Prognostic Model for Stratification of Radioresistant Nasopharynx Carcinoma to Curative Salvage Radiotherapy

2018 ◽  
Vol 36 (9) ◽  
pp. 891-899 ◽  
Author(s):  
You Quan Li ◽  
Yun Ming Tian ◽  
Sze Huey Tan ◽  
Ming Zhu Liu ◽  
Grace Kusumawidjaja ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Index ◽  
Intensity Modulated Radiotherapy ◽  
Training Data ◽  
Cancer Center ◽  
Weight Discrimination ◽  
Data Set ◽  
Training Cohort ◽  
Risk Patients ◽  
Grade 3

Purpose To investigate for a prognostic index (PI) to personalize recommendations for salvage intensity-modulated radiotherapy (IMRT) in patients with locally recurrent nasopharyngeal carcinoma (lrNPC). Methods Patients with lrNPC from two academic institutions (Sun Yat-Sen University Cancer Center [SYSUCC-A; n = 251 (training cohort)] and National Cancer Centre Singapore [NCCS; n = 114] and SYSUCC-B [n = 193 (validation cohorts)]) underwent salvage treatment with IMRT from 2001 to 2015. Primary and secondary clinical end points were overall survival (OS) and grade 5 toxicity-free rate (G5-TFR), respectively. Covariate inclusion to the PIs was qualified by a multivariable two-sided P < .05. Discrimination and calibration of the PIs were assessed. Results The primary PI comprised covariates that were adversely associated with OS in the training cohort (gross tumor volumerecurrence hazard ratio [HR], 1.01/mL increase [ P < .001], agerecurrence HR, 1.02/year increase [ P = .008]; repeat IMRT equivalent dose in 2-Gy fractions [EQD2] ≥ 68 Gy HR, 1.42 [ P = .03]; prior radiotherapy-induced grade ≥ 3 toxicities HR, 1.90 [ P = .001]; recurrent tumor [rT]-category 3 to 4 HR, 1.96 [ P = .005]), in ascending order of weight. Discrimination of the PI for OS was comparable between training and both validation cohorts (Harrell’s C = 0.71 [SYSUCC-A], 0.72 [NCCS], and 0.69 [SYSUCC-B]); discretization by using a fixed PI score cutoff of 252 determined from the training data set yielded low- and high-risk subgroups with disparate OS in the validation cohorts (NCCS HR, 3.09 [95% CI, 1.95 to 4.89]; SYSUCC-B HR, 3.80 [95% CI, 2.55 to 5.66]). Our five-factor PI predicted OS and G5-TFR (predicted v observed 36-month OS and G5-TFR, 22% v 15% and 38% v 44% for high-risk NCCS and 26% v 31% and 45% v 46% for high-risk SYSUCC-B). Conclusion We present a validated PI for robust clinical stratification of radioresistant NPC. Low-risk patients represent ideal candidates for curative repeat IMRT, whereas novel clinical trials are needed in the unfavorable high-risk subgroup.

The Addition of Rituximab to CHOP Chemotherapy Improves Response Rate, Failure-Free Survival and Overall Survival for Follicular Grade 3 Lymphoma Compared to CHOP Alone

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1289-1289 ◽  
Author(s):  
Michael J. Overman ◽  
Lei Feng ◽  
Barbara Pro ◽  
Peter McLaughlin ◽  
Mark Hess ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Response Rate ◽  
International Prognostic Index ◽  
High Risk Patient ◽  
Prognostic Index ◽  
Cancer Center ◽  
Free Survival ◽  
Historical Comparison ◽  
Grade 3

