Predictors Of Treatment Failure Research Articles

P017: The role of baseline bulk and dissemination measures as predictors of progression in advanced Hodgkin lymphoma

Figure 1: Probability of progression-free survival by baseline MTV (A) and Dmax (B) Introduction: Numerous clinical and FDG-PET/CT-associated models were proposed to predict treatment failure in Hodgkin’s lymphoma (HL). Baseline quantitative FDG-PET metrics are emerging biomarkers showing promising prognostic value. We retrospectively analysed the impact of tumour bulk and dissemination as measured by assessing Metabolic Tumor Volume (MTV) and D max - the distance between the furthest lesions identified by FDG-PET/CT - on the probability of progression in HL patients in clinical stages II to IV. Methods: Baseline FDG-PET/CT data of 117 patients with newly diagnosed HL from the PLRG-11 study was analysed and MTV was assessed by manual segmentation with the volume of interest (VOI) threshold of 41%SUVmax and Dmax was calculated by measuring the diameter between centroids of VOIs with SUVmax above SUVmax of the liver located furthest apart. The Median follow-up was months. The distance was measured in 3-dimensional space using Euclidean geometry. The cut-off values of MTV and Dmax were calculated with the maximally selected rank statistic method. Results: MTV cut-off value for progression-free survival (PFS) prediction was 214 ml with PPV 0,516 and NPV of 0.848 and for Dmax was 10 cm with PPV 0.291 and NPV of 1.0. In the cohort of 69 patients with negative interim PET/CT performed post-second cycle of ABVD PFS event was reported in 0% and 17% patients with Dmax below and above 10 cm, respectively and in 6% and 36% of patients with MTV below and above threshold value of 214 ml, respectively. Conclusion: Bulk and dissemination assessments in baseline PET/CT in Hodgkin lymphoma stage II-IV patients may help identify a population of patients with an especially good prognosis.

672P Nivolumab (Nivo) and ipilimumab (Ipi) combined with radiotherapy (RT) in patients (pts) with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN): Updated results on efficacy and correlative analysis

Immune checkpoint inhibitors are standard of care in recurrent/metastatic SCCHN. We evaluated concurrent radioimmunotherapy (RIT) with Nivo and Ipi in the definitive setting for patients with high-risk LA SCCHN. Pts with newly diagnosed, AJCC 7th edition stage IVA-IVB SCCHN of the oropharynx (OP; OP HPV+ were T4, N2c or N3), hypopharynx, and larynx that were eligible for chemotherapy received Nivo (3 mg/kg Q2 weeks x 17) and Ipi (1 mg/kg Q6 weeks x 6) starting 2 weeks prior to IMRT (2 Gy/fraction/day to a total of 70 Gy). The primary endpoint was safety of RIT. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Exploratory endpoints included the association of baseline PD-L1 expression as well as on-treatment changes in immune bias with treatment outcomes. 24 pts (16 OP of whom 14 HPV+) were enrolled and followed for a median of 36.1 months. At data cutoff, 7 PFS events were noted, including 5 distant recurrences, 1 regional recurrence and 1 death without evidence of disease progression. The 3-year PFS and OS rates were 74% (95% CI, 58%-94%) and 96% (95% CI, 88%-100%), respectively. PD-L1 CPS did not correlate with death or disease progression. Among peripheral blood cytokines, increased MCSF levels were associated with prolonged PFS at several timepoints (baseline [p=0.038], post-induction [p=0.031], and at the end of RT [p=0.023]); interval increase in IFNg inducing factor (IL18) within the induction phase was also associated with prolonged PFS (p=0.031), as were post-induction IFNg levels (p=0.041). 5 pts developed in-field ulcerations during consolidation immunotherapy (median time to detection was 3 months post RT completion). PD-L1 CPS did not correlate with ulceration. Interestingly, interval increase in IL9, IL4, IL12, and IL17a during concurrent RIT appeared to protect from in-field ulcerations. Definitive RIT has sufficient clinical activity to support further development. Cytokine profiles appear able to predict treatment failure, as well as in-field ulcerations early during treatment.

Intravenous Corticosteroid Therapy for Acute Lumbar Radicular Pain.

Introduction: The efficacy of pharmacological interventions for acute lumbar radicular pain (ALRP) is limited, and systemic steroid use remains controversial. We evaluated the effectiveness and tolerance of systemic steroid use in a cohort of patients with ALRP. Methods: A retrospective cohort of 56 patients (including 24 females) were admitted with intractable ALRP resistance to conservative treatment of NSAIDs and opiates between the years 2016 and 2018. Medical records were studied for demographics, physical examination findings, Visual Analogue Score (VAS), IV steroids side effects, and recent imaging findings. All patients received a daily dose of IV 24 mg Dexamethasone until discharge, SNRB, or surgery. Results: The average IV steroid treatment was 3.9 (±2.8) days, with most patients showing significant pain relief allowing discharge (69.7%). SNRB was required in 19.6% and surgical intervention in 10.7% within the same admission. Multivariate analysis did not find any parameter to predict treatment failure (age, gender, motor/sensory deficit, CT/MRI findings). The motor deficit, positive straight leg raising (SLR), and dural sac compression on CT were higher in the intervention group but did not reach statistical significance. One patient required discontinuation of IV steroids due to elevated blood pressure. Conclusions: Despite the insufficient evidence in the literature, IV steroid treatment is still a viable option in ALRP treatment, with pain relief allowing discharge in 70% of patients and a low complication rate. Our study found daily 24 mg IV dexamethasone for ALRP to be an effective treatment and helpful in most patients admitted. This study supports the common practice used by spine units.

