Prognostic Impact of Comorbidities In A Cohort of 788 MDS Patients Based On A CIRS-G Derived Score. A MDS Piedmont Registry Prospective Study

Abstract Abstract 1729 Background: Management of neoplastic patients is strongly influenced by comorbidities, especially in more advanced ages. Due to that, comorbidities evaluation is a critical issue in the global assessment of patients (pts) affected by myelodysplastic syndromes (MDS). Until now, there is no agreement on which comorbidity index (CI) is more suitable in this setting and different CI has been proposed. Recently a new MDS-specific score (MDS-CI) has been published by Della Porta et al., while the majority of CI in use has been developed in geriatric oncology setting. One of the most useful is Cumulative Illness Rating Scale of Geriatrics (CIRS-G). Aim of our study: Aim of our study was to test the usefulness of the conventional and easy to apply CIRS-G score among a cohort of MDS pts enrolled in the MDS Piedmont Registry from 1999 to 2010 in predicting OS and leukemic progression. Materials and methods: 788 patients from the MDS Piedmont Registry with CIRS-G evaluation at diagnosis were included in our statistical analysis. 78% of the patients were low and Int-1 IPSS risk, the remaining 22% were Int-2-high risk. The majority of patients (69%) carried an histological diagnosis of non RAEB MDS according to WHO classification, the remaining 31% were RAEB I-II. Age stratification was as follows: 10% up to 60, 23% from 61 to 70, 43% from 71 to 80, 24% over 80 years. Comorbidities with score up to 2 were considered mild while the ones with values higher than 2 were considered severe. We evaluated the global impairment of each patient creating two comorbidity scores based on the number of mild comorbidities (mild comorbidities score, MCS) and severe comorbidities (severe comorbidities score, SCS). Results: The majority of our patients showed only mild comorbidities and the comorbidities with the greater number of patients carrying severe grade of impairment are the cardiac (25%), hypertensive (30%) and endocrinological (20%) ones. COX analysis did not show an impact of comorbidities on leukemic progression risk while there is a statistically significant impact on overall survival of respiratory, renal, urological and osteo-muscular comorbidities (HR respectively of 1,18; 1,3; 1,3; 1,16). There is a trend of increased risk of non MDS related death in patients with severe grade of each comorbidity. Then we set up a Fine and Gray regression model in order to evaluate the global impact of comorbidities on leukemic progression and overall survival according to SCS and MCS. Neither SCS nor MCS showed an impact on the leukemic progression risk. Considering overall survival (OS), MCS showed a HR of 1,12 (p= 0,009) and moreover SCS has a strong impact on the risk of death (HR 1,59; p= 0,000). MCS remains statistically significant in low IPSS risk patients (p<0,001) while there is no influence of MCS on OS considering high IPSS risk patients (p=0,244). COX analysis stratifying pts for performance status (PS) and age classes confirmed the results obtained in the whole population. We performed a multivariate analysis and confirmed that SCS score (p=0,0006), age and IPSS (all p<0,0001) but not PS (p=0,22) are independent prognostic factors in OS prediction. Conclusions: Our data based on a prospective evaluation of 788 MDS patients enrolled in the MDS Piedmont Registry showed that CIRS-G evaluation is a suitable and easy to apply method useful in patients evaluation at diagnosis and during disease management. In our multivariate analysis IPSS is the most useful tool for leukemic progression evaluation, while SCS score (derived from CIRS-G evaluation) and age are the most important variables able to predict overall survival while PS at diagnosis does not add any useful information for this evaluation. Disclosures: No relevant conflicts of interest to declare.

