Selective benefit of adjuvant chemoradiation in resectable pancreatic cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4122-4122 ◽  
Author(s):  
Jesse P Wright ◽  
Cameron Schlegel ◽  
Rebecca A Snyder ◽  
Liping Du ◽  
Yu Shyr ◽  
...  
Keyword(s):  
Cox Regression ◽  
Margin Status ◽  
Resectable Pancreatic Cancer ◽  
Adjuvant Chemoradiation ◽  
Related Factors ◽  
Large Hospital ◽  
Positive Margins ◽  
Kaplan Meier ◽  
Independent Effects ◽  
The Impact

4122 Background: Although level 1 data supports the use of adjuvant chemotherapy (ACT) in resected pancreatic adenocarcinoma (PDAC), the role of adjuvant chemoradiation (ACRT) remains controversial. The objective of this study is to investigate the impact of adding ACRT to ACT on overall survival (OS), based on lymph node (LN) and margin status. Methods: Resected AJCC Stage I and II PDAC patients from 2004-2013 identified within the National Cancer Database were classified into groups based on treatment: surgery alone (SX), ACT alone, ACT+ACRT, and ACRT only. Kaplan-Meier analyses were performed to determine median OS. Multivariable (MV) Cox regression models with interactions of treatment with LN and margin status were constructed to examine the independent effects of ACT and ACT+ACRT in these subgroups. Results: Of 31,348 patients, 30% were treated with SX, 30% with ACT, 38% with ACT+ACRT, and 2% with ACRT alone. Median OS (mos.) for ACT (22.5, 95% CI 21.9-23.1) and ACT+ACRT (23.7, 23.3-24.2) were significantly longer than SX (14, 13.4-14.5) or ACRT (11.2, 9.8-12.9). MV analysis confirmed a significant OS benefit of both ACT and ACT+ACRT controlling for patient and tumor related factors. ACRT+ACT was associated with improved OS compared to ACT in patients with positive margins and/or LN. Those with negative margins and LN did not benefit from the additional use of ACRT (Table). Conclusions: This large hospital-based study demonstrates that ACT and ACRT are associated with improved OS when compared to SX. The addition of ACRT to ACT, however, was only beneficial in high-risk patients with positive margins and/or LN. ACT+ACRT in patients with both margin and LN negative disease may not be warranted. Future clinical trials should stratify patients based on LN and margin status in order to determine which patients are most likely to benefit from the use of ACRT. [Table: see text]

scholarly journals A Nomogram Model to Predict Prognosis of Patients With Genitourinary Sarcoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Linde Li ◽  
Jiayu Liang ◽  
Turun Song ◽  
Saifu Yin ◽  
Jun Zeng ◽  
...  
Keyword(s):  
Cox Regression ◽  
Surgical Excision ◽  
Rank Test ◽  
Training Set ◽  
Positive Margins ◽  
Prognostic Effect ◽  
Kaplan Meier ◽  
Sufficient Power ◽  
Validation Set ◽  
The Impact

ObjectivesThe aim of this study is to evaluate the significant factors influencing the overall survival (OS) and recurrence free survival (RFS) and make an attempt to develop a nomogram for predicting the prognosis of patients with genitourinary sarcoma (GS).MethodsData on adult GS from 1985 to 2010 were collected. The impact of clinical factors on OS and RFS were estimated by Kaplan–Meier (KM) analysis, and differences between groups were analyzed by the log-rank test. To establish a nomogram, all patients were randomly divided into a training set (n = 125) and a testing set (n = 63). Cox proportion hazard model was utilized to assess the prognostic effect of variables. Then, a nomogram was established to estimate 1-, 3-, and 5-year OS based on Cox regression model. Subsequently, the nomogram was validated by a training set and a validation set.ResultsA total of 188 patients were enrolled into our study. Male patients with bladder sarcoma had better OS rather than RFS when stratified by gender (P = 0.022). According to histological subtypes, patients with leiomyosarcoma (LMS) undergoing chemotherapy were associated with favorable OS (P = 0.024) and RFS (P = 0.001). Furthermore, LMS in kidney sarcoma were associated with lower recurrence rate in comparison to rhabdomyosarcoma (RMS) (P = 0.043). Margin status after surgical excision markedly influenced the OS and RFS of GS patients and negative margins presented optimal prognosis. Chemotherapy was associated with improved OS for patients without surgery (P = 0.029) and patients with positive margins (P = 0.026). Based on the multivariate analysis of the training cohort, age, gender, surgery status, histological subtype, and chemotherapy were included in our nomogram for prediction of OS. The nomogram had sufficient power with concordance index (C-index) of OS: 0.770, 95%CI: 0.760–0.772 and area under curve (AUC) of OS: 0.759, 95%CI: 0.658–0.859 in the training set and with C-index of OS: 0.741, 95%CI: 0.740–0.765, and AUC of OS: 0.744, 95%CI: 0.576–0.913 in the validation set.ConclusionsAdults GS is a group of extremely rare tumors with poor prognosis. Of all histological types, LMS is sensitive to chemotherapy. We highlighted the cardinal role of surgical resection and the importance of achieving negative margins. We identified the efficacy of chemotherapy for patients with positive margins and those without surgery as well. A nomogram is validated as an effective tool predicting short-term outcomes.

