Cumulative Incidence Of Treatment Failure Research Articles

Treatment of newly diagnosed moderate or severe chronic graft-versus-host disease with prednisone and everolimus (PredEver first): a prospective multicenter phase IIA study.

Although most patients with chronic graft-versus-host disease (cGVHD) show initial response to first-line therapy, long-term clinically meaningful success of first-line treatment remains rare. In a prospective multicentre phase II trial in 6 German centers, patients with newly diagnosed moderate or severe cGVHD received prednisone and everolimus for 12 months followed by a 1-year follow-up period. Primary endpoint was treatment success (TS) at 6 months defined as patient being alive, achieving PR or CR of cGVHD, having no relapse of underlying disease and requiring no secondary treatment for cGVHD. Of the 34 patients evaluable for efficacy, 19 (56%) had TS at 6 months with 22 and 52% of the patients in a CR and PR respectively. Overall 30 patients (88%) had a CR or PR as best response, nearly all responses (29/30) occurring within the first 6 weeks of treatment. The cumulative incidence of treatment failure at 1 year was 63%, corresponding to 37% TS. Predefined safety endpoint (thrombotic microangiopathy, pneumonitis, and avascular necrosis) were not observed in any patient. Addition of everolimus to prednisolone is well tolerated and may improve long-term treatment success. Larger studies are necessary to ascertain the possible role of everolimus in first-line treatment of cGVHD.

A Prognostic Score for the Prediction of Local Treatment Failure in Plaque Brachytherapy of Uveal Melanoma

To develop a prognostic score that correlates to a low, medium, and high incidence of treatment failure after plaque brachytherapy of uveal melanoma (UM). All patients who have received plaque brachytherapy for posterior UM at St. Erik Eye Hospital in Stockholm, Sweden from 1995 through 2019 were included (n=1636). Treatment failure was defined as tumor recurrence, lack of tumor regression, or any other condition requiring a secondary transpupillary thermotherapy (TTT), plaque brachytherapy, or enucleation. The total sample was randomized into 1 training and 1 validation cohort, and a prognostic score for the risk for treatment failure was developed. In multivariate Cox regression, low visual acuity, tumor distance to the optic disc ≤2 mm, American Joint Committee on Cancer (AJCC) stage, and a tumor apical thickness of >4 (for Ruthenium-106) or >9 mm (for Iodine-125) were independent predictors of treatment failure. No reliable threshold could be identified for tumor diameter or cancer stage. In competing risk analyses of the validation cohort, the cumulative incidence of treatment failure, as well as of secondary enucleation, increased with the prognostic score: In the low, intermediate, and high-risk classes, the 10-year incidence of treatment failure was 19, 28, and 35% and of secondary enucleation 7, 19, and 25 %, respectively. Low visual acuity, American Joint Committee on Cancer stage, tumor thickness, and tumor distance to the optic disc are independent predictors of treatment failure after plaque brachytherapy for UM. A prognostic score was devised that identifies low, medium, and high risk for treatment failure.

990. Sex-Specific Analysis of Clinical Features and Outcomes in Staphylococcal Periprosthetic Joint Infections Managed with Two-Stage Exchange Arthroplasty

Abstract Background There are anatomical, pharmacokinetic, and joint biomechanical differences between males and females. Whether these differences result in differing presentation, treatment tolerability and outcomes in periprosthetic joint infection (PJI) has not been widely evaluated. Methods We undertook a retrospective case matched study of patients with staphylococcal PJI managed with two-stage exchange arthroplasty. In order to control for differences other than sex which may influence outcome or presentation, males and females were case-matched for age, causative organism (Coagulase-negative staphylococci vs Staphylococcus aureus) and joint involved. The two matched groups were analyzed for differences in duration of symptoms, inflammatory markers, duration of hospital stay, antimicrobial side effects, post-operative complications and recurrence rate. Recurrence of infection was defined as per Musculoskeletal Infection Society criteria for PJI and included both relapse with original microorganism or with an additional organism. Results 78 pairs of males and females with staphylococcal PJI were successfully matched. There were no significant baseline differences by sex, except for greater use of chronic immunosuppression among females (16.7% vs. 4.1%; p=0.012). Clinical characteristics and outcomes of the patients are summarized in table 1. We did not detect a statistically significant between the outcomes of the two groups. Overall, 16 recurrent infections occurred during a median follow-up time of 2.9 (IQR: 1.5 - 5.3) years. The 3-year cumulative incidence of treatment failure depicted in figure 1 was 16.1% for females, compared with 8.8% for males (p=0.434). Conclusion Success rates for PJI treated with two-stage exchange arthroplasty are high consistent with previously reported literature. A larger cohort of patients may be required to detect differences in relapse rates. This study included only staphylococcal PJI and was thus unable to evaluate the differences in microbiology of PJI between males and females, which could also impact outcomes. This retrospective case-matched study did not detect any significant differences in outcomes between males and females with staphylococcal PJI who underwent two stage exchange arthroplasty. Disclosures Gina A. Suh, M.D., Adaptive Phage Therapeutics (APT): Grant/Research Support|Adaptive Phage Therapeutics (APT): Dr. Suh received grants and has an equity and royalty-bearing know-how agreement with Adaptive Phage Therapeutics but is unrelated to project Aaron J. Tande, M.D., Uptodate: Dr Tande has received an honorarium from Uptodate for medical writing unrelated to this project.