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Impact of the G8 score on the outcome of a cohort of elderly patients with solid or hematological malignancies.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.12038 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 12038-12038

Author(s):

Federica Biello ◽

Alessia Mennitto ◽

Abdurraouf Mahmoud ◽

Francesca Platini ◽

Daniela Ferrante ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Elderly Patients ◽

Solid Tumors ◽

Hematological Malignancies ◽

Screening Tool ◽

Tumor Type ◽

Risk Of Death ◽

Increased Risk ◽

G8 Screening Tool

12038 Background: Elderly cancer patients may have important benefits from innovative treatments. However, they are often barred from clinical trials because of highly selective eligibility criteria, or due to biased and subjective physician standpoints including reluctance to invite elderly patients and fear of excessive toxicity. Indeed, geriatric assessment has been increasingly recognized as predictive and prognostic instrument to detect frailty in older adults with cancer. In this perspective, the G8 score is a simple and reproducible instrument to identify elderly patients who should undergo full geriatric evaluation. The aim of our study was to evaluate the impact of frailty assessment by the G8 screening tool on the outcome of onco-hematological patients. Methods: Between January 2017 and December 2020 the G8 screening tool was administered to patients, aged >65 years, referred to our center for solid and hematological malignancies. G8 score was assessed at the time of first access. The primary endpoint was overall survival. Multivariate analysis was performed according to G8 score, age, tumor type, stage and treatment. Results: In the observation period, 430 patients were screened for frailty by G8; median age was 77 years (65-92); of these, 331 (77%) had a G8 score <14. Pts with solid tumors were 310 (72%), 175 (57%) of whom had metastatic diseases; 227 (73%) had a G8 score <14. Pts with hematological malignancies were 120 (28%), 100 (83%) of whom had a G8 score <14. Systemic therapy was administered to 336 patients (78%). At a median follow up of 7.2 months (range 1 to 52) 101 pts (24%) were dead. Median overall survival (mOS) was 27 months (1-52+).Patients with solid tumors, classified as frail by a G8 score <14 had a 3-fold risk of death compared with those with G8 > 14 (OR 3.26, CI 95 1.5-7.2, p = 0.003). Conversely, this increased risk was not observed in hematological malignancies (OR 1.4, CI 95 0.4-4.6, p = 0.57). By multivariate analysis, G8 score was associated with a worse prognosis only in patients with solid tumors. Conclusions: Our analysis suggest that elderly frail patients with solid tumors have a significantly increased risk of death as compared to elderly fit patients. Conversely, no impact of frailty, as assessed by a G8 score < 14, was evident in elderly patients with hematological malignancies.

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Increase in Mortality and Second Neoplasms in Chronic Lymphocytic Leukemia with Pro/Pro Genotype of TP53 Codon 72

Blood ◽

10.1182/blood-2020-141768 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 13-14

Author(s):

Martin Cabero-Becerra ◽

Jose Antonio Garcia Vela ◽

Pedro Sanchez-Godoy ◽

Angel Arias-Arias ◽

Miguel Piris-Villaespesa ◽

...

Keyword(s):

