Potential Prognostic Variables Research Articles

Survival Rate Against Fracture of Endodontically Treated Premolars Restored with Crowns and Resin Composites: A Retrospective Study

The purpose of this study was to assess the survival rate of endodontically treated premolars that were restored with resin composites or crowns. Additionally, possible risk factors were identified through the use of a retrospective cohort design. Based on inclusion and exclusion criteria, dental records of premolar ETT with crowns or composite restorations (recall period, 2018–2023) were gathered. Both the existence of the fracture and any potential prognostic variables were noted. Analysis using statistical methods was done at a significance level of P <0.05. The Chi square test was used for all comparisons, and frequency and percentages were used to depict the qualitative data. There was a significant difference in the survival rates against breakage between teeth replaced with crowns (95.1%) and resin composites (62.1%) (P<0.05). The results showed that there was a significant difference between them in terms of sex, age, opposing dentition, crestal bone level, and fracture incidence. Regarding premolars that have undergone endodontic treatment, crown restorations outperformed resin composites in terms of survival rate. Premolars receiving endodontic therapy and having crestal bone loss up to the middle third of the root were shown to be at an increased risk of fracture.

The efficacy of subsequent therapy after failure of anti-PD-1 antibody in metastatic renal cell carcinoma.

The optional regimens of subsequent therapy after failure of anti-programmed cell death protein-1 (PD-1) antibody in metastatic renal cell carcinoma (mRCC) remain to be explored. There are reports of the efficacy of single-agent vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) in patients with mRCC after failure of anti-PD-1 antibody therapy. However, it is not clear whether it is beneficial for patients to receive anti-PD-1 antibody as post-progression treatment. It has great significance to explore whether continuous application of anti-PD-1 antibody is beneficial for patients with mRCC whose diseases progressed to the state of pre-anti-PD-1 therapy. The purposes of this study are to explore the efficacy and safety of subsequent treatment on whether to continue using anti-PD-1 antibody therapy for patients who have progressive mRCC after prior treatment with anti-PD-1 antibody. The clinical data of patients with mRCC from the Department of Immunotherapy in the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital from February 1, 2019 to December 31, 2021 were analyzed retrospectively. The primary endpoints were the objective response rate (ORR) and progression-free survival (PFS). The ORR and disease control rate (DCR) were estimated with Fisher's exact test. PFS and overall survival (OS) were assessed using the Kaplan-Meier method and log-rank tests. The associations between potential prognostic variables and PFS were evaluated with univariate and multivariate Cox regression analyses. A P value of less than or equal to 0.05 was deemed as statistically significant. A total of 35 patients were included in this study, during which 19 received VEGFR-TKI monotherapy and 16 received the VEGFR-TKI plus anti-PD-1 antibody therapy. Until the last follow-up on June 30, 2022, 19 patients experienced progressive disease (PD), five were in remission, and 11 kept stable disease (SD). After a median follow-up of 28.7 [95% confidence interval (CI): 17.0-35.6] months, the median PFS (mPFS) was 11.6 months for the VEGFR-TKI group and 9.1 months for the VEGFR-TKI plus anti-PD-1 antibody group [hazard ratio (HR) =0.81, 95% CI: 0.32-1.03, P=0.44]. Median OS (mOS) were 16.9 and 11.2 months respectively (HR =0.99, 95% CI: 0.44-2.27, P=0.90). The ORRs were 26.3% and 0% (P=0.049), and the DCRs were 47.4% and 43.8% (P=0.55) respectively. Treatment-related adverse events (TRAEs) occurred in 14 patients (73.7%) in the VEGFR-TKI group and 14 patients (87.5%) in the VEGFR-TKI plus anti-PD-1 antibody group (P=0.42); grade 3/4 TRAEs occurred in two patients (10.5%) and six patients (37.5%) respectively (P=0.11). VEGFR-TKI monotherapy is an efficacious regimen for patients with mRCC whose diseases progressed on previous anti-PD-1 antibody therapy, and continuous anti-PD-1 therapy after failure of anti-PD-1 antibody could not provide additional clinical benefit but increased the incidence of TRAEs.

Long-term outcomes in patients with COPD treated with non-invasive ventilation for acute hypercapnic respiratory failure

PurposeChronic Obstructive Lung Disease (COPD) remains a major cause of morbidity and mortality across the world. We evaluated survival over 9 years in a cohort of patients with COPD requiring acute inpatient non-invasive ventilation (NIV). We analyzed prognostic indices to evaluate if they were associated with mortality.Patients and methodsWe performed a retrospective chart review of all patients who were admitted to St. James’s Hospital respiratory ward with COPD and acute hypercapnic respiratory failure who required NIV over a 12-month period and followed their outcomes over 9 years. We investigated the association between survival and potential prognostic variables using univariate analysis and multivariate Cox proportional hazards model. We evaluated the association between survival and the following parameters: age, gender, multiple admissions requiring NIV (> 1 admission in within 12 months of index presentation), home NIV use preadmission, initial arterial blood gas pH, days spent on NIV, serum albumin and serum albumin to serum CRP ratio at admission.ResultsNinety-nine patients with COPD and acute hypercapnic respiratory failure were identified over a 12-month period from January to December 2011. Survival at 1, 2, 5 and 9 years was 65% (n = 64), 42% (n = 42), 25% (n = 25) and 21% (n = 21), respectively. Increasing age (p value < 0.001) and a lower serum albumin (p value < 0.005) were associated with a higher mortality. There was a trend towards improved survival in the group who were treated with home NIV prior to admission compared to no NIV therapy at home but this did not reach statistical significance (Fig. 3, p value = 0.088).ConclusionThis study highlights the long-term mortality in patients with COPD admitted with hypercapnic respiratory failure requiring NIV and correlates with prior studies. Increasing age and lower serum albumin were associated with increased mortality. Home NIV may have a protective long-term survival benefit in patients with COPD who have been admitted for acute NIV.

Outcomes and prognostic factors of advanced biliary tract cancers in Saudi Arabia.