Rehospitalization as a predictor of mortality in Polish population of heart failure patients-national registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Zaleska-Kociecka ◽  
K Witczak ◽  
K Bartolik ◽  
D Was ◽  
A Kleinork ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cox Regression ◽  
National Registry ◽  
Funding Source ◽  
Polish Population ◽  
The European Union ◽  
Related Factors ◽  
Comorbidity Burden ◽  
All Cause Mortality ◽  
The Impact

Abstract Background High mortality risk in heart failure (HF) is related to repeat HF hospitalizations but also individual patient characteristics. Purpose To evaluate the impact of HF re-/hospitalizations and patient-related factors (sex, HF etiology, age, comorbidity) on all-cause mortality. Methods Our study represents one of the most extensive retrospective cohort analyses consisting of 1,686,861 adult Polish HF patients who presented into public health system in years 2013–2018. It is a part of a nationwide National Health Fund registry covering out- and in-patient data for the entire Polish population (38,495,659 in 2013) since 2009. HF hospitalizations were extracted using ICD-10 coding, whereas the comorbidity was evaluated by means of Charlson Comorbidity Index (CCI). Results In years 2013–2018 the absolute number of HF hospitalizations in Poland grew by 33% to 264,808 in 2018, whereas the number of rehospitalizations increased 1.5-fold to reach 137,708 in 2018. In fact, nearly half of HF patients (n=817,432; 48.5%) experienced at least one hospitalization, while 15.4% (n=259,868) were rehospitalized during the study period. After initial hospitalization the readmission rate due to HF/all circulatory diseases at 30, 60, 180, 360, and 720 days was 10.4%/15.1%, 21.2%/28.3%, 43.9%/52.8%, 62%/70.4%, and 81%/87%, respectively. As compared to patients who were hospitalized just once, those who underwent at least one rehospitalization were more often female (p<0.001), slightly older (p<0.001), and with higher burden of comorbidities based on CCI (p<0.001). Patient survival was highly dependent on hospitalization frequency (Fig. 1). Mean survival rate at day 720 was 66.4%, 59.8%, 54.9%, 51%, and 43.9% for 1st, 2nd, 3rd, 4th, and ≥5th hospitalization, respectively. After adjusting for age, sex, etiology (ischemic/non-ischemic) and CCI using a multivariate stratified Cox regression model, the estimated hazard ratios (HR) for all-cause mortality amounted to 1.22 (95% CI: 1.21–1.23, p<0.001) for 2nd, 1.4 (95% CI: 1.39–1.42, p<0.001) for 3rd, 1.58 (95% CI: 1.56–1.6, p<0.001) for 4th, and 1.97 (95% CI: 1.95–1.98 p<0.001) for 5th and subsequent hospitalizations, as compared to the first hospitalization. Conclusions Hospitalization rate in Poland is alarmingly high. Repeat HF hospitalizations strongly predict mortality rate for HF patients even after adjustment for age, sex, etiology, and comorbidity burden. Figure 1. Kaplan-Meier for survival post hosp. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): The project is co-financed by the European Union from the European Social Fund under the Operational Programme Knowledge Education Development and it is being carried out by the Analyses and Strategies Department of the Polish Ministry of Health.

scholarly journals Survival analysis of time to SARS-CoV-2 PCR negativisation to optimise PCR prescription in health workers: the Henares COVID-19 healthcare workers cohort study