Concerns about Prognostic Meaning of Quantitative PET Analysis in Classical Hodgkin Lymphoma

Introduction: Currently, interim PET analysis (iPET) according to the Deauville score (DS) is the most important prognostic factor used in clinical trials and clinical practice, guiding treatment decisions. However, the results of iPET studies are heterogeneous highlighting that this prognostic factor is not perfect and the need of studies trying to improve the accuracy of iPET assessment. Quantitative PET-CT analysis at baseline (PET0) and iPET with total metabolic tumor volume (TMTV) or total lesion glycolysis (TLG) has been studied as an additional predictor of progression free survival (PFS) and overall survival (OS). This study aims to evaluate the prognostic value of PET quantitative analysis (PET0/iPET) in a real-life cohort from a public oncohematology facility at the Instituto do Cancer do Estado de Sao Paulo-Brazil. Methods: Patients (pts) from the oncohematology database with confirmed CHL diagnosis from January 2011 to December 2017, PET/CT evaluation and treated with ABVD protocol were included in this retrospective study. HIV positive pts were excluded. PET images were reviewed by two nuclear medicine physicians, blinded to the outcomes. SUVmax, TMTV, and TLG were calculated using commercial software VCAR (GE Healthcare, Waukehsa, WI, USA). Lesions were delimited by using a threshold of 41% of the maximum SUV in each lesion. TMTV and TLG at baseline were dichotomized to find an optimal cutoff value by using the method of Contal and O'Quigley. For iPET+ pts, the percentage reduction compared to PET0 (delta), ΔSUVmax, ΔTMTV and ΔTLG were calculated and also their cutoffs. Cumulative incidence of treatment failure (CIF) was estimated and death was considered a competitive event. OS and PFS were also estimated. Cox regression and regression model of Fine-Gray were used for multiple analyses. Results: 234 pts were included in this analysis and the median follow-up was 6.8 years. The median age was 30 years old(14-79), 56% were female, 59.4% had CS III/IV, 70.5% had B symptoms, 68,3% had high-risk score (according to GHSG criteria) and 7.7% had ECOG>2. Of the 210 pts with iPET evaluation, 52 (24.7%) were positive (DS 4-5). The quantitative measures at PET0 and iPET are showed in Table 1. The OS and PFS at 5y were 85.1% and 71.1%, respectively. The CIF (5y) was 21.5% and 12% had non-disease-related death. At baseline, pts with TLG>1392.55 had higher incidence of treatment failure (HR 1.92 IC: 95% 1.05-3.51). Neither TMTV nor TLG at PET0 had an impact on PFS or OS. In multiple regression analysis (TMTV, TLG, iPET by DS, age, clinical stage), only iPET remain independent prognostic for predicting treatment failure (HR:3.70, IC95% 2.04-6.71, p< 0.001), and iPET (HR: 2.06, IC 95% 1.12-3.77, p=0.019) and age>45 (HR: 2.17, IC 95% 1.20-3.93,p=0.011) were independent predictor of PFS. In addition, better PFS was observed for those with ΔSUVmax >68.8 in iPET analysis (HR: 0.25, IC 95% 0.092-0.59, p=0.005) and for those with ΔTMTV >92.7(HR: 0.42, IC 95% 0.19-0.50, p=0.037). Cox proportional model (ΔSUVmax, ΔTMTV and ΔTLG) showed that only ΔSUVmax remain predictor of PFS (HR: 0.29, IC 95% 0.11-0.82, p=0.019). The combination of iPET+ according to DS and quantitative ΔSUVmax ≤68.8% allows identifying a group of patients with inferior PFS (Figure). Conclusion: In a real-life cohort from developing countries, with the general profile of high-risk and high volume of tumor disease, quantitative analysis of PET0 is not predictor of PFS, OS, or CIF. However, quantitative analysis at PET0 and iPET+ (DS 4/5) together could identify a group with a worse prognosis. This information requires confirmation in prospective trials and could support future studies in iPET-guided treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

