End Of Treatment In Patients Research Articles

Effect of emergent nephrostomy on long-term total and split renal function in patients with upper urinary tract obstruction due to pelvic malignant tumors

PurposeThis study aimed to investigate the impact of nephrostomies on the outcome of total renal function (TRF) and split renal function (SRF) in patients with malignant pelvic tumors associated with upper urinary tract obstruction (UUTO).MethodsPatients with pelvic tumors suffering severe unilateral hydronephrosis treated at our hospital from 2000 to 2022 were included. Data for nephrostomy placement, short- and long-term renal function, and radiological and nuclear imaging studies were collected. The TRF and SRF of patients who underwent nephrostomy were compared to those who did not.ResultsSeven patients were included (rhabdomyosarcoma: 5, ovarian germ cell tumor: 1, malignant rhabdoid tumor: 1). Nephrostomies were placed in four, which were successfully managed without severe infections. Estimated glomerular filtration rate (eGFR) was significantly improved at the end of treatment in patients with nephrostomy. In contrast, eGFR in patients who did not undergo nephrostomy was not improved. Nuclear imaging studies (renograms or renal scintigrams) revealed impaired SRF of the affected kidney compared to the contralateral kidney, even in patients whose eGFR was within normal levels. Notably, SRF showed a trend to improve over time in one patient treated with nephrostomy.ConclusionNephrostomy for UUTO caused by pelvic tumors may improve renal outcome.

Evaluation of the impact of a course of therapy with an injectable form of chondroitin sulfate on the duration of remission and quality of life in patients with osteoarthritis

Ensuring a long-lasting effect of the therapy and its safety are important tasks in the treatment of patients with osteoarthritis (OA). Parenteral forms of chondroitin sulfate (CS) used for the background therapy of OA are characterized by proven efficacy and safety and, compared to oral forms, have greater bioavailability, faster onset of symptom-modifying effect and maintenance of more stable remission, which can significantly improve patients' quality of life.Objective: to evaluate the clinical efficacy and safety of two-month therapy with injectable CS and the duration of positive dynamics after the end of treatment in patients with knee OA (KOA).Material and methods. The open prospective observational study involved 35 patients (mainly women) aged 50–75 years with stage II–III KOA. All patients were prescribed intramuscular therapy with a CS solution (Mucosat® solution), with the first three injections of 1 ml, followed by 2 ml every second day (25 injections in total). Standard indices and questionnaires were used to assess the main clinical indicators at baseline and over time (14, 30, 60 days, 5 and 8 months after the start of treatment), as well as the results of ultrasound examination of the knee at baseline and at the end of treatment.Results and discussion. 14 days after the start of therapy, a statistically significant decrease in pain was observed applying the visual analogue scale (VAS), and after 2 months, 94% of patients had a significant decrease in knee pain according to VAS, Lequesne index and WOMAC index (total score and components). The KOOS parameters and quality of life according to EQ-5D-3L improved significantly. There was no pain or only minor pain (VAS ≤40 mm) in 54% of patients. The number of patients who had to take nonsteroidal anti-inflammatory drugs (NSAIDs) constantly fell threefold, while occasional use fell fivefold. The thickness of the synovial membrane of the knee joint and the number of patients with signs of synovitis decreased significantly. At 3 and 6 months after the end of therapy, most patients (60%) still had minor pain (≤40 mm according to VAS) and a significantly lower need for NSAIDs compared to baseline. The injectable CS was well tolerated and no adverse drug events were noted.Conclusion. We demonstrated both safety and efficacy and long-term maintenance of the clinical effect (6 months after the end of therapy) of injectable CS in the majority of OA patients, against the background of a low need for NSAIDs.

Significance of thyroperoxidase and thyroglobulin antibodies in medically treated Graves' disease.

Thyroperoxidase (TPOAb) and thyroglobulin (TgAb) antibodies are highly prevalent in Graves' disease (GD), but their significance is controversial. We retrospectively analyzed TPOAb and TgAb levels and evolution in 136 patients with newly diagnosed GD between 2000 and 2022, treated with anti-thyroid drugs (ATD) in a block-and-replace (B+R) regimen for at least 12 months and followed up for at least 1 year after ATD discontinuation or until disease relapse. At diagnosis, 98 out of 136 (72%) patients were TPOAb positive and 73 out of 136 (54%) patients were TgAb positive. The presence of TPOAb or TgAb antibodies at diagnosis was generally not related to GD presentation and did not influence the risk of relapse (P = 0.304 and P = 0.348, respectively). There was less TED (thyroid eye disease) in TgAb-positive patients than TgAb-negative patients at diagnosis (11 out of 73 (15.1%) versus 21 out of 63 (33.3%) P = 0.012). In contrast, the presence of TPOAb at diagnosis was not associated with TED (P = 0.354). The absence of TgAb at diagnosis (P = 0.05) and time to euthyroidism (P = 0.009), but not smoking or TRAb levels, were associated with TED in multivariate logistic regression. TPOAb and TgAb levels during treatment and after its discontinuation were not predictive of relapse, except for lower titers of TgAb at 18 months in patients who relapsed (P = 0.034). In GD patients treated with a first course of ATD in a B+R regimen we observed lower titers of TgAb at the end of treatment in patients who relapsed and a significant protection against TED in patients with positive TgAb at diagnosis, irrespectively of TPOAb.