460 Background: Biliary tract cancers which include gallbladder adenocarcinoma, intrahepatic and extrahepatic cholangiocarcinoma are rare, and carry a poor prognosis. There is limited data on biliary tract cancers in the Saudi population. Methods: This single center retrospective study was conducted with data of eligible cases from the last 4 years. Survival, chemotherapy regimens, and variables such as neutrophil to lymphocyte ratio (NLR), and other potential prognostic variables were collected. Results: The study included 155 patients of which 75 had intrahepatic cholangiocarcinoma and 74 had gallbladder adenocarcinoma. The majority were females at 63% of patients. Overweight to obese patients represented 59% of the study cohort. The majority of patients (62%) had an ECOG performance status of 2 and below. Comprehensive genomic profiling was done to 20% of cholangiocarcinoma cases. Elevated CA19-9 tumor marker (&gt; 37 micromol/L) was found in 57% of patients. De novo metastatic disease affected 82% of patients. One third of patients (33%) were not fit for first line chemotherapy, and were given best supportive care. First line chemotherapy of platinum + gemcitabine was given to 53% of fit patients, followed by gemcitabine alone given to 38%, followed by 5-Fluorouracil chemotherapy given to 9% of patients. Very few patients lived for 12 months or more at 16%. There was a significant association between NLR and progression free survival (PFS) with median PFS being 3.5 months in the NLR &gt; 3 group (95% CI 1.2-6 months) versus median PFS of 9.8 months in the NLR &lt; 3 group (95% CI 7.5-12 months, p=0.019). Conclusions: Biliary tract cancers still carry a poor prognosis. NLR ratio of more than 3 was found to predict a low PFS.

Pomalidomide, Dexamethasone, and Daratumumab Versus Other Triplet Regimens in Patients with Relapsed or Refractory Multiple Myeloma: A Population-Adjusted Indirect Treatment Comparison

Introduction: Multiple myeloma (MM) is an incurable malignant plasma cell disorder in which most patients eventually relapse or become refractory to treatment. Lenalidomide (LEN) is typically administered as part of first-line regimens; however, patients who receive LEN usually relapse, necessitating improved options in later lines of therapy. The phase 2, non-randomized MM-014 trial (NCT01946477) demonstrated promising efficacy of pomalidomide (POM) plus dexamethasone and daratumumab (DPd) among patients with relapsed or refractory MM (RRMM), with an overall response rate of 77.7% and a median overall survival (OS) of 56.7 months at a median follow-up of 41.9 months. With the evolving treatment landscape of RRMM, however, there is limited head-to-head data comparing DPd to other standard of care therapies to inform clinical decision-making. Objective: To investigate the comparative efficacy of DPd versus non-POM-containing triplets in adult patients with RRMM using population-adjusted indirect comparison (PAIC) approaches. Methods: A PAIC was conducted using individual patient-level data of 112 adult patients with RRMM who were exposed to LEN (75.9% refractory to LEN) from cohort B of the MM-014 trial. Investigator-assessed OS was the primary endpoint of this analysis. A systematic literature review was performed to identify comparable interventional studies assessing the efficacy of non-POM-containing triplets for RRMM as well as potential prognostic variables (PVs). PVs verified by clinicians were selected for inclusion if significantly associated with OS (p &amp;lt; 0.1) in the MM-014 trial based on univariate Cox regression model. The suitability of these potential trials for PAIC was assessed by considering the comparability of study design, inclusion/exclusion criteria, patients' baseline characteristics, and outcomes. A retrospective analysis utilizing Flatiron electronic health record data from Jan 2011 to July 2022 was previously performed to evaluate the effect of LEN-refractory status on OS using multivariable Cox regression. Given the lack of a common comparator, unanchored PAIC was performed for OS using matching-adjusted indirect comparison (MAIC) and confirmatory simulated trial comparison (STC). A sensitivity analysis was conducted to explore the impact of LEN-refractory status as a PV. Results: Six trials were systematically identified as eligible comparators in initial screening including TOURMALINE-MM1, CANDOR, CASTOR, POLLUX, ASPIRE, and LEPUS. The analyses using Flatiron data showed that patients who were refractory to LEN had significantly shorter OS than those exposed to LEN but not refractory (Hazard ratio: 1.51; 95% CI: 1.17, 1.94), indicating the unsuitability to compare treatments based on studies with large variations in proportion of LEN-refractory patients. Four trials were excluded due to differences violating the transitivity assumption (0% LEN-refractory patients in TOURMALINE-MM1 and POLLUX; LEN-refractory status not reported in ASPIRE; only Chinese patients in LEPUS). The remaining two trials are phase 3 randomized controlled trials investigating carfilzomib plus dexamethasone and daratumumab (DKd) (CANDOR; NCT03158688; Usmani et al. Blood Adv. 2023; Epub ahead of print) and daratumumab plus bortezomib and dexamethasone (DVd) (CASTOR; NCT02136134; Sonneveld et al. J Clin Oncol. 2023; 41:1600-1609). In the base case MAIC adjusting for creatinine clearance, time from diagnosis, International Staging System score, and refractory to LEN, DPd was associated with numerical reduction in the risk of death compared to DKd and DVd (Table). In addition, the base case STC showed significant improvement of OS for DPd over DKd and DVd, confirming the findings from MAIC (Table). In the sensitivity analyses excluding LEN-refractory status, the effect estimates were substantially different from those in the base case analyses (&amp;gt;40% difference), demonstrating the importance of adjusting for LEN refractory status. Conclusions: In patients with RRMM, consistent OS benefit was found for DPd versus DKd and DVd regardless of the PAIC technique used. These findings support the use of DPd over DKd and DVd in treating patients with RRMM, especially given the oral route of administration of pomalidomide. This study also highlighted the importance of considering LEN refractory status when comparing efficacy of treatments for RRMM across trials.

