Predictor Of Better Survival Research Articles

Predicting benefit of radium 223 based on biochemical response and site of metastasis: A real life multicenter UK study.

e17034 Background: Studies have shown an improvement in overall survival (OS) and symptom control in metastatic castration-resistant prostate cancer (mCRPC) with Radium-223 treatment. However, there is little information about predicting outcomes using either PSA or Alkaline Phosphatase (ALP) response or comparing bone only disease to bone and lymph node (LN) involvement. Methods: 335 patients receiving Radium 223 at 6 UK centres between March 2014 and June 2020 were included. The primary endpoint was overall survival, secondary endpoints were toxicity, symptomatic benefit and skeletal-related events(SRE) Results: The median age was 75, with 71% having bone only metastases and 29% also having lymph node involvement. Those with PSA response (30%) had a statistically significant improvement in OS, compared to non-responders (18.2 vs 13.8 months, p = 0.026). They also showed highest rate of imaging response/stable disease (54% vs 34%). ALP response was seen in 82%. This did not translate to significantly improved OS, but did correlate with better symptomatic benefit (40% vs 29%). Those with bone only disease showed a survival benefit compared to those with LN involvement (19.4 vs 11.4 months, p = 0.046). Other than anaemia (23.5%), Grade 2 or above toxicities were uncommon including thrombocytopenia and neutropenia(5.5 and 6.2% respectively ) . 14% patients required at-least one blood transfusion. SRE were seen in 24% overall, but lower of in PSA responders(18%). Conclusions: Real life multicentre data suggests that PSA response and bone only disease could be predictors for better survival following Radium-223, whereas ALP response correlates better with symptomatic benefit.

Low PDL1 Expression in Tumour Infiltrating Lymphocytes Predicts Local Recurrence in Oral Squamous Cell Carcinoma.

In oral squamous cell carcinoma (OSCC), expression of PDL1 is controversial with expressions showing a positive and negative correlation with survival in previous studies. Additionally, it is unclear whether expression on the tumour or tumour infiltrating lymphocytes (TIL) is a better predictor of survival. We performed this study on a cohort of Indian patients with OSCC to determine impact of PDL1 expression on survival. Retrospective analysis of 64 patients of OSCC treated with curative intent surgery with or without adjuvant therapy was performed. Stored tissue blocks were extracted and quantitative immunohistochemistry was performed for PDL1 expression separately on the tumour and the TIL using commercially available Dako kits. Correlation of clinical and pathological variables with PDL1 expression was performed using chi-square test. Survival analysis was performed using Kaplan-Meier method and Cox proportional hazards ratio. In our cohort, PDL1 expression was low, both in tumour (92% had <1% expression) and TIL (56% had <1% expression). Tumour low PDL1 expression (<1%) was associated with a higher risk of lymphovascular invasion (p= 0.044) and bone invasion (p= 0.01) but did not impact survival. Low TIL PDL1 expression (<1%) was more common in younger patients (<45years) (p= 0.023) significantly predicting local recurrence (p= 0.02). PDL1 expression in OSCC was low. Low TIL PDL1 was common in younger patients and predicted local recurrence. Further study is required to better understand the relationship between age, tumour microenvironment and local recurrence.

Extracorporeal membrane oxygenation survival: External validation of current predictive scoring systems focusing on influenza A etiology.