Mosunetuzumab Monotherapy Continues to Demonstrate Durable Responses in Patients with Relapsed and/or Refractory Follicular Lymphoma after ≥2 Prior Therapies: 3-Year Follow-up from a Pivotal Phase II Study

Background: Mosunetuzumab is a CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. In a pivotal Phase II study (NCT02500407), mosunetuzumab demonstrated a high complete response (CR) rate with a manageable safety profile in patients with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior lines of therapy (Budde et al. Lancet Oncol 2022). Mosunetuzumab is a fixed-duration treatment that can be administered in an outpatient setting. Here, we present updated data for patients with R/R FL and ≥2 prior lines of therapy, after 3 years of follow-up. Methods: Eligible patients with R/R FL Grade (Gr) 1-3a and ≥2 prior therapies received intravenous mosunetuzumab in 21-day cycles with step-up dosing in Cycle (C) 1 (C1 Day [D] 1, 1mg; C1D8, 2mg; C1D15/C2D1, 60mg; C3D1 and onwards, 30mg). Hospitalization for treatment was not required. Patients achieving a CR by C8 completed treatment without additional cycles; patients with a partial response or stable disease received a total of 17 cycles. The primary endpoint was CR rate as determined by an Independent Review Committee (as best response; Cheson 2007 criteria). Duration of response (DOR), duration of complete response (DOCR), progression-free survival (PFS), event-free survival (EFS), and safety were secondary endpoints. Time to next treatment (TTNT), response to retreatment, biomarkers of minimal residual disease (MRD), and circulating B-cell counts were exploratory endpoints. Results: Ninety patients with R/R FL were enrolled. As of May 2, 2023, median time on study was 37.4 (range: 2.0-48.0) months. Investigator-assessed best overall response and CR rates were 77.8% (95% CI: 67.8-85.9) and 60.0% (95% CI: 49.1-70.2), respectively. The median DOR was 35.9 months (95% CI: 20.7-not reached [NR]). Median DOCR was NR (95% CI: 33.0-NR); the estimated 30-month DOCR rate was 72.4% (95% CI: 59.2-85.6) ( Table). Three years after the end of treatment, 57.1% of 70 responding patients were alive and disease progression-free. Median PFS was 24.0 months (95% CI: 12.0-NR) ( Figure). The median TTNT was 37.3 months (95% CI: 18.0-NR); estimated EFS at 36 months was 51.8% (95% CI: 40.8-62.8). After initial mosunetuzumab treatment, 34/90 (37.8%) patients had received a new anti-lymphoma therapy, including 33/90 (36.7%) patients who received a new systemic treatment (8/33 [24.2%] of these patients received chimeric antigen receptor T-cell therapy); 8/90 (8.9%) had radiotherapy; 2/90 (2.2%) had excision of tumor; 2/90 (2.2%) had an allogeneic stem cell transplant; and 1/90 (1.1%) had an autologous stem cell transplant. Five patients received retreatment with mosunetuzumab, 3/5 of these patients had a CR. No new cytokine release syndrome (CRS) events, serious, or Gr ≥3 adverse events (AEs) were reported since the previous analysis (median follow-up of 28.3 months; Bartlett et al. ASH 2022). CRS events occurred in 44.4% of patients and 2.2% were Gr 3/4 in severity; all CRS events resolved. Overall AEs and serious AEs were comparable to the previous analysis (Bartlett et al. ASH 2022); febrile neutropenia was not reported. Forty-six (51.1%) patients experienced Gr 3/4 AEs related to mosunetuzumab; the rate of AEs leading to discontinuation was low (4.4%). Peripheral blood B-cell depletion following treatment with mosunetuzumab occurred in all patients, and recovery was observed after a median of 18 months following the end of treatment in patients with a sustained response using follow-up samples. MRD kinetics following mosunetuzumab therapy will be presented. Conclusions: In this updated analysis, with a median follow-up of 37.4 months, durable responses continued to be observed with fixed-duration mosunetuzumab in patients with R/R FL. The manageable safety profile was consistent with previous reports. Evidence of B-cell recovery was observed after a median of 18 months following the end of treatment.