Three-Year Outcomes of a Schlemm Canal Microstent (Hydrus Microstent) with Concomitant Phacoemulsification in Open-Angle Glaucoma

HORIZON trials have reported the medium- and long-term outcomes of the Hydrus microstent. However, outside of randomized clinical trials, outcomes beyond 24 months have not been previously reported. Here, we examine the 3-year outcomes of the Hydrus microstent with cataract surgery outside of a randomized clinical trial setting. Single-surgeon consecutive case series. Glaucomatous eyes that underwent implantation of a Hydrus microstent with concomitant cataract surgery at a single ophthalmology center in Montreal, Canada. Success was defined according to the absence of specific failure criteria: (A) glaucoma reoperation; (B) selective laser trabeculoplasty; (C) intraocular pressure (IOP) < 5 mmHg, > 18 mmHg, or increase in the number of antiglaucoma medications (AGMs) used (after the first postoperative month), or loss of light perception due to glaucoma; (D) aggregation of criteria A-C. Predictors of treatment failure and postoperative changes in IOP and AGM use were assessed. Safety included best-corrected visual acuity (BCVA), cup-to-disc ratio (CDR), retinal nerve fiber layer (RNFL) thickness, ganglion cell inner plexiform layer (GC-IPL) thickness, visual field mean deviation (VF-MD) and pattern standard deviation (VF-PSD), and adverse events. Surgical success, predictors of treatment failure, postoperative changes in IOP and AGM use, and structural and functional markers of disease stability. One hundred six eyes were included. The 3-year surgical success according to Criteria A to D was 86%, 83%, 91%, and 67%, respectively. Intraocular pressure decreased by 26.5% from 18.9 ± 4.8 to 13.9 ± 2.3 mmHg (P < 0.001) and AGM use reduced by 33% from 3.0 ± 1.2 to 2.0 ± 1.2 medications (P < 0.001). The postoperative improvement in BCVA was preserved (P < 0.001). The structural and functional markers of disease stability, including CDR, RNFL, and GC-IPL thickness, as well as VF-MD and VF-PSD, remained stable (P > 0.05). Postoperative adverse events were few and transient. The 36-month results from this study show that the Hydrus microstent with phacoemulsification is safe and effective in reducing the IOP and AGM among patients with mild to severe open-angle glaucoma and can slow down the disease progression by preserving both structural and functional parameters. Proprietary or commercial disclosure may be found after the references.

High Accuracy Indicators of Androgen Suppression Therapy Failure for Prostate Cancer-A Modeling Study.

Simple SummaryHormonal therapy for prostate cancer is often applied past the point of resistance, hence losing any future clinical value to the evolution of resistant strains. If the undesirable outcome of the treatment is forewarned, then clinicians can have an opportunity to adjust the treatment, which can result in better management of the cancer. Using a mechanistic mathematical model, we introduce two methods to enhance the accuracy of classical biomarkers for hormonal therapy failure. Our results show the value in measuring both prostate-specific antigen and androgen during hormonal treatment, which can potentially allow for better management of prostate cancer.Prostate cancer is a serious public health concern in the United States. The primary obstacle to effective long-term management for prostate cancer patients is the eventual development of treatment resistance. Due to the uniquely chaotic nature of the neoplastic genome, it is difficult to determine the evolution of tumor composition over the course of treatment. Hence, a drug is often applied continuously past the point of effectiveness, thereby losing any potential treatment combination with that drug permanently to resistance. If a clinician is aware of the timing of resistance to a particular drug, then they may have a crucial opportunity to adjust the treatment to retain the drug’s usefulness in a potential treatment combination or strategy. In this study, we investigate new methods of predicting treatment failure due to treatment resistance using a novel mechanistic model built on an evolutionary interpretation of Droop cell quota theory. We analyze our proposed methods using patient PSA and androgen data from a clinical trial of intermittent treatment with androgen deprivation therapy. Our results produce two indicators of treatment failure. The first indicator, proposed from the evolutionary nature of the cancer population, is calculated using our mathematical model with a predictive accuracy of 87.3% (sensitivity: 96.1%, specificity: 65%). The second indicator, conjectured from the implication of the first indicator, is calculated directly from serum androgen and PSA data with a predictive accuracy of 88.7% (sensitivity: 90.2%, specificity: 85%). Our results demonstrate the potential and feasibility of using an evolutionary tumor dynamics model in combination with the appropriate data to aid in the adaptive management of prostate cancer.

