End Of Treatment Research Articles

Patient-reported outcomes (PROs) in patients (pts) with primary advanced or recurrent endometrial cancer (pA/rEC) treated with dostarlimab (D) plus carboplatin/paclitaxel (CP) compared with CP in the ENGOT-EN6/GOG3031/RUBY trial.

332 Background: In RUBY (NCT03981796), a phase 3, global, randomized, double-blind trial, D+CP demonstrated significant and clinically meaningful improvement in PFS vs placebo + CP (P+CP) in pA/rEC. Methods: 494 pts with pA/rEC were randomized 1:1 to D+CP or P+CP Q3W for 6 cycles (C), followed by D or placebo monotherapy Q6W for ≤2 y. EORTC QLQ-C30 and EN24 (prespecified secondary endpoints) were administered on day 1 of each C, at end of treatment (EOT), and at safety and survival follow-ups. Change (chg) from baseline (BL) to C7 (end of chemotherapy) and C13 (1 y) was calculated in the overall and mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) populations. Least-squares means (LSM) were generated using mixed models for repeated measures, adjusting for correlations across multiple assessments within a pt and controlling for BL global, pain, fatigue, and physical function (PF) scores. Results: In the overall population, PROs were similar with D+CP and P+CP through C7, and no differences between arms across the 3-y period were reported; mean chg from BL to EOT showed numerical improvement with D+CP in back/pelvic pain and deterioration with P+CP in global QOL/GHS, social function (SF), body image, and chg in taste. In the dMMR/MSI-H population, at C7, nominally significant improvements in QOL, PF, role function (RF), pain, and back/pelvic pain were seen with D+CP vs P+CP (Table). Conclusions: Dostarlimab+CP significantly improved PFS and maintained HRQOL in dMMR/MSI-H and overall populations, further supporting its use as a standard of care in pA/rEC. Clinical trial information: NCT03981796 .[Table: see text]

A Nutraceutical Compound Containing a Low Dose of Monacolin K, Polymethoxyflavones, Phenolic Acids, Flavonoids, and Hydroxytyrosol Improves HDL Functionality.

In earlier studies, it has been observed that 8-week treatment with a novel nutraceutical compound (NC) containing low monacolin K dose, polymethoxyflavones, phenolic acids, flavonoids, and hydroxytyrosol improves lipid profile and endothelial function and reduces the level of oxidized low-density lipoprotein (oxLDL). We hypothesize that this effect might be, at least in part, explained by positive modulation exerted by the NC on the atheroprotective function of high-density lipoprotein (HDL). This study aimed to evaluate whether the NC could influence determinants of HDL function. Forty-five subjects with low-moderate dyslipidaemia were enrolled and treated for 8 weeks with the NC, followed by 4 weeks of washout. Blood samples were collected at every time point to evaluate changes in lipid profile, endothelial function, oxLDL, and markers of HDL function, such as the anti-oxidant activities of paraoxonase-1, glutathione peroxidase-3 (Gpx3), lipoprotein-phospholipase A2 (Lp-PLA2), and pro-oxidant activity of myeloperoxidase (MPO). Although the concentration of HDL-C did not change, the activity of Lp-PLA2 significantly decreased upon treatment (-11.6%, p<0.001) and returned to baseline level 4 weeks after the end of treatment. In contrast, Gpx3 increased after treatment (+5%, p<0.01) and remained unvaried after 4 weeks. Both MPO activity and concentration significantly decreased after the washout period (-33 and 32%, p<0.001). For the first time, it was found that the administration of an NC with beneficial effects on lipid homeostasis also positively impacts HDL function by improving the balance between protective and damaging determinants. Further investigation is required to corroborate our findings.

Physician- and Patient-Reported Outcomes of the MC1635 Phase 3 Trial of Ultrahypofractionated Versus Moderately Hypofractionated Adjuvant Radiation Therapy After Breast-Conserving Surgery