2021 ◽  
pp. oemed-2020-106903
Author(s):  
Julio González Martin-Moro ◽  
Marta Chamorro Gómez ◽  
Galicia Dávila Fernández ◽  
Ana Elices Apellaniz ◽  
Ana Fernández Hortelano ◽  
...  
Keyword(s):  
Cohort Study ◽  
Healthcare Workers ◽  
Cox Regression ◽  
Health Workers ◽  
Upper Respiratory Tract ◽  
Rt Pcr ◽  
Kaplan Meier ◽  
Confounding Variables ◽  
The Impact ◽  
Associated Variables

ObjectivesReverse transcriptase PCR (RT-PCR) is considered the gold standard in diagnosing COVID-19. Infected healthcare workers do not go back to work until RT-PCR has demonstrated that the virus is no longer present in the upper respiratory tract. The aim of this study is to determine the most efficient time to perform RT-PCR prior to healthcare workers’ reincorporation.Materials and methodsThis is a cohort study of healthcare workers with RT-PCR-confirmed COVID-19. Data were collected using the medical charts of healthcare workers and completed with a telephone interview. Kaplan-Meier curves were used to determine the influence of several variables on the time to RT-PCR negativisation. The impact of the variables on survival was assessed using the Breslow test. A Cox regression model was developed including the associated variables.Results159 subjects with a positive RT-PCR out of 374 workers with suspected COVID-19 were included. The median time to negativisation was 25 days from symptom onset (IQR 20–35 days). Presence of IgG, dyspnoea, cough and throat pain were associated with significant longer time to negativisation. Cox logistic regression was used to adjust for confounding variables. Only dyspnoea and cough remained in the model as significant determinants of prolonged negativisation time. Adjusted HRs were 0.68 (0.48–096) for dyspnoea and 0.61 (0.42–0.88) for dry cough.ConclusionsRT-PCR during the first 3 weeks leads to a high percentage of positive results. In the presence of respiratory symptoms, negativisation took nearly 1 week more. Those who developed antibodies needed longer time to negativisate.

scholarly journals The Effect of Marital Status on Survival of Patients with Gastrointestinal Stromal Tumors: A SEER Database Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Wei Song ◽  
Chuan Tian
Keyword(s):  
Prognostic Factor ◽  
Marital Status ◽  
Gastrointestinal Stromal Tumors ◽  
Cox Regression ◽  
Seer Database ◽  
Cancer Specific Survival ◽  
Stromal Tumors ◽  
Kaplan Meier ◽  
Risk Of Cancer ◽  
The Impact

Background. Marital status has been reported to be a prognostic factor in multiple malignancies. However, its prognostic value on gastrointestinal stromal tumors (GISTs) have not yet been determined. The objective of the present analysis was to assess the effects of marital status on survival in patients with GISTs. Methods. The Surveillance, Epidemiology, and End Results (SEER) database was used to analyze 6195 patients who were diagnosed with GISTs from 2001 to 2014. We also use Kaplan-Meier analysis and Cox regression to analyze the impact of marital status on cancer-specific survival (CSS). Results. Patients in the married group had more frequency in white people, more high/moderate grade tumors, and were more likely to receive surgery. Widowed patients had a higher proportion of women, a greater proportion of older patients (>60 years), and more common site of the stomach. Multivariate analysis demonstrated that marital status was an independent prognostic factor for GISTs (P<0.001). Married patients had better CSS than unmarried patients (P<0.001). Subgroup analysis suggested that widowed patients had the lowest CSS compared with all other patients. Conclusions. Marital status is a prognostic factor for survival in patients with GISTs, and widowed patients are at greater risk of cancer-specific mortality.

H3K27M-mutant Diffuse Midline Gliomas should be Further Molecularly Stratified: An Integrated Analysis of 669 Patients

2021 ◽  
Author(s):  
Huy Gia Vuong ◽  
Hieu Trong Le ◽  
Tam N.M. Ngo ◽  
Kar-Ming Fung ◽  
James D. Battiste ◽  
...  
Keyword(s):  
Cox Regression ◽  
Fatal Outcome ◽  
Extent Of Resection ◽  
Tumor Location ◽  
Genetic Alterations ◽  
Integrated Analysis ◽  
Prognostic Impact ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
The Impact

Abstract Introduction: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients.Methods: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan-Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS).Result: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR = 1.446; 95% CI = 1.143-1.829) whereas ACVR1 (HR = 0.712; 95% CI = 0.518-0.976) and FGFR1 mutations (HR = 0.408; 95% CI = 0.208-0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR = 0.620; 95% CI = 0.386-0.996). Adjusted for age, gender, tumor location, and the extent of resection, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors.Conclusions: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. It could help neuro-oncologists better evaluate the risk stratification of patients and consider pertinent treatments.

