Independent Prognostic Factor For Outcome Research Articles

Evaluation of the prognostic impact of pathologic tumor regression grade on patients with colorectal cancer after preoperative chemoradiotherapy.

The prognostic value of the pathological response to preoperative chemoradiotherapy (CRT) in rectal cancer (RC) remains unknown. We aimed to assess the predictive value of the response to CRT that was derived from an evaluation of the histological findings (whole-section vs. representative-section sampling) and attempted to determine an objective cut-off value for the tumor regression grade (TRG). We examined the association of the TRG with the outcomes (recurrence-free survival [RFS] and overall survival [OS]) of 78 patients with RC. Patients with RC treated with preoperative CRT were divided into development (30 cases) and validation (48 cases) cohorts. The TRG was classified as grades I (Ia, Ib), II, and III. The cut-off value was determined by receiver operating characteristic (ROC) curve analysis. The TRG determined from whole-section sampling versus representative-section sampling was more strongly correlated with patient survival. We found that in both cohorts, patients with a cut-off value of <73% had a poor prognosis. Finally, the cut-off value was found to be an independent predictive factor in both univariate and multivariate analysis. The TRG that was used to evaluate patients with RC who underwent preoperative CRT was an independent prognostic factor for outcome.

Radiation Therapy Plays an Important Role in the Treatment of Atypical Teratoid/Rhabdoid Tumors: Analysis of the EU-RHAB Cohorts and Their Precursors

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignancy of the central nervous system in young children with a dismal prognosis. Prognostic markers have been extensively investigated but have not been validated. The role of radiation therapy (RT) remains controversial. We evaluated the impact of RT as part of multimodality treatment by analyzing data of a European AT/RT cohort. We retrospectively analyzed data of the European Registry for Rhabdoid Tumors and its precursors. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Potential impact of prognostic factors was analyzed using univariable and multivariable Cox regression analyses with RT as a time-dependent factor. Data of 186 children (118 male, 68 female) treated from 1990 to 2016 were evaluable. The median age at diagnosis was 1.57 years (range, 0.01-26.70 years); 47% (87/186) of the patients were under the age of 18 months. Sixty-nine percent (128/186) received RT (focal RT, n = 93; craniospinal treatment with local boost, n = 34; spinal irradiation, n = 1). The median follow-up duration of the entire cohort was 1.73 years (range, 0.06-20.11 years). The estimated PFS and OS rates were 48% (95% CI, 41%-55%) and 72% (95% CI, 65%-78%) at 1 year and 33% (95% CI, 26%-40%) and 49% (95% CI, 41%-56%) at 2 years, respectively. On multivariable analysis, RT was an independent significant prognostic factor for PFS (hazard ratio, 0.45; 95% CI, 0.27-0.75; P = .002) and OS (hazard ratio, 0.54; 95% CI, 0.32-0.93; P = .025). This analysis confirms the relevance of local therapies. RT was an independent prognostic factor for outcomes in children experiencing AT/RT. However, long-term sequelae have to be carefully evaluated and considered given the young age at time of RT.

Phenotyping cardiogenic shock that showed different clinical outcomes and responses to vasopressor use: a latent profile analysis from MIMIC-IV database.

Cardiogenic shock (CS) is increasingly recognized as heterogeneous in its severity and response to therapies. This study aimed to identify CS phenotypes and their responses to the use of vasopressors. The current study included patients with CS complicating acute myocardial infarction (AMI) at the time of admission from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Laboratory and clinical variables were collected and used to conduct latent profile (LPA) analysis. Furthermore, we used a multivariable logistic regression (LR) model to explore the independent association between the use of vasopressors and endpoints. A total of 630 eligible patients with CS after AMI were enrolled in the study. The LPA identified three profiles of CS: profile 1 (n = 259, 37.5%) was considered as the baseline group; profile 2 (n = 261, 37.8%) was characterized by advanced age, more comorbidities, and worse renal function; and profile 3 (n = 170, 24.6%) was characterized by systemic inflammatory response syndrome (SIRS)-related indexes and acid-base balance disturbance. Profile 3 showed the highest all-cause in-hospital mortality rate (45.9%), followed by profile 2 (43.3%), and profile 1 (16.6%). The LR analyses showed that the phenotype of CS was an independent prognostic factor for outcomes, and profiles 2 and 3 were significantly associated with a higher risk of in-hospital mortality (profile 2: odds ratio [OR] 3.95, 95% confidence interval [CI] 2.61-5.97, p < 0.001; profile 3: OR 3.90, 95%CI 2.48-6.13, p < 0.001) compared with profile 1. Vasopressor use was associated with an improved risk of in-hospital mortality for profile 2 (OR: 2.03, 95% CI: 1.15-3.60, p = 0.015) and profile 3 (OR: 2.91, 95% CI: 1.02-8.32, p = 0.047), respectively. The results of vasopressor use showed no significance for profile 1. Three phenotypes of CS were identified, which showed different outcomes and responses to vasopressor use.