Stereotactic Body Radiation Therapy and High-Dose Rate Brachytherapy Boost in Combination with Intensity Modulated Radiation Therapy for Localized Prostate Cancer: A Single-Institution Cohort Study

The use of dose-escalated external beam radiation (EBRT) and brachytherapy (BT) boost with ADT has emerged as an option with superior biochemical control compared to dose-escalated EBRT alone. BT is traditionally delivered using low-dose rate techniques, but more recently high-dose rate (HDR) BT has also emerged as a boost option for these patients with promise of low toxicity rates. SBRT is a favorable modality for monotherapy for low and intermediate risk group patients, however its safety and efficacy as a boost in combination with EBRT is less well understood. The aim of this study is to compare SBRT boost, HDR boost and LDR boost for localized prostate cancer. A single-institution retrospective chart review was performed of men receiving EBRT delivered using intensity modulated RT and either SBRT boost (650cGy x 3), HDR-BT boost (1500cGy x 1), or LDR boost with I-125 (110Gy). Of patients treated w/ SBRT boost, 39 (80%) were treated with an SIB to the MRI-detectable lesion(s) to 700cGy x 3. Treatment characteristics for each strategy were reviewed and on-treatment toxicity outcomes for each of the cohorts were compared using Chi-square tests. From 2017-2022, 49 patients were treated with EBRT+SBRT boost, 44 patients received EBRT+ HDR-BT boost, and 46 patients received EBRT+ LDR-BT boost. The average age of patients included in the study was 71.2 years (median age 69.55 years, range 51.42-83.70 years) with average baseline PSA of 11 (median 7.6, range 3.3-64). In addition, 55% of the patients had high-risk/very high-risk disease, 39% had unfavorable intermediate disease and 6% had favorable intermediate disease. 139 patients received androgen deprivation therapy (93%). There were no differences in these baseline demographics and clinical or treatment factors between SBRT, HDR and LDR boost (p>0.05). The median dose/fx of EBRT was 4500cGy/25 fx (range 4500-5040cGy/23-28 fractions). At the end of treatment, 69% of the patients had 0-1 change in nocturia. There is an increase in nocturia episodes of 2-3 from baseline in 27% of the patients, while 4% had an increase in nocturia episodes of 4 or more from baseline with no difference between the SBRT, HDR and LDR boost. At baseline 36 patients (26%) reported urinary frequency symptoms, increasing to 80 patients (58%) by end of treatment with no difference between the SBRT, HDR and LDR boost. Similarly, there was a trend to increased use of urinary modifiers at end of treatment in patients treated with EBRT+HDR boost compared to EBRT+SBRT and EBRT+ LDR boost (89% vs. 71% v 72% respectively). There was no significant difference in acute urinary toxicity and nocturia between SBRT, HDR and LDR boost (p>0.05).

SAT-393 - Early aminotransferase improvement in the phase 2b NATIVE study is predictive of response pattern of liver histology as well as hepatic and cardiometabolic health markers at the end of treatment in patients with non-cirrhotic NASH

SAT-393 - Early aminotransferase improvement in the phase 2b NATIVE study is predictive of response pattern of liver histology as well as hepatic and cardiometabolic health markers at the end of treatment in patients with non-cirrhotic NASH

Therapy outcome of day treatment for people with anorexia nervosa before and during the COVID-19 pandemic.

Objective: The current research aimed to compare clinical outcome measures of two National Eating Disorder (ED) Day Services at the Maudsley Hospital from before the COVID‐19 lockdown, when treatment was face to face, with after the lockdown when treatment moved online. Method: Clinical outcome measures collected as part of the admission and discharge process were compared from the beginning and end of treatment for patients treated either via face‐to‐face or online delivery. Twenty‐nine patients’ data were analyzed (89% of them female, 11% male, 89% from White ethnic backgrounds, 11% from BAME ethnic backgrounds and a mean age of 25.99 years). Additionally, the mean change in outcome measures was also compared between the two groups (pre‐lockdown face to face and during lockdown online). Results: Treatment delivered face to face led to significant improvements in body mass index (BMI) but not in Eating Disorder Examination Questionnaire (EDEQ) Global and Work and Social Adjustment Scale (WSAS) Total scores. In contrast, treatment delivered online led to significant improvements in EDEQ Global and WSAS Total scores but not in BMI. Neither one of the delivery modalities created significantly larger mean changes in any of the clinical outcome measures than the other. Conclusions: Both face‐to‐face and online delivery of eating disorder day treatment show some success. Suggested improvements for using online delivery of treatment include implementing additional support opportunities, adapting the online format to improve communication and commitment and using a hybrid model of specific face‐to‐face elements with some online treatment.