The impact of multimodality therapies in marginally inoperable soft tissue sarcomas (STS): The Toronto Sarcoma Program (TSP) experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11548-11548
Author(s):  
Olga Vornicova ◽  
Jay Wunder ◽  
Peter W. M. Chung ◽  
Abha A. Gupta ◽  
Rebecca Anne Gladdy ◽  
...  
Keyword(s):  
Cox Regression ◽  
Soft Tissue Sarcomas ◽  
Tumor Board ◽  
Disease Characteristics ◽  
Kaplan Meier ◽  
Progression Of Disease ◽  
Modality Approach ◽  
Poor Outcomes ◽  
The Impact

11548 Background: The mainstay therapy of operable STS remains surgery, which may include (neo)adjuvant therapies. Within the TSP, marginally inoperable STS are often treated with sequential chemo (CTX) and radiation (RT) therapy, followed by surgery (SX). Herein we present our experience of multi-modality therapies for marginally inoperable STS patients (pts). Methods: This was a dual-center, single program, retrospective review. Pts were included if deemed to have marginally inoperable primary or recurrent STS, as determined at the TSP tumor board. Pts included must have had CTX with the intent of having RT and SX after. Pts demographics, treatment details and clinical outcomes data were collected. Relapse free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Multivariate analysis of the influence of disease characteristics and treatment on outcomes was assessed using Cox regression. Results: From June 2005 to May 2019, 75 pts were identified. Median age was 52 years (range 16-72). Pts were predominantly male (55%). Histological subtypes included dedifferentiated liposarcoma (29%), leiomyosarcoma (27%), synovial sarcoma (19%) and others (25%). Primary tumor was located in the retroperitoneum (48%), extremity (23%), pelvis (12%), thorax (9%), and other sites (8%). All pts had doxorubicin and ifosfamide CTX (median 4 cycles; range 1-6), while RT dose delivered was 50.4Gy/28 fractions in 58 (77%) of cases. Twenty three pts (31%) achieved partial response, 40 pts (53%) had stable disease and 12 pts (16%) had progression of disease (PD) on CTX, of which half (8%) did not undergo further treatment. Nine pts (12%) underwent CTX followed by SX due to significant response, 9 pts (12%) underwent CTX and RT without SX due to persistent tumor unresectability or PD. The final 50 pts (67%) completed multi-modality treatment (CTX, RT & SX). Overall, 59 pts (79%) had SX; negative margins were achieved in 53 (71%). 19 pts (25%) had postoperative complications, causing death in 2 pts (2.7%). With a median follow-up of 72 months, median RFS and OS were 26.9 months (95% CI: 0-86.0), and 65 months (95% CI: 13.5-116.4). Extremity location was associated with superior RFS (median not reached [NR], HR 0.28 95% CI 0.09-0.83, p = 0.022), and OS (median NR, HR 0.29 95% CI 0.09-0.90, p = 0.032). Receipt of RT was associated with superior RFS (median NR, HR 0.23 95% CI 0.10-0.52, p < 0.001); and OS (median NR, HR 0.21 95% CI 0.09-0.50, p < 0.001). Pts who had PD after CTX were associated with poor outcomes - RFS (median 4.7 months, HR 2.03 95% CI 0.61-6.76, p = 0.24); and OS (median 21.9 months, HR 2.48 95% CI 0.73-8.47, P = 0.144). Conclusions: Multi-modality approach resulted in successful resection for most pts with marginally inoperable STS. Extremity location and RT administration were associated with better RFS and OS, while progression on CTX confers worse survival outcomes.

scholarly journals Camptocormia in patients with multiple system atrophy at different disease durations: frequency and related factors

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ling Yu Zhang ◽  
Bei Cao ◽  
Qian-Qian Wei ◽  
Ru Wei Ou ◽  
Bi Zhao ◽  
...  
Keyword(s):  
Multiple System Atrophy ◽  
Disease Severity ◽  
Disease Duration ◽  
Rating Scale ◽  
Cox Regression ◽  
Age Of Onset ◽  
Older Age ◽  
Related Factors ◽  
Cox Regression Analysis ◽  
The Impact