Predictors of Treatment Failure in Patients With Pyogenic Brain Abscess

BackgroundPyogenic brain abscess poses a significant management challenge to clinicians, hence early diagnosis and interventions are critical. Our objective was to assess predictors of failure of therapy among patients with pyogenic brain abscesses according to surgical versus medical treatment.MethodsRetrospectively reviewed adults with pyogenic brain abscesses at our institution between 2009 and 2020. Treatment was classified as early surgical intervention and no early surgical treatment (medical therapy). Propensity score (PS) adjustment and multivariable regression were used to assess risk of treatment failure from surgical intervention and baseline covariates.ResultsA total of 224 patients had pyogenic brain abscess, of whom 106 (47.3%) had early surgical treatment and 118 (52.7%) had medical treatment only. Significant predictors of surgical (vs. medical) treatment included essential hypertension (odds ratio [OR] 95% confidence interval [95% CI] = 2.06 [1.01–4.18]), abscesses number (single vs. multiple, OR [95% CI] =4.81 [1.64–14.08]), midline shift (OR [95% CI] = 3.09 [1.22–7.82]). At 6 months, treatment failure cumulative incidence was 27.1% in the medical group (n = 31) and 21.3% in early surgical group (n = 22). PS-adjusted analysis showed beneficial effect of early surgical treatment (hazard ratio [HR] [95% CI] = 0.55 [0.31–0.98]). Multivariable regression showed similar but statistically nonsignificant estimate of surgical benefit (HR [95% CI] =0.59 [0.34–1.01]; P = 0.056), and significant associations of Charlson Comorbidity Index (CCI) (P = 0.019) and pre-existing central nervous system hardware (P = 0.034) with increased risk of treatment failure.ConclusionsHigher CCI and pre-existing CNS hardware were significant risk factors associated with treatment failure. In propensity-adjusted analysis, early surgery was associated with a 45% reduction in risk of 6-month treatment failure.

Continuous Positive Airway Pressure in Elderly Patients with Severe COVID-19 Related Respiratory Failure.

The elderly population represents a high percentage of patients hospitalized for COVID-19 pneumonia and severe respiratory failure, for whom CPAP may be a treatment option. The aim of this study was to describe the CPAP support modalities and to explore factors associated with CPAP failure. In this retrospective study, 110 consecutive patients aged ≥ 75 years were enrolled. Median frailty score, baseline partial arterial pressure of oxygen to fraction of inspired oxygen ratio (P/F), and respiratory rate (RR) were 5, 108, and 30 cycles/min, respectively. Of the 110 patients that began CPAP treatment, 17 patients died within 72 h from baseline, while in 2 patients, CPAP was withdrawn for clinical improvement. Thus, of the 91 patients still on CPAP at day 3, 67% of them needed continuous CPAP delivery. Patients with RR ≥ 30 and with frailty score ≥ 5 had an odds ratio of continuous CPAP needing of 3 and 4, respectively. Patients unable to tolerate CPAP-free periods demonstrated higher mortality risk as compared to those able to tolerate intermittent CPAP (OR: 6.04, 95% CI 2.38–16.46, p < 0.001). The overall in-hospital mortality was 63.6%. Delirium occurred in 59.1%, with a mortality rate in this subgroup of 83.1%. In a time-varying Cox model, the hazard ratio of death was 2.9 in patients with baseline RR ≥ 30 cycle/min, 2.4 in those with baseline P/F < 100. In the same model, the hazard ratio of death was 20 in patients with delirium and a frailty score < 5 and 8.8 in those without delirium and with frailty ≥ 5, indicating a competitive effect between these two variables on the death risk. Conclusions: Respiratory impairment, frailty, and delirium predict treatment failure, with the latter two factors demonstrating a competitive effect on mortality risk. CPAP support may represent a feasible therapeutic option in elderly patients, although chances of a therapeutic benefit are markedly reduced in case of severe respiratory impairment, very frail baseline condition or delirium occurrence.

Effect of Condom Use after CIN Treatment on Cervical HPV Biomarkers Positivity: Prolonged Follow Up Study.

