic therapy for metastatic sarcomatoid renal cell carcinoma: A retrospective analysis☆

A prognostic scoring system for colorectal cancer liver metastases that is derived from unselected patients referred for hepatic resection would improve the applicability and increase the accuracy of prognostication. Retrospective analysis of prospectively documented data; validation against an unrelated cohort from another institution. The median follow-up was 16.4 months (95% confidence interval, 15.0-17.8 months) (original cohort). Two tertiary referral centers at unrelated university hospitals. Independent prognosticators of survival were derived from 337 patients with colorectal cancer liver metastases referred for consideration of liver resection, and prognostic scores were calculated in 269 patients (79.8%) (original cohort). Calculation of prognostic scores was also applied to 193 patients referred and treated in an unrelated institution (validation cohort). Kaplan-Meier survival curve analysis (log-rank test) between different prognostic groups in the original and the validation cohorts. Independent prognosticators of survival were Dukes stage, number of metastases, and serum concentrations of carcinoembryonic antigen, alkaline phosphatase, and albumin. Significant differences were found in cumulative overall survival between patients assigned to good, moderate, and poor prognoses in the original and validation cohorts (P<.05). Liver resection improved survival in all prognostic groups. However, no patient with poor prognosis and only 19.7% (13 of 66) of patients with moderate prognosis survived 5 years, compared with 62.5% (10 of 16) of patients with good prognosis (P<.001). This prognostic scoring system is derived from and can be applied to patients with colorectal cancer liver metastases at the time of referral for consideration of surgery. Patients with poor prognosis have no long-term benefit from curative liver resection and should therefore be considered for combined multimodal treatment.