Despite increasing clinical experience with extracorporeal membrane oxygenation (ECMO), its optimal indications remain unclear. Here, we externally evaluated all currently available ECMO survival-predicting scoring systems and the APACHE II score in subjects undergoing veno-venous ECMO (VV ECMO) support due to acute respiratory distress syndrome (ARDS) with influenza (IVA) and non-influenza (n-IVA) etiologies. Our aim was to find the best scoring system for influenza A ARDS ECMO success prediction. Retrospective data were analyzed to assess the abilities of the PRESERVE, RESP, PRESET, ECMOnet, Roch, and APACHE II scores to predict patient outcome. Patients treated with veno-venous ECMO support for ARDS were divided into two groups: IVA and n-IVA etiologies. Parameters collected within 24hours before ECMO initiation were used to calculate PRESERVE, RESP, PRESET, ECMOnet, Roch, and APACHE II scores. Compared to the IVA group, the n-IVA group exhibited significantly higher ICU, 28-day, and 6-month mortality (P=.043, .034, and .047, respectively). Regarding ECMO support success predictions, the area under the receiver operating characteristic curve (AUC) was 0.62 for PRESERVE, 0.44 for RESP, 0.57 for PRESET, and 0.67 for ECMOnet, and 0.62 for Roch calculated for all subjects according to the original papers. In the IVA group, APACHE II had the best predictive value for ICU, hospital, 28-day, and 6-month mortality (AUC values of 0.73, 0.73, 0.70, and 0.73, respectively). In the n-IVA group, APACHE II was the best predictor of survival in the ICU and hospital (AUC 0.54 and 0.57, respectively). From all possible ECMO survival scoring systems, the APACHE II score had the best predictive value for VV ECMO subjects with ARDS caused by influenza A-related pneumonia with a cut-off value of about 32 points.

Characterization of arrhythmias, evaluation of cardiac biomarkers and their association with survival in calves suffering from foot-and-mouth disease

IntroductionFoot-and-mouth disease (FMD) causes mortality in calves due to myocarditis; however, the effects of FMD virus on cardiac arrhythmogenesis and Purkinje cells are unknown. Identifying diagnostic and prognostic markers in FMD-affected calves may be useful in disease management in the endemic countries. Materials and methodsA total of 81 FMD-affected calves were prospectively monitored till death or recovery. Foot-and-mouth disease was diagnosed by serology and reverse transcriptase–polymerase chain reaction (RT-PCR). Electrocardiography was recorded and serum cardiac biomarkers were measured. Histopathological examination of the ventricular myocardium was carried out in the calves that died of FMD (n = 33). Apparently healthy calves (n = 15) served as control. ResultsSerology and RT-PCR consistently revealed that the FMD was caused by serotype O virus. Arrhythmias occurred in 62 of 81 (76.5%) FMD-affected calves, of which, ventricular premature complexes (VPCs) were the most common type (22%). The combined mortality rate due to ventricular tachycardia, polymorphic VPCs, and atrial fibrillation was 27.6%. Receiver operating characteristic curve analysis revealed that cardiac troponin I (cTnI) concentrations of ≥1.3 ng/mL were diagnostic of myocarditis with a sensitivity and specificity of 90% and 100%, respectively. Similarly, serum cTnI concentrations of <6.4 ng/mL were a good predictor of survival [odds ratio of 263; 95% confidence interval: 29–2371]. Histopathology of the myocardium revealed hyaline degeneration, necrosis, edema, mononuclear cell infiltration, and disruption by fibroblasts. Atrophy of the Purkinje cells was also present. ConclusionsFMD induces cardiac arrhythmias and Purkinje cell pathology in the calf. Portable ECG coupled with assay of serum cTnI would help in predicting survival in FMD-affected calves.

Machine-learning algorithm as a prognostic tool in non-obstructive acute-on-chronic kidney disease in the cat.

The aim of this study was to develop an algorithm capable of predicting short- and medium-term survival in cases of intrinsic acute-on-chronic kidney disease (ACKD) in cats. The medical record database was searched to identify cats hospitalised for acute clinical signs and azotaemia of at least 48 h duration and diagnosed to have underlying chronic kidney disease based on ultrasonographic renal abnormalities or previously documented azotaemia. Cases with postrenal azotaemia, exposure to nephrotoxicants, feline infectious peritonitis or neoplasia were excluded. Clinical variables were combined in a clinical severity score (CSS). Clinicopathological and ultrasonographic variables were also collected. The following variables were tested as inputs in a machine learning system: age, body weight (BW), CSS, identification of small kidneys or nephroliths by ultrasonography, serum creatinine at 48 h (Crea48), spontaneous feeding at 48 h (SpF48) and aetiology. Outputs were outcomes at 7, 30, 90 and 180 days. The machine-learning system was trained to develop decision tree algorithms capable of predicting outputs from inputs. Finally, the diagnostic performance of the algorithms was calculated. Crea48 was the best predictor of survival at 7 days (threshold 1043 µmol/l, sensitivity 0.96, specificity 0.53), 30 days (threshold 566 µmol/l, sensitivity 0.70, specificity 0.89) and 90 days (threshold 566 µmol/l, sensitivity 0.76, specificity 0.80), with fewer cats still alive when their Crea48 was above these thresholds. A short decision tree, including age and Crea48, predicted the 180-day outcome best. When Crea48 was excluded from the analysis, the generated decision trees included CSS, age, BW, SpF48 and identification of small kidneys with an overall diagnostic performance similar to that using Crea48. Crea48 helps predict short- and medium-term survival in cats with ACKD. Secondary variables that helped predict outcomes were age, CSS, BW, SpF48 and identification of small kidneys.