NCMP-08. THE EFFECTIVENESS OF ANTISEIZURE MEDICATION TRIPLETHERAPY IN GLIOMA PATIENTS WITH REFRACTORY EPILEPSY: A MULTICENTER OBSERVATIONAL COHORT STUDY

Abstract BACKGROUND About 10% of glioma patients with epilepsy need antiseizure medication (ASM) tripletherapy due to refractory epilepsy. This study aimed to determine whether levetiracetam combined with valproic acid and clobazam (LEV+VPA+CLB), a commonly prescribed tripletherapy, has favorable effectiveness compared to other tripletherapy combinations in glioma patients. METHODS In this multicenter retrospective observational cohort study, the primary outcome was to estimate the cumulative incidence of treatment failure for any reason, from initiation of ASM tripletherapy. Secondary outcomes included cumulative incidences of: 1) treatment failure due to uncontrolled seizures; 2) treatment failure due to adverse effects; and 3) recurrent seizure. Maximum duration of follow-up was 36 months. RESULTS Out of n=1435 patients in the original cohort, n=90 patients received ASM tripletherapy after second-line ASM treatment failure due to uncontrolled seizures. LEV+VPA+CLB was prescribed to 48% (43/90) and other ASM tripletherapy to 52% (47/90) patients. The cumulative incidence of treatment failure for any reason of LEV+VPA+CLB did not significantly differ from other tripletherapy (12 months: 47% [95%CI, 31-62%] versus 42% [95%CI, 27-56%], p=0.892). No statistical significant differences for treatment failure due to uncontrolled seizures (12 months: 12% [95%CI, 4-25%] versus 18% [95%CI, 8-30%], p=0.445), due to adverse effects (12 months: 22% [95%CI, 11-36%] versus 15% [95%CI, 7-27%], p=0.446), or recurrent seizure (1 month: 65% [95%CI, 48-78%] versus 63% [95%CI, 47-75%], p=0.911) were found. CONCLUSIONS LEV+VPA+CLB showed equivalent effectiveness compared to other ASM tripletherapy combinations in glioma patients.

P09.06.B The effectiveness of antiepileptic drug tripletherapy in refractory epileptic glioma patients: a multicenter observational cohort study

Abstract Background About 10% of the glioma patients need antiepileptic drug (AED) tripletherapy due to refractory epilepsy. This study aimed to determine whether levetiracetam combined with valproic acid and clobazam (LEV+VPA+CLB), a commonly prescribed tripletherapy, has favourable effectiveness compared to other tripletherapy combinations in glioma patients. Material and Methods In this multicenter retrospective observational cohort study, the primary outcome was the cumulative incidence of treatment failure for any reason, from initiation of AED tripletherapy. Secondary outcomes included cumulative incidences of: 1) treatment failure due to uncontrolled seizures; 2) treatment failure due to adverse effects; and 3) recurrent seizure. Maximum duration of follow-up was 36 months. Results Ninety patients, from an initial cohort of n=1435 patients, received AED tripletherapy after second-line AED duotherapy treatment failure due to uncontrolled seizures. LEV+VPA+CLB was prescribed to 43 (48%) and other AED tripletherapy to 47 (52%) patients. The cumulative incidence of treatment failure for any reason of LEV+VPA+CLB did not significantly differ from other tripletherapy combinations (12 months: 47% [95%CI, 31-62%] versus 42% [95%CI, 27-56%], p=0.892). No statistical significant differences for treatment failure due to uncontrolled seizures (12 months: 12% [95%CI, 4-25%] versus 18% [95%CI, 8-30%], p=0.445), due to adverse effects (12 months: 22% [95%CI, 11-36%] versus 15% [95%CI, 7-27%], p=0.446), or recurrent seizure (1 month: 65% [95%CI, 48-78%] versus 63% [95%CI, 47-75%], p=0.911) were found. Conclusion LEV+VPA+CLB has not shown favourable efficacy or tolerability compared to other AED tripletherapy combinations in glioma patients. Therefore, we cannot specifically recommend CLB as tripletherapy add-on AED to LEV+VPA.