An Exploratory Analysis of the “Was It Worth It?” Questionnaire as a Novel Metric to Capture Patient Perceptions of Cancer Treatment

ObjectivesAsking “Was it worth it?” (WIWI) potentially captures the patient perception of a treatment’s benefit weighed against its harms. This exploratory analysis evaluates the WIWI questionnaire as a metric of patients’ perspectives on the worthwhileness of cancer treatment. MethodsA 3-item WIWI questionnaire was assessed at end of treatment in patients with cancer on the COMET-2 trial (NCT01522443). WIWI items were evaluated to determine their association with quality of life (QOL), treatment duration, end-of-treatment reason, patient-reported adverse events (AEs), and disease response. ResultsA total of 65 patients completed the questionnaire; 40 (62%), 16 (25%), and 9 (14%) patients replied yes, uncertain, and no to “Was it worthwhile for you to receive the cancer treatment given in this study?” (item 1), respectively; 39 (60%), 12 (18%), and 14 (22%) to “If you had to do it over again, would you choose to have this cancer treatment?”; and 40 (62%), 14 (22%), and 11 (17%) to “Would you recommend this cancer treatment to others?” Patients responding yes to item 1 remained on treatment longer than those responding uncertain or no (mean 23.0 vs 11.3 weeks, P<.001). Patients responding uncertain/no to item 1 discontinued treatment because of AEs more frequently than those responding yes (36% vs 7.5%, P=.004) and demonstrated meaningful decline in QOL from baseline (−2.5 vs −0.2 mean change, P<.001). Associations between WIWI responses and most patient-reported AEs or treatment efficacy did not reach statistical significance. ConclusionsPatients who responded affirmatively on WIWI items remained on therapy longer, were less likely to stop treatment because of AEs, and demonstrated superior QOL. The WIWI may inform clinical practice, oncology research, and value frameworks.

Brentuximab Vedotin in Combination with Nivolumab, Doxorubicin, and Dacarbazine in Newly Diagnosed Patients with Advanced Stage Hodgkin Lymphoma (SGN35-027, Trial in Progress)

Brentuximab Vedotin in Combination with Nivolumab, Doxorubicin, and Dacarbazine in Newly Diagnosed Patients with Advanced Stage Hodgkin Lymphoma (SGN35-027, Trial in Progress)

Impact of timely BCR-ABL1 monitoring before allogeneic stem cell transplantation among patients with BCR-ABL1-positive B-acute lymphoblastic leukemia.

BackgroundWith the emergence of tyrosine kinase inhibitors and the incorporation of stringent measurable residual disease (MRD) monitoring, risk stratification for BCR-ABL1-positive acute lymphoblastic leukemia (ALL) patients has changed significantly. However, whether this monitoring can replace conventional risk factors in determining whether patients need allogeneic stem cell transplantation is still unclear. This study aimed to determine the impact of BCR-ABL1 monitoring on the outcome of patients with BCR-ABL1-positive ALL after allogeneic stem cell transplantation.MethodsWe retrospectively analyzed the survival outcome of patients with BCR-ABL1-positive ALL based on the quantification of BCR-ABL1 at 3 timepoints the end of induction (timepoint 1), post-consolidation week 16 (timepoint 2), and the end of treatment for patients who were either transplant-eligible or non-transplant eligible (timepoint 3).ResultsFrom 2006 to 2018, a total of 96 patients newly diagnosed with BCR-ABL1-positive ALL were treated with chemotherapy and tyrosine kinase inhibitors. Thirty-eight (41.3%) patients achieved complete remission, and 33 patients underwent allogeneic stem cell transplantation. Our data showed that pre-transplant MRD monitoring by real-time quantitative polymerase chain reaction had the highest correlation with survival in patients with BCR-ABL1-positive ALL, especially for those who underwent allogeneic stem cell transplantation.ConclusionPatients without MRD pre-transplantation had superior survival compared with those who had MRD, and they had excellent long-term outcomes after allogeneic stem cell transplantation.

Treatment of Chinese Patients with Hypertriglyceridemia with a Pharmaceutical-Grade Preparation of Highly Purified Omega-3 Polyunsaturated Fatty Acid Ethyl Esters: Main Results of a Randomized, Double-Blind, Controlled Trial

IntroductionThe lipid-modifying potential of omega-3 polyunsaturated fatty acids in Chinese patients is under-researched. We conducted a multicenter, randomized, placebo-controlled, double-blind, parallel-group study of twice-daily treatment with OMACOR (OM3EE), a prescription-only formulation of highly purified ethyl esters of omega-3 polyunsaturated fatty acids in Chinese adult patients (≥18 years) who had elevated baseline fasting serum triglycerides (TG).MethodsPatients were stratified according to the severity of their hypertriglyceridemia (severe HTG, with baseline TG ≥500 and <1000 mg/dL or moderate HTG, with baseline TG >200 and <500 mg/dL) or use of statins. Patients randomized to OM3EE therapy received 2 g/day for 4 weeks, then 4 g/day for 8 weeks. The primary efficacy endpoint was the percentage change in fasting serum TG between baseline and the end of treatment in patients with severe HTG. The study was concluded after a planned interim analysis demonstrated a significant TG-lowering effect of OM3EE in that contingent (p=0.0019).ResultsThe mean TG end-of-treatment effect of OM3EE was –29.46% (standard deviation 40.60%) in the severe HTG contingent compared with +0.26% (standard deviation 54.68%) in the placebo group. Corresponding changes were –12.12% and –23.25% in the moderate HTG and combination cohorts (vs +55.45% and +6.24% in relevant placebo groups). A dose-dependent reduction in TG was evident in all patient contingents. Safety and tolerability of OM3EE were in line with previous experience.DiscussionThese data indicate that OMACOR therapy at a dose of 2–4 g/day is an effective treatment for Chinese patients with raised TG levels and is well tolerated.