Impact of age on survival according to molecular tumor findings in children and adolescents with soft-tissue and bone sarcoma: The BIOSCA project

BackgroundAdolescents (15–19 years) with sarcoma are known to have significantly worse survival than children (0–14 years). One possible reason may be that the adolescent sarcomas exhibit specific biological characteristics resulting in differences in clinical presentation and treatment resistance behaviors. The BIOSCA project aims to further explore these age-related differences in survival accounting for molecular tumor characteristic in children and adolescents with sarcoma. MethodsA retrospective national population-based observational study with documented somatic genetic analyses was conducted between 2011 and 2016 of all patients aged from 0 to 17 years with a diagnosis of sarcoma using the National Registry of Childhood Cancers Database. ResultsA total of 1637 children (0–9years: 40%), preadolescents (10–14years: 35%) and adolescents (15–17 years: 25%) with a diagnosis of bone (N = 845) or soft-tissue (N = 792) sarcoma were included. Adolescents had significantly worse outcome for undifferentiated small round cell sarcoma (USRCS), alveolar rhabdomyosarcoma (ARMS), and epithelioid sarcoma. Five-year overall survivals were worse among CIC-rearranged USRCS cases (47% [95%CI:21–69]) as compared to other USRCS, and PAX3::FOXO1 ARMS patients (44% [95%CI:32–55]) as compared to other ARMS. Adjusting for stage and genomic-profiling status, adolescents with USRCS were 1.6-fold more likely to die than children (P = 0.05), while the difference in survival between age of ARMS patients was weaken. Indeed, the prevalence of PAX3::FOXO1 increased significantly with age. ConclusionAge was an independent prognostic factor of outcome only in patients with USRCS, while the association between age and survival of patients with ARMS could be partly explained by differences in prevalence of PAX3::FOXO1.

Degree Of Cisternal Compression As An Independent Prognostic Factor For Outcome In Both Craniotomy and Primary Decompressive Craniectomy Groups In Acute Subdural Hematoma Population

Degree Of Cisternal Compression As An Independent Prognostic Factor For Outcome In Both Craniotomy and Primary Decompressive Craniectomy Groups In Acute Subdural Hematoma Population

Quantitative Whole-Body Diffusion-weighted MRI after One Treatment Cycle for Aggressive Non-Hodgkin Lymphoma Is an Independent Prognostic Factor of Outcome.

To evaluate the prognostic utility of apparent diffusion coefficient (ADC) changes at whole-body diffusion-weighted (WB-DW) MRI after one treatment cycle for aggressive non-Hodgkin lymphoma (NHL) compared with response assessment at interim and end-of-treatment fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT. This was a secondary analysis of a prospective study (ClinicalTrials.gov identifier: NCT01231269) in which participants with aggressive NHL were recruited between March 2011 and April 2015 and underwent WB-DW MRI before and after one cycle of immunochemotherapy. Volunteers were recruited for test-retest WB-DW MRI (ClinicalTrials.gov identifier: NCT01231282) to assess ADC measurement repeatability. Response assessment was based on ADC change after one treatment cycle at WB-DW MRI and Deauville criteria at 18F-FDG PET/CT. To evaluate prognostic factors of disease-free survival (DFS), Kaplan-Meier survival analysis and univariable and multivariable Cox regression were performed; intraclass correlation coefficient (ICC) and mean difference with limits of agreement were calculated to determine inter- and intraobserver repeatability of ADC measurements. Forty-five patients (mean age, 58 years ± 17 [standard deviation]; 31 men) and nine volunteers (mean age, 22 years ± 3; seven men) were enrolled. Median DFS was 48 months (range, 2-48 months). Outcome prediction accuracy was 86.7% (39 of 45), 71.4% (30 of 42), and 73.8% (31 of 42) for WB-DW MRI and interim and end-of-treatment 18F-FDG PET/CT, respectively. WB-DW MRI (hazard ratio [HR], 17.8; P < .001) and interim (HR, 5; P = .008) and end-of-treatment (HR, 4.3; P = .017) 18F-FDG PET/CT were prognostic of DFS. After multivariable analysis, WB-DW MRI remained an independent predictor of outcome (HR, 26.8; P = .002). Intra- and interobserver agreement for ADC measurements were excellent (ICC = 0.85-0.99). Quantitative WB-DW MRI after only one cycle of immunochemotherapy predicts DFS in aggressive NHL and is noninferior to routinely performed interim and end-of-treatment 18F-FDG PET/CT.Keywords: MR-Diffusion Weighted Imaging, Lymphoma, Oncology, Tumor Response, Whole-Body ImagingSupplemental material is available for this article.© RSNA, 2021.