Key Prognostic Factors in Patients with Relapsed/Refractory Follicular Lymphoma: An Evidence Based Systematic Literature and Medical Review

Introduction: A multi-center multi-country retrospective cohort study (FLORA [NCT05338879]), using real-world data (RWD) from electronic medical records (EMRs) and research databases, for patients with relapsed/refractory follicular lymphoma grade 1-3a (r/r FL) treated with standard of care is being conducted to contextualize treatment outcomes in a single-arm trial. A systematic literature review (SLR) was carried out to identify baseline prognostic factors that will be evaluated for imbalances between cohorts in the single-arm trial and RWD study. This SLR was followed by an evidence-based clinical expert review and ranking of prognostic variables in order of importance for the FLORA study as described herein. Methods: The approach and methods of the SLR (International Prospective Register of Systematic Reviews [PROSPERO] CRD42022307561) were informed by guidelines set forth by the Cochrane Handbook for Systematic Reviews of Interventions (Higgins et. al. 2021) and PRISMA (Page et. al. BMJ 2021) and described previously (Hampp et. al. ISPOR 2023). Following the conduct of the SLR, the identified potential prognostic variables were evaluated by the FLORA study team to remove treatment-specific and outcome variables, determine their availability in the single-arm trial and FLORA RWD study, and develop a questionnaire. In the questionnaire, prognostic variables were grouped by type of variable - clinical, laboratory data, or treatment characteristic. Each prognostic variable was reviewed by an international panel consisting of 3 clinical experts in the field of lymphoma who categorized the prognostic impact on treatment response and survival on a 5-point scale ranging from “Very high importance” to “Not important”. The clinicians were asked to consider possible correlation among the variables, possible effect modifiers, specific variable definitions (e.g., chemoresistant), and whether there were any other prognostically important variables not captured in the questionnaire. For each variable the clinical experts categorized the availability within routine care on a 3-point scale ranging from “Readily available” to “Limited availability”. The results of the 3 expert completed questionnaires were reviewed and the top 10 highest ranking variables were determined by summing the clinicians' categorization of prognostic impact and considering variable availability in the event of a tie. Individual interviews with each clinical expert were held to clarify variables and definitions, discuss discrepant categorization, and rank the prognostic variables from 1-10. Following the 3 interviews, the ranking of each variable was summed across the 3 experts to determine the final ranking. Results: Across the 13 studies included, the SLR identified 28 prognostic factors, including patient demographics and clinical characteristics, disease and treatment characteristics, and laboratory data. Seven clinical outcomes with statistically significant associations were identified (most commonly, overall survival [OS], progression-free survival [PFS], and relapse/progression). No additional prognostic factors were identified by the clinical experts. The final ranked list of the 10 most important prognostic variables in descending order of importance includes: progression of disease within 2 years (POD24), chemo-immunorefractory/chemoresistant, refractory to last line of therapy (LoT), number of prior LoTs, serum lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group (ECOG) performance status, Follicular Lymphoma International Prognostic Index (FLIPI), age at start of LoT, Ann Arbor disease stage, and refractory to rituximab. Conclusion: SLR-based identification of prognostic factors combined with expert clinical review provides an unbiased evaluation and ranking of the level of evidence to assist in selecting prognostic factors to collect for the FLORA real-world cohort study. The appropriate selection of prognostic factors is critical for valid outcome estimation. These factors will be used for the evaluation of balance with the single-arm trial and for adjustment in a propensity score model. With this approach, the prognostic factors are chosen a priori to enable balancing of baseline covariates prior to outcome estimation.

Key Prognostic Factors in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma: An Evidence Based Systematic Literature and Medical Review

Introduction: A multi-center multi-country retrospective cohort study (ORCHID [NCT05338879]), using real-world data (RWD) from electronic medical records (EMRs) and research databases, for patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) treated with standard of care is being conducted to contextualize treatment outcomes in a single-arm trial. A systematic literature review (SLR) was carried out to identify baseline prognostic factors that will be evaluated for imbalances between cohorts in the single-arm trial and RWD study. This SLR was followed by an evidence-based clinical expert review of prognostic variables and ranking in order of importance for the ORCHID study as described herein. Methods:The approach and methods of the SLR (International Prospective Register of Systematic Reviews [PROSPERO] CRD42022307557) were informed by guidelines set forth by the Cochrane Handbook for Systematic Reviews of Interventions (Higgins et. al. 2021) and PRISMA (Page et. al. BMJ 2021) and described previously (Hampp et. al. ISPOR 2023). Following the conduct of the SLR, the identified potential prognostic variables were evaluated by the ORCHID study team to remove treatment-specific and outcome variables, determine their availability in the single-arm trial and ORCHID RWD study, and develop a questionnaire. In the questionnaire, prognostic variables were grouped by type of variable - clinical, laboratory data, molecular characteristic, or treatment characteristic. Each prognostic variable was reviewed by an international panel consisting of 3 clinical experts in the field of lymphoma who categorized the prognostic impact on treatment response and survival on a 5-point scale ranging from “Very high importance” to “Not important”. The clinicians were asked to consider possible correlation among the variables, possible effect modifiers, specific variable definitions (e.g., early chemoimmunotherapy failure), and whether there were any other prognostically important variables not captured in the questionnaire. For each variable, the clinical experts categorized the availability within routine care on a 3-point scale ranging from “Readily available” to “Limited availability”. The results of the 3 expert completed questionnaires were reviewed and the top 10 highest ranking variables were determined by summing the clinicians' categorization of prognostic impact and considering variable availability in the event of a tie. Individual interviews with each clinical expert were held to clarify variables and definitions, discuss discrepant categorization, and rank the prognostic variables from 1-10. Following the 3 interviews, the ranking of each variable was summed across the 3 experts to determine the final ranking. Results: Across the 46 studies included, the SLR identified 36 prognostic factors, including patient demographics and clinical characteristics, disease and treatment characteristics, and laboratory data. Seven clinical outcomes with statistically significant associations were identified (most commonly, overall survival [OS], progression-free survival [PFS], and overall response rate [ORR]). No additional prognostic factors were identified by the clinical experts. The final ranked list of the 10 most important prognostic variables in descending order of importance includes: early chemoimmunotherapy failure, Eastern Cooperative Oncology Group (ECOG) performance status, refractory to last line of therapy (LoT), number of prior LoTs, double or triple-hit lymphoma, age at start of LoT, Internal Prognostic Index (IPI) risk classification, Ann Arbor disease stage, serum lactate dehydrogenase (LDH), and Deauville score. Conclusion:SLR-based identification of prognostic factors combined with expert clinical review provides an unbiased evaluation and ranking of the level of evidence to assist in selecting prognostic factors to collect for the ORCHID real-world cohort study. The appropriate selection of prognostic factors is critical for valid outcome estimation. These factors will be used for the evaluation of balance with the single-arm trial and for adjustment in a propensity score model. With this approach, the prognostic factors are chosen a priori to enable balancing of baseline covariates prior to outcome estimation.