Abstract Background: FL3 is a subcategory of follicular lymphomas that is challenging in that it behaves aggressively like large cell lymphomas. If treated with CHOP, however it has a clinical course of relapse and treatment failure similar to grade 1–2 follicular lymphoma. We looked at the outcome of FL3 patients treated with RCHOP, combining rituximab with CHOP. There are no large study reports of this regimen’s results in FL3 to our knowledge. Patients and Methods: We retrospectively reviewed the records of 45 patients with follicular grade 3 lymphoma who were treated with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) at The University of Texas MD Anderson Cancer Center (UTMDACC). Response rate (RR), failure-free survival (FFS), and overall survival (OS) were estimated and a historical comparison to 111 CHOP only treated patients was made. Results: The International Prognostic Index (IPI) distribution was: 47% Low, 36% Low-Intermediate, 13% High-intermediate, and 4% High-risk. The complete response rate was 96%. Forty-four out of 45 patients are still alive. Median follow-up is 3.5 years. The 3-year FFS rate according to IPI was 80% (95% CI: 64% to 100%) in low risk, 81% in low-intermediate (95% CI 64% to 100%), and was 50% (95% CI: 25% to 100%) in high-intermediate/high-risk patient group. The addition of rituximab to CHOP improved both 5-year FFS, 71% (95% CI: 58% to 87%) compared to 44% of CHOP alone (95% CI: 36% to 55%) with p-value of 0.019 and 5-year OS, 98% (95% CI: 93% to 100%) compared to 75% (95% CI: 67% to 84) with p-valule of 0.0034. The addition of rituximab to CHOP improve the FFS compared to CHOP alone when subgroups of IPI were analyzed and compared (p=.002) Conclusion: The addition of rituximab to CHOP provided a high response rate and excellent early survival. Poor risk patients continue to demonstrate a high rate of failure despite the use of rituximab.

Efficacy and Toxicity of Rituximab and Brief Duration, High Intensity Chemotherapy with Filgrastim Support for Burkitt or Burkitt – Like Leukemia/Lymphoma: Cancer and Leukemia Group B (Calgb) Study 10002

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 858-858 ◽  
Author(s):  
David A. Rizzieri ◽  
Jeffrey L Johnson ◽  
John C. Byrd ◽  
Gerard Lozanski ◽  
Bayard L. Powell ◽  
...  
Keyword(s):  
High Risk ◽  
High Intensity ◽  
International Prognostic Index ◽  
Tumor Lysis Syndrome ◽  
Prognostic Index ◽  
Adult Patients ◽  
Term Survival ◽  
Risk Patients ◽  
Grade 3

Abstract Abstract 858 Prior studies have shown that combination chemotherapy using high doses of antimetabolites and alkylating agents over a short duration is effective treatment for Burkitt leukemia and lymphoma. Adults able to tolerate this therapy have had > 50% long term survival, although those with higher risk by the International Prognostic Index (IPI) have had inferior outcomes. Between 5/2002 and 9/2009, we enrolled 105 adults (19-79 yrs old) with untreated Burkitt leukemia/lymphoma onto a phase II study of a high intensity chemo-immunotherapy regimen to assess the benefit of adding rituximab plus growth factor support to the intensive chemotherapy regimen developed in CALGB 9251 and evaluated patterns of relapse when prophylactic cranial irradiation was not given. All subjects were HIV negative and had serum creatinine and bilirubin ≤1.5 × upper limit. Complete data are available on 105 patients for toxicity and 103 patients for efficacy. Methods: Treatment began with cyclophosphamide (CY) 200 mg/m2 × 5 days and prednisone 60 mg/m2 × 7 days. Cycle 2 was started on Day 8 after entry. Cycles 2, 4, and 6 consisted of ifosfamide 800 mg/m2 on days 1–5, methotrexate (MTX) 1.5 g/m2 infused over day 1 with leucovorin rescue, vincristine (VCR) 2 mg day 1, Ara-C 1 gm/m2 days 4 and 5, VP-16 80 mg/m2 days 4 and 5, and dexamethasone 10 mg/m2 on days 1–5. Cycles 3, 5, and 7 included the same doses of MTX, VCR, and dexamethasone, with CY 200 mg/m2 IV on days 1–5 and doxorubicin 25 mg/m2 days 4 and 5. Cycles were delivered every 21 days if blood counts had recovered. Filgrastim was given at 5μg/kg/day SC beginning day 7 of each cycle and continuing until the absolute neutrophil count recovered to > 5000/μL. Rituximab was initiated during cycle 2 on day 8 at 50 mg/m2 and on days 10 and 12 at 375 mg/m2. During cycles 3 through 7, rituximab was infused only on day 8 of each course at 375 mg/m2. Central nervous system (CNS) prophylaxis consisted of triple intrathecal therapy on day 1 of cycles 2–7 (6 total doses). Results: 27% of patients were ≥60 years old; 70% were male; 46% had intermediate or high risk disease by the IPI (Table). Overall, 75 of 105 subjects completed all 7 planned courses of therapy. 82% attained a complete response (CR), and 87% of these remain in CR at last follow up. 7% had a partial response. With median follow up of survivors of 3.2 years, 2 year event free survival (EFS) and overall survival (OS) were 77% and 79%, respectively, with a trend favoring those <60 years old (87% and 87%, respectively). There were clear differences in outcome based on IPI score with 2 year EFS and OS for low risk patients of 90% and 92% versus 55% and 55% for high risk patients, respectively (Figure). This protocol did not use prophylactic CNS radiation, and 4 pts had documented CNS relapses; 2 had intermediate and 1 high IPI disease; the 4th was unknown. Relapse after 2 years was rare. 7 subjects (6.8%) died from treatment related causes (1 CNS bleed, 4 infections, 2 respiratory failure). Nearly all subjects experienced the anticipated severe hematologic toxicities. The most common grade 3 and 4 non-hematologic toxicities included stomatitis/upper GI toxicity (∼ 66%), nausea/vomiting (20%), fatigue (26%), rash or erythema multiforme (10%), diarrhea (10%), pulmonary or CNS bleeding (11%), clinically documented infections (72%), neurologic disturbances (8%), and dyspnea (10%). 8 pts (8%) had tumor lysis syndrome (all grade 3). Conclusion: This regimen provides a high rate of durable remissions in adult patients with a manageable side effect profile. Chemoimmunotherapy should be the standard for adult patients with Burkitt leukemia/lymphoma. Disclosures: Off Label Use: Rituximab for use in Burkitt's. Cheson:Genentech: Consultancy.