Predicting nodal status in male breast cancer using mammogram based radiomic metrics

Background: Axillary lymph node (ALN) status is one of the most important prognostic factors. Staging based on tumor size and nodal status are good predictors of survival. Accurate preoperative assessment of nodal status currently could be improved. All current imaging analysis depends on the operator observation of a lesion. Radiomics utilizes assigning a characteristic to each pixel in a tumor and captures data not seen by the naked eye. Patterns within a tumor that make nodal metastasis possible are recognized. Therefore, we wanted to know if radiomics of a tumor on mammography could predict nodal status. There is a suggestion this can be done in female breast cancer (FBC). We wanted to ask this question in male breast cancer (MBC) patients.

Defining the Zostera marina (Eelgrass) Niche from Long-Term Success of Restored and Naturally Colonized Meadows: Implications for Seagrass Restoration

Seagrass restoration can help reverse global meadow loss and restore ecosystem services, including habitat provision for commercial fish and shellfish, carbon sequestration, and improved water quality. However, restoration projects are generally expensive, and site selection remains a challenge due to uncertainty about how environmental variables affect the survival and spread of seedlings. Long-term Zostera marina (eelgrass) success/failure and expansion data from the Virginia Coast Reserve can be used to determine whether the factors that control seedling survival also explain the regional distribution of seagrass meadows. We tracked plant survival and failure within restoration plots and at natural recruitment sites from 2001 to 2015 and used machine learning methods to identify the relative importance of multiple environmental predictors, including water residence time, fetch distance, water temperature, depth, and sediment grain size. Low water residence time was the best predictor of survival, but short fetch length best explained the natural recruit distribution, consistent with hydrodynamic control of seed dispersal. Restoration plot data suggests that the eelgrass fundamental niche covers > 100 km2 within this system, triple both the current extent and the realized niche predicted by the observed natural spread. Our results corroborate historical records that eelgrass was formerly widespread in areas where it has not spread naturally, likely due to insufficient seed delivery. Additional seeding in these areas would, therefore, increase total seagrass coverage and accelerate recovery. Mapping the total habitable area can help managers maximize the extent of seagrass and other bottom uses, including shellfish aquaculture.

Clinical Impact of Natural Killer Group 2D Receptor Expression and That of Its Ligand in Ovarian Carcinomas: A Retrospective Study.

PurposeNatural killer (NK) cells are innate immune cells with antitumor activity. NKG2D is the most important activating receptor expressed on the NK cell surface; this receptor binds to the ligands MICA/B and ULBPs to activate NK cells. The current study aimed to evaluate the expression of NKG2D by NK cells, and to the evaluate expression of its ligands in ovarian carcinomas; it also examined the clinical relevance of NK receptor/ligand expression by analyzing the relationship between expression, clinicopathological parameters, and prognosis.Materials and MethodsFormalin-fixed paraffin-embedded archival ovarian high-grade serous carcinoma (HGSC, n=79) tissue samples were used for tissue microarray analysis. The expressions of NK cell markers (CD56 and NKG2D) and NKG2D ligands (MICA/B, ULBP1, ULBP3, and ULBP2/5/6) in carcinoma tissues were evaluated by immunohistochemical staining, and the association between these results and clinical prognostic parameters was analyzed statistically.ResultsULBP1 was highly expressed in 51 cases (64.6%), and ULBP2/5/6 was highly expressed in 56 cases (70.9%) of HGSC. High expression of ULBP1 and ULBP2/5/6 was significantly associated with lower recurrence of HGSC, whereas high expression of ULBP3 was significantly associated with higher recurrence. Multivariate Cox regression analysis revealed that high expression of ULBP1 was associated with increased overall survival and a decreased hazard ratio (0.150, p=0.044), suggesting that it is an independent predictor of better survival.ConclusionHigh expression of ULBP1 predicts a better prognosis for HGSC, suggesting that ULBP1 expression could be a novel prognostic indicator in this subset of carcinomas.