Prognostic role of the duration of response to androgen deprivation therapy in patients with metastatic castration resistant prostate cancer treated with enzalutamide or abiraterone acetate.

Our retrospective study aims to evaluate the prognostic role of duration of response to androgen deprivation therapy (ADT) in metastatic castration resistant prostate cancer (mCRPC) patients treated with enzalutamide (E) or abiraterone acetate (AA). Data about ADT start and duration were available in 255 (82%) of 311 patients treated with AA or E. Patients were divided in three groups according to ADT response (group 1 [G1]: <12 months; group 2 [G2]: 12-36 months; group 3 [G3]: >36 months). Outcome measures were progression-free survival (PFS) and overall survival (OS). Patients with longer ADT response had better OS (median 17.3 months G1, 19.9 months G2, 31.6 months G3; HR G3 vs G1 0.41, 95% CI 0.25-0.64; p = 0.001) and better PFS (median 5.9 months G1, 8.8 months G2, 11.7 months G3; HR G3 vs G1 0.41, 95% CI 0.41-0.27; p < 0001). In docetaxel-naive patients, median OS was 18.8 in G1, 35.2 in G2, and not reached in G3 (HR G3 vs G1 0.33, 95% CI 0.14-0.78; p = 0.038), median PFS was 7 months G1, 9.3 months G2, and 20 months G3 (HR G3 vs G1 0.31, 95% CI 0.15-0.62; p = 0.003). In postdocetaxel patients, median OS was 13.1 months in G1, 17.2 months in G2, and 21.4 months in G3 (HR G3 vs G1 0.52, 95% CI 0.29-0.94; p = 0.082), while median PFS was 5.2 months in G1, 6.8 months in G2, and 8.3 months in G3 (HR G3 vs G1 0.54, 95% CI 0.32-0.91; p = 0.067). Duration of ADT response is an independent prognostic factor of outcome with AA or E.

Abstract PS6-43: The prognostic impact of breast cancer subtype based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) statuses for end-stage disease

Abstract Background: Most patients with metastatic cancer request information regarding their prognosis, most notably when death is clearly approaching. Several clinical indices are used to predict the prognosis of end-stage cancer based on performance status and clinical factors. For example, the Palliative Prognostic Index (PPI) includes a range of scores from 0-15 based on factors that include performance status, oral intake, presence of edema, dyspnea at rest, and delirium. For scores greater than six, survival for an additional three weeks was predicted with a sensitivity of 80% and a specificity of 85%. However, the predictive power of these indices is currently insufficient; the quality of life of end-stage breast cancer patients would be markedly improved with a more accurate prediction model. Breast cancer subtypes based on the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) statuses are important prognostic factors with respect to the outcome of initial breast cancer therapy; the subtype defined by these parameters was also identified as an independent prognostic factor for outcomes in cases of metastatic breast cancer. However, the prognostic impact of breast cancer subtype with respect to end-stage disease remains unclear. In this retrospective observational study, we evaluated the relationship between survival time and associated clinicopathological factors, including breast cancer subtype, in order to develop a more accurate prognostic model for end-stage breast cancer patients. Methods: Seventy-three patients with end-stage breast cancer who were admitted to our hospice care unit from January 2014 to December 2018 were enrolled in the study. Patients in this unit were not provided with anticancer therapy but did receive highest-quality supportive care. The primary endpoint was survival time from the admission. Patient information, including age, PPI, disease-free interval (DFI), the number of treatments for the metastatic disease, metastatic site, and breast cancer subtypes were collected from medical records. Breast cancer subtypes included Luminal (Lum), Lum-HER2, HER2, and triple negative (TN) with respect to those that were HR+HER2−, HR+HER2−, HR−HER2+, and HR−HER2−, respectively. The study was approved by the ethical committee of the Oikawa Hospital (OHCT022). Results: The median survival time was 23 days (1-359 days). From the univariate analysis, PPI scores of less than six were associated with significantly shorter survival (14 days vs. 36.5 days, P = 0.001). Patients diagnosed with Lum-HER2 subtype, those who were older and were without liver metastasis, those with a shorter DFI, and those who underwent fewer treatments for metastatic disease showed a tendency toward a favorable prognosis, although these findings did not reach statistical significance. Multivariate logistic regression analysis revealed that a PPI score less than six (P = 0.001), Lum-HER2 subtype (P = 0.003), absence of liver metastasis (P = 0.001), and DFI lower than the median (33 months; P = 0.028) all contributed to longer survival time. Discussion &amp; Conclusion: In addition to the PPI, breast cancer subtype can be used to provide more precise prognoses for end-stage breast cancer patients. Survival of patients diagnosed with the Lum-HER2 subtype was longer than that observed among those with any of the other subtypes who had not undergone any anticancer treatment for metastatic disease; these results suggest that anti-HER2 therapy may be associated with critical immunological modifications. Taken together, our results indicate that breast cancer subtype should be included to provide a more accurate prognostic model for end-stage breast cancer patients. Citation Format: Masahiro Oikawa, Yumika Setoguchi, Yasuko Enomoto, Kazuhumi Hisamatsu, Tetsuaki Inamitsu, Tatsuji Oikawa. The prognostic impact of breast cancer subtype based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) statuses for end-stage disease [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-43.