scholarly journals Follicular lymphoma: are we ready for a risk-adapted approach?

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 358-364 ◽  
Author(s):  
Brad S. Kahl
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Randomized Clinical Trials ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Predictive Biomarkers ◽  
Western Hemisphere ◽  
Ongoing Research ◽  
High Risk Patients ◽  
Risk Patients

Abstract Follicular lymphoma is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. The natural history of FL appears to have been favorably impacted by the introduction of rituximab after randomized clinical trials demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival. Yet, the disease is biologically and clinically heterogeneous with wide variations in outcomes for individual patients. The ability to accurately risk-stratify patients and then tailor therapy to the individual is an area of ongoing research. Historically, tumor grade, tumor burden, and the FL international prognostic index (version 1 and version 2) have been used to distinguish low-risk from high-risk patients. Biologic factors such as mutations in key genes can identify patients at high risk for poor outcomes to first-line therapy (mutational status of 7 genes [EZH2, ARID1A, MEF2B, EP300, FOX01, CREBBP, and CARD11] with Follicular Lymphoma International Prognostic Index). More recently, the quality of the response to initial therapy, as measured by either PET imaging or by remission duration, has been show to identify individuals at high risk. However, several unmet needs remain, including a better ability to identify high-risk patients at diagnosis, the development of predictive biomarkers for targeted agents, and strategies to reduce the risk of transformation.

scholarly journals Does the implementation of a novel intensive care discharge risk score and nurse-led inpatient review tool improve outcome? A prospective cohort study in two intensive care units in the UK

BMJ Open ◽  
2017 ◽  
Vol 7 (12) ◽  
pp. e018322
Author(s):  
Jez Fabes ◽  
William Seligman ◽  
Carolyn Barrett ◽  
Stuart McKechnie ◽  
John Griffiths
Keyword(s):  
Intensive Care ◽  
High Risk ◽  
Risk Score ◽  
Prospective Cohort ◽  
Data Set ◽  
High Risk Patients ◽  
Poor Outcome ◽  
Icu Discharge ◽  
Risk Patients ◽  
Risk Scoring