Aberrant Subclavian Arteries and Associated Kommerell Diverticulum: Endovascular vs Open Repair

BackgroundVarious surgical options have been described for the treatment of aberrant subclavian arteries and an associated Kommerell diverticulum. MethodsBetween 1999 and 2019, 43 patients underwent a repair, comprising 26 (61%) endovascular and 17 (39%) open approaches. The endovascular approach consisted of initial subclavian revascularization followed by thoracic endovascular aortic repair. The open approach included total arch replacement (12%) and reverse hemiarch repair with left thoracotomy (53%) or right thoracotomy (35%). The perioperative and long-term outcomes were retrospectively reviewed. ResultsNo mortality occurred in the endovascular group, whereas there was 1 (6%) in the open approach group. Patients in the endovascular group demonstrated a shorter hospital stay (3.5 days vs 10.0 days; P = .001) and less frequent prolonged mechanical ventilation (0% vs 24%; P = .019), with a lower occurrence of pneumonia (0% vs 24%; P = .019). Among patients who had the endovascular approach, shrinkage of Kommerell diverticulum or aberrant vessel origin was seen in 96%. Furthermore, relief of dysphagia was confirmed in 92% (12/13), including patients without Kommerell diverticulum (n = 3) after endovascular repair. The cumulative incidence of treatment failure or aortic reintervention at 7 years was 21% and 14 % in the endovascular and open approach groups, respectively (P = .62). Two (8%) patients in the endovascular group required an open reintervention. One reintervention was performed for persistent dysphagia in the setting of an untreated complete vascular ring, and the other was for persistent false lumen flow associated with aortic dissection. ConclusionsThe treatment approach should be individualized on the basis of the aortic disease and comorbidities. The endovascular approach is a viable and effective alternative in the presence of suitable landing zones.

P12.01 The effectiveness of antiepileptic drug treatment in glioma patients: lamotrigine versus lacosamide

Abstract BACKGROUND Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide. MATERIAL AND METHODS In this multicenter study we retrospectively analyzed data of patients with diffuse grade 2–4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity. RESULTS We included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI: 26–51%) versus 30% (95%CI: 20–41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI: 0.46–1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide. CONCLUSION Lamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy.

The effectiveness of antiepileptic drug treatment in glioma patients: lamotrigine versus lacosamide

PurposeOptimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide.MethodsIn this multicenter study we retrospectively analyzed data of patients with diffuse grade 2–4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity.ResultsWe included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI 26–51%) versus 30% (95%CI 20–41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI 0.46–1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide.ConclusionLamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy.

Rituximab Maintenance after First-Line Immunochemotherapy in Mantle Cell Lymphoma: Long-Term Follow-up of the Randomized European MCL Elderly Trial

Rituximab Maintenance after First-Line Immunochemotherapy in Mantle Cell Lymphoma: Long-Term Follow-up of the Randomized European MCL Elderly Trial

First-line antiepileptic drug treatment in glioma patients with epilepsy: Levetiracetam vs valproic acid.

ObjectiveThis study aimed at estimating the cumulative incidence of antiepileptic drug (AED) treatment failure of first‐line monotherapy levetiracetam vs valproic acid in glioma patients with epilepsy.MethodsIn this retrospective observational study, a competing risks model was used to estimate the cumulative incidence of treatment failure, from AED treatment initiation, for the two AEDs with death as a competing event. Patients were matched on baseline covariates potentially related to treatment assignment and outcomes of interest according to the nearest neighbor propensity score matching technique. Maximum duration of follow‐up was 36 months.ResultsIn total, 776 patients using levetiracetam and 659 using valproic acid were identified. Matching resulted in two equal groups of 429 patients, with similar covariate distribution. The cumulative incidence of treatment failure for any reason was significantly lower for levetiracetam compared to valproic acid (12 months: 33% [95% confidence interval (CI) 29%–38%] vs 50% [95% CI 45%–55%]; P < .001). When looking at specific reasons of treatment failure, treatment failure due to uncontrolled seizures was significantly lower for levetiracetam compared to valproic acid (12 months: 16% [95% CI 12%–19%] vs 28% [95% CI 23%–32%]; P < 0.001), but no differences were found for treatment failure due to adverse effects (12 months: 14% [95% CI 11%–18%] vs 15% [95% CI 11%–18%]; P = .636).SignificanceOur results suggest that levetiracetam may have favorable efficacy compared to valproic acid, whereas level of toxicity seems similar. Therefore, levetiracetam seems to be the preferred choice for first‐line AED treatment in patients with glioma.

Treatment Failure and Associated Factors among Individuals on Second Line Antiretroviral Therapy in Eastern Uganda: A Retrospective Cohort Study.