Overall Survival ◽

Tp53 Mutation ◽

Conflicts Of Interest ◽

The Other ◽

Complex Karyotype ◽

Codon 72 ◽

Risk Of Death ◽

Second Neoplasms ◽

Number Of Patients ◽

Increased Risk

Chronic Lymphocytic Lymphoma (CLL) is a heterogeneous disease in which many important factors for its prognosis have been identified. The normal functioning of p53 is one of the most critical barriers against cancer; therefore, if it has a deletion and/or mutation, it is a robust biomarker for the therapeutic response in CLL. The possibility was raised that some germline single - nucleotide polymorphisms of TP53 in healthy populations may also affect p53 function. One of the most studied polymorphisms of the TP53 gene is codon 72 in exon 4, a CGC to CCC transition (R72P), due to its potential effect on cancer risk. As with many types of cancer, its association with a worse prognosis in CLL is unclear. We analyzed the relationship of the genotypes of the TP53 codon 72 polymorphism in a large cohort of patients with CLL, to demonstrate the association of codon 72 with the evolution of the disease. Using the IDIPHIM patient database, 558 patients with a diagnosis of CLL were included, with clinical data, immunophenotype studies, FISH, IgHV, and karyotype, at the time of diagnosis and during follow-up. The TP53 codon 72 Arg/Arg, Arg/Pro, and Pro/Pro genotypes were analyzed using RT-PCR and Sanger sequencing techniques. After analyzing the sample of patients, 321 patients with the Arg/Arg genotype, 202 with the Arg/Pro genotype, and 35 with the Pro/Pro genotype were found. In the comparative analysis of the three groups, the patients with the Pro/Pro genotype had a higher number of patients in advanced stages B and C. The latter had a significant association with Binet staging (p = 0.002) compared to the other groups. Likewise, patients with the Pro/Pro genotype had a higher incidence of Richter transformation, whose association was significant (p = 0.013). Also, the patients who were within the Pro/Pro genotype group showed a significant association (p = 0.030) with the Time to the first treatment (TFT), also observing that the group of patients with the Arg/Pro genotype had a more considerable time until your first treatment. 19.7% (110/558) had a second neoplasm, having a significantly higher association with the homozygous groups (Arg/Arg and Pro/Pro) than with the Arg/Pro group, which on the contrary, had fewer second neoplasms (p = 0.016) (see Table 1). Regarding the type of tumors, we found 14.5% of the bladder, 14.5% of the skin, 14.5% of the colon, 13.6% of the prostate, and 12.7% of the lung. No associations were found between Codon 72 and CD38+, ZAP70+, complex karyotype, IgHV, NOTCH-1, del 11q, 12+, p53, del 13q, TP53 mutation. Still, when forming a group between the p53 deletion and TP53 mutation, if significant differences were found (p = 0.023), Pro / Pro group had the highest percentage. The overall survival was 156.32 months (139.92 - 172.72), showing that patients with the Arg/Pro genotype live 40 months more significantly than the other groups (p = 0.028) (see Figure 1). Finally, in the multivariate analysis, age, complex karyotype, 11q deletion, p53 deletion, unmutated IgHV, and Pro/Pro genotype at codon 72 were identified as independent variables associated with an increased risk of death (see Table 2). In conclusion, the Pro/Pro genotype of TP53 Codon 72 has a potential role in the progression and the higher mortality of patients with CLL. Conversely, the Arg / Pro genotype was associated with a lower incidence of second malignancies and higher overall survival. Disclosures No relevant conflicts of interest to declare.

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Survival after Relapse Following Tandem Allogeneic Vs. Tandem Autologous Hematopoietic Cell Transplantation (HCT) for Myeloma (MM)

Blood ◽

10.1182/blood.v128.22.833.833 ◽

2016 ◽

Vol 128 (22) ◽

pp. 833-833

Author(s):

Myo Htut ◽

Anita D'Souza ◽

Benedetto Bruno ◽

Mei-Jie Zhang ◽

Mingwei Fei ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Survival Analysis ◽