ObjectiveTo develop a clinical prediction model for poor outcome after intensive care unit (ICU) discharge in a large observational data set and couple this to an acute post-ICU ward-based review tool (PIRT) to identify high-risk patients at the time of ICU discharge and improve their acute ward-based review and outcome.DesignRetrospective patient cohort of index ICU admissions between June 2006 and October 2011 receiving routine inpatient review. Prospective cohort between March 2012 and March 2013 underwent risk scoring (PIRT) which subsequently guided inpatient ward-based review.SettingTwo UK adult ICUs.Participants4212 eligible discharges from ICU in the retrospective development cohort and 1028 patients included in the prospective intervention cohort.InterventionsMultivariate analysis was performed to determine factors associated with poor outcome in the retrospective cohort and used to generate a discharge risk score. A discharge and daily ward-based review tool incorporating an adjusted risk score was introduced. The prospective cohort underwent risk scoring at ICU discharge and inpatient review using the PIRT.OutcomesThe primary outcome was the composite of death or readmission to ICU within 14 days of ICU discharge following the index ICU admission.ResultsPIRT review was achieved for 67.3% of all eligible discharges and improved the targeting of acute post-ICU review to high-risk patients. The presence of ward-based PIRT review in the prospective cohort did not correlate with a reduction in poor outcome overall (P=0.876) or overall readmission but did reduce early readmission (within the first 48 hours) from 4.5% to 3.6% (P=0.039), while increasing the rate of late readmission (48 hours to 14 days) from 2.7% to 5.8% (P=0.046).ConclusionPIRT facilitates the appropriate targeting of nurse-led inpatient review acutely after ICU discharge but does not reduce hospital mortality or overall readmission rates to ICU.

scholarly journals Evaluating upfront high-dose consolidation after R-CHOP for follicular lymphoma by clinical and genetic risk models

2020 ◽  
Vol 4 (18) ◽  
pp. 4451-4462
Author(s):  
Stefan Alig ◽  
Vindi Jurinovic ◽  
Mohammad Shahrokh Esfahani ◽  
Sarah Haebe ◽  
Verena Passerini ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Statistical Significance ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Risk Scores ◽  
High Dose ◽  
Risk Models ◽  
Progression Of Disease ◽  
Risk Patients

Abstract High-dose therapy and autologous stem cell transplantation (HDT/ASCT) is an effective salvage treatment for eligible patients with follicular lymphoma (FL) and early progression of disease (POD). Since the introduction of rituximab, HDT/ASCT is no longer recommended in first remission. We here explored whether consolidative HDT/ASCT improved survival in defined subgroups of previously untreated patients. We report survival analyses of 431 patients who received frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for advanced FL, and were randomized to receive consolidative HDT/ASCT. We performed targeted genotyping of 157 diagnostic biopsies, and calculated genotype-based risk scores. HDT/ASCT improved failure-free survival (FFS; hazard ratio [HR], 0.8, P = .07; as-treated: HR, 0.7, P = .04), but not overall survival (OS; HR, 1.3, P = .27; as-treated: HR, 1.4, P = .13). High-risk cohorts identified by FL International Prognostic Index (FLIPI), and the clinicogenetic risk models m7-FLIPI and POD within 24 months–prognostic index (POD24-PI) comprised 27%, 18%, and 22% of patients. HDT/ASCT did not significantly prolong FFS in high-risk patients as defined by FLIPI (HR, 0.9; P = .56), m7-FLIPI (HR, 0.9; P = .91), and POD24-PI (HR, 0.8; P = .60). Similarly, OS was not significantly improved. Finally, we used a machine-learning approach to predict benefit from HDT/ASCT by genotypes. Patients predicted to benefit from HDT/ASCT had longer FFS with HDT/ASCT (HR, 0.4; P = .03), but OS did not reach statistical significance. Thus, consolidative HDT/ASCT after frontline R-CHOP did not improve OS in unselected FL patients and subgroups selected by genotype-based risk models.

R-FND Followed by Radioimmunotherapy for High-Risk Follicular Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3056-3056 ◽  
Author(s):  
Peter McLaughlin ◽  
Sattva Neelapu ◽  
Michelle Fanale ◽  
Maria Rodriguez ◽  
Ana Ayala ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Ibritumomab Tiuxetan ◽  
Free Survival ◽  
Grade 3 ◽  
Anti Cd20 ◽  
Better Than