Lymph node ratio as a predictor for outcome in oral squamous cell carcinoma: a multicenter population-based cohort study

ObjectivesRecently, multiple studies addressed the importance of lymph node ratio (LNR) in specifying patients’ risk of disease recurrence in various malignancies. The present study examines the prognostic significance of LNR in predicting outcome of oral squamous cell carcinoma (OSCC) patients after surgical treatment with curative intent.MethodsHere, we describe a retrospective population-based cohort with 717 patients previously diagnosed with OSCC. Histopathologically verified lymph node metastasis was diagnosed in 290 patients. Among these patients, we evaluated the impact of LNR on overall survival (OAS) and recurrence-free survival (RFS) in uni- as well as multivariate analysis.ResultsA median cutoff (0.055) in LNR was found to significantly predict outcome in OSCC patients. Five-year OAS was 54.1% in patients with a low LNR, whereas a high LNR was associated with a 5-year OAS of 33.3% (p < 0.001). Similar results were detected for RFS with a 5-year survival rate of 49.8% (LNR low) and 30.3% (LNR high) (p = 0.002). Results were confirmed in multivariate Cox regression which substantiated the importance of LNR in predicting survival in OSCC patients.ConclusionsLNR was shown to be an independent prognostic factor for outcome of OSCC in a population-based cohort in uni- as well as multivariate analysis. Hereby, a LNR ≥ 0.055 predicted a shorter OAS and RFS in our cohort.Clinical relevanceBesides established histopathological factors, LNR can be used as a reliable predictor of outcome in OSCC and might therefore be further applied in evaluating adjuvant treatment after resection in curative intention.

Low Lymphocyte Count Is Associated With Radiotherapy Parameters and Affects the Outcomes of Esophageal Squamous Cell Carcinoma Patients.

Purpose: Lymphocytes are central players in systemic anti-tumor immune responses. In this study, we aimed to identify the relationship between absolute lymphocyte count (ALC) nadir during definitive radiotherapy (RT) and survival outcomes in patients with esophageal squamous cell carcinoma (ESCC), as well as evaluate the effect of RT parameters on ALC during RT.Materials and methods: We retrospectively reviewed 189 patients with stage I-IVA ESCC, who were treated with definitive RT at a single institution between 2012 and 2015. ALC values were assessed before, weekly during RT, and 1 month after the end of RT. Kaplan–Meier and Cox regression analyses were used to evaluate the relationship between ALC nadir during RT and patient outcomes. Predictors of low ALC nadir were assessed using univariate and multivariate logistic regression analyses.Results: The median ALC before treatment was 1.73 × 103 cells/μL. Fifty-eight (58.2) percent of the patients exhibited low ALC nadir (≤ 0.38 × 103 cells/μL) during RT. A low ALC nadir during RT was significantly associated with poor OS, PFS, and LRFS. The planning target volume (PTV) was larger in patients with low ALC nadir compared with patients with high ALC nadir (418.5 vs. 347.7 cm3, P = 0.023). Multivariate logistic regression analysis revealed that tumor stage III-IVA (P = 0.002), low ALC before treatment (P = 0.028), large Log10(PTV) (P = 0.01), high heart V10 (P = 0.003), and high heart V20 (P = 0.028) were associated with low ALC nadir during RT.Conclusions: In ESCC patients who received definitive RT, a low ALC nadir during RT was associated with large PTVs, and it was an independent prognostic factor of outcomes.