World Population ◽

Univariate Survival Analysis ◽

Risk Of Death ◽

Increased Risk ◽

Baseline Characteristics

Abstract Background: Five large prospective trials have shown a lack of improvement in OS from an autologous-allogeneic (auto-allo) HCT approach in MM, whereas 3 trials have demonstrated benefit. In long term follow up of the randomized EBMT-NMAM2000 trial, Gahrton et al* reported that overall survival (OS) after relapse among the auto-allo cohort was superior compared to auto-auto recipients. Objective: Compare OS rates after relapse from upfront auto-allo vs. auto-auto HCT. Eligibility: Recipients (N-1679) of either an upfront tandem autologous (n=1110) or auto-allo HCT (n=569) reported to the CIBMTR. Eligibility included age ≤70, planned tandem HCT and recipients of subsequent allo HCT following relapse were excluded. HLA-matched related (96%) and unrelated grafts (4%) were included. Methods: Cox proportional hazards (PH) regression modeling was used in multivariate analysis of OS after relapse with the clock starting at relapse, and events included death from any cause. Surviving patients were censored at the time of last contact. Results/Discussion: 404 patients relapsed in the auto-auto group and 178 patients in the auto-allo group (Table 1). Median time from diagnosis to 1st HCT was 8 months for auto-allo patients and 7 months for auto-auto patient with most patients receiving 1-2 lines of chemotherapy before 1st HCT (73% in auto-allo and 90% in auto-auto groups). Among auto-allo patients, 46% of relapses occurred in < 6 months from 2nd HSCT, compared to 26% in the auto-auto group suggesting that the auto-allo pts were a higher risk group. The median follow-up after relapse for the auto-allo and auto-auto groups were 102 and 99 months respectively. In univariate survival analysis, patients in the auto-allo group had a similar probability of survival (48%) at 5 years post relapse, compared with the auto-auto arm (41%) (Table-2). 101 patients in auto-allo patients died due to MM (69%) vs. 229 (83%) deaths in auto-auto groups due to MM. In multivariate analysis, a pattern of differential time dependent risk was observed. Both cohorts had a similar risk of death in the 1st year after relapse (HR of 0.72; p=0.12). However, for time points beyond 12 months after relapse, patients in the auto-allo group had superior OS compared with auto-auto cohort (HR for death in auto-auto =1.55; p=0.0052) (Figure-1). Other significant co-variates associated with superior survival were enrollment in a clinical trial for HCT, male sex and novel agent (lenalidomide/bortezomib) use in induction prior to HCT. Conclusion: We extend the post relapse survival findings reported by Gahrton et al in allogeneic HCT with matched sibling donors in a larger real world population of related and unrelated grafts. Despite a higher risk population with increased risk of early relapse undergoing tandem auto-allo HCT, we observed a long term reduction in post relapse mortality. This likely reflects an improved response to salvage therapy due to the donor derived immunologic milieu that potentiates the immune effects of agents such as lenalidomide and pomalidomide. With the availability of other agents that modulate immune mediated disease control such a daratumumab (reduction in T and B regulatory subsets) and check point inhibitors; we anticipate that post allo transplant immune manipulation can further augment these benefits. Table 1 Patients' Baseline characteristics * Gahrton et al. EBMT-NMAM2000 study (Blood 2013; 121 (25):5055-63) Table 1. Patients' Baseline characteristics. / * Gahrton et al. EBMT-NMAM2000 study (Blood 2013; 121 (25):5055-63) Table 2 Univariate survival analysis of patients who relapsed post tandem transplant (time 0 at time of relapse) Table 2. Univariate survival analysis of patients who relapsed post tandem transplant (time 0 at time of relapse) Figure 1 Adjusted overall survival for post relapse patients Figure 1. Adjusted overall survival for post relapse patients Disclosures Krishnan: celgene: Consultancy, Speakers Bureau; takeda: Consultancy, Speakers Bureau; janssen: Consultancy, Speakers Bureau; onyx: Speakers Bureau.

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Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma

Blood ◽

10.1182/blood-2012-05-432203 ◽

2013 ◽

Vol 121 (6) ◽

pp. 884-892 ◽

Cited By ~ 117

Author(s):

P. Leif Bergsagel ◽

María-Victoria Mateos ◽

Norma C. Gutierrez ◽

S. Vincent Rajkumar ◽

Jesús F. San Miguel

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

High Risk ◽

Prognostic Impact ◽

The Poor ◽

Number Of Patients ◽

Inadequate Sample Size ◽

Genetic Features ◽

Risk Patients ◽

Patient Subgroups

Abstract Multiple myeloma (MM) is a heterogeneous disease with certain genetic features [eg, t(4;14), del17p] associated with worse outcome. The introduction of thalidomide, lenalidomide, and bortezomib has dramatically improved the outlook for patients with MM, but their relative benefit (or harm) for different genetic patient subgroups remains unclear. Unfortunately, the small number of patients in each subgroup frequently limits the analysis of high-risk patients enrolled in clinical trials. Strategies that result in survival of high-risk genetic subgroups approximating that of patients lacking high-risk features are said to overcome the poor prognostic impact of these high-risk features. This outcome has been difficult to achieve, and studies in this regard have so far been limited by inadequate sample size. In contrast, strategies that compare the survival of high-risk genetic subgroups randomized to different treatment arms can identify approaches that improve survival. This type of analysis is clinically useful, even if the absolute gains do not improve outcomes to levels seen in patients without high-risk cytogenetics. Reviewing available data in high-risk MM from this perspective, it appears that bortezomib has frequently been associated with improved survival, whereas thalidomide maintenance has sometimes been associated with a shorter survival.