Abstract Follicular lymphoma (FL) patients, (pts) with high-risk features using the FL International Prognostic Index (FLIPI) have an expected 5-year survival of only about 50% with conventional therapy. With the incorporation of anti-CD20 monoclonal antibody (mAb) therapy, results are improving (e.g., Buske, Blood2006; 108: 1504). Starting in 2003, we have treated high-risk (FLIPI ≥3) FL pts with R-FND (rituximab, fludarabine, mitoxantrone, dexamethasone) for 4 cycles, followed by radioimmunotherapy (RIT) with ibritumomab tiuxetan, and subsequent rituximab maintenance. Results for the first 35 pts are: complete (CR) and partial (PR) remission 83% and 14%; 3-year overall (OS) and failure-free survival (FFS) 89% and 74% (median follow-up 24 mo.). RIT converted 5 PR pts to CR. Toxicity was mainly hematologic. Five pts did not receive RIT, one because of neutropenia after R-FND. Following RIT, platelet and neutrophil nadirs were 28 and 0.3, occurring at 4–7 weeks. 16 pts required transfusions, and 27 received growth factors. 13 pts had infections, only 2 of which were grade 3. Recovery occurred by 3 weeks in most, with prolonged cytopenias in 6. There has been 1 case of myelodysplasia. In conclusion, the additional complexity of this RIT intensification strategy is warranted in this high-risk FL population, resulting in OS and FFS outcomes that are better than non-mAb therapies, and at least as good as published chemotherapy-rituximab combination therapy.

The Absolute Monocyte and Lymphocyte Counts at Diagnosis Predict Survival and Identify High-Risk Patients In Diffuse Large-B-Cell Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3088-3088
Author(s):  
Ryan A. Wilcox ◽  
Kay Ristow ◽  
Thomas M. Habermann ◽  
David James Inwards ◽  
Ivana Micallef ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Confidence Interval ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Hazard Ratio ◽  
Poor Risk ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Good Risk

Abstract Abstract 3088 Background: Despite the use of modern immunochemotherapy (R-CHOP) regimens, almost 50% of patients with diffuse large-B-cell lymphoma (DLBCL) will relapse. Current prognostic models, most notably the International Prognostic Index, are comprised of patient and tumor characteristics and are unable to identify patients with less than a 50% chance of long-term survival. However, recent observations demonstrate that factors related to host adaptive immunity and the tumor microenvironment are powerful prognostic variables in non-Hodgkin lymphoma Methods: We retrospectively examined the absolute neutrophil count (ANC), monocyte count (AMC) and lymphocyte count (ALC), obtained from an automated complete blood count with differential, as prognostic variables in a cohort of 255 consecutive DLBCL patients that were uniformly treated with R-CHOP between 2000 and 2007 at a single institution. The primary study objective was to assess if ANC, AMC, and ALC at diagnosis were predictors of overall survival (OS) in DLBCL. Results: At diagnosis, the median ANC was 4720/uL (range 1190–17690), the median AMC was 610/uL (range 30–4040), and the median ALC was 1220/uL (range 140–5410). The median follow-up for these patients was 48 months. In the univariate analysis, each of these variables predicted OS as continuous variables. As dichotomized variables, an elevated ANC (≥5500/μL; hazard ratio 1.75, 95% confidence interval 1.14–2.60, p=0.01) and AMC (≥610/μL; hazard ratio 3.36, 95% confidence interval 2.10–5.59, p<0.0001) were each associated with inferior OS. In contrast, the presence of lymphopenia, defined as an ALC ≤1000/uL, was associated with inferior OS (hazard ratio 2.21, 95% confidence interval 1.43–3.39, p=0.0004). When components of the IPI were included on multivariate analysis only the AMC and ALC were independently significant prognostic factors for OS, with hazard ratios of 3.37 (95% confidence interval 2.05–5.74, p<0.0001) and 2.19 (95% confidence interval 1.38–3.44, p=0.0009), respectively. The dichotomized AMC and ALC generated the AMC/ALC prognostic index (PI) and stratified patients into 3 risk groups: very good (AMC <610/uL and ALC >1000/uL), good (AMC ≥610/uL or ALC ≤1000/uL), and poor-risk (AMC ≥610/uL and ALC ≤1000/uL) populations. For both the very good (n=79) and good-risk (n=134) groups median OS has not been reached with estimated 5-year overall survival of 88% and 69%, respectively. Median OS for poor-risk (n=42) patients was 1.7 years (95% confidence interval 1.1–2.7 years) with an estimated 5-year overall survival of 28% (p<0.0001). By comparison, the R-IPI was unable to identify a group of patients with a median survival less than 8 years. The estimated 5-year OS was 93%, 71% and 53% for very good, good and poor-risk patients, respectively. We sought to determine whether the AMC/ALC PI may provide additional prognostic information when combined with the R-IPI. To test this possibility, the 171 very good/good risk and 84 poor risk patients identified by the R-IPI were subsequently risk stratified using the AMC/ALC PI. Among R-IPI very good/good risk patients a subset of poor risk patients (n=21) with a median OS of 2.2 years (95% confidence interval 1.1–6.6 years) and 35% 5-year OS could be identified with the AMC/ALC PI. In contrast, 5-year OS ranged from 75%-88% among very good and good risk patients. Similarly, stratification of R-IPI poor risk patients by the AMC/ALC PI identified subsets of very good (n=19) and good risk (n=44) patients with median OS that had not been reached and 86% and 55% 5-year OS, respectively. High risk (n=21) patients had a median OS of 1.4 years (95% confidence interval 0.9–2.2 years) and an estimated 5-year OS of less than 25%. Conclusions: Measurement of AMC and ALC at diagnosis is widely applicable, cost effective, predicts OS, and identifies high-risk patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