Simple SummaryThe definite effects of consistent condom use following cervical local excisional procedures on preventing recurrent preinvasive disease as well as in biomarkers of HPV expression have not been studied so far. We embarked on a prospective observational study enrolling over 200 individuals who received strong advice for consistent condom use after undergoing local surgical CIN treatment. We assessed in the mid and long term (six and twenty-four-month post-op intervals, respectively) rates of CIN recurrence and the expression of HPV dependent and other biomarkers (HPV DNA, HPV mRNA E6 & E7, p16) in correlation with consistency of use. A favorable effect of routine condom use in rates of CIN relapse and biomarker expression was evident at the 6-month follow up; this was more pronounced at the 2-year assessment. In conclusion, consistent condom use following cervical local excisional treatment might influence favorably rates of CIN recurrence and biomarkers of HPV expression.Background: Several factors contribute in the cervical healing process following local surgical treatment; in a previous work our group has documented a beneficial mid-term role of regular condom use immediately postoperatively in terms of CIN relapse prevention and expression of active viral biomarkers. Materials and Methods: Aiming to investigate whether the favorable contribution of consistent condom use could be extrapolated in the longer term, we conducted a prospective single center observational study including women scheduled to undergo conservative excisional treatment for CIN (LLETZ procedure). In all women a strong recommendation for consistent use for the first 6 months was given. For 204 women who underwent the procedure and completed successfully the two-year follow up a complete dataset of HPV biomarkers’ results obtained six months and two years postoperatively was available. Patients were asked to complete a questionnaire to assess condom use compliance. A 90% compliance rate represented the threshold for consistent use. An LBC sample was obtained and tested for HPV genotyping, E6 & E7 mRNA by NASBA technique as well as flow cytometry, and p16 at 0 (pre-treatment), 6 and 24 months. HPV DNA and other related biomarkers status at 6 and 24 months, treatment failures at 24 months and condom use compliance rates represented study outcomes. Results: Six months post-operatively we documented a reduction in the rates of HPV DNA positivity, which was detected in only 23.2% of compliant condom users in comparison to 61.9% in the non-compliant group (p < 0.001, OR: 0.19, 95%CI: 0.1–0.36). For the HPV mRNA test, either assessed with the NASBA method or with flow cytometry, reduced positivity percentages were observed in the compliant group, in particular 1.6% vs. 8% for NASBA and 7.1% vs. 16.4% using flow cytometry, although these differences were not statistically significant (p = 0.1039 and 0.0791, respectively). Finally, reduced p16 positivity rates were documented in the compliant group. At the two year follow up, a more pronounced difference in HPV DNA positivity rates was observed, specifically only 13% positivity among the compliant women compared with 71% of the non-compliant (p < 0.0001); this illustrates a further decreasing trend compared with the 6th month in the compliant group as opposed to an increasing tendency in the non-compliant group, respectively (difference: 9.0%, 95% CI: 0% to 20.6%, p = 0.1523). At that time, 80% of the failed treatments were HPV mRNA positive compared to 10% positivity for the cases treated successfully (OR: 34, 95%CI: 6.8–173, p < 0.0001), a finding indicative that HPV mRNA E6 & E7 positivity accurately predicts treatment failure; p16 positivity was also observed at higher rates in cases with treatment failure. Conclusions: Consistent condom use following conservative excisional CIN treatment appears to significantly reduce rates of CIN recurrence and biomarkers of HPV expression. Additional HPV vaccination at the time of treatment could further enhance the positive effect of consistent condom use.

Genomics of Staphylococcus aureus and Staphylococcus epidermidis from Periprosthetic Joint Infections and Correlation to Clinical Outcome.

ABSTRACTThe approach of sequencing or genotyping to characterize the pathogenic potential of staphylococci from orthopedic device-related infection (ODRI) has been applied in recent studies. These studies described the genomic carriage of virulence in clinical strains and compared it with those in commensal strains. Only a few studies have directly correlated genomic profiles to patient outcome and phenotypic virulence properties in periprosthetic joint infections (PJIs). We investigated the association between genomic variations and virulence-associated phenotypes (biofilm-forming ability and antimicrobial resistance) in 111 staphylococcal strains isolated from patients with PJI and the infection outcome (resolved/unresolved). The presence of a strong biofilm phenotype in Staphylococcus aureus and an antibiotic-resistant phenotype in Staphylococcus epidermidis were both associated with treatment failure of PJI. In S. epidermidis, multidrug resistance (MDR) and resistance to rifampicin were associated with unresolved infection. Sequence type 45 (ST45) and ST2 were particularly enriched in S. aureus and S. epidermidis, respectively. S. epidermidis ST2 caused the majority of relapses and was associated with MDR and strong biofilm production, whereas ST215 correlated with MDR and non/weak biofilm production. S. aureus agr II correlated with resolved infection, while S. epidermidis agr I was associated with strong biofilm production and agr III with non/weak production. Collectively, our results highlight the importance of careful genomic and phenotypic characterization to anticipate the probability of the strain causing treatment failure in PJI. Due to the high rate of resistant S. epidermidis strains identified, this study provides evidence that the current recommended treatment of rifampicin and a fluoroquinolone should not be administered without knowledge of the resistance pattern.IMPORTANCE This study addresses the presence and frequency of particular genetic variants and virulence factors found in staphylococcal bacteria causing periprosthetic joint infection (PJI) of the hip and knee to ascertain their clinical relevance as predictors of treatment failure. We characterized the genetic virulence traits of a large collection of clinical staphylococci isolated from patients with PJI and evaluated their association with the patient’s infection outcome. The results showed that S. aureus strains that produced strong biofilms and S. epidermidis strains with resistance to several antibiotics associated significantly with unresolved infection. Some particular genetic variants associated with biofilm formation and multidrug resistance. These traits should be considered important risk factors for the diagnosis and treatment guidance in PJI.