Background:ART failure is a growing public health problem and a major threat to the progress of HIV/AIDS control. In Uganda however, little is documented on treatment outcomes and their associated factors among individuals on second line ART regimen. The rapid scale-up of ART over the past has resulted in substantial reductions in morbidity and mortality. However, as millions of people must be maintained on ART for life, individuals with ART treatment failure are increasingly encountered and the numbers are expected to rise. This could be attributed to factors such as sub-standard regimens, limited access to routine viral load monitoring, treatment interruptions, suboptimal adherence, among others. The purpose of this study was to estimate 5-year cumulative treatment failure and the associated factors among individuals on second line ART regimen Eastern Uganda.Materials and methods:A retrospective analysis of 541 records of HIV positive individuals, switched to second line ART regimen from January 2012 to December 2017. Inferential statistics including the Chi square test and multivariable logistic regression analysis was applied to determine associations of treatment failure against of the selected demographic, laboratory and clinical factors was performed. Associations between treatment failure and the predictors was based on a P-value of less than 5% and confidence intervals level of 95%.Results:We reviewed 541 records of individuals on second line ART regimen, of which 350 (64.7%) were female, 226 (41.8%) were married, and 197 (36.4%) were older than 35 years. The mean age at ART initiation was 30 years (SD = 14.8), while the mean weight at ART initiation was 47 kg (SD = 18.6), (range 4-97 kg). The overall proportion of treatment failure was 23%. The cumulative mortality risk for 5 years was 12.4% and the mortality rate was 2.5 deaths per 100 individuals per year. The odds of developing treatment failure among individuals switched to ATV/r-based regimen were 44% lower as compared to individuals who were switched to LPV/r (ORadj0.56, 95% CI 0.35-0.90, P = .016). while the odds of experiencing treatment failure among individuals that used AZT at ART initiation were 43% lower as compared to individuals that used a TDF based regimen at ART initiation (ORadj0.57, 95% CI 0.33-0.98, P = .041).Conclusion:The 5 year cumulative incidence of treatment failure in a cohort of 541 individuals was 23%. The type of protease inhibitor (PI) used in second line regimen and use of AZT at ART initiation were significantly associated with treatment failure. Our study also shows that the cumulative mortality risk while on second line ART regimen was 12.4% while the mortality rate was 2.5 deaths per 100 individuals per year. Given the high level of treatment failure among individuals on second line ART regimen, yet the current ART protocols limits the use of third line ART regimens to only regional referral hospitals, the Ministry of Health should strengthen the surveillance systems for identifying individuals failing on second line ART regimen even at district hospitals and lower health facilities to facilitate timely switch to optimal regimen. The Ministry of health through the Quality Improvement Division should conduct routine onsite support supervision to sites offering ART to ensure that treatment guides and other standard of care like timely switch to appropriate regimens among others are being adhered to. Knowledge gaps identified can also be addressed through onsite Continuous Medical Educations.

NCOG-45. FIRST-LINE ANTIEPILEPTIC DRUG TREATMENT IN GLIOMA PATIENTS WITH EPILEPSY: LEVETIRACETAM VERSUS VALPROIC ACID

Abstract BACKGROUND Levetiracetam and valproic acid are two of the most commonly prescribed antiepileptic drugs (AEDs) in patients with a glioma and epilepsy. This study aimed at estimating the cumulative incidence of treatment failure of first-line monotherapy levetiracetam versus valproic acid in glioma patients with epilepsy. METHODS In this retrospective observational study, a competing risk model was used to estimate the cumulative incidence of treatment failure, from AED treatment initiation, for the two AEDs with death as competing event. Patients were matched on baseline covariates potentially related to treatment assignment and/or outcomes of interest according to the nearest neighbour propensity score matching technique. Secondary outcomes were the cumulative incidence of recurrent seizure, from AED treatment initiation (estimated with a competing risk model), and severity of adverse effects. Maximum duration of follow-up was 36 months. RESULTS In total, 776 patients using levetiracetam and 659 using valproic were identified. Matching resulted in two equal groups of 429 patients, with similar covariate distribution. The cumulative incidence of treatment failure (any reason) at 12 months for levetiracetam and valproic acid was equal to 33% (95%CI=29-38%) versus 50% (95%CI=45-55%), respectively (p&amp;lt; 0.001). The cumulative incidence of treatment failure due to uncontrolled seizures was significantly lower for levetiracetam compared to valproic acid (12 months: 16% [95%CI=12-19%] versus 28% [95%CI=23-32%]; p&amp;lt; 0.001), but no differences were found for treatment failure due to adverse effects (12 months: 14% [95%CI=11-18%] versus 15% [95%CI=11-18%]; p=0.636). The cumulative incidence of recurrent seizure of levetiracetam was significantly lower compared to valproic acid (12 months: 54% [95%CI=49-59%] versus 67% [95%CI=62-71%]; p&amp;lt; 0.001). No significant differences were found for level of toxicity. CONCLUSION Our results suggest that levetiracetam has superior efficacy compared to valproic acid, while showing a similar level of toxicity. Therefore, levetiracetam seems the preferred choice for first-line AED treatment in glioma patients.

