Predictor Of Early Treatment Failure Research Articles

Predictors of treatment failures of plasmodium falciparum malaria in Vietnam: a 4-year single\u2010centre retrospective study

BackgroundDrug-resistant falciparum malaria is an increasing public health burden. This study examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam.MethodsMedical records of all 443 patients with malaria infection admitted to the Hospital for Tropical Diseases between January 2015 and December 2018 were used to extract information on demographics, risk factors, symptoms, laboratory tests, treatment, and outcome.ResultsMore than half (59.8%, 265/443, CI 55.1–64.4%) of patients acquired Plasmodium falciparum infection of whom 21.9% (58/265, CI 17.1–27.4%) had severe malaria, while 7.2% (19/265, CI 4.6–10.9%) and 19.2% (51/265, CI 14.7–24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. Among 58 patients with severe malaria, 14 (24.1%) acquired infection in regions where artemisinin resistance has been documented including Binh Phuoc (11 patients), Dak Nong (2 patients) and Gia Lai (1 patient). Under treatment with intravenous artesunate, the median (IQR) parasite half-life of 11 patients coming from Binh Phuoc was 3 h (2.3 to 8.3 h), two patients coming from Dak Nong was 2.8 and 5.7 h, and a patient coming from Gia Lai was 6.5 h. Most patients (98.5%, 261/265) recovered completely. Four patients with severe malaria died. Severe malaria was statistically associated with receiving treatment at previous hospitals (P < 0.001), hepatomegaly (P < 0.001) and number of inpatient days (P < 0.001). Having severe malaria was a predictor of ETF (AOR 6.96, CI 2.55–19.02, P < 0.001). No predictor of LTF was identified.ConclusionsPlasmodium falciparum remains the prevalent malaria parasite. Despite low mortality rate, severe malaria is not rare and is a significant predictor of ETF. To reduce the risk for ETF, studies are needed to examine the effectiveness of combination therapy including parenteral artesunate and a parenteral partner drug for severe malaria. The study alerts the possibility of drug-resistant malaria in Africa and other areas in Vietnam, which are known as non-endemic areas of anti-malarial drug resistance. A more comprehensive study using molecular technique in these regions is required to completely understand the magnitude of drug-resistant malaria and to design appropriate control strategies.

68 Ga-DOTATATE Positron Emission Tomography-Computed Tomography Quantification Predicts Response to Somatostatin Analog Therapy in Gastroenteropancreatic Neuroendocrine Tumors.

Somatostatin analogs (SSAs) are the frontline antitumor therapy in advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A subset of patients demonstrate early disease progression on SSA therapy, yet the currently known predictors for treatment failure lack specificity to affect therapeutic decision. SSAs target tumor somatostatin receptors, the level of which can be quantitatively assessed with 68 Ga-DOTATATE positron emission tomography-computed tomography (PET/CT). We investigated the ability of 68 Ga-DOTATATE PET/CT to predict response to SSA therapy. The records of 108 consecutive patients with well-differentiated grade 1-2 GEP-NETs on SSA monotherapy who received 68 Ga-DOTATATE PET/CT scans were retrospectively reviewed to obtain baseline characteristics, 68 Ga-DOTATATE maximum standardized uptake value (SUVmax), and progression-free survival (PFS) data. The optimal SUVmax cutoff for patient stratification was obtained with receiver operating characteristic curve analysis. PFS in the high versus low SUVmax groups was compared with Kaplan-Meier survival analysis. The effects of baseline characteristics and SUVmax on PFS were examined with univariate and multivariate Cox regression. 68 Ga-DOTATATE SUVmax predicted therapeutic failure with sensitivity and specificity of 39% and 98%, respectively. SUVmax of <18.35 was associated with shorter PFS, which was reproduced in the subgroup analysis of SSA-naïve patients. Low SUVmax was the only predictor of early treatment failure (hazard ratio, 6.85) in multivariate analysis, as well as in the subgroup analysis of grade 2 GEP-NETs. Low SUVmax on 68 Ga-DOTATATE PET/CT independently predicts early failure on SSA monotherapy in patients with well-differentiated grade 1-2 GEP-NET. Patients with lack of expected benefit from SSA therapy can be readily identified using routine 68 Ga-DOTATATE PET/CT with very high specificity. Based on 68 Ga-DOTATATE positron emission tomography-computed tomography imaging, clinicians can better inform patients on the expected benefit of somatostatin analog therapy for gastroenteropancreatic neuroendocrine tumors, especially when access to the therapy is difficult, and offer proactive discussion on alternative management options.