Microbiology and antibiotics after second-stage revision of periprosthetic joint infections: A two-year follow-up cohort

BackgroundOptimal duration of antimicrobial regimen after reimplantation of two-stage procedures for periprosthetic joint infection (PJI) is poorly standardized. The aim of this study was to assess the characteristics of reimplantation microbiology with 6 weeks (2nd stage positive culture) or 10 days (2nd stage negative culture) of antibiotics in patients with complex chronic PJI and factors associated with microbiology at reimplantation. Patients and methodsWe performed a retrospective single-center study including all consecutive complex PJI recipients managed by two-stage surgery in a referral centre, from 2015 to 2018. Outcome was assessed at a minimum 2-year follow-up. Logistic regression analysis was performed to assess predictors of reimplantation microbiology. ResultsFifty patients (median age 69 [62–77] years) were included. PJI predominantly involved the hip (48%). The most common microorganisms were Staphylococcus aureus (36%), and coagulase-negative staphylococci (24%). At the second stage, reimplantation microbiology was positive for 10 patients (20%). Documentation was obtained within 48hours. With median follow-up of 41 [30–50] months after reimplantation, treatment failure occurred in 4 patients (8%). Using log-rank to compare Kaplan–Meier survival curves, no difference in the probability of treatment failure was found according to reimplantation microbiology (P=0.34). After adjustment, relapse was not associated with positive reimplantation microbiology (P=0.53). ConclusionsIn this work, positive microbiology at reimplantation did not predict treatment failure. Rapid growth at post-reimplantation suggests that antibiotic use should not exceed 10 days when cultures are negative. Additional studies are needed to determine the optimal duration of antibiotic therapy in case of negative microbiology.

Leukocyte subtyping predicts for treatment failure and poor survival in anal squamous cell carcinoma

BackgroundAnal squamous cell carcinoma (SCC) generally carries a favorable prognosis, as most tumors are highly sensitive to standard of care chemoradiation. However, outcomes are poor for the 20–30% of patients who are refractory to this approach, and many will require additional invasive procedures with no guarantee of disease resolution.MethodsTo identify the patients who are unlikely to respond to the current standard of care chemoradiation protocol, we explored a variety of objective clinical findings as a potential predictor of treatment failure and/or mortality in a single center retrospective study of 42 patients with anal SCC.ResultsPatients with an increase in total peripheral white blood cells (WBC) and/or neutrophils (ANC) had comparatively poor clinical outcomes, with increased rates of death and treatment failure, respectively. Using pre-treatment biopsies from 27 patients, tumors with an inflamed, neutrophil dominant stroma also had poor therapeutic responses, as well as reduced overall and disease-specific survival. Following chemoradiation, we observed uniform reductions in nearly all peripheral blood leukocyte subtypes, and no association between peripheral white blood cells and/or neutrophils and clinical outcomes. Additionally, post-treatment biopsies were available from 13 patients. In post-treatment specimens, patients with an inflamed tumor stroma now demonstrated improved overall and disease-specific survival, particularly those with robust T-cell infiltration.ConclusionsCombined, these results suggest that routinely performed leukocyte subtyping may have utility in risk stratifying patients for treatment failure in anal SCC. Specifically, pre-treatment patients with a high WBC, ANC, and/or a neutrophil-dense tumor stroma may be less likely to achieve complete response using the standard of care chemoradiation regimen, and may benefit from the addition of a subsequent line of therapy.

Gut microbiota differs between treatment outcomes early after fecal microbiota transplantation against recurrent Clostridioides difficile infection

Abstarct In fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (CDI), clinical outcomes are usually determined after 8 weeks. We hypothesized that the intestinal microbiota changes earlier than this timepoint, and analyzed fecal samples obtained 1 week after treatment from 64 patients diagnosed with recurrent CDI and included in a randomized clinical trial, where the infection was treated with either vancomycin-preceded FMT (N = 24), vancomycin (N = 16) or fidaxomicin (N = 24). In comparison with non-responders, patients with sustained resolution after FMT had increased microbial alpha diversity, enrichment of Ruminococcaceae and Lachnospiraceae, depletion of Enterobacteriaceae, more pronounced donor microbiota engraftment, and resolution of gut microbiota dysbiosis. We found that a constructed index, based on markers for the identified genera Escherichia and Blautia, successfully predicted clinical outcomes at Week 8, which exemplifies a way to utilize clinically feasible methods to predict treatment failure. Microbiota changes were restricted to patients who received FMT rather than antibiotic monotherapy, indicating that FMT confers treatment response in a different way than antibiotics. We suggest that early identification of microbial community structures after FMT is of clinical value to predict response to the treatment.

Clinical trial: seven-day vonoprazan- versus 14-day proton pump inhibitor-based triple therapy for first-line Helicobacter pylori eradication.