Laparoscopic Heller myotomy or pneumatic dilatation in achalasia: results of a prospective, randomized study with at least a decade of follow-up.

The most efficient long-term treatment strategy for achalasia has yet to be established. This study compared the long-term results (≥ 10years) after either pneumatic dilatations or laparoscopic myotomy using treatment failure as the primary outcome. Secondary objectives were; the frequency and degree of dysphagia and effects on health-related quality of life (QoL). Out of the 53 patients with achalasia who were initially randomized to either laparoscopic myotomy with a posterior partial fundoplication (LM) or repetitive pneumatic dilatation (PD), 43 remained for scrutiny after a median observation period of 170months (LM; n = 20 and PD; n = 23). At the follow-up of 60months, 10 patients (36%) in the PD group and two patients (8%) in the LM group were classified as treatment failures (p = 0.016). At the latest follow-up time point (≥ 10years), the corresponding numbers were 13 (57%) and 4 (20%), respectively. The Kaplan-Meier analysis of the cumulative incidence of treatment failure revealed a significant advantage of LM over the dilatation strategy (p = 0.036)). QoL assessed by the generic instrument PGWB and the more disease-specific instrument GSRS revealed scores which were similar in the two study groups with no obvious changes over time. Reflux was better controlled in the LM group (p = 0.02 regarding PPI consumption). After more than a decade of follow-up, laparoscopic myotomy reinforces its superiority over repetitive pneumatic dilatation treatment strategy in the management of newly diagnosed achalasia.

Treatment of Newly Diagnosed Moderate or Severe Chronic Graft-Versus-Host Disease with Prednisone and Everolimus (PredEver first): A Prospective Multicenter Phase IIa Study

Background Chronic graft-versus-host disease (cGVHD) is the major cause of treatment related morbidity and mortality after allogeneic stem cell transplantation (allo-HSCT). Recently Paul Martin et al. reported that treatment success at 1 year (defined as a patient being in partial (PR) or complete remission (CR) of cGVHD, in ongoing remission of underlying disease and not requiring any secondary treatment for cGVHD) was the only endpoint associated with clinical benefit. Strikingly this robust endpoint was only achieved in less than 20% of patients undergoing primary treatment for cGVHD. Therefore, although most patients show initial response to first-line therapy, long-term clinically meaningful treatment success remains rare. Methods: We conducted a prospective multicentre phase II trial in 6 transplant centres across Germany (ClinicalTrials.gov Identifier: NCT01862965). Patients aged 18 years or older with newly diagnosed moderate or severe cGVHD were included. All patients received prednisone (1mg/kg BW) and everolimus (target level 3-8 ug/l). Study treatment was scheduled for 12 months followed by a one-year follow-up period. Primary endpoint was treatment success at 6 months defined as patient being alive, achieving PR or CR of cGVHD, having no relapse of underlying disease and requiring no secondary treatment for cGVHD. Secondary endpoints included time to treatment failure, overall survival at one and 2 years, time to response, incidence of PR /CR at 6 months, incidence of relapse, thrombotic microangiopathy, pneumonitis and osteonecrosis. Results: A total of 38 patients were included between March 2013 and February 2018 in the study. Four patients were excluded from the efficacy analysis because of screening failure. Of the 34 patients, 61% had moderate and 39% severe cGVHD. Of these 19 (56%) patients showed treatment success at 6 months with 22% and 52% of the patients in a CR and PR respectively. Overall 30 patients (88%) had a CR or PR as best response, nearly all responses (29/30) occurring within the first 6 weeks of treatment (figure 1). Median time to treatment failure was 24.7 weeks. The cumulative incidence of treatment failure at one year was 63%, resulting in a treatment success incidence of 37% (figure 2). Relapse of underlying disease was diagnosed in 2 (5.9%) patients. Other predefined side effects (thrombotic microangiopathy, pneumonitis and osteonecrosis) were not observed in any patient. Conclusion: This, to the best of our knowledge, is the first prospective study analysing the endpoint treatment success as defined by Paul Martin et al. Our results indicate that addition of everolimus to prednisolone is well tolerated and may help improve long-term outcome of patients with cGVHD. Acknowledgements: This study was supported by a research grant from Novartis to Nicolaus Kröger and Francis Ayuk Disclosures Ayuk: Novartis: Honoraria, Other: Advisory Board, Research Funding. Wagner:MEDAC: Other: Travel support; Novartis: Other: Advisory board; Pfizer: Other: Advisory board; MSD: Other: Advisory board. Wolff:Neovi: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Mallinckrodt: Honoraria. von Harsdorf:Novartis: Other: none. Koenecke:Novartis: Other: none. Sayer:Novartis: Other: none. Kroeger:Novartis: Honoraria, Other: Advisory Board, Travel Costs, Research Funding. OffLabel Disclosure: Everolimus used for Treatment of chronic GVHD