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The effect of adjuvant radiotherapy on overall survival in adults with intracranial ependymoma

Neuro-Oncology Practice ◽

10.1093/nop/npz070 ◽

2019 ◽

Vol 7 (4) ◽

pp. 391-399

Author(s):

Roshan S Prabhu ◽

Christopher D Corso ◽

Matthew C Ward ◽

John H Heinzerling ◽

Reshika Dhakal ◽

...

Keyword(s):

Overall Survival ◽

Propensity Score ◽

Adjuvant Radiotherapy ◽

Subtotal Resection ◽

National Cancer Database ◽

Risk Of Death ◽

Increased Risk ◽

Intracranial Ependymoma ◽

Male Sex ◽

Grade 3

Abstract Background Adult intracranial ependymoma is rare, and the role for adjuvant radiotherapy (RT) is not well defined. Methods We used the National Cancer Database (NCDB) to select adults (age ≥ 22 years) with grade 2 to 3 intracranial ependymoma status postresection between 2004 and 2015 and treated with adjuvant RT vs observation. Four cohorts were generated: (1) all patients, (2) grade 2 only, (3) grade 2 status post–subtotal resection only, (4) and grade 3 only. The association between adjuvant RT use and overall survival (OS) was assessed using multivariate Cox and propensity score matched analyses. Results A total of 1787 patients were included in cohort 1, of which 856 patients (48%) received adjuvant RT and 931 (52%) were observed. Approximately two-thirds of tumors were supratentorial and 80% were grade 2. Cohorts 2, 3, and 4 included 1471, 345, and 316 patients, respectively. There was no significant association between adjuvant RT use and OS in multivariate or propensity score matched analysis in any of the cohorts. Older age, male sex, urban location, higher comorbidity score, earlier year of diagnosis, and grade 3 were associated with increased risk of death. Conclusions This large NCDB study did not demonstrate a significant association between adjuvant RT use and OS for adults with intracranial ependymoma, including for patients with grade 2 ependymoma status post–subtotal resection. The conflicting results regarding the efficacy of adjuvant RT in this patient population highlight the need for high-quality studies to guide therapy recommendations in adult ependymoma.

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A Novel Autophagy-Related lncRNA Gene Signature to Improve the Prognosis of Patients with Melanoma

10.21203/rs.3.rs-57306/v1 ◽

2020 ◽

Author(s):

Yi Ding ◽

Tian Li ◽

Min Li ◽

Tuersong Tayier ◽

MeiLin Zhang ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Risk Model ◽

Risk Group ◽

Clinical Information ◽

Low Risk ◽

Gene Set Enrichment Analysis ◽

Positive Regulation ◽

Risk Patients ◽

Cox Analysis

Abstract Background: Autophagy and long non-coding RNAs (lncRNAs) have been the focus of research on the pathogenesis of melanoma. However, the autophagy network of lncRNAs in melanoma has not been reported. The purpose of this study was to investigate the lncRNA prognostic markers related to melanoma autophagy and predict the prognosis of patients with melanoma.Methods: We downloaded RNA-sequencing data and clinical information of melanoma from The Cancer Genome Atlas. The co-expression of autophagy-related genes (ARGs) and lncRNAs was analyzed. The risk model of autophagy-related lncRNAs was established by univariate and multivariate COX regression analyses, and the best prognostic index was evaluated combined with clinical data. Finally, gene set enrichment analysis was performed on patients in the high- and low-risk groups.Results: According to the results of the univariate COX analysis, only the overexpression of LINC00520 was associated with poor overall survival, unlike HLA-DQB1-AS1, USP30-AS1, AL645929, AL365361, LINC00324, and AC055822. The results of the multivariate COX analysis showed that the overall survival of patients in the high-risk group was shorter than that recorded in the low-risk group (p<0.001). Moreover, in the receiver operating characteristic curve of the risk model we constructed, the area under the curve (AUC) was 0.734, while the AUC of T and N was 0.707 and 0.658, respectively. The Gene Ontology was mainly enriched with the positive regulation of autophagy and the activation of the immune system. The results of the Kyoto Encyclopedia of Genes and Genomes enrichment were mostly related to autophagy, immunity, and melanin metabolism.Conclusion: The positive regulation of autophagy may slow the transition from low-risk patients to high-risk patients in melanoma. Furthermore, compared with clinical information, the autophagy-related lncRNAs risk model may better predict the prognosis of patients with melanoma and provide new treatment ideas.