Serum Uric Acid and Hemoglobin Levels as Prognostic Factors for COVID-19 Disease in Lung Cancer Patients

Objective: Cancer patients have a higher risk of COVID-19 infection compared to the healthy population. Therefore, the aim of this study is to assess the parameters and inflammatory indices that influence mortality in lung cancer patients who contract COVID-19. Material and Methods: The sample of this single-center retrospective study comprised 66 patients diagnosed with lung cancer and treated for COVID-19 between April 2020 and July 2021. The neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, prognostic index, modified Glasgow prognostic score, and COVID inflammatory score were calculated for all patients. A total of twenty-seven potential prognostic variables were identified for further analysis through univariate and multivariate analyses. Results: Seven variables with statistically significant prognostic values were identified as a result. The identified variables include having received chemotherapy in the last 28 days, hospitalization in the intensive care unit, the need for mechanical ventilation, receipt of COVID-19 corticosteroid treatment, serum uric acid level, hemoglobin level, and platelet count. The seven variables with prognostic value were subjected to Cox regression analysis. The results of the multivariate logistic regression analysis indicated that low hemoglobin and low uric acid levels emerged as independent risk factors for survival in lung cancer patients infected with COVID-19. Conclusion: To the best of our knowledge, this is the first study to suggest that serum hemoglobin levels less than 10 g/dL and serum uric acid levels less than 3.5 mg/dL can serve as prognostic factors in lung cancer patients infected with COVID-19, aiding in predicting mortality.

Prognostic value of SLC4A4 and its correlation with the microsatellite instability in colorectal cancer.

To explore new biomarkers related to microsatellite instability in order to better predict prognosis and guide medication. The "limma" R package was used to identify differentially expressed genes in GSE24514, and then weighted correlation network analysis was used to select key genes. Different cell types in the tumor microenvironment were identified and analyzed by single-cell sequencing, with a Lasso regression model used to screen prognostic variables. Furthermore, the correlation between microsatellite instability and potential prognostic variables was explored, as well as the expression characteristics and clinical characteristics of the prognostic variables in the TCGA, UALCAN, and HPA databases. PCR assay was used to investigate the expression of SLC4A4 in colorectal cancer cell lines. Finally, we further verified the expression of SLC4A4 by immunohistochemistry. First, 844 differentially expressed genes in GSE24514 were identified. Subsequently, weighted co-expression network analysis (WGCNA) of GSE24514 obtained all the genes significantly associated with microsatellite instability (MSI), a total of 1452. Analysis of GSE166555 single cell sequencing data set yielded 1564 differentially expressed genes. The gene sets obtained from the above three analysis processes were intersected, and 174 genes were finally obtained. The Lasso regression model revealed two potential prognostic genes, TIMP1 and SLC4A4, of which, there was a stronger correlation between microsatellite instability and SLC4A4. The mRNA and protein expression of SLC4A4 was significantly decreased in tumors, and patients with low SLC4A4 expression had a poor prognosis. In addition, SLC4A4 was specifically expressed in epithelial cells. In the microenvironment of colorectal cancer, malignant cells have a strong interaction with different stromal cells. PCR showed that SLC4A4 was significantly down-regulated in colorectal cancer cell lines Caco-2, HCT116 and HT29 compared with normal control NCM460 cell lines. Immunohistochemistry also showed low expression of SLC4A4 in colorectal cancer. SLC4A4, as a tumor suppressor gene, is significantly downregulated and positively correlated with microsatellite instability, thus it may be combined with microsatellite instability to guide colorectal cancer treatment.

Comparison of efficacies of haploidentical transplantation and matched sibling donor transplantation in treating T‐cell lymphoblastic lymphoma

To investigate the differences in efficacy and safety between haploidentical donor hematopoietic stem cell transplantation (HID-HSCT) and matched sibling donor HSCT (MSD-HSCT) in patients with T-cell lymphoblastic lymphoma (T-LBL). In this retrospective analysis, we enrolled 38 patients who had undergone allogeneic HSCT at our institution between 2013 and 2021. The study participants included 28 patients who underwent HID-HSCT and 10 patients who underwent MSD-HSCT. We compared the patient characteristics and treatment effectiveness and safety between the two groups and evaluated potential prognostic variables for patients with T-LBL. The median follow-up durations in the HID-HSCT and MSD-HSCT groups were 23.5 (range: 4-111) and 28.5 (range: 13-56) months, respectively. All patients showed full-donor chimerism after hematopoietic stem cell transplantation (HSCT). Except for two patients in the HID-HSCT cohort who developed poor graft function, all patients showed neutrophil and platelet engraftments after HSCT. The cumulative incidences of grades III-IV acute graft-versus-host disease were 37.5% and 28.57% in the HID-HSCT and MSD-HSCT groups, respectively (p = 0.84). The cumulative incidences of limited (34.13% vs. 28.57%, p = 0.82) and extensive (31.22% vs. 37.50%, p = 0.53) chronic graft-versus-host disease did not differ between the two cohorts. In the HID-HSCT and MSD-HSCT cohorts, the estimated 2-year overall survival rates were 70.3% (95% confidence interval [CI]: 54.9%-90.0%) and 56.2% (95% CI: 31.6%-100%), respectively (p = 1.00), and the estimated 2-year progression-free survival (PFS) rates were 48.5% (95% CI: 32.8%-71.6%) and 48.0% (95% CI: 24.6%-93.8%), respectively (p = 0.94). Furthermore, the Cox proportional-hazards model showed that a positive positron emission tomography/computed tomography (PET/CT) status before HSCT in patients who had completed chemotherapy was an independent risk factor for PFS in the multivariate analysis (p = 0.0367). This study showed that HID-HSCT had comparable effectiveness and safety to MSD-HSCT in treating T-LBL. HID-HSCT could serve as an alternate treatment option for T-LBL in patients without an eligible identical donor. Achievement of the PET/CT-negative status before HSCT may contribute to better survival.