Tandem Autologous Hematopoietic Stem Cell Transplantation for Treatment of Adult T-Cell Lymphoblastic Lymphoma: A Multiple Center Prospective Study in Southwestern China

Background: T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive form of lymphoma with poor clinical outcomes and lack of a standard treatment regimen. Accordingly, this study evaluated the safety and efficacy of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) treatment for adult T-LBL and assessed factors affecting survival. Methods: Newly-diagnosed adult T-LBL patients (n=181) were divided into three groups: chemotherapy (no HSCT) group (89 patients), single auto-HSCT group (46 patients), and tandem auto-HSCT group (46 patients). The measurement of primary outcome was progression-free survival (PFS). The secondary outcomes were progression/relapse rate and overall survival (OS). Additionally, this study analyzed factors influencing toxicities related to tandem auto-HSCT treatment and patient prognosis. Results: The 3-year progression/relapse rate of the tandem auto-HSCT group was significantly lower than that of the single auto-HSCT group and chemotherapy group (26.5% vs 53.1% and 57.6%, p < 0.05). The 3-year PFS rate and OS rate of the tandem auto-HSCT group (73.5% and 76.3%, respectively) were significantly higher than those of the single auto-HSCT group (46.9% and 58.3%, respectively, p < 0.05) and the chemotherapy group (42.3% and 56.1%, respectively, p < 0.05). In the tandem auto-HSCT group, age and disease status after the first transplantation impacted the OS and PFS. Multivariate analysis identified disease status after the first transplantation as the only independent prognostic factor for outcome in T-LBL treated with tandem-HSCT. Conclusions: Tandem auto-HSCT improves long-term survival of adult T-LBL patients compared to recipients of chemotherapy alone or chemotherapy plus single auto-HSCT, and disease status after the first transplantation is an independent prognostic indicator for these patients. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (No.81370594, 81070388, 81270569, 81600166), the Scientific and Technological Innovation Program of Chongqing social undertakings and people's livelihood guarantee (cstc2016shms-ztzx10003), and Youth Innovation Project of Military Medicine of Chinese People’s Liberation Army (No.13QNP116). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The study was performed in accordance with the Declaration of Helsinki and local laws. The protocol was approved by the ethic committee of each center, and written informed consent was obtained from all patients.

PS1093 IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED DLBCL, CHANGE WEIGHT AFTER THE FIRST COURSE R-CHOP (-LIKE) CHEMOTHERAPY IS AN ADVERSE PROGNOSTIC FACTOR

Background: T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive form of lymphoma with poor clinical outcomes and lack of a standard treatment regimen. Aims: This study evaluated the safety and efficacy of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) treatment for adult T-LBL and assessed factors affecting survival. Methods: Newly-diagnosed adult T-LBL patients (n = 160) were divided into three groups: chemotherapy (no HSCT) group (68 patients), single auto-HSCT group (46 patients), and tandem auto-HSCT group (46 patients). The measurement of primary outcome was progression-free survival (PFS). The intermediate outcomes were progression/relapse rate and overall survival (OS). Additionally, this study analyzed factors influencing toxicities related to tandem auto-HSCT treatment and patient prognosis. Results: The 3-year progression/relapse rate of the tandem auto-HSCT group was significantly lower than that of the single auto-HSCT group and chemotherapy group (19.6% vs 45.7% and 70.6%, p < 0.05). The 3-year PFS rate and OS rate of the tandem auto-HSCT group (68.3% and 72.5%, respectively) were significantly higher than those of the single auto-HSCT group (41.5% and 55.4%, respectively, p < 0.05) and the chemotherapy group (23.3% and 43.3%, respectively, p < 0.05). In the tandem auto-HSCT group, age and disease status after the first transplantation impacted the OS and PFS. Multivariate analysis identified disease status after the first transplantation as the only independent prognostic factor for outcome in T-LBL treated with tandem-HSCT. Summary/Conclusion: Tandem auto-HSCT improves long-term survival of adult T-LBL patients compared to recipients of chemotherapy alone or chemotherapy plus single auto-HSCT and disease status after the first transplantation is an independent prognostic indicator for these patients.