One-week triple therapy with vonoprazan is endorsed by Japanese guidelines as an alternative to proton pump inhibitor (PPI)-based triple therapy for first-line Helicobacter pylori eradication. This contrasts with Western guidelines recommending 2-week PPI-based triple therapy. To verify the non-inferiority of 1-week vonoprazan-based triple therapy versus 2-week PPI-based triple therapy as first-line H. pylori eradication in a multiracial Asian cohort. Randomised controlled trial of treatment-naïve patients with H. pylori infection assigned 1:1 to either 7 days amoxicillin 1g + clarithromycin 500 mg + vonoprazan 20 mg twice per day or 14 days amoxicillin 1g + clarithromycin 500 mg + omeprazole OR esomeprazole OR rabeprazole 20 mg twice/day. Subjects were randomly assigned to each PPI 1:1:1 Demographics, H. pylori resistance, CYP 2C19 genotype, eradication success and safety profiles were compared between groups. Between June 2019 and June 2021, 252 of 1097 subjects screened were randomised. 244 (age [SD] 51.7 [14.6]) received vonoprazan- (n= 119) or PPI-based (n= 125) triple therapy. Eradication rates by intention-to-treat analysis were 87.4% (vonoprazan-based triple therapy) versus 88.0% (PPI-based triple therapy. By per protocol analysis: 96.3% (vonoprazan-based triple therapy) versus 94.0% (PPI-based triple therapy). Clarithromycin resistance predicted treatment failure on multivariate analysis: RR 11.4; 95% CI [1.4-96.3], p= 0.025. No significant differences in CYP 2C19 genotypes or adverse events occurred between groups. One-week vonoprazan-based triple therapy achieved comparable efficacy to 2-week PPI-based triple therapy and was well tolerated.

Treatment failure, death, and predictors among PLWHIV on second-line antiretroviral therapy in Dessie Comprehensive Specialized Hospital, northeast Ethiopia: A retrospective cohort study.

BackgroundThe proportion of HIV patients on second-line antiretroviral therapy is becoming a growing public health concern, especially in a low-income country setting. However, unlike first-line therapy, to date, very little is known about the outcomes of second-line therapy in the Ethiopia context. Thus, this study was conducted to determine the rate of treatment failure, death, and their predictors among HIV patients receiving second-line therapy.MethodsA retrospective cohort study was conducted on 642 people living with HIV in Dessie Comprehensive Specialized Hospital from October 2016 to November 2019. Poisson and competitive risk survival models were computed to explore predictors of treatment failure and death, respectively.ResultsDuring follow-up period, 39 (6.87%, 95% CI: 5–9.2%) of 568 patients had second-line treatment failure with 4.07 per 100 person-year rate of failure. Being on anti-TB treatment [Rate ratio, RR = 2.57 (95% CI: 1.25–5.25)], not having optimal medication adherence [RR = 2.29 (95% CI: 1.09–4.78)], and not timely switched [RR = 5.89 (95% CI: 1.36–25.54)] were positively associated with treatment failure. Similarly, 44 (6.85%, 95% CI: 5–9%) of 642 patients died with 4.5 per 100 person-year rate of death. Being on advanced clinical condition [Sub distribution Hazard ratio, SHR = 2.49 (95% CI: 1.31–4.74)], not having optimal medication adherence [SHR = 2.65 (95% CI: 1.31–4.74)], lower CD4 cell counts, and high viral load measurement were positively associated with death.ConclusionsA significant number of patients had failed to respond to second-line therapy. A large number of patients had also died. Patient medical profile and monitoring practice were associated with treatment failure and death. Hence, patient-centered monitoring and interventions should be strengthened, besides treatment switch.

Predictive Modeling of Survival and Toxicity in Patients With Hepatocellular Carcinoma After Radiotherapy.

To stratify patients and aid clinical decision making, we developed machine learning models to predict treatment failure and radiation-induced toxicities after radiotherapy (RT) in patients with hepatocellular carcinoma across institutions. The models were developed using linear and nonlinear algorithms, predicting survival, nonlocal failure, radiation-induced liver disease, and lymphopenia from baseline patient and treatment parameters. The models were trained on 207 patients from Massachusetts General Hospital. Performance was quantified using Harrell's c-index, area under the curve (AUC), and accuracy in high-risk populations. Models' structures were optimized in a nested cross-validation approach to prevent overfitting. A study analysis plan was registered before external validation using 143 patients from MD Anderson Cancer Center. Clinical utility was assessed using net-benefit analysis. The survival model stratified high-risk versus low-risk patients well in the external validation cohort (c-index = 0.75), better than existing risk scores. Predictions of 1-year survival and nonlocal failure were excellent (external AUC = 0.74 and 0.80, respectively), especially in the high-risk group (accuracy > 90%). Cause-of-death analysis showed differential modes of treatment failure in these cohorts and indicated that these models could be used to stratify RT patients for liver-sparing treatment regimen or combination approaches with systemic agents. Predictions of liver disease and lymphopenia were good but less robust (external AUC = 0.68 and 0.7, respectively), suggesting the need for more comprehensive consideration of dosimetry and better predictive biomarkers. The liver disease model showed excellent accuracy in the high-risk group (92%) and revealed possible interactions of platelet count with initial liver function. Machine learning approaches can provide reliable outcome predictions in patients with hepatocellular carcinoma after RT in diverse cohorts across institutions. The excellent performance, particularly in high-risk patients, suggests novel strategies for patient stratification and treatment selection.