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Neonatal Outcomes Associated with Noncephalic Presentation at Delivery in Preterm Birth

American Journal of Perinatology ◽

10.1055/s-0037-1619450 ◽

2018 ◽

Vol 35 (12) ◽

pp. 1131-1137

Author(s):

Annalisa Post ◽

Geeta Swamy ◽

Chad Grotegut ◽

Amber Wood

Keyword(s):

Intensive Care Unit ◽

Multivariate Analysis ◽

Intensive Care ◽

Neonatal Intensive Care ◽

Mode Of Delivery ◽

Secondary Analysis ◽

Neonatal Outcomes ◽

Risk Of Death ◽

Increased Risk ◽

Stratified Analysis

Objective The objective of this study is to evaluate the effect of noncephalic presentation on neonatal outcomes in preterm delivery. Study Design In this study a secondary analysis of the BEAM trial was performed. It included women with singleton, liveborn, and nonanomalous fetuses. Neonatal outcomes were compared in noncephalic versus cephalic presentation. Adjusted odds ratios and 95% confidence intervals were calculated for each outcome with logistic regression while controlling for possible confounders. A stratified analysis by mode of delivery was also performed in this study. Results A total of 458 noncephalic deliveries were compared with 1,485 cephalic deliveries. In multivariate analysis, noncephalic presentation was associated with increased risk of death in the neonatal intensive care unit (NICU) or death at <15 months corrected gestational age (cGA), and a decreased risk of IVH. The risk of death persisted in stratified analysis, with increased risk of death at <15 months cGA in noncephalic neonates born via cesarean delivery. In the vaginal delivery group, there was an increased risk of death at <15 months cGA and NICU death. Conclusion After controlling for possible confounders, neonates who are noncephalic at delivery have higher risk for death <15 months cGA and death in the NICU while their risk of IVH is reduced. The risk of death persisted in stratified analyses by mode of delivery.

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Prognostic impact of chemoradiation-related lymphopenia in patients with gastric and gastroesophageal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.249 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 249-249

Author(s):

Daniel W Kim ◽

Grace Lee ◽

Theodore S. Hong ◽

Guichao Li ◽

Eric Roeland ◽

...

Keyword(s):