An Auxiliary Approach to Prediction of Binary Outcome with Bayesian Network Model: Exploration with Data for Recurrence of Breast Cancer

Introduction: Logistic regression is the classical statistical model that is incorporated to predict a binary outcome variable. These models have theoretical assumptions of independence of predictor variables and linearity of association with the outcome in the logarithmic scale. Alternative models developed in the machine learning context like Naïve Bayes model with similar assumptions and Bayesian Network (BN) model can be used for binary prediction. Aim: To compare the predictive performance of logistic regression, Naïve Bayes and BN model in predicting the recurrence of Breast cancer. Materials and Methods: The dataset was procured from UCI Machine Learning repository on recurrence of breast cancer. The study was done on retrospective data from December 2021 to July 2022. The sample size was boosted with the bootstrapping with logistic regression model. The dataset was split into training (70%) and testing (30%) dataset for internal validation. The effect estimates of the potential prognostic variables were estimated using multiple logistic regression model. Naïve Bayes and BN model was also learnt from the training dataset. The indices of predictive accuracy were estimated for the models in both training and testing dataset. Results: Degree of malignancy and side of affected breast were found to be significant predictors of recurrence of breast cancer. BN model had the least misclassification rate and the best sensitivity in comparison to other models in spite of imbalance in outcome variable. Conclusion: BN model performed the best in comparison to logistic regression model when the assumptions of logistic regression model were violated and there is imbalance in proportion of outcome.

Matching-Adjusted Indirect Comparisons of the Efficacy and Safety of Acalabrutinib Versus Ibrutinib in Relapsed/Refractory Mantle Cell Lymphoma

Introduction: Acalabrutinib (Acala) and ibrutinib (Ibr), as single agents, are both highly effective Bruton tyrosine kinase inhibitors approved for the treatment of relapsed/refractory mantle cell lymphoma and chronic lymphocytic leukemia. Both are given as continuous oral treatments until disease progression or unacceptable toxicity. In the absence of a head-to-head clinical study in this setting, this analysis aims to compare the efficacy and safety of Acala versus Ibr for the treatment of relapsed/refractory mantle cell lymphoma (MCL) using matching-adjusted indirect comparison (MAIC). This MAIC slightly differs from the published analysis by Telford et al (Clin Ther. 2019;41:2357-79) by using long-term follow-up data for efficacy outcomes and assessing whether the safety profile of Acala is sustained over a longer term when compared with Ibr. Methods: Individual patient data for Acala from LY-004 (38 months median follow-up) (Wang et al. ASCO 2021) were weighted to match the aggregate baseline characteristics of the Ibr monotherapy arm from a pooled analysis with 41.4 months median follow-up (Rule et al. Hematologica. 2019.04:e212). These baseline characteristics, Eastern Cooperative Oncology Group performance status, simplified MCL International Prognostic Index score, lactate dehydrogenase, prior lines of therapy, bulky disease, and blastoid histology, are potential prognostic variables (PVs). Pseudo-individual patient data were generated from the digitized Kaplan-Meier curves published in the aforementioned comparator trials. As the LY-004 trial is a single-arm trial, an unanchored MAIC was conducted to adjust for these PVs. The PVs selected were based on literature, clinical judgment, and demonstrated statistically significant association with progression-free survival (PFS) in univariate and multivariate regression analysis (Ahn et al. J Clin Oncol. 2020;39:576-85; Eichorst and Hallek. Hematol Am Soc Hematol Educ Prog. 2016;1:149-55). After matching, a weighted Cox proportional-hazards model was used to analyze PFS and overall survival (OS) while a weighted logistic regression model was used for comparative safety analysis (grade ≥3 adverse events [AEs]). Two-sided P<0.05 was considered statistically significant. Results: In the Acala vs Ibr comparison before matching, PFS and OS favored Acala and were statistically significant. After matching, PFS and OS numerically favored Acala but the difference was not significant (Table). In the Telford et al study, significant differences were observed in grade 3/4 atrial fibrillation (afib) and thrombocytopenia. Similarly, in the current analysis, rates of afib and thrombocytopenia were significantly lower with Acala vs Ibr. In addition, rates of grade 3/4 AEs were numerically lower with Acala than Ibr for neutropenia, pneumonia, and hypertension. Conclusions: Based on these MAIC results, in addition to a similar efficacy benefit vs Ibr, Acala was associated with a consistent safety profile over the long term. A limitation of this MAIC is not including all potential PVs as a trade-off to conserve the effective sample size. However, the use of longer follow-up data improved the robustness of the indirect comparisons of safety and efficacy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Prediction of Survival Outcome and Prognosis Factor in Association with Comorbidity Status in Patients with Colorectal Cancer: A Research-Based Study.