Comprehensive Clinical-Molecular Transplant Risk Model for Myelofibrosis Undergoing Allogeneic Stem Cell Transplantation

Background The Dynamic International Prognostic Scoring System (DIPSS) is commonly applied to predict survival among patients with primary myelofibrosis (PMF) but has been shown to perform less precisely in secondary myelofibrosis (SMF) and after transplantation. Furthermore, the prognostic relevance of mutation profile resulted in the mutation-enhanced IPSS (MIPSS70) in PMF, as well as in a model specific to SMF (MYSEC-PM). We aimed to develop a comprehensive clinical-molecular prognostic scoring system to determine outcome for myelofibrosis undergoing allogeneic stem cell transplantation. Patients and Methods We examined 361 myelofibrosis patients, of whom 260 had PMF and 101 SMF at time of transplantation. A training cohort of 205 patients was used to create a clinical-molecular transplant scoring system (MTSS) predicting survival from Cox models, internally validated by use of bootstrap and cross-validation. Model discrimination was measured by the concordance index (C). The final MTSS was externally validated in a cohort of 156 patients and was furthermore applied to posttransplant non-relapse mortality as a secondary objective. Results Multivariable analysis on 5-year survival identified age ≥57 years, Karnofsky performance status 25 × 109/L at time of transplantation, HLA-mismatched unrelated donor, ASXL1 mutated and CALR-/MPL-unmutated genotype being independent prognostic factors for outcome. The uncorrected concordance index for the final survival model was 0.723 (95% CI, 0.713-0.733), and bias-corrected indices were similar. A weighted score of 2 was assigned to transplantation from an HLA-mismatched unrelated donor and an CALR-/MPL-unmutated genotype, whereas a score of 1 was assigned to older age, leukocytosis, thrombocytopenia, ASXL1 mutation, and poor performance status. The MTSS consisted of four distinct risk groups showing 5-year survival in the validation cohort of 83% (95% CI, 71-95%) for low (score 0-2), 64% (95% CI, 53-75%) for intermediate (score 3-4), 37% (95% CI, 17-57%) for high (score 5), and 22% (95% CI, 4-39%) for very high risk (score >5), respectively (P Conclusion The MTSS integrates clinical, molecular as well as transplant-specific risk factors that independently affected survival. We show here that this internally and externally validated system accurately discriminated different risk for death and may improve counseling compared with currently existing systems, as well as facilitate design of clinical trials in the transplant setting.

Tandem Autologous Hematopoietic Stem Cell Transplantation Treatment for Adult T-Cell Lymphoblastic Lymphoma: A Multiple Center Prospective Study in Southwestern China

BackgroudT-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma with very poor clinical outcomes which has not standard treatment. This study evaluated the efficacy and safety of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) treatment for adult T-LBL and assessed the factors that affect survival.Methods160 newly diagnosed adult T-LBL patients were divided into three groups: chemotherapy group (68 patients), single auto-HSCT group (46 patients), and tandem auto-HSCT group (46 patients). The primary outcome measure was failure-free survival. The intermediate primary outcomes were progression/relapse rate and overall survival. Factors influencing toxicity related to tandem auto-HSCT treatment and prognosis for the patients were analyzed as well.ResultsThe 3-year progression/relapse rate of the tandem auto-HSCT group was significantly lower than that of the single auto-HSCT group and chemotherapy group (19.6% vs 45.7% and 70.6%, p < 0.05). The 3-year PFS rate and OS rate of the tandem auto-HSCT group (68.3% and 72.5%, respectively) were significantly higher than those of the single auto-HSCT group (41.5% and 55.4%, respectively, p < 0.05) and the chemotherapy group (23.3% and 43.3%, respectively, p < 0.05). In the tandem auto-HSCT group, age and disease status after the first transplant had an influence on the OS and PFS. Multivariate analysis identified disease status after the first transplant as the only independent prognostic factor for outcome in T-LBL.ConclusionsTandem auto-HSCT improves long-term survival of adult T-LBL patients. Disease status after the first transplant was an independent prognostic indicator for those patients. DisclosuresNo relevant conflicts of interest to declare.

Mutant TP53 modulates metastasis of triple negative breast cancer through adenosine A2b receptor signaling.