Long term oncological outcomes of laparoscopic pancreatoduodenectomy

Background: Two hundred and fifty laparoscopic pancreatoduodenectomies (LPDE) were performed in single center in patients with periampullary area diseases. Objective is to assess the long-term oncological outcomes of LPDE performed in patients with pancreatic head and ampullary carcinoma Methods: 250 patients underwent LPDE during 2007-2018 years. 216 patients had malignancies (125 had pancreatic cancer, 44 patients had ampullary carcinoma) and 34 had benign diseases. Patients were followed up by control examination and phone calls every year. Kaplan-Maier survival analysis was performed in order to analyze long term results of treatment. Results: 119 patients with PDAC and 44 patients with ampullary carcinoma were followed up. 114 patients with PDAC were referred to adjuvant. Only 63 patients received chemotherapy, 26 patients had no chemotherapy and data about 25 patients was not available. Median overall survival rate (OSR) of patients with PDAC was 21 months. 5-years OSR was 24%. Patient who did not receive adjuvant had significantly worse results with median OSR of 16 months vs 24 months. 5-years OSR of patients received chemo was significantly higher (27% vs 17%, p< 0.05). Another predictor of better survival was lymph nodes negativity, N+ patients had lower median OSR (26 months vs 18 months, p< 0.05) and 5-years OSR (27% vs 15%, p< 0.05). Patients with ampullary carcinoma had better oncological outcomes. Median OSR was 44 months and 5-years OSR was 52%. Conclusion: Lymph nodes positivity and non-receiving of adjuvant chemotherapy are predictors of lower survival rates in patients with pancreatic adenocarcinoma.

CD34+ hematopoietic progenitor cell dose as a predictor of engraftment and survival in multiple myeloma patients undergoing autologous stem cell transplantation

Background/aimHigh-dose melphalan and autologous hematopoietic stem cell transplantation (AHSCT) is the standard treatment strategy for multiple myeloma (MM) patients who are eligible for it. The recommended dose of CD34+ hematopoietic progenitor cells (HPCs) for adequate engraftment is above 2 × 106/kg. The aim of this study was to evaluate the relationship between the dose of CD34+ HPCs and survival in MM patients who underwent AHSCT at a tertiary care center.Materials and methodsEnrolled in this study were 271 MM patients who underwent AHSCT between 2003 and 2019. Clinical characteristics of the patients, disease status pre-AHSCT, reinfused CD34+ cell doses, and neutrophil and platelet engraftment days were recorded, retrospectively. The patients were divided into 2 groups according to whether the dose of reinfused CD 34+ HPCs was <5 × 106/kg or ≥5 × 106/kg. The groups were compared in terms of engraftment and overall survival (OS) times.ResultsThe median age of the patients was 54.8 (33–76) years. The median dose of infused CD34+ HPCs was 5.94 × 106/kg (1.47–59.5 × 106/kg). The median follow-up period was 54 months (4–211). The median OS of the patients was 103 months (11–144). The median neutrophil and platelet engraftment time was 10 (8–24) and 11 (7–40) days. Doses of <5 × 106/kg and ≥5 × 106/kg CD34+ HPC were reinfused in 38.1% and 61.9% of the patients, respectively. There was a negative significant correlation between the reinfused CD34+ cell level and neutrophil/platelet engraftment times (r = –0.32, P < 0.001; r = –0.27, P < 0.001, respectively). The median OS times were observed as 103 months (11–144) and 145 months (123–166) for patients who had been administered <5 × 106/kg and ≥5 × 106/kg of CD34+ HPCs, respectively (P = 0.009).ConclusionThe increased amount of CD34+ autologous hematopoietic stem cell dose after high dose melphalan chemotherapy in MM patients shortened the platelet and neutrophil engraftment time and increased OS. Early platelet engraftment and administration of a CD34+ HPC count that is ≥5 × 106/kg can be considered as predictors of better survival in patients.