Abstract Background Camptocormia is common in patients with multiple system atrophy (MSA). The current study was aimed at assessing the frequency of camptocormia and its related factors in MSA patients with different disease durations. Also, the impact of camptocormia on disability was evaluated. Methods A total of 716 patients were enrolled in the study. They were classified into three groups based on disease duration (≤ 3, 3–5, ≥ 5 years). Specific scales were used to evaluate the motor and non-motor symptoms. Disease severity was assessed using the Unified Multiple System Atrophy Rating Scale (UMSARS). The binary logistic regression model was used to explore the factors related to camptocormia. To analyze the impact of camptocormia on disability in patients with disease duration less than 5 years, propensity score matching (PSM) and stratified Cox regression analysis were used. Results In the current study, we found that the frequency of camptocormia was 8.9, 19.7 and 19.2% when the disease duration was ≤3, 3–5, ≥ 5 years, respectively. In the disease duration ≤3 years group, we found that MSA-parkinsonian subtype (MSA-P) (OR = 2.043, P = 0.043), higher total UMSARS score (OR = 1.063, P < 0.001), older age of onset (OR = 1.047, P = 0.042), and lower score on the frontal assessment battery (FAB) (OR = 0.899, P = 0.046) were associated with camptocormia. Only greater disease severity was associated with camptocormia in the group of patients with disease duration 3–5 years (OR = 1.494, P = 0.025) and in the group of patients with disease duration ≥5 years (OR = 1.076, P = 0.005). There was no significant impact of camptocormia on disability in patients with a disease duration of < 5 years (HR = 0.687, P = 0.463). Conclusion The frequency of camptocormia increased with prolonged disease duration. Disease severity was related to camptocormia at different stages of the disease. The MSA-P subtype, older age of onset, and lower FAB score were associated with camptocormia in the early stage of the disease.

Type I Versus Type II Endometrial Cancer: Differential Impact of Comorbidity

2018 ◽  
Vol 28 (3) ◽  
pp. 586-593 ◽  
Author(s):  
Mette Calundann Noer ◽  
Sofie Leisby Antonsen ◽  
Bent Ottesen ◽  
Ib Jarle Christensen ◽  
Claus Høgdall
Keyword(s):  
Cox Regression ◽  
Type I ◽  
Prognostic Impact ◽  
Type Ii ◽  
Regression Analyses ◽  
Differential Impact ◽  
Kaplan Meier ◽  
Prediction Of Survival ◽  
Comorbidity Index ◽  
The Impact

ObjectiveTwo distinct types of endometrial carcinoma (EC) with different etiology, tumor characteristics, and prognosis are recognized. We investigated if the prognostic impact of comorbidity varies between these 2 types of EC. Furthermore, we studied if the recently developed ovarian cancer comorbidity index (OCCI) is useful for prediction of survival in EC.Materials and MethodsThis nationwide register-based cohort study was based on data from 6487 EC patients diagnosed in Denmark between 2005 and 2015. Patients were assigned a comorbidity index score according to the Charlson comorbidity index (CCI) and the OCCI. Kaplan-Meier survival statistics and adjusted multivariate Cox regression analyses were used to investigate the differential association between comorbidity and overall survival in types I and II EC.ResultsThe distribution of comorbidities varied between the 2 EC types. A consistent association between increasing levels of comorbidity and poorer survival was observed for both types. Cox regression analyses revealed a significant interaction between cancer stage and comorbidity indicating that the impact of comorbidity varied with stage. In contrast, the interaction between comorbidity and EC type was not significant. Both the CCI and the OCCI were useful measurements of comorbidity, but the CCI was the strongest predictor in this patient population.ConclusionsComorbidity is an important prognostic factor in type I as well as in type II EC although the overall prognosis differs significantly between the 2 types of EC. The prognostic impact of comorbidity varies with stage but not with type of EC.