Large Retroperitoneal Lymphadenopathy As a Predictor of Venous Thromboembolism in Patients With Disseminated Germ Cell Tumors Treated With Chemotherapy

2015 ◽  
Vol 33 (6) ◽  
pp. 582-587 ◽  
Author(s):  
Amirrtha Srikanthan ◽  
Ben Tran ◽  
Michel Beausoleil ◽  
Michael A.S. Jewett ◽  
Robert J. Hamilton ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
High Risk ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Venous Stasis ◽  
Training Cohort ◽  
Axial Diameter ◽  
Discriminatory Accuracy ◽  
London Health ◽  
Risk Patients

Purpose Cisplatin-based chemotherapy, a mainstay of treatment for disseminated germ cell tumors (GCTs), is associated with venous thromboembolism (VTE). Many patients with disseminated GCTs have large retroperitoneal lymph node (RPLN) metastases that may cause venous stasis and increase the risk of VTE development. We hypothesized that there was an association between large RPLN and chemotherapy-associated VTE risk. Patients and Methods The training cohort was composed of patients with disseminated GCT receiving first-line chemotherapy at Princess Margaret Cancer Centre between January 2000 and December 2010. Large RPLN was defined as more than 5 cm in maximal axial diameter. The predictive and discriminatory accuracies of a model using large RPLN in predicting VTE were compared with high-risk Khorana score (≥ 3) using logistic regression and area under receiver operator characteristic curves (AUROCs). The model was externally validated in a cohort of patients treated at the London Health Sciences Centre. Results The training cohort comprised 216 patients, 21 (10%) of whom developed VTE during chemotherapy. VTE was associated with large RPLN (odds ratio [OR], 5.26; P = .001), high-risk Khorana score (OR, 11.8; P < .001), intermediate-/poor-risk disease (OR, 3.76; P = .005), and hospitalization during chemotherapy (OR, 4.24; P = .002). Large RPLN showed higher discriminatory accuracy than high-risk Khorana score (AUROC, 0.71 v 0.67, respectively). Superior discriminatory accuracy of large RPLN over high-risk Khorana score was validated in the London cohort (AUROC, 0.61 v 0.57, respectively). Conclusion Large RPLN is associated with VTE in patients with disseminated GCT and provides higher discriminatory accuracy than high-risk Khorana score. Results should be validated in larger, prospective studies. Prophylactic anticoagulation may be considered in high-risk patients.

scholarly journals How High-Risk Comorbidities Co-Occur in Readmitted Patients With Hip Fracture: Big Data Visual Analytical Approach (Preprint)

2019 ◽  
Author(s):  
Suresh K Bhavnani ◽  
Bryant Dang ◽  
Rebekah Penton ◽  
Shyam Visweswaran ◽  
Kevin E Bassler ◽  
...  
Keyword(s):  
Hip Fracture ◽  
High Risk ◽  
Prediction Models ◽  
Significant Risk ◽  
Training Data ◽  
Integrated Analysis ◽  
Bipartite Network ◽  
Data Set ◽  
Targeted Interventions ◽  
Patient Subgroups