Tuberculosis in the intensive care unit: alternative treatment regimens and association with mortality.

Adequate anti-tuberculosis (TB) treatment is an important factor that can affect the patient's outcome. Higher mortality is found in patients who do not receive optimal treatment that includes isoniazid and rifampicin. The objective of this study is to evaluate the association of use of alternative TB treatment regimens (without rifampicin and isoniazid) and mortality among patients requiring intensive care. Retrospective cohort study, from January 2010 to December 2018. Patients aged >18years with a TB diagnosis, admitted to the ICU of a general, tertiary care, university-affiliated hospital (Hospital de Clínicas de Porto Alegre - HCPA) were included. Data on TB treatment used and outcomes of treatment were collected. 462 patients met the inclusion criteria and were included in the analysis; 284 used the usual treatment regimen (rifampicin, isoniazid, pyrazinamide and ethambutol - all orally), and 178 used alternative treatment regimens (IV levofloxacin plus oral ethambutol plus IM streptomycin or IV amikacin, without rifampicin and isoniazid). The mortality was higher among users of alternative treatment regimens (63.5%) than among usual treatment regimen users (51.4%) (P=0.011). In a multivariate analysis, age, albumin and death were independently associated with alternative treatment regimens use. TB programmes in which IV rifampicin is not widely available should consider including it, especially for critically ill TB patients, for whom there may be improved survival.

FACTORS INFLUENCING NEST SURVIVAL OF MOURNING DOVES IN THE LOWER RIO GRANDE VALLEY, TEXAS

In the United States, mourning doves (Zenaida macroura) are harvested more than all other game birds combined. In the Lower Rio Grande Valley of South Texas, mourning doves nest in citrus and remnant woodland habitats, both of which are decreasing in the region. The objectives of this study were to compare nest survival between woodland and citrus land cover types and to model the influence of habitat characteristics and observer disturbance on nest survival. In 2016, we located 100 nests in four citrus groves (n = 21) and two woodlots (n = 79) in Hidalgo and Cameron counties, Texas. We monitored nests every 3 days and collected nest site vegetation measurements. We used logistic-exposure and Akaike information criterion model selection to determine which environmental and temporal variables best predicted nest survival. Candidate models included temporal variables and nest concealment variables such as overhead cover, side cover, distance to foliage edge, and vertical density below the nest. We found considerable differences in the vegetation structure between citrus and woodland sites. Density of vegetation below the nest was the best predictor of survival. Our results suggest that nest survival is higher in citrus groves likely because of increased cover below, to the side, and above nests. Although not considered native habitat, citrus groves might mitigate the loss of native woodland for mourning doves. Thus, the conversion of citrus agriculture to urban areas and row cropping should trouble wildlife managers in the region. Breeding mourning dove populations may be negatively affected by the loss of citrus and woodland land cover that has occurred over the last 50 years.

Outcome of Adults with Relapsed T-Cell Acute Lymphoblastic Leukemia (T-ALL) Included in Minimal Residual Disease (MRD)-Oriented Trials