MP45-17 CORRELATION BETWEEN CTC COUNTS AND RADIOMIC METRICS FROM MULTIPLE OSSEOUS METASTATIC LESIONS IN METASTATIC PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022MP45-17 CORRELATION BETWEEN CTC COUNTS AND RADIOMIC METRICS FROM MULTIPLE OSSEOUS METASTATIC LESIONS IN METASTATIC PROSTATE CANCER Bino Varghese, Steven Cen, Gareth Morrison, Jonathan Buckley, Dejerianne Ostrow, David Quinn, Timothy Triche, Amir Goldkorn, and Vinay Duddalwar Bino VargheseBino Varghese More articles by this author , Steven CenSteven Cen More articles by this author , Gareth MorrisonGareth Morrison More articles by this author , Jonathan BuckleyJonathan Buckley More articles by this author , Dejerianne OstrowDejerianne Ostrow More articles by this author , David QuinnDavid Quinn More articles by this author , Timothy TricheTimothy Triche More articles by this author , Amir GoldkornAmir Goldkorn More articles by this author , and Vinay DuddalwarVinay Duddalwar More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002611.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Identify CT radiomic correlates for liquid biopsy metrics such as circulating tumor cells (CTC) counts in patients with metastatic prostate cancer (PC). Together, CT radiomics and liquid biopsy could detect clonal heterogeneity and aid in improved patient management. METHODS: Under IRB-approved informed consent, blood was collected from 22 patients with metastatic castrate resistant PC (mCRPC). CTC counts were enumerated using CellSearch platforms. Five osseous metastatic lesions were manually segmented from CT scans in the same patients using ITK-SNAP by an experienced radiologist. Cancer imaging phenomics toolkit (CaPTk) was used for radiomics analysis. A panel of 6 metrics representing first-order statistical measures: Intensity and second-order statistical measures: Greylevel cooccurrence matrix (GLCM) were calculated from each segmented lesion per patient. Mixed model correlation was used to examine correlation between weighted average of radiomic features from the five bone lesions per patient and their CTC counts. Benjamini-Hochberg Procedure was used to control false discovery rate from multiple comparisons. RESULTS: The distribution of CTC counts was 102±198 (min: 0, max: 692). Among the 69 texture features extracted from the bone lesions, the weighted average of Intensity-based inter-quartile-range and GLCM-based kurtosis, variance and standard-deviation extracted from the 5 bone lesions per patient showed statistically significant correlation with CellSearch enumerated CTC counts ranged between 0.71 to 0.79 with adjusted p-value < 0.01). Radiomics and liquid biopsy have theoretically comparable advantages: they are both noninvasive, can be quantified and followed serially to evaluate disease progression. While their exact role in clinical practice is yet to be established, we conducted a preliminary integrative assessment of the two, within a small cohort. We show that the weighted average of select radiomic metrics extracted from multiple bone lesions (N=5) provide strong correlates for CTC counts. CONCLUSIONS: Post validation in larger cohorts, radiomic corelates of liquid biopsy parameters such as CTC counts may provide surrogates for assessment of the likelihood of recurrence and metastasis in PC. With the widespread applicability of artificial intelligence in healthcare, diverse information about tumor behavior based on its genotype and phenotype decoded via imaging, may predict treatment failures earlier than with conventional methods. Source of Funding: NCI: 1R01CA257610-01 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e769 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bino Varghese More articles by this author Steven Cen More articles by this author Gareth Morrison More articles by this author Jonathan Buckley More articles by this author Dejerianne Ostrow More articles by this author David Quinn More articles by this author Timothy Triche More articles by this author Amir Goldkorn More articles by this author Vinay Duddalwar More articles by this author Expand All Advertisement PDF DownloadLoading ...

Development and validation of a prediction model for treatment failure in peritoneal dialysis-associated peritonitis patients: a multicenter study

To develop and validate a risk prediction model of treatment failure in patients with peritoneal dialysis-associated peritonitis (PDAP). We retrospectively analyzed the data of patients undergoing peritoneal dialysis (PD) in 3 dialysis centers in Jilin Province who developed PDAP between January 1, 2013 and December 31, 2019. The data collected from the Second Hospital of Jilin University and Second Division of First Hospital of Jilin University) were used as the training dataset and those from Jilin Central Hospital as the validation dataset. We developed a nomogram for predicting treatment failure using a logistic regression model with backward elimination. The performance of the nomogram was assessed by analyzing the C-statistic and the calibration plots. We also plotted decision curves to evaluate the clinical efficacy of the nomogram. A total of 977 episodes of PDAP were included in the analysis (625 episodes in the training dataset and 352 episodes in the validation dataset). During follow-up, 78 treatment failures occurred in the training dataset and 35 in the validation dataset. A multivariable logistic regression prediction model was established, and the predictors in the final nomogram model included serum albumin, peritoneal dialysate white cell count on day 5, PD duration, and type of causative organisms. The nomogram showed a good performance in predicting treatment failure, with a C-statistic of 0.827 (95% CI: 0.784-0.871) in the training dataset and of 0.825 (95% CI: 0.743-0.908) in the validation dataset. The nomogram also performed well in calibration in both the training and validation datasets. The established nomogram has a good accuracy in estimating the risk of treatment failure in PDAP patients.