ABCL-334: Impact of COVID-19 Pandemic on Treatment Duration in Curable Cancers: Comparison of Patients with DLBCL Treated Before and During: A Retrospective Record-Based Study

ContextTreatment delays can compromise outcomes in aggressive hematological malignancies primarily treated with chemotherapy. Due to the burden of the COVID-19 pandemic on healthcare systems, there is a potential risk of delayed therapy of various diseases, including cancers. However, efforts were made in our center (despite being a COVID-19-designated hospital) to ensure that “curative-intent” treatment for cancers should not be affected, and hence, the diagnostic (pathology, imaging) and therapeutic services for hematological cancers were continued. In this study we analyzed the impact of the COVID-19 pandemic on diagnosis and treatment procedures and survival outcomes among patients with Diffuse Large B-Cell Lymphoma (DLBCL).ObjectiveTo compare treatment duration among patients with DLBCL during the COVID-19 period with those treated prior to the onset of the pandemic.DesignRetrospective record-based study.SettingRegional cancer center, JIPMER, India.Patients or Other ParticipantsThe medical records of treatment naïve DLBCL patients registered between January 2019 and December 2019 (Group 1; pre-pandemic) and January 2020 until December 2020 (Group 2: during pandemic) were accessed, and the following data were collected: baseline characteristics, time from diagnosis to treatment, time for completion of planned chemotherapy, and proportion of patients defaulting treatment.InterventionsNot applicable, as it is a retrospective record-based study.Main Outcome MeasuresPrimary endpoint was treatment duration during the COVID-19 period with those treated prior to the onset of the pandemic.ResultsA total of 67 patients were identified (Group 1: 46 (69%) Group 2: 21 (31%). The median age of patients registered in 2019 and 2020 were 50 (39–64) years and 44 (34–62) years, respectively. The duration between diagnosis to start of treatment for patients in 2019 and 2020 was 28 (13–43) days and 19 (11-40) days respectively. The duration between start of treatment to end of treatment for patients in 2019 and 2020 was 119 (107–137) days and 121 (101–145) days, respectively.ConclusionsThere was no significant difference in treatment duration among DLBCL patients during the COVID-19 pandemic. Treatment completion rates were similar.

Neuropathy severity at the time of oxaliplatin treatment alteration in patients with colon cancer (Alliance A151912).

Clinical guidelines recommend altering chemotherapy treatment by decreasing, delaying, or discontinuing dosing in patients who are experiencing chemotherapy-induced peripheral neuropathy. There are few data available on the clinical use of treatment alteration including the severity of CIPN at the time of treatment alteration. This was a retrospective analysis of patients receiving oxaliplatin on the NCCTG N08CB trial. Neuropathy severity was assessed at each cycle by clinicians and patients. Patients were classified as (1) completed treatment without alteration, (2) dose reduction or delay due to neuropathy, (3) discontinuation due to neuropathy, (4) discontinuation for other toxicity, or (5) discontinuation for another reason (5). Comparisons focused primarily on patients with alteration due to neuropathy (groups 2 and/or 3) compared with patients who completed treatment without alteration (group 1). In 350 participants, 135 (39%) completed treatment without alteration, 70 (20%) had a dose reduction or delay due to neuropathy, and 35 (10%) discontinued early due to neuropathy. Clinician-assessed neuropathy severity was greater in patients at the time of dose reduction or delay compared with severity at the end of treatment in patients without alteration (p < 0.0001). Patient-reported neuropathy severity at cycle 4 was worse in patients who eventually had a reduction or delay as compared with patients who completed treatment without alteration (p = 0.017). Treatment alterations due to neuropathy are common in patients receiving oxaliplatin for colon cancer and are associated with clinician-assessed neuropathy severity. Rapid increases in patient-reported neuropathy severity indicate a potential need for monitoring and intervention. Clinicaltrials.gov Identifier: NCT01099449 (NCCTG N08CB).

Effect of Direct-Acting Antiviral Therapy on Thrombocytopenic Patients with Hepatitis C Virus-Related Chronic Liver Disease.