Colorectal carcinoma (CRC) is rising exponentially in Asia, representing 11% of cancer worldwide. This study analysed the influence of CRC on patients’ life expectancy (survival and prognosis factors) via clinicopathology data and comorbidity status of CRC patients. Methodology: A retrospective study performed in HUSM using clinical data from the Surgery unit from 2015 to 2020. The demographic and pertinent clinical data were retrieved for preliminary analyses (data cleansing and exploration). Demographics and pathological characteristics were illustrated using descriptive analysis; 5-year survival rates were calculated using Kaplan–Meier methods; potential prognostic variables were analysed using simple and multivariate logistic regression analysis conducted via the Cox proportional hazards model, while the Charlson Comorbidity Scale was used to categorize patients’ disease status. Results: Of a total of 114 CRC patients, two-thirds (89.5%) were from Malay tribes, while Indian and Chinese had 5.3% each. The 50–69.9 years were the most affected group (45.6%). Overall, 40.4% were smokers (majorly male (95.7%)), 14.0% ex-smokers, and 45.6% non-smokers (p-value = 0.001). The Kaplan–Meier overall 5-year median survival time was 62.5%. From the outcomes, patients who were male and >70 years had metastasis present, who presented with per rectal bleeding and were classified as Duke C; and who has tumour in the rectum had the lowest survival rate. Regarding the prognosis factors investigated, “Gender” (adjusted hazard ratio (HR): 2.62; 95% CI: 1.56–7.81, p-value = 0.040), “Presence of metastases” (HR: 3.76; 95% CI: 1.89–7.32, p-value = 0.010), “Metastasis site: Liver” (HR: 5.04; 95% CI: 1.71–19.05, p-value = 0.039), “Lymphovascular permeation” (HR: 2.94; 95% CI: 1.99–5.92, p-value = 0.021), and “CEA-level” (HR: 2.43; 95% CI: 1.49–5.80, p-value = 0.001) remained significant in the final model for multiple Cox proportional hazard regression analyses. There was a significant mean association between tumour grades and the patient’s comorbidity status. Conclusions: Histopathological factors (gender, metastases presence, site of metastases, CEA level, and lymphovascular permeation) showed the best prognosis-predicting factors in CRC.

Clinical Prediction Nomograms to Assess Overall Survival and Disease-Specific Survival of Patients with Salivary Gland Adenoid Cystic Carcinoma.

Aim Salivary gland adenoid cystic carcinoma (SACC) is the second highest incidence of malignant salivary gland tumor. The purpose of this study was to establish nomograms combined with SACC patients based on the Surveillance, Epidemiology, and End Results (SEER) database. Methods Patients with SACC were included in the SEER∗Stat Database from 2004 to 2016. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to filter potential prognostic clinical variables. Multivariate analysis from the Cox proportional hazards model was performed to determine the independent prognostic factors on overall survival (OS) and disease-specific survival (DSS), applied to develop nomograms. The Schönfeld residual test verified the proportional hazard assumption. The discrimination and consistency of nomograms was assessed and validated according to concordance index (C-index), receiver operating characteristic (ROC) curves, and calibration curves using an internal 1,000 times bootstrap resampling. The nomogram's net clinical benefit was assessed through decision curve analysis (DCA). Results A total of 658 patients with SACC were included. Age, T stage, N stage, M stage, histologic grade, and surgery were independent prognostic factors for OS and DSS. Based on these independent prognostic factors, nomograms were developed to predict 3-, 5-, and 10-year OS and DSS. In the validation of 1,000 times bootstrap resampling, the C-index and ROC curves had good discriminatory ability. The calibration curves indicated excellent consistency between the predicted and actual survival results in the nomograms. The DCA curves demonstrated that the nomograms had good clinical benefit and were superior to the TNM stage and other variables. Conclusions Two nomograms developed in this study precisely predicted the 3-, 5-, and 10-year OS and DSS rates of patients with SACC in accordance with independent prognostic factors, and their clinical value is better than TNM staging, providing a prognostic reference for other SACC patients.

Impact of Metastasectomy on Cancer Specific and Overall Survival in Metastatic Renal Cell Carcinoma: Analysis of the REMARCC Registry.

Treatment paradigms for management of metastatic renal cell carcinoma (mRCC) are evolving. We examined impact of surgical metastasectomy on survival across in mRCC stratified by risk-group. Multicenter retrospective analysis from the Registry of Metastatic RCC database. The cohort was subdivided utilizing Motzer criteria (favorable-, intermediate-, high-risk). Primary outcome was all-cause mortality (ACM)/overall survival (OS); secondary outcome was cancer-specific mortality (CSM)/cancer-specific survival (CSS). Impact of metastasectomy was analyzed via Cox-Regression analysis adjusting for potential prognostic variables and Kaplan-Meier analysis (KMA) within each risk-group. Four hundred thirty-one patients (59 favorable-risk, 274 intermediate-risk, 98 high-risk; median follow-up 27.2 months) were analyzed. Metastasectomy was performed in 22 (37%), 66 (24%), and 32 (16%) of favorable-, intermediate- and high-risk groups (P=.012). Median number of metastases at diagnosis differed significantly (favorable-risk 2, intermediate-risk 3.4, high-risk 5.1, P < .001). On Cox-regression, high-risk (HR=1.72, P=.002) was associated with worsened ACM, while metastasectomy was associated with improved ACM (HR=0.56, P=.005). On KMA, median OS (months) was longer with metastasectomy in favorable- (92.7 vs. 25.8, P=.003) and intermediate-risk (26.3 vs. 20.1, P=.038), but not high-risk (P=.911) groups. Metastasectomy was associated with longer CSS in favorable- (76.1 vs. 32.8, P=.004) but not intermediate- (P=.06) and high-risk (P=.595) groups. Metastasectomy was independently associated with improved ACM and CSM, as well as improved CSS and OS in favorable- and intermediate-risk mRCC patients. Metastasectomy may be considered as component of multimodal management strategy in favorable and intermediate-risk subgroups. In high-risk patients, metastasectomy should be deferred except in select circumstances.

Outcome and Prognostic Factors in Cats Undergoing Resection of Intestinal Adenocarcinomas: 58 Cases (2008-2020).