Baseline parameters and the prediction of treatment failure in patients with intravenous drug use-associated spinal epidural abscesses.

Despite the increasing incidence of spinal epidural abscess (SEA), the baseline parameters potentially predictive of treatment failure remain poorly characterized. In this study, the authors identify the relevant baseline parameters that predict multimodal treatment failure in patients with either intravenous drug use (IVDU)-associated SEA or non-IVDU-associated SEA. The authors reviewed the electronic medical records of a large institutional series of consecutive patients with diagnosed SEA between January 2011 and December 2017 to characterize epidemiological trends as well as the complement of baseline measures that are predictive of failure after multimodal treatment in patients with and without concomitant IVDU. The independent impact of clinical and imaging factors in detecting treatment failure was assessed by performing stepwise binary logistic regression analysis. A total of 324 consecutive patients with diagnosed SEA were identified. Overall, 226 patients (69.8%) had SEA related to other causes and 98 (30.2%) had a history of recent IVDU. While non-IVDU SEA admission rates remained constant, year-over-year admissions of patients with IVDU SEA nearly tripled. At baseline, patients with IVDU SEA were distinct in many respects including younger age, greater unemployment and disability, less frequent diabetes mellitus (DM), and more frequent methicillin-resistant Staphylococcus aureus infection. However, differences in length of stay, loss to follow-up, and treatment failure did not reach statistical significance between the groups. The authors constructed independent multivariate logistic regression models for treatment failure based on identified parameters in the two cohorts. For the non-IVDU cohort, the authors identified four variables as independent factors: DM, hepatitis B/C, osteomyelitis, and compression deformity severity. In contrast, for patients with IVDU, the authors identified three variables: albumin, endocarditis, and endplate destruction. Receiver operating characteristic and area under the curve (AUC) analyses were undertaken for the multivariate models predicting the likelihood of treatment failure in the two cohorts (AUC = 0.88 and 0.89, respectively), demonstrating that the derived models could adequately predict the risk of multimodal treatment failure. Treatment failure risk factor point scales were derived for the identified variables separately for both cohorts. Patients with IVDU SEA represent a unique population with a distinct set of baseline parameters that predict treatment failure. Identification of relevant prognosticating factors will allow for the design of tailored treatment and follow-up regimens.

Study to investigate the prevalence of human papillomavirus in Barrett’s oesophagus using a novel screening methodology

IntroductionHuman papillomavirus (HPV) is strongly associated with Barrett’s dysplasia and oesophageal cancer suggesting a role in carcinogenesis. HPV persistence predicts treatment failure after endotherapy for Barrett’s dysplasia. This pilot study...

Plasma secretome analyses identify IL-8 and nitrites as predictors of poor prognosis in nasopharyngeal carcinoma patients

Predicting tumor recurrence and death in patients with nasopharyngeal carcinoma (NPC) remains to date challenging. We here analyzed the plasmatic secretomes of NPC untreated and relapsing patients, and explored possible correlations with the clinical and pathological features and survival characteristics of the corresponding patient cohorts, with the aim of identifying novel prognostic biomarkers. This study included 27 controls, 45 untreated NPC and 11 relapsed patients. A set of 14 plasma cytokines were analyzed using Millipore multiplex assay. Nitrites were assessed by Griess method. A comparative analysis of each groups’ secretome showed upregulation of IL-8, IL-12p70, IL-10 and IP-10 in untreated patients, and of IL-6, IL-10, MCP-1 and IP-10 in relapsing patients. Nitrites significantly correlated with IL-8 during relapse. Secretomes’ network analyses revealed prevalence of high correlations between IL8/IL-17A and IFN-γ/IL12p70 in the control group, between TNF-α/IL-8/IL-6, TNF-α/VEGF/IFN-γ and IL-10/MCP-1 in the untreated group, and between IL-8/IL-6/IL-10, TNF-α/IL-8/IL-6, IL12-p70/VEGF/IL-10/IFN-γ, IL-6/IL-10/IFN-γ and IL-8/IP-10 in the relapse group. IL-12p70, IP-10 and MCP-1 levels respectively associated with gender, age and node metastasis respectively. Recurrence-free survival (RFS) analysis showed that patients presenting High IL-8/Low NO immunological scores presented a combined 80% probability of relapse/death after 53 months (combined log-rank test p = 0.0034; individual p = 0.012 and p = 0.016). Multivariate Cox hazard regression analysis revealed that IL-8 (HR = 7.451; 95% CI [2.398–23.152]; p = 0.001) and treatment type (HR = 0.232; 95% CI 0.072–0.749; p = 0.015) were independent prognostic factors. C&RT decision tree analysis showed that High IL-8/Low NO immunological scores predicted treatment failure in 50% cases starting the 36th month of follow-up (AUC = 1) for all of the studied cases and in 57% cases for patients receiving chemotherapy alone (AUC = 1). Altogether, our results showed that NPC development is accompanied with cytokines deregulation to form specific interaction networks at time of diagnosis and relapse, and demonstrate that High IL-8/Low NO signature may constitute a predictor of poor prognosis which may be useful to improve risk stratification and therapy failure management.