PurposeThe identification of genes with synthetic lethality in the context of mutant TP53 is a promising strategy for the treatment of basal-like triple negative breast cancer (TNBC). This study investigated regulators of mutant TP53 (R248Q) in basal-like TNBC and their impact on tumorigenesis.Experimental DesignTNBC cells were analyzed by RNA-seq, and synthetic-lethal shRNA knock-down screening, to identify genes related to the expression of mutant TP53. A tissue microarray of 232 breast cancer samples, that included 66 TNBC cases, was used to assess clinicopathological correlates of tumor protein expression. Functional assays were performed in vitro and in vivo to assess the role of ADORA2B in TNBC.ResultsTranscriptome profiling identified ADORA2B as up-regulated in basal-like TNBC cell lines with R248Q-mutated TP53, with shRNA-screening suggesting the potential for a synthetic-lethal interaction between these genes. In clinical samples, ADORA2B was highly expressed in 39.4% (26/66) of TNBC patients. ADORA2B-expression was significantly correlated with ER (P < 0.01), PgR (P = 0.027), EGFR (P < 0.01), and tumor size (P = 0.037), and was an independent prognostic factor for outcome (P = 0.036). In line with this, ADORA2B-transduced TNBC cells showed increased tumorigenesis, and ADORA2B knockdown, along with mutant p53 knockdown, decreased metastasis both in vitro and in vivo. Notably, the cytotoxic cyclic peptide SA-I suppressed ADORA2B expression and tumorigenesis in TNBC cell lines.ConclusionsADORA2B expression increases the oncogenic potential of basal-like TNBC and is an independent factor for poor outcome. These data suggest that ADORA2B could serve as a prognostic biomarker and a potential therapeutic target for basal-like TNBC.

Overexpression of folate receptor alpha is an independent prognostic factor for outcomes of pancreatic cancer patients.

Pancreatic cancer has a poor prognosis; hence, novel prognostic markers and effective therapeutic targets should be identified. We aimed to evaluate folate receptor alpha (FR-α) expression in pancreatic cancer and examine its association with clinicopathological features. We utilized tissue samples from 100 primary pancreatic cancer patients who underwent surgery. FR-α was expressed in 37 of 100 cases (37%). The FR-α-positive group (median, 18.8 months) had a significantly poorer prognosis than the FR-α-negative group [median 21.3 months; HR 1.89 (1.12-3.12); P = 0.017]. These groups were not significantly different regarding progression-free survival (P = 0.196). Furthermore, other serum tumor markers including CA19-9 (mean, 186 vs. 822U/ml; P = 0.001), Dupan-2 (286 vs. 1133U/ml; P = 0.000), and Span-1 (69.7 vs. 171.9U/ml; P = 0.006) were significantly downregulated in the FR-α-positive group. CA19-9 was another prognostic factor, in addition to FR-α, and patient prognosis showed clear stratification curves with the expression of these two molecules. Along with CA19-9, FR-α expression was an independent prognostic factor for the overall survival. FR-α and CA19-9 helped predict patient prognosis based on stratification curves.

Prognostic Factors and Outcomes of Adult Lymphoblastic Lymphoma in the United States.

T-lymphoblastic lymphoma (T-LL) and B-lymphoblastic lymphoma (B-LL) are aggressive lymphoid neoplasms accounting for 2% to 4% of adult non-Hodgkin lymphoma. The aim of the present analysis was to characterize the clinical features and histologic subtypes and to assess the clinical prognostic factors for 696 adult patients with LL, the largest epidemiologic sample to date. The present retrospective cohort study used the Surveillance, Epidemiology, and End Results database to identify adult patients (age, > 18 years) with LL with data recorded from 2001 to 2012. We used multivariate Cox regression models to test the clinical prognostic factors, stratified by the histologic subtype. Of 696 patients with LL (median age, 39 years), 367 (53%) had T-LL and 131 (19%) had B-LL. Patients with T-LL tended to be younger (33 years vs. 48 years), male (66% vs. 50.4%), and less likely to have extranodal involvement (6% vs. 32%) compared with those with B-LL. The 5-year survival rate for those with B-LL versus those with T-LL was not significantly different (45% vs. 48%; P= .58), even in a model adjusted for clinical features, disease stage, primary site, radiotherapy, and year of diagnosis (adjusted hazard ratio, 0.93; 95% confidence interval, 0.69-1.25; P= .63). Multivariate analysis identified age, race, and radiotherapy as independent prognostic factors for outcome in T-LL. Limited tumor stage and the most recent year of diagnosis were favorable prognostic factors for B-LL. Adult patients with LL have poor long-term outcomes and novel therapies are needed. Radiotherapy had a positive effect on T-LL outcomes.

Quantitative pretreatment CT volumetry: Association with oncologic outcomes in patients with T4a squamous carcinoma of the larynx.