Introduction and objective. Despite a high complete remission (CR) rate obtained with frontline therapy most adults with T-ALL eventually relapse. Although promising therapies are emerging, salvage options for T-ALL are currently limited. Little is known about outcome of patients (pts) with relapsed T-ALL (R T-ALL) treated with contemporary MRD-oriented trials. Our goal was to analyze the outcome of pts with R T-ALL included in two successive MRD-oriented trials (ALL-AR-03 and ALL-HR-11) from the Spanish PETHEMA Group. Methods. Retrospective study of R T-ALL adults diagnosed between 2003 and 2019 and included in the protocols ALL-AR-03 (NCT00853008) and ALL-HR-11 (NCT01540812). The clinical characteristics at baseline and at relapse, salvage therapies and outcomes (CR and OS) were analyzed and a study of prognostic factors for OS was performed. Results Forty-nine patients were identified (ALL-AR-03 [n=27], ALL-HR-11 [n=22]). Median age (range) at diagnosis was 29 (16-58) yrs, 38 males (78%), CNS involvement 6 (12%), mediastinal mass 30 (61%), WBC count 40.8 x109/L (0.6-351.0), early T-cell precursor 11 (23%), pre-T 8 (16%), cortical 16 (33%), mature 9 (18%), T unspecified 5 (10%). Post-induction-1 MRD level ≥0.1%: 14/42 (33%), ≥0.01%: 17/39 (44%). Nine pts (18%) required 2nd induction therapy (resistant disease after induction-1 [n=5], MRD≥0.1% after induction-1 [n=4]). Allogeneic HSCT in CR1: 8 pts. Interval CR1-relapse: 11.2 [0.1-36.7] months. Relapse was located in BM (n=20, 41%), BM+extramedullary (n=16, 33%) and extramedullary (n=13, 26%). CNS at relapse was involved in 18 pts (37%, isolated in 8 cases). Median number of rescue lineages was 2 (range 1-5). The most frequent first salvage schedules were FLAG-Ida (n=24, 49%), HyperCVAD (n=8, 16%) and nelarabine (n=4, 8%) (other schedules in 13 pts). Second CR was attained in 21/48 pts (44%). The patients with poor morphologic and/or poor MRD response after Induction-1 in first line therapy (n=9) did not respond to first salvage therapy (0/9 vs. 21/39, p=0.003). AlloHSCT was performed in 19 pts (15 in CR2) (HLA-identical sibling: 9, URD: 9, haploidentical: 1, myeloablative conditioning: 16). Thirty-nine pts died (progression: 27, toxicity of rescue regimens: 7, TRM: 5) and 9/10 alive patients were submitted to HSCT (the remaining is on rescue therapy). Median OS (95%CI) was 6.1 (4.9-7.2) months, 5yr OS probability 21% (9%-33%) (Figure 1). By multivariable analysis, only the CR after first salvage regimen emerged as favorable prognostic factor for OS (HR 3.110, 95%CI: 1.579-6.124) (Figure 2). Conclusion. This study shows poor outcome of adults with R T-ALL, with CR to first salvage therapy of 44% and a median OS of 6 months. Poor early response to first line therapy correlated with poor response to salvage-1. The only independent predictor for better survival was CR to first salvage regimen. This study highlights the unmet need for novel effective therapies for T-ALL. Supported in part by grant 2017 SGR288 (GRC) Generalitat de Catalunya and "La Caixa" Foundation; ISCIII (PI19/01828), co-funded by ERDF/ESF, "A way to make Europe"/"Investing in your future". Disclosures Ribera: Pfizer, Amgen, Ariad, Novartis: Consultancy, Speakers Bureau; Pfizer, Amgen: Research Funding. Barba:Amgen, Celgene, Gilead, Jazz Pharmaceuticals, Novartis, Pfizer, Shire: Consultancy; Amgen, Celgene, Novartis, Pfizer: Speakers Bureau. Tormo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; MSD: Honoraria; Daiichi Sankyo: Honoraria; Servier: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Sanchez:Abbvie: Other: travel grants; Amgem: Other: travel grants; Janssen: Other: travel grants; Celgene: Other: travel grants; Roche: Other: travel grants. Giménez Conca:AbbVie: Honoraria, Speakers Bureau.

Poorly differentiated histologic grade correlates with worse survival in SMAD4 negative pancreatic adenocarcinoma patients.

This study investigated the influence of the transcription factor SMAD4 on overall patient survival following surgical resection of pancreatic ductal adenocarcinoma (PDAC). The SMAD4 status of 125 surgically resected PDAC specimens at a large academic center from 2014 to 2017 was routinely determined prospectively and correlated with clinicopathologic characteristics and overall survival. SMAD4 loss was identified in 62% of patients and was not associated with overall survival (OS). On multivariate Cox proportional hazards survival analysis, histologic grade was the best predictor of survival in the SMAD4(-) population (adjusted hazard ratio = 4.8, p < .0001). In the SMAD4(+) population, histologic grade was not associated with survival on multivariate analysis. In the SMAD4(-) population, median OS for well/moderately differentiated patients and poorly differentiated patients was 39.6 and 8.6 months, respectively. In this large cohort of resected PDAC, routine SMAD4 assessment identified a subpopulation of patients with SMAD4(-) and histologically poorly differentiated tumors that had significantly poor prognosis with median OS of 8.6 months. Characterization of the role of SMAD4 within the context of poorly differentiated tumors may help settle the controversy regarding SMAD4 in PDAC and lead to identification of personalized therapeutic strategies for subgroups of PDAC.