Our aim was to report physician- and patient-reported outcomes of patients with localized breast cancer treated with moderate versus ultrahypofractionated whole breast irradiation (WBI) after breast-conserving surgery (BCS). Between February 2018 and February 2020, patients with localized breast cancer (pT0-3 pN0-1 M0) were offered participation in a phase 3 randomized clinical trial assessing adjuvant moderate hypofractionation (MHF) to 40 Gy in 15 fractions versus ultrahypofractionation (UHF) to 25 Gy in 5 fractions after BCS, with an optional simultaneously integrated boost. Toxicities, cosmesis, and quality of life were assessed at baseline, end of treatment (EOT), and 3 months, 1 year, 2 years, and 3 years from irradiation using validated metric tools. One hundred seven patients were randomized to MHF (n = 54) or UHF (n = 53) adjuvant WBI. The median follow-up was 42.8 months. Grade 2 radiation dermatitis was experienced by 4 patients (7.4%) in the MHF arm and 2 patients (3.7%) in the UHF arm at EOT (P = .726). No grade 3 or higher toxicities were observed. Deterioration of cosmesis by physician assessment was observed in 2 (6.7%) patients treated in the UHF arm and 1 (1.9%) patient treated in the MHF arm at EOT (P = .534), whereas at 3 months, only 1 (1.8%) patient treated in the MHF arm demonstrated deterioration of cosmesis (P = .315). At EOT, 91% and 94% of patients reported excellent/good cosmesis among those treated with MHF and UHF regimens, respectively (P = .550). At 3 months, more patients within the MHF arm reported excellent/good cosmesis compared with those in the UHF arm (100% vs 91%; P = .030). However, the difference in patient-reported cosmesis disappeared at the 1-, 2-, and 3-year time points. UHF WBI showed similar treatment-related late toxicities and similar provider-scored cosmesis compared with MHF radiation in patients treated adjuvantly after BCS.

Clinical outcome after cessation of nucleos(t)ide analog treatment in chronic hepatitis B patients who achieved HBsAg seroclearance.

We determined the long-term clinical outcome and the durability of treatment cessation after HBsAg seroclearance following nucleos(t)ide analog (NA) therapy in patients with chronic hepatitis B (CHB). We analyzed virological relapse (VR), HBsAg reversion, clinical relapse, and changes in HBsAg and HBcrAg levels by iTACT assay after treatment cessation of 90 CHB patients who achieved HBsAg seroclearance by NA treatment. Median age of patients at treatment cessation was 57years. Median duration of NA treatment and follow-up from cessation of NA were 9.25 and 5.2years, respectively. Although VR occurred in 19 of 90 (21.1%) patients, HBV DNA levels of 18 patients had temporal elevations and sustained levels under the detection level thereafter. HBsAg reversion using Architect HBsAg QT assay occurred in six patients (6.7%) after cessation of NA. Five patients had temporal HBsAg level elevations and sustained levels under the detection level thereafter. One patient had virological and clinical relapse at 6months after cessation of NA, and received NA re-treatment. HBsAg levels by iTACT assay from end of treatment (EOT) gradually decreased and in 18 of 28 (64%) patients reached an undetectable level at 5years after EOT. In contrast, HBcrAg levels by iTACT assay slowly decreased, and in 8 of 29 patients (28%) reached an undetectable level at 5years after EOT. Patients receiving NA treatment who achieved HBsAg seroclearance as determined by HBsAg QT assay rarely experienced virological or clinical relapse after the cessation of treatment.

Posttreatment liver function, but not baseline liver function stratifies patient survival after direct-acting antiviral treatment in decompensated cirrhosis with hepatitis C virus

BackgroundThe prognosis of cirrhosis is clearly stratified by liver function. Although direct-acting antiviral (DAA) has recently been used to eliminate hepatitis C virus (HCV), it is not clear whether liver function stratifies the prognosis of decompensated cirrhotic patients treated with DAA.MethodsA total of 206 HCV-associated decompensated cirrhotic patients who started DAA from February 2019 to December 2021 at 31 Japanese hospitals were prospectively registered.ResultsThe median age was 68, and the proportions of patients with Child–Pugh class A (CP-A), CP-B and CP-C were 10% (20/206), 76% (156/206) and 15% (30/206), respectively. Twenty-six patients died, and two patients underwent liver transplantation (LT); the 2- and 3-year LT-free survival rates were 90.0% and 83.2%, respectively. We examined factors associated with LT-free survival using 2 models including either CP class (Model 1) or MELD score (Model 2). In multivariate Cox proportional hazard analysis, CP class at 12 weeks after the end of treatment (EOT) in Model 1 and MELD score at 12 weeks after the EOT in Model 2 were significant factors, while baseline CP class or MELD score was not. Two-year LT-free survival rates were 100%, 91.6% and 60.4% for patients with CP-A, CP-B and CP-C at 12 weeks after the EOT and 95.2% and 69.6% for patients with MELD < 15 and MELD ≥ 15 at 12 weeks after the EOT, respectively.ConclusionsThe prognosis of decompensated cirrhotic patients receiving DAA was stratified by liver function at 12 weeks after the EOT, not by baseline liver function.