Background and Aims Thrombocytopenia is a common complication in patients with chronic hepatitis C virus (HCV) that increases the risk of bleeding. We aimed to analyze the hematologic effects of the new direct-acting antiviral (DAA) therapy, particularly on the platelet count in chronic HCV-infected patients with thrombocytopenia. Patients and Methods. One hundred thrombocytopenic patients chronically infected with HCV were included in a prospective study. All patients were eligible for receiving anti-HCV treatment with sofosbuvir-based regimens for 12 weeks, according to the protocol of the National Program for treatment of HCV in Egypt sponsored by the Ministry of Health. Results At the end of treatment (EOT), there was a highly significant increase in platelet count (p < 0.001), a significant increase in white blood cells (WBCs) count (p ≤ 0.032), and a highly significant decrease in hemoglobin level (p < 0.001) as compared to pretreatment levels. Patients with mild to moderate hepatic fibrosis had significantly higher median and interquartile range (IQR) platelet count at baseline and EOT than those with advanced fibrosis and cirrhosis (p ≤ 0.023 and p < 0.001, respectively). There was more elevation in platelet count at EOT in patients with mild to moderate fibrosis than those with advanced fibrosis and cirrhosis. Out of the hundred patients, 73% showed improvement of platelet count, while 27% showed no improvement or even decrease in the platelet count. Conclusion Sofosbuvir-based DAA therapy is a highly effective and safe treatment regimen that results in the improvement of platelet count in thrombocytopenic patients, particularly in mild to moderate stages of hepatic fibrosis.

Direct acting antivirals are associated with more liver stiffness regression than pegylated interferon therapy in chronic hepatitis C patients

ABSTRACT Objectives Extent of post-treatment fibrosis change in patients with different stages of fibrosis not fully known. We aimed to study changes in liver fibrosis in chronic hepatitis C patients who were treated with pegylated interferon/ribavirin (PEG/RBV) or direct acting antivirals (DAAs). Methods Retrospective evaluation of results of transient elastography (TE) was done before and 1 year after end of treatment for patients treated with PEG/RBV (n = 268) and DAAs (n = 245). Results The average age was 45.54 ± 10.64 years; mainly males. All patients in the DAAs group achieved sustained virological response (SVR), unlike 56.3% of the patients in the PEG/RBV group. F3-F4 fibrosis was predominant in the PEG/RBV nonresponder patients (51.3%) and DAAs responders (57.1%). TE decreased 1 year after end of treatment (p = 0.001) in the viral responders of the PEG/RBV group (7.44 ± 4.02 vs. 10.24 ± 7.29 kPa) and DAAs group (12.12 ± 9.21 vs. 16.81 ± 12.84 kPa) respectively. The delta TE change in the DAAs responders was higher than the PEG/RBV responders (p = 0.001) and PEG/RBV nonresponders (p = 0.001). The percentage of patients with liver fibrosis regression was higher in DAAs responders (52.5%) than in PEG/RBV responders (23.3%). Conclusion Treatment with DAAs is associated with fibrosis improvement more than treatment with PEG/RBV in chronic hepatitis C patients.

The Economic Value of Improved Productivity from Treatment of Chronic Hepatitis C Virus Infection: A Retrospective Analysis of Earnings, Work Loss, and Health Insurance Data.

IntroductionPatients with chronic hepatitis C virus infection (HCV) may incur significant indirect costs due to health-related work loss. However, the impact of curative HCV therapy on work productivity is not well characterized. We estimated the economic value of improved productivity following HCV treatment.MethodsAdults diagnosed with HCV infection (Optum Healthcare Solutions data; Q1 1999 to Q1 2017) were stratified into two cohorts: (1) treated cohort, patients who received HCV therapy and (2) untreated cohort, therapy-naïve patients. For the treated cohort, the index date was set at the end of the post-treatment monitoring period, assumed to be 6 months after the end of treatment for patients with cirrhosis or for those treated with interferon-based therapy, and 3 months after the end of treatment for patients without cirrhosis who received interferon-free therapy. For the untreated cohort, an index date was randomly selected post-HCV diagnosis. Time from the index date to the first work-loss event was assessed using time to event analyses. An economic modeling approach was used to monetize the improved productivity from reduced risk of work-loss event in the 4 years post-index.ResultsPatients in the treated cohort had a lower risk of experiencing a work-loss event compared to untreated patients [unadjusted and adjusted hazard ratios and 95% CI 0.72 (0.61–0.86), and 0.68 (0.55–0.85), respectively; p < 0.001 for both]. The mean cumulative added productivity value associated with HCV treatment was US$4511 (CI $2778–$6278) at 1 year post-index and $21,429 (CI $12,733–$30,199) at 4 years post-index.ConclusionHCV treatment reduces the risk of work loss resulting in productivity gains for employers and employees. The monetary value associated with these productivity gains is substantial, and, after about 4 years, it is comparable to the wholesale acquisition cost of some direct-acting antiviral regimens in the United States. Employers may derive economic benefits from adopting HCV elimination strategies.Electronic supplementary materialThe online version of this article (10.1007/s12325-020-01492-x) contains supplementary material, which is available to authorized users.