Despite Advances in Tumor Management Modalities, Surgery Prevails as Best Predictor of Survival for Osteosarcoma: An Analysis of Primary Osseous Tumor Characteristics, Management, and Outcomes from the National Cancer Database

Ottesen, Taylor D. BS; Shultz, Blake S. BS; Munger, Alana M. MD; Sibindi, Cosmas BS; Yurter, Alp BS; Varthi, Arya D. MD; Grauer, Jonathan D. MD, FACS Author Information

ALL-315: Outcome of Adults with Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Context Limited data are available on the outcome of adults with relapsed-refractory (R/R) T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL). Objective We aimed to identify factors predictive for long-term survival and to establish the benchmark for expected outcomes in this setting. Main outcomes measured We reviewed characteristics and outcome of adults with R/R T-cell ALL or LBL treated at our institution between 2009 and 2019. We assessed response to salvage therapy and overall survival. To determine prognostic factors for survival, we performed univariate and multivariate analyses using the following baseline characteristics: age, disease type (ALL versus LBL), immunophenotypic subtype (early T-cell precursor [ETP] versus non-ETP), complex cytogenetics, central nervous system involvement at salvage, first complete remission (CR1) duration Results We identified 82 patients, including 39% in S1, 27% in S2, and 34% in S3+. ETP subtype was present in 35% of cases, and 16% had complex cytogenetics. Salvage therapy included standard-of-care regimens in 48 patients (59%), including nelarabine-based therapy in 21 patients (26%), pediatric-inspired asparaginase-based therapy in 11 patients (13%), clofarabine-based therapy in 9 patients (11%), and investigational-based therapies in 34 patients (41%), mainly venetoclax-based (18 patients; 22%). The CR/complete remission with incomplete hematological recovery (CRi) rate was 46%, with a median duration of response of 4 months. With a median follow-up of 37 months, the median OS was 8 months, and the 2-year OS was 23%. Only 14 patients were alive in remission at their last follow-up. In multivariate analysis, earlier salvage therapy was the only predictor for better survival (hazard ratio 0.57 [95% confidence interval, 0.33-0.99], P=0.049). A 3-month landmark analysis showed a survival benefit for consolidative hematopoietic stem cell transplant (HSCT) after CR to salvage therapy (2-year OS rate of 56% versus 24%, P=0.002). Conclusions The current study highlights the continuous unmet need of patients with R/R T-cell ALL treated with contemporary standard regimens and provides a reference for future clinical trials in this population.

Diagnostic and prognostic value of serum NfL and p-Tau181 in frontotemporal lobar degeneration

ObjectiveTo assess the diagnostic and prognostic value of serum neurofilament light (NfL) and serum phospho-Tau181 (p-Tau181) in a large cohort of patients with frontotemporal lobar degeneration (FTLD).MethodsIn this retrospective study,...

Apgar score or birthweight in Chihuahua dogs born by elective Caesarean section: which is the best predictor of the survival at 24\xa0h after birth?