The purpose of this multi-institutional retrospective study was to expand the available data pertaining to pre-operative clinical findings, progression-free and overall survival times, and potential prognostic factors for cats undergoing surgery for intestinal adenocarcinomas. Fifty-eight cats treated over a 12-year period were included in the study. Progression-free and overall survival times were estimated using Kaplan-Meier analyses. Potential prognostic variables were evaluated for associations with progression-free and overall survival using univariate Cox proportional hazards regression analyses. Prior to surgery, the intestinal mass was identified using ultrasonography in 89% of cats in which it was applied; however, imaging findings suggestive of intrathoracic metastases were observed in only 9% of cats. Among 22 cats undergoing ultrasound-guided fine needle aspiration cytology, the results agreed with the results of histopathology in only 10 cats. Discordant results were most commonly related to the presence of marked inflammation in cytology samples, which may have obscured the presence of neoplastic cells. Diffuse intestinal small cell lymphoma was identified as a comorbidity in 5 cats. Resection of the tumor with the objective of obtaining wide surgical margins was performed in each cat. On histopathology, 20 tumors were classified as mucinous adenocarcinoma and 28 were adenocarcinoma not otherwise specified. Intestinal transection site margins were complete in 94% of cats; however, complete mural margins were present in only 15% of cats. Local lymph node metastases were identified in 52% of cats and carcinomatosis was diagnosed in 81% of cats. Disease progression was documented in 32 of the 58 cats (55%). Of these 32 cats, 14 (43%) had local recurrence of the primary intestinal tumor. Median progression-free survival was 203 days (95% CI 130–299 days), and median overall survival time was 284 days (95% CI 200–363 days). Mitotic count was inversely associated with progression-free survival (HR 1.04; 95% CI 1.01–1.07, P = 0.005); however, none of the remaining potential prognostic factors, including administration of adjuvant chemotherapy, were significantly associated with progression-free or overall survival. Feline intestinal adenocarcinoma remains an aggressive and highly fatal disease. Large, randomized controlled clinical trials will be needed to improve the survival prospects for affected cats.

Co-relation of SARS-CoV-2 related 30-d mortality with HRCT score and RT-PCR Ct value-based viral load in patients with solid malignancy.

BACKGROUNDCoronavirus disease 2019 (COVID-19) patients with malignancy are published worldwide but are lacking in data from India.AIMTo characterize COVID-19 related mortality outcomes within 30 d of diagnosis with HRCT score and RT-PCR Ct value-based viral load in various solid malignancies.METHODSPatients included in this study were with an active or previous malignancy and with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the institute database. We collected data on demographic details, baseline clinical conditions, medications, cancer diagnosis, treatment and the COVID-19 disease course. The primary endpoint was the association between the mortality outcome and the potential prognostic variables, specially, HRCT score, RT-PCR Ct value-based viral load, etc. using logistic regression analyses treatment received in 30 d.RESULTSOut of 131 patients, 123 met inclusion criteria for our analysis. The median age was 57 years (interquartile range = 19-82) while 7 (5.7%) were aged 75 years or older. The most prevalent malignancies were of GUT origin 49 (39.8%), hepatopancreatobiliary (HPB) 40 (32.5%). 109 (88.6%) patients were on active anticancer treatment, 115 (93.5%) had active (measurable) cancer. At analysis on May 20, 2021, 26 (21.1%) patients had died. In logistic regression analysis, independent factors associated with an increased 30-d mortality were in patients with the symptomatic presentation. Chemotherapy in the last 4 wk, number of comorbidities (≥ 2 vs none: 3.43, 1.08-8.56). The univariate analysis showed that the risk of death was significantly associated with the HRCT score: for moderate (8-15) [odds ratio (OR): 3.44; 95% confidence interval (CI): 1.3-9.12; P = 0.0132], severe (> 15) (OR: 7.44; 95%CI: 1.58-35.1; P = 0.0112).CONCLUSIONTo the best of our knowledge, this is the first study from India reporting the association of HRCT score and RT-PCR Ct value-based 30-d mortality outcomes in SARS-CoV-2 infected cancer patients.

Computed Tomography Texture Analysis of Carotid Plaque as Predictor of Unfavorable Outcome after Carotid Artery Stenting: A Preliminary Study

Novel biomarkers are advocated to manage carotid plaques. Therefore, we aimed to test the association between textural features of carotid plaque at computed tomography angiography (CTA) and unfavorable outcome after carotid artery stenting (CAS). Between January 2010 and January 2021, were selected 172 patients (median age, 77 years; 112/172, 65% men) who underwent CAS with CTA of the supra-aortic vessels performed within prior 6 months. Standard descriptors of the density histogram were derived by open-source software automated analysis obtained by CTA plaque segmentation. Multiple logistic regression analysis, receiver operating characteristic (ROC) curve analysis and the area under the ROC (AUC) were used to identify potential prognostic variables and to assess the model performance for predicting unfavorable outcome (periprocedural death or myocardial infarction and any ipsilateral acute neurological event). Unfavorable outcome occurred in 17/172 (10%) patients (median age, 79 years; 12/17, 70% men). Kurtosis was an independent predictor of unfavorable outcome (odds ratio, 0.79; confidence interval, 0.65–0.97; p = 0.029). The predictive model for unfavorable outcome including CTA textural features outperformed the model without textural features (AUC 0.789 vs. 0.695, p = 0.004). In patients with stenotic carotid plaque, kurtosis derived by CTA density histogram analysis is an independent predictor of unfavorable outcome after CAS.

Matching-Adjusted Indirect Treatment Comparison (MAIC) of Acalabrutinib Alone or in Combination with Obinutuzumab Versus Ibrutinib or Venetoclax Plus Obinutuzumab in Patients with Treatment-Naïve Chronic Lymphocytic Leukemia