Abstract TP209: Effect of Chemotherapy on Stroke Risk in Cancer Patients

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Takaya Kitano ◽  
Tsutomu Sasaki ◽  
Yasufumi Gon ◽  
Kenichi Todo ◽  
Shuhei Okazaki ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Propensity Scores ◽  
Stroke Risk ◽  
Cox Regression ◽  
Treatment Plan ◽  
University Hospital ◽  
Chemotherapy Group ◽  
Kaplan Meier ◽  
Increased Risk ◽  
The Impact

Introduction: Chemotherapy may be a cause of cancer-associated stroke, but whether it increases stroke risk remains uncertain. We aimed to clarify the impact of chemotherapy on stroke risk in cancer patients. Methods: We investigated 27,932 patients enrolled in a hospital-based cancer registry at Osaka University Hospital between 2007 and 2015. The registry collects clinical data, including cancer status (site and stage), on all patients treated for cancer. Of them, 19,006 patients with complete data were included. A validated algorithm was used to identify stroke events within 2 years of cancer diagnosis. Patients were divided based on whether their initial treatment plan included chemotherapy. The association between chemotherapy and stroke was analyzed using the Kaplan-Meier method and stratified Cox regression. Results: Of the 19,006 patients, 5,887 (31%) patients were in the chemotherapy group. Non-targeted chemotherapy was used in 5,371 patients. Stroke occurred in 44 patients (0.75%) in the chemotherapy group and 51 patients (0.39%) in the no-chemotherapy group. Kaplan-Meier curve analysis showed that patients in the chemotherapy group had a higher stroke risk than patients in the no-chemotherapy group (HR 1.84; 95% CI 1.23-2.75; Figure [A]). However, this difference was insignificant after adjustment for cancer status using inverse probability of treatment weighting with propensity scores (HR 1.20; 95% CI 0.76-1.91; Figure [B]). Similarly, in the stratified Cox regression model, chemotherapy was not associated with stroke after adjustment for cancer status (HR 1.26; 95% CI 0.78-2.03). These findings were consistent with analysis wherein the effect of chemotherapy was treated as a time-dependent covariate (HR 1.02; 95% CI 0.55-1.88). Conclusions: In this population, the elevated stroke risk in cancer patients who received chemotherapy was presumably due to advanced cancer stage; chemotherapy was not associated with the increased risk of stroke.

Type and intensity of FVIII exposure on inhibitor development in PUPs with haemophilia A

2015 ◽  
Vol 113 (05) ◽  
pp. 958-967 ◽  
Author(s):  
Maria Elisa Mancuso ◽  
Elena Santagostino ◽  
Gili Kenet ◽  
Mohssen Elalfy ◽  
Susanne Holzhauer ◽  
...  
Keyword(s):  
Cox Regression ◽  
Meta Analysis ◽  
Treatment Intensity ◽  
Haemophilia A ◽  
Related Factors ◽  
Inhibitor Development ◽  
Patient Level ◽  
Level Data ◽  
Statistical Approaches ◽  
The Impact

SummaryThe impact of treatment-related factors on inhibitor development in previously untreated patients (PUPs) with haemophilia A is still debated. We present the results of a collaborative, individual patient data meta-analytic project. Eligible data sources were published cohorts of PUPs for which patient-level data were available. The exposures of interest were factor (F)VIII type (recombinant [rFVIII] vs plasma-derived [pdFVIII]) and treatment intensity (≥ vs < 150 IU/kg/week) at first treatment. Family history of inhibitors, F8 mutations, age, treatment regimen (on-demand vs prophylaxis), secular trend and surgery were analysed as putative confounders using different statistical approaches (multivariable Cox regression, propensity score analyses, CART). Analyses accounted for the multi-centre origin of the data. We included 761 consecutive, unselected PUPs with moderate to severe haemophilia A from 10 centres in Egypt, Germany, Israel and Italy. A total of 27 % of patients developed inhibitors; 40 % and 22 % of patients treated with rFVIII and pdFVIII (unadjusted HR 2.2, 95 % CI 1.6–2.9), respectively; 51 % and 24 % of patients receiving high-and low-intensity treatment (unadjusted HR 2.9, 95 % CI 2.0–4.2), respectively. In adjusted analyses, only treatment intensity remained an independent predictor; the effect of FVIII type was largely due to confounding, but with a significant interaction between FVIII type and treatment intensity. This patient-level meta-analysis confirms, across different statistical approaches, that high-intensity treatment is a strong risk factor for inhibitor development. The possible role of FVIII type in subgroups is suggested by the test for interactions but could not be proven because of the limited subgroups sample sizes.

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