BACKGROUND When older adult patients with hip fracture (HFx) have unplanned hospital readmissions within 30 days of discharge, it doubles their 1-year mortality, resulting in substantial personal and financial burdens. Although such unplanned readmissions are predominantly caused by reasons not related to HFx surgery, few studies have focused on how pre-existing high-risk comorbidities co-occur within and across subgroups of patients with HFx. OBJECTIVE This study aims to use a combination of supervised and unsupervised visual analytical methods to (1) obtain an integrated understanding of comorbidity risk, comorbidity co-occurrence, and patient subgroups, and (2) enable a team of clinical and methodological stakeholders to infer the processes that precipitate unplanned hospital readmission, with the goal of designing targeted interventions. METHODS We extracted a training data set consisting of 16,886 patients (8443 readmitted patients with HFx and 8443 matched controls) and a replication data set consisting of 16,222 patients (8111 readmitted patients with HFx and 8111 matched controls) from the 2010 and 2009 Medicare database, respectively. The analyses consisted of a supervised combinatorial analysis to identify and replicate combinations of comorbidities that conferred significant risk for readmission, an unsupervised bipartite network analysis to identify and replicate how high-risk comorbidity combinations co-occur across readmitted patients with HFx, and an integrated visualization and analysis of comorbidity risk, comorbidity co-occurrence, and patient subgroups to enable clinician stakeholders to infer the processes that precipitate readmission in patient subgroups and to propose targeted interventions. RESULTS The analyses helped to identify (1) 11 comorbidity combinations that conferred significantly higher risk (ranging from <i>P</i>&lt;.001 to <i>P</i>=.01) for a 30-day readmission, (2) 7 biclusters of patients and comorbidities with a significant bicluster modularity (<i>P</i>&lt;.001; Medicare=0.440; random mean 0.383 [0.002]), indicating strong heterogeneity in the comorbidity profiles of readmitted patients, and (3) inter- and intracluster risk associations, which enabled clinician stakeholders to infer the processes involved in the exacerbation of specific combinations of comorbidities leading to readmission in patient subgroups. CONCLUSIONS The integrated analysis of risk, co-occurrence, and patient subgroups enabled the inference of processes that precipitate readmission, leading to a comorbidity exacerbation risk model for readmission after HFx. These results have direct implications for (1) the management of comorbidities targeted at high-risk subgroups of patients with the goal of pre-emptively reducing their risk of readmission and (2) the development of more accurate risk prediction models that incorporate information about patient subgroups.

scholarly journals Development of a Gene-Based Prediction Model for Recurrence of Colorectal Cancer Using an Ensemble Learning Algorithm

2021 ◽  
Vol 11 ◽  
Author(s):  
Han-Ching Chan ◽  
Amrita Chattopadhyay ◽  
Eric Y. Chuang ◽  
Tzu-Pin Lu
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Prediction Models ◽  
Stage I ◽  
Training Data ◽  
Differentially Expressed ◽  
Support Vector ◽  
Data Set ◽  
Risk Of Recurrence

It is difficult to determine which patients with stage I and II colorectal cancer are at high risk of recurrence, qualifying them to undergo adjuvant chemotherapy. In this study, we aimed to determine a gene signature using gene expression data that could successfully identify high risk of recurrence among stage I and II colorectal cancer patients. First, a synthetic minority oversampling technique was used to address the problem of imbalanced data due to rare recurrence events. We then applied a sequential workflow of three methods (significance analysis of microarrays, logistic regression, and recursive feature elimination) to identify genes differentially expressed between patients with and without recurrence. To stabilize the prediction algorithm, we repeated the above processes on 10 subsets by bagging the training data set and then used support vector machine methods to construct the prediction models. The final predictions were determined by majority voting. The 10 models, using 51 differentially expressed genes, successfully predicted a high risk of recurrence within 3 years in the training data set, with a sensitivity of 91.18%. For the validation data sets, the sensitivity of the prediction with samples from two other countries was 80.00% and 91.67%. These prediction models can potentially function as a tool to decide if adjuvant chemotherapy should be administered after surgery for patients with stage I and II colorectal cancer.

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