Prognostic Factor ◽

Cox Model ◽

Gastroesophageal Junction ◽

Concurrent Chemotherapy ◽

Rank Test ◽

Prognostic Impact ◽

Poor Prognostic Factor ◽

Risk Of Death ◽

Increased Risk ◽

Ecog Ps

249 Background: Limited data exists on how chemoradiation (CRT)-induced lymphopenia affects survival outcomes in patients with gastric and gastroesophageal junction (GEJ) cancer. We evaluated the association between severe lymphopenia and its association with survival in gastric and GEJ cancer patients treated with CRT. We hypothesized that severe lymphopenia would be a poor prognostic factor. Methods: We performed a retrospective analysis of 154 patients with stage 1-3 gastric or GEJ cancer who underwent CRT at our institution. Patients underwent photon-based radiation therapy (RT) with a median dose of 50.4 Gy (IQR 45.0-50.4 Gy) over 28 fractions and concurrent chemotherapy (CTX) with carboplatin/paclitaxel, 5-fluorouracil based regimen, or capecitabine. 49% received CTX prior to RT. 84% underwent surgical resection, 57% pre-CRT and 26% post-CRT. Absolute lymphocyte count (ALC) at baseline and at 2 months since initiating RT were analyzed. Severe lymphopenia, defined as Grade 3 or worse lymphopenia (ALC < 0.5 k/μl), was analyzed for any association with overall survival (OS). Results: Median time of follow up was 48 months. Median age was 65. 77% were male and 86% were Caucasian. ECOG PS was 0 or 1 in 90% and 2 in 10%. Tumor location was stomach in 38% and GEJ in 62%. Timing of CRT was preoperative among 68% and postoperative among 32%. The median ALC at baseline for the entire cohort was 1.6 k/ul (range 0.3-7.0 k/ul). At 2 months post-CRT, 49 (32%) patients had severe lymphopenia. Patients with severe lymphopenia post-CRT had a slightly lower baseline TLC compared to patients without severe lymphopenia (median TLC 1.4 k/ul vs. 1.6 k/ul; p = 0.005). There were no differences in disease and treatment characteristics between the two groups. On the multivariable Cox model, severe lymphopenia post-CRT was significantly associated with increased risk of death (HR = 3.99 [95% CI 1.55-10.28], p = 0.004). ECOG PS 2 (HR = 34.97 [95% CI 2.08-587.73], p = 0.014) and postoperative CRT (HR = 5.55 [95% CI 1.29-23.86], p = 0.021) also predicted worse OS. The 4-year OS among patients with severe lymphopenia was 41% vs. 61% among patients with vs. without severe lymphopenia (log-rank test p = 0.041). Conclusions: Severe lymphopenia significantly correlated with poorer OS in patients with gastric or GEJ cancer treated with CRT. CRT-induced lymphopenia may be an important prognostic factor for survival in this patient population. Closer observation in high-risk patients and treatment modifications may be potential approaches to mitigating CRT-induced lymphopenia.

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Biomarker-assisted identification of sepsis-related acute liver impairment: a frequent and deadly condition in critically ill patients

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2018-1350 ◽

2019 ◽

Vol 57 (9) ◽

pp. 1422-1431 ◽

Cited By ~ 1

Author(s):

Jens-Ulrik Stæhr Jensen ◽

Lars Peters ◽

Theis S. Itenov ◽

Morten Bestle ◽

Katrin M. Thormar ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Prognostic Impact ◽

Surgical Intensive Care ◽

Positive Interaction ◽

Liver Impairment ◽

Risk Of Death ◽

Increased Risk ◽

Co Morbidity ◽

All Cause Mortality

Abstract Background The prognostic impact of mild/moderate liver impairment among critically ill patients is not known. We aimed to determine whether acute liver impairment, as measured by several biomarkers, (i) is frequent, (ii) influences prognosis and (iii) to determine whether such an effect is specific for infected critically ill patients. Methods A biomarker and clinical cohort study based on a randomized controlled trial. All-cause mortality was the primary endpoint. Biomarkers hyaluronic acid (HA), bilirubin, albumin, alkaline phosphatase and the international normalized ratio (INR) were determined. Multivariable statistics were applied to estimate risk increase according to liver biomarker increase at baseline and the model was adjusted for age, APACHE II, severe sepsis/septic shock vs. milder infection, chronic alcohol abuse Charlson’s co-morbidity index, cancer disease, surgical or medical patient, body mass index, sex, estimated glomerular filtration rate, mechanical ventilation and the other biomarkers. Time-to-event graphs were used. The patients were critically ill patients (n = 1096) from nine mixed medical/surgical intensive care units without known hepatobiliary disease. Results HA levels differed between infected patients (median 210.8 ng/mL [IQR: 93.2–556.6]) vs. the non-infected (median 56.8 ng/mL [IQR: 31.9–116.8], p < 0.001). Serum HA quartiles 2, 3 and 4 were independent predictors of 90-day all-cause mortality for the entire population (infected and non-infected). However, the signal was driven by the infected patients (positive interaction test, no signal in non-infected patients). Among infected patients, HA quartiles corresponded directly to the 90-day risk of dying: 1st quartile: 57/192 = 29.7%, 2nd quartile: 84/194 = 43.3%, 3rd quartile: 90/193 = 46.6%, 4th quartile: 101/192 = 52.3 %, p for trend: <0.0001. This finding was confirmed in adjusted analyses: hazard ratio vs. 1st quartile: 2nd quartile: 1.3 [0.9–1.8], p = 0.14, 3rd quartile: 1.5 [1.1–2.2], p = 0.02, 4th quartile: 1.9 [1.3–2.6], p < 0.0001). High bilirubin was also an independent predictor of mortality. Conclusions Among infected critically ill patients, subtle liver impairment, (elevated HA and bilirubin), was associated with a progressive and highly increased risk of death for the patient; this was robust to adjustment for other predictors of mortality. HA can identify patients at high risk.