The utility of serial procalcitonin measurements in addition to pneumonia severity scores in hospitalised community-acquired pneumonia: A multicentre, prospective study

ObjectivesThe usefulness of serial procalcitonin (PCT) measurements for predicting the prognosis and treatment efficacy for hospitalised community-acquired pneumonia (CAP) patients was investigated. MethodsThis prospective, multicentre, cohort study enrolled consecutive CAP patients who were hospitalised at 10 hospitals in western Japan from September 2013 to September 2016. PCT and C-reactive protein (CRP) were measured on admission (PCT D1 and CRP D1), within 48–72 h after admission (PCT D3 and CRP D3), and within 144–192 h after admission. CURB-65 and the Pneumonia Severity Index (PSI) were assessed on admission. The primary outcome was 30-day mortality; secondary outcomes were early and late treatment failure rates. ResultsA total of 710 patients were included. The 30-day mortality rate was 3.1%. On multivariate analysis, only PCT D3/D1 ratio >1 [odds ratio (95% confidence interval): 4.33 (1.46–12.82),P = 0.008] and PSI [odds ratio (95% confidence interval): 2.32 (1.07–5.03), P = 0.03] were significant prognostic factors. Regarding treatment efficacy, PCT D3/D1 >1 was a significant predictor of early treatment failure on multivariate analysis. PCT D3/D1 with the PSI significantly improved the prognostic accuracy over that of the PSI alone. ConclusionsPCT should be measured consecutively, not only on admission, to predict the prognosis and treatment efficacy in CAP.

Predictors of early treatment failure following initial therapy for systemic immunoglobulin light-chain amyloidosis

We analysed factors predicting early treatment failure (ETF), after first-line therapy for light-chain amyloidosis (AL). AL amyloidosis patients seen at Mayo Clinic within 90 days of diagnosis, from 2006 to 2015, excluding those who died within 3 months of initial therapy, were analysed retrospectively. ETF was defined as progression requiring treatment change or death within 12 (ETF12) or 24 (ETF24) months of first-line treatment. Non-ETF included those with a follow-up of more than 12 or 24 months who had progression beyond 12 or 24 months. A total of 724 patients met the study criteria; 244 (33.7%) had ETF12 and 388 (53.6%) had ETF24. Patients with ETF12 were older (64.1 vs. 62.2 years) with higher prevalence of cardiac (81 vs. 64.1%) and multi-organ involvement (67.2 vs. 45.4%) and higher proportion of patients with t(11; 14) (58.5 vs. 44.3%) or in higher Mayo 2012 stage (58.5 vs. 41.1%).The median follow-up was 5.4 years from start of initial therapy. In multivariate analysis, presence of t(11; 14) and non-incorporation of autologous transplant in initial therapy are significant predictors of ETF12 (p = .01and p = .003) and ETF24 (p = .0001 and p = .005) while Mayo stage is predictive of ETF24 (p = .002), but not ETF12.

Predictors of Early Treatment Failure following initial therapy for Systemic Immunoglobulin Light Chain Amyloidosis

Predictors of Early Treatment Failure following initial therapy for Systemic Immunoglobulin Light Chain Amyloidosis

Factors associated with early treatment failure in adult hospitalized patients with community-acquired pneumonia

Background/Aim. Early treatment failure (ETF) in patients hospitalized for community-acquired pneumonia (CAP) is associated with prolonged hospitalization, increased risk of mortality and high treatment costs. The aim of this study was to analyze the relative importance of factors influencing ETF in hospitalized adult patients with CAP that are still insufficiently explored. Methods. A retrospective case-control study was carried out on a sample of 126 adult patients treated for serious CAP at the Clinic for Pulmonary Diseases, Clinical Center of Serbia, Belgrade, Serbia, during the 5-year period (2007?2011). The cases (n = 63) were consecutive patients with ETF, observed within the three days upon the admission to hospital, while the control group consisted of the equal number of randomly selected patients without such an outcome. The association between potential risk/protective factors and ETF was estimated using logistic regression analysis. Results. The coexistence of gastrointestinal disorders [adjusted odds ratio (OR) 18.83, 95% confidence interval (CI) 1.15?309.04], higher CURB-65 (C ? confusion; U ? urea) 7 mmol/L; R ? respiratory rate ? 30 breaths/min; B ? systolic blood pressure &lt; 90 mmHg or diastolic blood pressure ? 60 mmHg; 65 ? age ? 65 years) score on admission (adjusted OR 2.57, 95%CI 1.05?6.25), initial use of nonsteroidal anti-inflammatory drugs (NSAIDs) in hospital (adjusted OR 38.19, 95%CI 3.61?404.51) and previous outpatient use of inhaled corticosteroids (adjusted OR 22.41, 95%CI 1.03?489.06) were found to be significant risk factors for ETF. On the other hand, older age and use of antibiotics before the hospitalization were associated with a significantly lower chance of experiencing ETF, reducing the odds for 98% and almost 90%, respectively. Conclusion. The avoidance of the routine inhospital use of NSAIDs as well as the outpatient use of appropriate antibiotics may be beneficial for patients hospitalized for CAP in terms of reducing the risk of ETF. The CURB-65 score could be a better predictor of ETF than Pneumonia Severity Index. Further prospective studies are required to confirm these findings.