BackgroundIn the dog, the correct management of parturition and the prompt neonatal evaluation and assistance can reduce the perinatal mortality rates that are particularly high in toy breeds. Newborn evaluation and factors addressing prognosis are pivotal to guarantee the correct neonatal assistance. Assessment of the Apgar score with viability classification and birthweight are recognized as predictors for neonatal survival in dogs, but breed-specific data are needed for a more feasible application in the dog species, in which wide differences among breeds are known. The present study aimed therefore to: (a) assess the role of Apgar score and birthweight as predictors for the survival of Chihuahua newborn puppies in the first 24 h of life; (b) to assess a cut-off of the Apgar score and birthweight values that can predict the survival of Chihuahua newborn puppies in the first 24 h after birth; (c) to assess the possible effect played by maternal parity, newborn gender and litter-size on Apgar score in Chihuahua newborn puppies, in order to provide breed-specific data for a better neonatal assistance.ResultsData obtained from 176 normal developed Chihuahua puppies born by elective Caesarean section, showed that 62%, 28% and 10% of puppies were classified in the Apgar score classes 7–10, 4–6 and 0–3, respectively, with survival at 24 h after birth of 97%, 96%, 39%, in the three Apgar classes of viability, respectively. Apgar score was a better predictor for survival at 24 h after birth than birthweight (AUC 0.93, P < 0.0001; AUC 0.69, P < 0.01, respectively). Litter-size of 7 puppies/litter plays a negative effect on Apgar score. Apgar score is a better predictor of survival at 24 h than birthweight, and the best cut-off of Apgar score for survival at 24 h after birth is 4, with 96% sensitivity and 77% specificity.ConclusionsThe different proportion of “normal viable” and “less viable” neonates in comparison to other studies highlights that Chihuahua puppies born by elective Caesarean section should be carefully evaluated at birth to provide correct assistance.

Prognostic Significance of the Pluripotency Factors NANOG, SOX2, and OCT4 in Head and Neck Squamous Cell Carcinomas.

Cancer stem cells (CSCs) play major roles in tumor initiation, progression, and resistance to cancer therapy. Several CSC markers have been studied in head and neck squamous cell carcinomas (HNSCC), including the pluripotency factors NANOG, SOX2, and OCT4; however, their clinical significance is still unclear. NANOG, SOX2, and OCT4 expression was evaluated by immunochemistry in 348 surgically-treated HNSCC, and correlated with clinicopathological parameters and patient outcomes. mRNA expression was further analyzed in 530 The Cancer Genome Atlas (TCGA) HNSCC. NANOG protein expression was detected in 250 (72%) cases, more frequently in patients with lymph node metastasis (p = 0.003), and was an independent predictor of better survival in multivariate analysis. While OCT4 expression was undetectable, SOX2 expression was observed in 105 (30%) cases, and strongly correlated with NANOG expression. Combined expression of both proteins showed the highest survival rates, and double-negative cases the worst survival. Strikingly, the impact of NANOG and SOX2 on outcome varied depending on tumor site and lymph node infiltration, specifically showing prognostic significance in pharyngeal tumors. Correlation between NANOG and SOX2 at mRNA and protein was specifically observed in node positive (N+) patients, and consistently correlated with better survival rates. According to our findings, NANOG protein expression is frequent in HNSCC, thereby emerging as an independent predictor of better prognosis in pharyngeal tumors. Moreover, this study uncovers a differential impact of NANOG and SOX2 expression on HNSCC prognosis, depending on tumor site and lymph node infiltration, which could facilitate high-risk patient stratification.

Neoadjuvant therapy for pancreatic cancer: an intention-to-treat analysis.

This study aimed to reassess the duration of neoadjuvant therapy (NAT) for patients with borderline resectable pancreatic cancer (BRPC). The medical records of patients with BRPC who received NAT before intended curative resection were retrospectively reviewed. Patient demographics, clinicopathological factors, and prognostic factors for overall survival were analyzed. The serum carbohydrate antigen (CA) 19-9 level was examined monthly during NAT. A total of 118 patients with BRPC were enrolled. The median survival time and 5-year overall survival were 28.0months and 31%, respectively. Three months after NAT, the CA19-9 levels were normal in 57% of the patients, and 92% underwent resection. Multivariate analysis showed that radiological partial response (hazard ratio (HR), 0.53; 95% confidence interval (CI), 0.26-0.99; p = 0.047); a normal CA19-9 level after NAT (HR, 0.30; 95% CI, 0.22-0.66; p = 0.006); and tumor resection (HR, 0.29; 95% CI, 0.13-0.67; p = 0.005) were independent predictors of better survival. The median CA19-9 level and the rate of normal CA19-9 levels before and after NAT were 256 (interquartile range (IQR), 23-1197) U/mL and 33%, and 27 (IQR, 7-176) U/mL and 57%, respectively. A normal CA19-9 level after NAT was an independent predictor of better survival in patients with BRPC. A longer NAT duration might contribute to improved prognosis of patients with elevated CA19-9 levels.