Conventional mood stabilizers and/or second-generation antipsychotic drugs in bipolar disorders: A population-based comparison of risk of treatment failure

BackgroundThe study compared treatment failure when using three therapeutic strategies in bipolar disorders: (i) mood stabilizers (MSs: lithium, valpromide, divalproate, carbamazepine, lamotrigine) without second-generation antipsychotic (SGAP); (ii) SGAPs (aripiprazole, olanzapine, risperidone, quetiapine) without MS; (iii) combination of MSs and SGAPs. MethodsA historical cohort study was conducted using the French national healthcare databases in 20,086 outpatients aged 21+, newly treated with one of the three treatment strategies in 2011–2012, and diagnosed with a bipolar disorder. A composite outcome was based on indicators of treatment failure identified over 12 months: treatment discontinuation, switch or addition, psychiatric hospitalisation, suicide attempt, and death. For each strategy, the cumulative incidence of treatment failure was calculated while adjusting for covariates by propensity score weighting. ResultsA total of 8,225 patients (40.9%) were newly dispensed MSs, 9,342 (46.5%) SGAPs, and 2,519 (12.5%) both MSs and SGAPs. The one-year adjusted cumulative incidence of treatment failure was 75.7% (95%CI 74.9;76.3) in patients using MSs, 75.3% (74.6;76.0) in patients using SGAPs, and 60.5% (58.3;62.6) in patients with the combination. The adjusted difference in incidence for SGAPs compared with MSs was −0.40% (-1.4;0.6 p = 0.4) in the whole population, −2.2% (-3.3; −1.2 p < 0.002) in patients under 65 years and +6.7% (4.1;9.1 p < 0.002) in patients 65 years and over. LimitationsCombinations of MSs and SGAPs could not be directly compared with MS or SGAP monotherapies. ConclusionsOne-year treatment failure was high. Overall, no difference in treatment failure was observed between MS or SGAP strategy but differences might exist depending on age.

Causal inference in continuous time: an example on prostate cancer therapy.

In marginal structural models (MSMs), time is traditionally treated as a discrete parameter. In survival analysis on the other hand, we study processes that develop in continuous time. Therefore, Røysland (2011. A martingale approach to continuous-time marginal structural models. Bernoulli 17, 895-915) developed the continuous-time MSMs, along with continuous-time weights. The continuous-time weights are conceptually similar to the inverse probability weights that are used in discrete time MSMs. Here, we demonstrate that continuous-time MSMs may be used in practice. First, we briefly describe the causal model assumptions using counting process notation, and we suggest how causal effect estimates can be derived by calculating continuous-time weights. Then, we describe how additive hazard models can be used to find such effect estimates. Finally, we apply this strategy to compare medium to long-term differences between the two prostate cancer treatments radical prostatectomy and radiation therapy, using data from the Norwegian Cancer Registry. In contrast to the results of a naive analysis, we find that the marginal cumulative incidence of treatment failure is similar between the strategies, accounting for the competing risk of other death.

Ethanol Lock Treatment and Secondary Prophylaxis for Central Line-Associated Bloodstream Infection in Pediatric Hematology and Oncology: A Randomized, Double-Blind, Placebo-Controlled, Intervention Trial