Baseline predictors of early treatment failure in patients with platinum resistant/refractory (PRR) and potentially platinum sensitive (PPS ≥ 3) recurrent ovarian cancer (ROC) receiving ≥ 3 lines of chemotherapy: The Gynaecologic Cancer Intergroup (GCIG) Symptom Benefit Study (SBS).

5564 Background: Women with PRR/PPS ≥ 3 ROC are a heterogeneous group with unpredictable response to palliative chemotherapy (PC). GCIG SBS recently completed recruitment of 949 patients treated wi...

Abstract 1710: Quantitative 3D mapping of total choline in human breast cancer using high-speed MR spectroscopic imaging at 3T

Abstract INTRODUCTION We report initial experience with 3D mapping of tCho to monitor treatment response in patients undergoing neoadjuvant chemotherapy to predict outcome [1]. METHOD Eleven patients aged: 28 - 77 years with biopsy-confirmed, infiltrating ductal carcinoma (IDC) were studied before and during neoadjuvant therapy. Data were collected on a 3T MR scanner equipped with 8- and 16-channel breast array using PRESS volume prelocalized 3D high-speed Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) [2] with MEGA lipid suppression (TR/TE=2000ms/135ms, matrix size up to 32×16×8, voxel size=1cc, scan time: 10 minutes including a water reference scan). Spectral quantification was performed using LCModel-based spectral fitting in reference to tissue water [3] using a customized basis set with empirically modeled Lorentzian singlet peaks to account for broad and irregular line shapes of residual lipid signals, relaxation correction and automated spectral quality thresholds. RESULTS Strongly elevated tCho with mean concentrations up to 5.1 mmol/kg was measured in 7 patients with single and multi-centric enhancing lesions (Table 1). Decreases in tCho concentration and number of voxels with detectable tCho were measured in 4 patients who underwent neoadjuvant therapy. DISCUSSION AND CONCLUSION This study demonstrates feasibility of quantitative 3D mapping of tCho in invasive breast carcinoma and assessment of regional tCho changes during neoadjuvent therapy. The long-term goal is to utilize 3D high-speed MRSI as an early predictor of treatment failure in women undergoing neoadjuvant therapy. REFERENCES [1] Danishad, A., et al. NMR Biomed. 2010; 23: 233-241. [2] Posse, S., et al., Magn Reson Med, 1997. 37(6): p. 858-65. [3] Provencher et al MRM 1993. GRANT SUPPORT: NIH, DoD, UNM Cancer Center. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1710. doi:1538-7445.AM2012-1710

P2-10-04: 3D Mapping of Total Choline in Human Breast Cancer Using High-Speed MR Spectroscopic Imaging at 3T: A Feasibility Study.

Abstract PURPOSE: To assess the feasibility of quantitative high-speed MR spectroscopic imaging (MRSI) of total Choline (tCho) as an adjunct to dynamic-contrast enhanced (DCE) MRI to improve lesion characterization and monitor treatment response in patients undergoing neoadjuvant chemotherapy. METHOD AND MATERIALS: Seven patients with biopsy-confirmed, infiltrating ductal carcinoma were studied using a clinical 3T MR scanner (Siemens Medical Solutions, Erlangen, Germany) equipped with 8- and 16-channel breast array (Hologic Inc., Bedford, MA). Measurements were performed using PRESS prelocalized 3D Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) using TR/TE=2000ms/135ms, matrix size up to 32×16x8, voxel size=1cc, and total acquisition time of 10 minutes (including water reference scan). Additional data were collected at TE 60 ms to enhance sensitivity for detecting tCho and J-coupled resonances. TE-averaging (8 steps, ΔTE: 2.5 ms) was employed to minimize gradient sideband artifacts. Quantification of tCho in reference to tissue water was performed using spectral fitting and relaxation correction. RESULTS: Strongly elevated tCho with maximum concentration ranging from 0.3 to 4.1 mmol/kg was measured in five patients with single and multi-centric enhancing lesions larger than 2 cc volume (Table 1). The measured tCho concentration in Grade 3 tumors was higher than in lower grade untreated and treated tumors. Strong decreases in tCho concentration were measured in 2 patients undergoing neoadjuvant therapy in a follow-up scan. At short TE an additional resonance was detected that was elevated in enhancing lesions and tentatively assigned to Taurine. Two patients had lesions smaller than 2 cc with surgical clips in which tCho was not detectable due to line broadening. MRSI data sets were preferentially collected before contrast injection, since it increased spectral line width by up to 50%. CONCLUSION: This study demonstrates feasibility of quantitatively mapping tCho in invasive breast carcinoma using high-speed MRSI. The long-term goals are to utilize high-speed MRSI as an early predictor of treatment failure in women undergoing neoadjuvant therapy (i.e. chemotherapy, endocrine therapy or biologic therapy) for breast cancer and to develop an improved screening protocol for high-risk patients. Grant support: 1RC1EB010617-01 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-10-04.