The purpose of this study was to determine the impact of CT-determined pretreatment primary tumor volume on survival and disease control in T4a laryngeal squamous cell carcinoma (SCC). We retrospectively reviewed 124 patients with T4a laryngeal cancer from 2000-2011. Tumor volume measurements were collected and correlated with outcomes. Five-year overall survival (OS) for patients with tumor volume ≥21 cm3 treated with larynx preservation (n = 26 of 41) was significantly inferior compared to <21 cm3 (42% vs 64%, respectively; P = .003). Five-year OS for patients with tumor volumes ≥21 cm3 in the cohort treated with total laryngectomy followed by radiotherapy (RT; n = 42 of 83) was not statistically significant when compared to <21 cm3 (50% vs 63%, respectively; P = .058). On multivariate analysis, tumor volume ≥21 cm3 was a significant independent correlate of worse disease-specific survival (DSS; P = .004), event-free survival (P = .005), recurrence-free survival (RFS; P = .04), noncancer cause-specific survival (P = .02), and OS (P = .0002). Pretreatment CT-based tumor volume is an independent prognostic factor of outcomes in T4a laryngeal cancer.

A population-based study on epidemiology of intensive care unit treated traumatic brain injury in Iceland.

Traumatic brain injury is a worldwide health issue and a significant cause of preventable deaths and disabilities. We aimed to describe population-based data on intensive care treated traumatic brain injury in Iceland over 15 years period. Retrospective review of all intensive care unit admissions due to traumatic brain injury at The National University Hospital of Iceland 1999-2013. Data were collected on demographics, mechanism of injury, alcohol consumption, glasgow come scale upon admission, Injury Severity Scoring, acute physiology and chronic health evaluation II score, length of stay, interventions and mortality (defined as glasgow outcome score one). All computerized tomography scans were reviewed for Marshall score classification. Intensive care unit admissions due to traumatic brain injury were 583. The incidence decreased significantly from 14/100.000/year to 12/100.000/year. Males were 72% and the mean age was 41 year. Majority of patients (42%) had severe traumatic brain injury. The most common mechanism of injury was a fall from low heights (36.3%). The mortality was 18.2%. Increasing age, injury severity score, Marshall score and acute physiology and chronic health evaluation II score are all independent risk factors for death. Glasgow coma scale was not an independent prognostic factor for outcome. Incidence decreased with a shift in injury mechanism from road traffic accidents to falls and an increased rate of traumatic brain injury in older patients following a fall from standing or low heights. Mortality was higher in older patients falling from low heights than in younger patients suffering multiple injuries in road traffic accidents. Age, injury severity score, acute physiology and chronic health evaluation II score and Marshall score are good prognostic factors for outcome. Traumatic brain injury continues to be a considerable problem and the increase in severe traumatic brain injury in the middle age and older age groups after a seemingly innocent accident needs a special attention.

Potential Benefit Associated With Delaying Initiation of Hemodialysis in a Japanese Cohort

IntroductionLate referral to a nephrologist, the type of vascular access, nutritional status, and the estimated glomerular filtration rate (eGFR) at the start of hemodialysis (HD) have been reported as independent risk factors of survival for patients who begin HD. The aim of this study was to clarify the influence of the HD-free interval from the time of an eGFR of 10 ml/min per 1.73 m2 (IGFR10-HD) on patient outcome.MethodsWe enrolled 124 patients aged older than 20 years who had HD initiated in a general hospital. The predictive factor was the HD-free IGFR10-HD. The primary outcome was the relationship of the HD-free interval on death or the onset of a cardiovascular event. Survival analysis was performed using the Cox regression model.ResultsThe median IGFR10-HD was 159 days (range: 2–1687 days). The median eGFR at the initiation of HD was 5.48 ml/min per 1.73 m2. Sixty-seven of 124 patients (54.0%) reached the primary outcome. Of these, 29 died and 38 experienced a cardiovascular event. In univariate analysis, older age, a history of cardiovascular disease, nephrologic care for <6 months, higher modified Charlson comorbidity index score, poor performance status, temporary catheter, edema, diabetic retinopathy, and nonuse of erythropoiesis-stimulating agent were statistically related to the primary outcome. The unadjusted hazard ratio per log-transformed IGFR10-HD was 0.393 (95% confidence interval [CI]; 0.244−0.635; P < 0.001) and the hazard ratio adjusted for confounding factors was 0.507 (95% CI: 0.267−0.956; P = 0.036).DiscussionA longer HD-free IGFR10-HD was associated with a lower risk of death or a cardiovascular event. The interval could be considered an independent prognostic factor for outcomes in patients on HD.