Introduction: Acalabrutinib (A) and ibrutinib (I) are both highly effective Bruton tyrosine kinase inhibitors (BTKi) approved for the treatment of chronic lymphocytic leukemia (CLL) and given as continuous treatments until disease progression or unacceptable toxicity. Venetoclax is a BH3 mimetic compound and B-cell lymphoma-2 inhibitor prescribed in combination with obinutuzumab (V+O) for a fixed (12-cycle) duration in treatment-naïve CLL patients. Although the ELEVATE-RR study demonstrated an improved safety profile of A compared with I in a head-to-head clinical trial, this study did not include treatment-naïve CLL patients (Byrd et al. J Clin Oncol. 2021). This MAIC builds upon the published analysis by Davids et al (Leuk Lymphoma. 2021) in treatment-naïve patients with CLL (which demonstrated a favorable safety profile for A-based therapy compared with other targeted therapies without compromising efficacy) by including longer follow-up data for A and the comparators.Methods: Individual patient data for A ± obinutuzumab (A+O) from ELEVATE-TN (47 months median follow-up) (Sharman et al. ASCO 2021) were weighted to match the aggregate baseline characteristics of the I monotherapy arm from the ALLIANCE trial (Woyach et al. NEJM. 2018) (I + rituximab was not included as this treatment is not approved for CLL) and the V+O arm from the CLL-14 trial (Al-Sawaf et al. Lancet Oncol 2020). These baseline characteristics, TP53 mutation, serum β 2 microglobulin, ECOG, IGHV status, del(11q), CrCl, Rai stage or CLL-IPI, are potential prognostic variables (PV). Pseudo-individual patient data were generated from the digitized Kaplan-Meier curves published in the aforementioned comparator trials. An unanchored MAIC was conducted to adjust for these PVs between trials. The PVs selected were based on literature, clinical judgement, and demonstrated statistically significant association with progression-free survival (PFS) in univariate and multivariate regression analysis (Ahn et al. J Clin Oncol. 2020; Eichorst and Hallek. Hematol Am Soc Hematol Educ Prog. 2016). After matching, a weighted Cox proportional hazard model was used to analyze PFS and overall survival (OS) while a weighted logistic regression model was used for comparative safety analysis (grade ≥3 adverse events [AEs]). Two-sided p<0.05 was considered statistically significant.Results: This MAIC included 47-month data from ELEVATE-TN, 38-month data from ALLIANCE, and 40-month data from CLL-14 as opposed to 28-month data from ELEVATE-TN, 29-month data from RESONATE-2, and 29-month data from CLL-14 included in the previously published analysis. In the A vs I comparison, the PFS (hazard ratio [HR] 0.83 [95% CI 0.50, 1.37]) and OS (HR 0.69 [95% CI 0.37, 1.29]) numerically favored A but the difference was not significant. The A vs V+O comparison did not show significant differences in PFS (HR 0.96 [95% CI 0.56, 1.65] and OS (HR 0.99 [95% CI 0.51, 1.91]). For A+O vs I, significant differences in PFS (HR 0.48 [95% CI 0.27, 0.88]) and OS (HR 0.41 [95% CI 0.18, 0.91]) were observed. Similarly, for A+O vs V+O, significant differences were observed for PFS (HR 0.38 [95% CI 0.20, 0.73]) and OS (HR 0.43 [95% CI 0.19, 0.99]). Significant differences in rate of grade ≥3 AEs in favor of A and A+O were observed vs I for atrial fibrillation, hypertension, decreased neutrophil count, and decreased platelet count. Compared with V+O, patients treated with A had significantly lower rates of febrile neutropenia, leukopenia, neutropenia, thrombocytopenia, non-melanoma skin cancer, and secondary primary malignancies, excluding non-melanoma skin cancer. For A+O vs V+O, significantly lower rates of infusion-related reaction, neutropenia, and non-melanoma skin cancer were observed among patients treated with A+O.Conclusions: Based on these MAIC results, A and A+O are associated with a favorable safety profile vs both I and V+O while, with longer follow-up, these MAIC results demonstrate that A+O is associated with a significant efficacy benefit vs both I and V+O. A limitation of this MAIC is not including all potential PVs as a trade-off to conserve the effective sample size. Our findings are consistent with the results of ELEVATE-RR comparing A with I in the relapsed population and also provide insight into comparisons of A-based therapy with V+O as we await more definitive prospective data on this question from a phase 3 trial. [Display omitted] DisclosuresDavids: Genentech: Consultancy, Research Funding; Ascentage Pharma: Consultancy, Research Funding; Surface Oncology: Research Funding; AbbVie: Consultancy; Adaptive Biotechnologies: Consultancy; BeiGene: Consultancy; Celgene: Consultancy; Eli Lilly and Company: Consultancy; BMS: Consultancy, Research Funding; MEI Pharma: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Verastem: Consultancy, Research Funding; Janssen: Consultancy; Novartis: Consultancy, Research Funding; Astra-Zeneca: Consultancy, Research Funding; MEI Pharma: Consultancy; Merck: Consultancy; Research to Practice: Consultancy; Takeda: Consultancy. Emeribe: AstraZeneca: Current Employment, Current holder of stock options in a privately-held company. Gaitonde: AstraZeneca: Current Employment, Current holder of stock options in a privately-held company, Research Funding. Cai: AstraZeneca: Current Employment, Current equity holder in publicly-traded company; Google: Current equity holder in publicly-traded company; Celgene Corporation: Ended employment in the past 24 months.

Timing of adjuvant chemotherapy after limb amputation and effect on outcome in dogs with appendicular osteosarcoma without distant metastases.

To determine an optimal time interval between amputation and initiation of adjuvant chemotherapy (TIamp-chemo) in dogs with appendicular osteosarcoma without distant metastases and whether TIamp-chemo was associated with outcome. 168 client-owned dogs treated at 9 veterinary oncology centers. Data were collected from the dogs' medical records concerning potential prognostic variables and outcomes. Dogs were grouped as to whether they received chemotherapy within 3, 5, 7, 10, 15, 20, 30, or > 30 days after amputation of the affected limb. Analyses were performed to identify variables associated with time to tumor progression and survival time after limb amputation and to determine an optimal TIamp-chemo. Median TIamp-chemo was 14 days (range, 1 to 210 days). Median time to tumor progression for dogs with a TIamp-chemo ≤ 5 days (375 days; 95% CI, 162 to 588 days) was significantly longer than that for dogs with a TIamp-chemo > 5 days (202 days; 95% CI, 146 to 257 days). Median overall survival time for dogs with a TIamp-chemo ≤ 5 days (445 days; 95% CI, 345 to 545 days) was significantly longer than that for dogs with a TIamp-chemo > 5 days (239 days; 95% CI, 186 to 291 days). Findings indicated that early (within 5 days) initiation of adjuvant chemotherapy after limb amputation was associated with a significant and clinically relevant survival benefit for dogs with appendicular osteosarcoma without distant metastases. These results suggested that the timing of chemotherapy may be an important prognostic variable.