Prospective evaluation of vascular changes in acute respiratory infections in children with cystic fibrosis

Background/aim Acute exacerbations and chronic inflammation are risk factors for cardiovascular disease (CVD) in cystic fibrosis (CF) patients. The aim of this study was to investigate the effects of acute exacerbation therapy on arterial stiffness in children with CF.Materials and methods Augmentation index (Aix) and pulse wave velocity (PWV) were measured before and after treatment and 1 month after the end of treatment in patients with acute exacerbation. The relationship between hemodynamic measurements and c-reactive protein (CRP) and pulmonary function tests (PFTs) was investigated.Results Measurements before and after treatment were evaluated in 27 patients and were repeated in 21 patients who were clinically stable 1 month following acute exacerbation. There was a significant decrease in CRP and an increase in spirometry parameters after treatment. While no significant difference was found between PWV (P = 0.33), a significant difference for Aix before (41.95 ± 12.96%) and after (30.95 ± 11.47%) treatment and before treatment and stable clinical condition (34.19 ± 14.36%) was obtained (P =0.00, and P =0.01, respectively). No significant difference in heart rate and other hemodynamic measurements was found. Pretreatment Aix is associated with poor clinical condition (PFTs, BMI, and clinical score) and systemic inflammation (CRP) (P <0.05).Conclusion The decrease of arterial stiffness (Aix) with acute exacerbation treatment in children with CF has been demonstrated. This result shows that systemic inflammation in CF may cause an increase in arterial stiffness and recurrent exacerbations may increase the risk of CVD.

Does a regular nurse-led distress screening and discussion improve quality of life of breast cancer patients treated with curative intent? A randomized controlled trial.

We performed a randomized controlled trial (RCT) to investigate whether regular screening with the distress thermometer (DT) by a nurse improved global quality of life (QOL) of patients with breast cancer (BC) treated with curative intent. BC patients were randomized between regular screening for distress with a nurse-led DT intervention (NDTI) and usual care (UC). Both groups filled out questionnaires at baseline, after each received treatment modality and at follow-up visits up to 2 years. At these points, the intervention group received also the NDTI. The primary outcome was the global QOL of the EORTC QLQ C30 at 2 years after the end of treatment. Analyses were done on an intention-to-treat basis, using analysis of covariance (ANCOVA), generalized least squares, and interaction analyses. Of 194 randomized patients, 153 filled out the questionnaires up to 2 years after treatment. There was no significant difference between NDTI and UC in global QOL 2 years after the end of treatment (mean diff. = -1∙273, P = .610; 95% CI [-6.195; 3.649]). Subgroup analysis of patients who received multimodality treatment (surgery, radiotherapy, and chemotherapy, n = 66) showed a significant between-group difference in global QOL over time (mean diff. = -10, P < .001; 95% CI [-14.835; -5.167]) together with other secondary outcome measures in favor of the NDTI. NDTI did not lead to a significant improvement in global QOL 2 years after the end of treatment for patients with BC. However, the findings indicate that BC patients who received multimodality treatment may benefit from NDTI.

P1.16-40 Real-World Neurocognitive Function in Lung Cancer: Initial Results of the PRO-Long Study

Changes in neuro-cognitive function (NCF) as a result of treatment and disease have been repeatedly reported in cancer patients. However, contradictions exist on the prevalence and extent of impairment. Evidence in the lung cancer population is very limited. We here report the initial results of NCF in non-small cell lung (NSCLC) cancer patients receiving radiotherapy and/or systemic therapy in the PRO-Long study. PRO-Long is a monocentric, prospective, longitudinal study, investigating the effect of first-line chemotherapy, radiotherapy and/or immunotherapy on patient-reported health-related quality of life (HRQoL), toxicity, functional exercise capacity (6-minute walking test – 6MWT) and NCF in locally-advanced and metastatic NSCLC patients. HRQoL and toxicity data are collected with patient-reported outcome measurements (PROMs). NCF data is collected with the Reys-Osterrieth Complex Figure Test (ROCF), Hopkins Verbal Learning Test-Revidsed (HVLT-R) free recall, delayed recall and recognition; Trail Making Test (TMT) A and B, Controlled Oral Word Association Test (COWA), Wechsler Adult Intelligence Scale (WAIS) digit span and the Stroop Color and Word Test (SCWT). Demographic data are collected at baseline; outcome data (survival, local and loco-regional control and metastatic relapse) during follow-up. NCF data is collected pre-treatment, and 2-3 months, 6 and 12 months after the end of treatment in patients receiving chemo- and/or radiotherapy or after start of immunotherapy. The mixed model approach was applied to determine statistical significance (p < 0.05). Meaningful clinical important difference (MCID) in NCF is defined as a decline greater than one standard deviation from baseline. Between January 2016 and December 2018, 50 patients (mean age: 63) were recruited. The majority was male (60%), had locally-advanced disease (54%) and received chemotherapy with (50%) or without (24%) radiotherapy. NCF data is available of 49, 28, 16 and 10 patients at baseline, 2-3 months, 6 months and 1 year respectively. So far no significant decline was found in any NCF test. At 2-3 and 6 months after treatment, 42% and 34% of patients had a MCID decline in one or more tests. NCF decline was mostly detected in the HVLT-R free recall test, respectively 15 and 23% at 2-3 and 6 months. The initial data suggest that systemic treatment, all or not combined with radiotherapy may result in a clinically meaningful NCF decline in locally-advanced and metastatic NSCLC patients. Particularly, immediate recall seems to be affected. Updated results will be presented.