Abstract P2-06-16: Total Choline Measurement in Human Breast Using High-Speed MR Spectroscopic Imaging at 3T

Abstract PURPOSE: We developed a novel, quantitative and high-speed MR spectroscopic imaging (MRSI) method to map total Choline (tCho), a sensitive biomarker of breast tumor status, as an adjunct to enhance the limited specificity of routine dynamic-contrast enhanced (DCE) MRI. Quantitative tCho maps measured in 7 minutes were compared with tCho obtained with conventional Single Voxel Spectroscopy (SVS). METHOD AND MATERIALS: Measurements on a total of 18 healthy female subjects (mean age: 25.6±5) were performed using 3T MR scanners (Siemens Trio, Erlangen, Germany) located at the two partner sites equipped with 4-channel breast coil (Siemens, Erlangen, Germany) or 8-channel breast coil (Sentinelle Medical, Toronto, Canada). 2D MRSI data of an entire oblique slice were collected using Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) [1] with MEGA lipid suppression. Acquisition parameters were: TR/TE=1500ms/125ms, matrix size=32x32, voxel size=2x2x2mm3 (8cc), number of signal averages= 16 with weighted k-space sampling and total acquisition time=7 minutes. PRESS SVS data were acquired with 8 cc voxel size using identical TR/TE and acquisition time. The absolute metabolite concentration was calculated in reference to tissue water (millimoles of tCho per kilogram of solute) using LCModel (s-provencher.com) fitting to estimate the Choline peak baseline and subsequent spectral integration using a Cramer-Rao lower bound threshold of 25%. RESULTS: tCho was detected in 7 of the 15 subjects (47%) in both SVS and PEPSI data. In the PEPSI data sets, tCho was detected in multiple voxels (Fig. 1). Subjects in which tCho was detected exhibited narrower water line width and smaller lipid content than subjects in which tCho was not detectable (2-tailed t-test, P&amp;lt;0.01). The absolute tCho concentrations corrected for relaxation effects in these 7 subjects using SVS and PEPSI was 0.43±0.34 mmol/kg and 0.51±0.19 mmol/kg, respectively. In comparison with SVS data (21.8±8.6Hz), PEPSI spectra demonstrated larger water line width (33.9±12.6Hz) and displayed greater lipid contamination from adipose tissue areas and larger baseline distortion due to the spatial point spread function. CONCLUSION: Despite less favorable shimming and lipid suppression conditions compared to SVS, it is feasible to quantitatively map tCho in healthy breast tissue using high-speed MRSI, with concentration values that are consistent with those from SVS. Studies in breast cancer patients are in progress to assess the feasibility of breast cancer diagnosis and treatment monitoring with MRSI. Results will be reported at the Symposium. The long-term goals are to utilize high-speed MRSI as an early predictor of treatment failure in women undergoing systemic therapy (i.e. chemotherapy, endocrine therapy) for breast cancer and to develop an improved screening protocol for high risk patients. Fig. 1: PEPSI slice localization (left) and spectral array (right) with superimposed LCModel fit and integrated tCho peak Ref: (1) Posse et al. Magn. Reson. Med. 2007;58(2):236-244. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-16.

Age, temperature, and parasitaemia predict chloroquine treatment failure and anaemia in children with uncomplicated Plasmodium falciparum malaria

The prevalence of chloroquine-resistant Plasmodium falciparum malaria has been increasing in sub-Saharan Africa and parts of South America over the last 2 decades, and has been associated with increased anaemia-associated morbidity and higher mortality rates. Prospectively collected clinical and parasitological data from a multicentre study of 788 children aged 6–59 months with uncomplicated P. falciparum malaria were analysed in order to identify risk factors for chloroquine treatment failure and to assess its impact on anaemia after therapy. The proportion of chloroquine treatment failures (combined early and late treatment failures) was higher in the central-eastern African countries (Tanzania, 53%; Uganda, 80%; Zambia, 57%) and Ecuador (54%) than in Ghana (36%). Using logistic regression, predictors of early treatment failure included younger age, higher baseline temperature, and greater levels of parasitaemia. We conclude that younger age, higher initial temperature, and higher baseline parasitaemia predict early treatment failure and a higher probability of worsening anaemia between admission and days 7 or 14 post-treatment.