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Sarcomatoid Renal Cell Carcinoma: Biologic Behavior, Prognosis, and Response to Combined Surgical Resection and Immunotherapy

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.2.523 ◽

1999 ◽

Vol 17 (2) ◽

pp. 523-523 ◽

Cited By ~ 128

Author(s):

Thomas Cangiano ◽

Joseph Liao ◽

John Naitoh ◽

Frederick Dorey ◽

Robert Figlin ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Multivariate Analysis ◽

Cell Carcinoma ◽

Surgical Resection ◽

Median Duration ◽

Renal Cell ◽

High Dose ◽

Risk Of Death

PURPOSE: Sarcomatoid variants of renal cell carcinoma (RCC) are aggressive tumors that respond poorly to immunotherapy. We report the outcomes of 31 patients with sarcomatoid RCC treated with a combination of surgical resection and immunotherapy. PATIENTS AND METHODS: Patients were identified from the database of the University of California Los Angeles Kidney Cancer Program. We retrospectively reviewed the cases of 31 consecutive patients in whom sarcomatoid RCC was diagnosed between 1990 and 1997. Clinical stage, sites of metastasis, pathologic stage, and type of immunotherapy were abstracted from the medical records. The primary end point analyzed was overall survival, and a multivariate analysis was performed to distinguish any factors conferring an improved survivorship. RESULTS: Twenty-six percent of patients were male and 74% were female, and the median age was 59 years (range, 34 to 73 years). Length of follow-up ranged from 2 to 77 months (mean, 21.4 months). Twenty-eight patients (84%) had known metastases at the time of radical nephrectomy (67% had lung metastases and 40% had bone, 21% had liver, 33% had lymphatic, and 15% had brain metastases). Twenty-five patients (81%) received immunotherapy, including low-dose interleukin (IL)-2–based therapy (five patients), tumor-infiltrating lymphocyte–based therapy plus IL-2 (nine patients), high-dose IL-2–based therapy (nine patients), dendritic cell vaccine–based therapy (one patient), and interferon alpha–based therapy alone (one patient). Two patients (6%) achieved complete responses (median duration, 46+ months) and five patients (15%) achieved partial responses (median duration, 36 months). One- and 2-year overall survival rates were 48% and 37%, respectively. Using a multivariate analysis, age, sex, and percentage of sarcomatoid tumor (< or > 50%) did not significantly correlate with survival. Improved survival was found in patients receiving high-dose IL-2 therapy compared with patients treated with surgery alone or any other form of immunotherapy (P = .025). Adjusting for age, sex, and percentage of sarcomatoid tumor, the relative risk of death was 10.4 times higher in patients not receiving high-dose IL-2 therapy. Final pathologic T stage did not correlate significantly with outcome, but node-positive patients had a higher death rate per year of follow-up than did the rest of the population (1.26 v 0.76, Cox regression analysis). CONCLUSION: Surgical resection and high-dose IL-2–based immunotherapy may play a role in the treatment of sarcomatoid RCCs in select patients.

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