Evaluation of the application of the diagnostic protocol in a single step of Hepatitis C

Direct-acting antivirals for chronic hepatitis C (HCV) infection have reduced the need for on-treatment HCV RNA monitoring. We assessed the accuracy and cost implications of using HCV core antigen testing to replace HCV RNA testing for confirmation of diagnosis, on-treatment monitoring, and determination of sustained virological response (SVR).In a retrospective screening cohort study, de-identified residual serum from unselected samples were obtained from commercial laboratories in Ontario, Canada. Samples from each 5-year age-sex band from birth years 1945–74 collected from Aug 1, 2014, to Feb 28, 2015, were included. All samples that tested positive for HCV antibodies, and 10% of samples that tested negative for HCV antibodies, were tested for HCV core antigen and HCV RNA. A retrospective clinical cohort study was also done using blood samples from patients with confirmed HCV infection collected at four tertiary academic centres: one in Canada, two in Germany, and one in the USA. For assessment of SVR, we included samples from patients who started direct-acting antiviral-based treatment (excluding telaprevir and boceprevir) with or without peginterferon, ribavirin, or both, from Jan 1, 2014, to March 31, 2015. To ensure inclusion of adequate numbers for analysis, patients who relapsed after any treatment regimen were included. Serum samples included in the study were from baseline, week 4 on-treatment (only for patients treated with direct-acting antivirals), end of treatment, and week 12 or 24 of follow-up. The sensitivity and specificity of core antigen testing as a diagnostic tool was assessed in the screening cohort, using HCV RNA as a reference. The sensitivity and specificity of core antigen testing as well as its concordance with HCV RNA testing in the clinical cohort was assessed at baseline, week 4 on-treatment, and at weeks 12 or 24 after the end of treatment in patients undergoing therapy with direct-acting antivirals. The cost-effectiveness of core antigen testing with and without confirmatory HCV RNA testing for negative samples was also assessed.From 10 006 samples in the screening cohort, 75 of 80 viraemic (HCV RNA-positive) samples tested positive for HCV core antigen (sensitivity 94%, 95% CI 86–98), and none of the 993 HCV RNA-negative samples tested positive for HCV core antigen (specificity 100%, 95% CI 94–100). The five viraemic samples that tested negative for HCV core antigen had low corresponding HCV RNA concentrations. In the clinical cohort, two (1%) of 202 baseline samples tested negative for HCV core antigen; one had a low HCV RNA concentration (468 IU/mL), the other had a high HCV RNA concentration (>2 000 000 IU/mL). By week 4 of treatment, HCV core antigen concentrations decreased in all patients but were not predictive of SVR. Although there was good concordance between HCV RNA and HCV core antigen results at 12 weeks after the end of treatment (r=0·97; p<0·0001), three of the 148 patients who achieved SVR at 12 weeks tested HCV core antigen positive. 12 weeks after the end of treatment, HCV core antigen was undetectable in one (1%) of 71 samples from patients who were identified as having relapsed according to HCV RNA detection. On-treatment and end-of-treatment testing of core antigen or HCV RNA provided little clinical value. The use of HCV core antigen testing as a confirmatory diagnostic strategy was cost saving relative to HCV RNA testing, with a reduction of CAD$0·29–3·70 per patient screened depending on whether HCV RNA testing was used to confirm HCV core antigen-negative results.These data support the use of HCV core antigen testing to document HCV viraemia in a cost-saving diagnostic algorithm. In a treatment setting, HCV core antigen testing can be used instead of HCV RNA testing for diagnosis and documentation of treatment adherence, but it might not be adequate to determine SVR. This approach might improve access to care, particularly in low-income and middle-income countries.Abbott Diagnostics and Toronto Centre for Liver Disease.