BackgroundCentral line-associated bloodstream infection (CLABSI) commonly affects children with cancer and hematological disorders, with significant attributable costs and morbidity. Treatment failure, comprising persistent infection, infection relapse or new infection, occurs in ~50% of cases. Adjunctive ethanol lock therapy (ELT) has been proposed to prevent failure, but has never been tested in a prospective controlled study.MethodsA prospective, dual-center, double-blind, block-randomized, placebo-controlled trial of ELT (70% ethanol in water) for CLABSI, given as treatment (2 hours per lumen per day) for 5 days, followed by secondary prophylaxis (2 hours per lumen up to 3 days per week) for 24 weeks, in children with oncologic or hematologic disorders (NCT01472965). Risk of treatment failure was compared between intervention and control groups according to proportional and cumulative incidence models, using intention-to-treat and per-protocol analyses. The study was discontinued at a pre-specified futility analysis.ResultsOf 94 evaluable participants, 48 were randomized to ELT and 46 to placebo; groups were similar at baseline for all measured variables. Forty-one (43.6%) participants had treatment failure (11 early failure, 9 relapse, and 21 reinfection). There was no difference between patients receiving ELT or placebo for risk of treatment failure (43.8% vs. 43.5%; P = 0.9) or for cumulative incidence of treatment failure in intention to treat (Figure 1) and per-protocol analyses (Figure 2). Catheter occlusion was significantly more common in participants receiving ethanol (58.3% vs. 32.6%, P = 0.01) but other adverse events, including LFT elevations (14.6% vs. 26.1%) and infusion reactions (18.8% vs. 8.7%), were not significantly different between groups.ConclusionAlthough observational studies suggested ELT might be effective for treatment of CLABSI in pediatric oncology, we found no benefit in treatment outcome and an increase in adverse effects. These results may not apply to patients receiving dialysis or with fungal CLABSI as these were not well-represented. Routine use of ELT for CLABSI in children with oncologic or hematologic disorders is not recommended.DisclosuresAll authors: No reported disclosures.

Granulomatosis with polyangiitis: endoscopic management of tracheobronchial stenosis: results from a multicentre experience.

Tracheobronchial stenosis (TBS) is noted in 12-23% of patients with granulomatosis with polyangiitis (GPA), and includes subglottic stenosis and bronchial stenosis. We aimed to analyse the endoscopic management of TBS in GPA and to identify factors associated with the efficacy of endoscopic interventions. We conducted a French nationwide retrospective study that included 47 patients with GPA-related TBS. Compared with patients without TBS, those with TBS were younger, more frequently female and had less frequent kidney, ocular and gastrointestinal involvement and mononeuritis multiplex. Endoscopic procedures included 137 tracheal and 50 bronchial interventions, mainly endoscopic dilatation, local steroid injection and conservative laser surgery, and less frequently stenting. After the first endoscopic procedure, the cumulative incidence of endoscopic treatment failure was 49% at 1 year, 70% at 2 years and 80% at 5 years. Factors significantly associated with a higher cumulative incidence of treatment failure were a shorter time from GPA diagnosis to endoscopic procedure [hazard ratio (HR) 1.08 (95% CI 1.01, 1.14); P = 0.01] and a bronchial stenosis [HR 1.96 (95% CI 1.28, 3.00); P = 0.002]. A prednisone dose ≥30 mg/day at the time of the procedure was associated with a lower cumulative incidence of treatment failure [HR 0.53 (95% CI 0.31, 0.89); P = 0.02]. TBS represents severe and refractory manifestations with a high rate of restenosis. High-dose systemic CSs at the time of the procedure and increased time from GPA diagnosis to bronchoscopic intervention are associated with a better event-free survival. In contrast, bronchial stenoses are associated with a higher rate of restenosis than subglottic stenosis.

Respuesta terapéutica del Plasmodium vivax a la cloroquina, en Riberalta, Guayaramerín y Yacuiba, Bolivia

Introduction. Knowledge of the therapeutic efficacy of chloroquine for Plasmodium vivax infections improves the capacity for surveillance of anti-malarial drug resistance.Objective. The therapeutic efficacy of chloroquine as treatment was evaluated for uncomplicated Plasmodium vivax malaria in Bolivia.Materials and methods. An in vivo efficacy study of chloroquine was undertaken in three regions of Bolivia--Riberalta, Guayaramerín and Yacuiba. Two hundred and twenty-three patients (84, 80, and59 in the three regions, respectively) aged over 5 years old were administered with chloroquine (25mg/kg/three days) and followed for 28 days. Blood levels of chloroquine and desethylchloroquine were measured on day 2 and on the day of reappearance of parasitemia. The cumulative incidence of treatment failure was calculated using the Kaplan and Meier survival analysis.Results. The mean parasitemias (asexual) on day 0 were 6,147 parasites/μl of blood in the Riberalta population, 4,251 in Guayaramerín and 5,214 in Yacuiba. The average blood concentrations of chloroquine-desethylchloroquine during day 2 were 783, 817, and 815 ng/ml, respectively. No treatment failures were observed in Yacuiba, whereas in Riberalta and Guayaramerín, the frequencies of treatment failures were 6.2% and 10%. Blood levels of chloroquine and desethylchloroquine in patients with treatment failure showed values below 70 ng/ml on the day of reappearance of parasitemia.Conclusion. Resistance of Plasmodium vivax to chloroquine was not demonstrated in three regions of Bolivia. doi: http://dx.doi.org/10.7705/biomedica.v32i4.750