A comparison of the prognostic performance of the Lugano 2014 and RECIL 2017 response criteria in patients with NHL from the phase III GOYA and GALLIUM trials.

The Lugano 2014 criteria are the standard for response assessment in lymphoma. We compared the prognostic performance of Lugano 2014 and the more recently developed response evaluation criteria in lymphoma (RECIL 2017), which relies primarily on computed tomography and uses unidimensional measurements, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) from the phase III GOYA and GALLIUM trials, respectively. Concordance between responses according to the Lugano 2014 and RECIL 2017 criteria was analyzed. Landmark analyses of progression-free survival (PFS) and overall survival (OS) by end of treatment (EOT) and end of induction (EOI) response status according to RECIL 2017 and Lugano 2014 criteria, and prognostic value of response at EOT/EOI were also compared. Overall, 1333 patients were included from GOYA and 502 from GALLIUM. Complete response (CR) status according to RECIL 2017 criteria showed high concordance with complete metabolic response (CMR) status by Lugano 2014 criteria in both GOYA (92.5%) and GALLIUM (92.4%). EOT and EOI CR/CMR status by both criteria was highly prognostic for PFS in GOYA (RECIL 2017 [CR]: hazard ratio [HR], 0.35 [95% confidence interval [CI] 0.26-0.46]; Lugano 2014 [CMR]: HR, 0.35 [95% CI 0.26-0.48]; both p<.0001) and GALLIUM (RECIL 2017 [CR]: HR, 0.35 [95% CI 0.23-0.53]; Lugano 2014 [CMR]: HR, 0.21 [95% CI 0.14-0.31]; both p<.0001). In conclusion, response categorization by RECIL 2017 is similar to that by Lugano 2014 criteria, with high concordance observed. Both were prognostic for PFS and OS.

Reduction in Depressive Symptoms in People who Inject Drugs who Are Cured of Hepatitis C Virus Infection: The HERO Study.

Depressive symptoms are prevalent among people who inject drugs (PWID) and people with hepatitis C virus (HCV). We examined changes in depressive symptoms among HCV-infected PWID following direct-acting antiviral treatments to evaluate whether these changes differed by history of depressive symptoms, substance use, or HCV treatment outcome. We conducted a secondary analysis of the HERO Study (NCT02824640), a pragmatic randomized clinical trial among PWID, to test the effectiveness of HCV care models. Depressive symptoms (primary outcome) were measured using the Patient Health Questionnaire (PHQ-9) at baseline, end of treatment (EOT), and at follow-up 12 and 24 weeks after EOT. Sustained virologic response (SVR) was defined as undetectable HCV RNA at ≥12 weeks following EOT. Baseline drug use was defined as having a positive urine screening test for amphetamine, methamphetamine, benzodiazepine, cocaine, cannabis, opiate, or oxycodone. The sample (n = 498) was 72.3% male, 64.2% White, and on average 43.9 years old. In patients who achieved SVR (F(3432) = 4.58; P = .004) and those with drug use at baseline (F(3478) = 5.11; P < .01), PHQ-9 scores significantly declined over time, with scores lower at EOT and both follow-ups as compared with baseline. Mean PHQ-9 scores at EOT and follow-ups were significantly lower than at baseline, except for those with no depression or mild depression at baseline. This study showed that HCV treatment in PWID is associated with sustained declines in depression up to 24 weeks post-treatment among those who achieve SVR and that drug use does not interfere with improvement in depressive symptoms.

Orally administered Chinese herbal therapy to assist post-surgical recovery for chronic rhinosinusitis-A systematic review and meta-analysis.

This systematic review and meta-analysis aims to: assess the effectiveness and safety of orally administered Chinese herbal medicines (CHMs) as adjuncts to the post-surgical management of chronic rhinosinusitis (CRS); inform clinicians of the current evidence; identify the best available evidence; and suggest directions for further research. Randomised controlled trials (RCTs) were identified from searches of nine databases plus clinical trial registries. Participants were adults and/or children diagnosed with sinusitis or rhinosinusitis, with or without nasal polyps, who had received surgery. Interventions were CHMs used orally following surgery for CRS as additions to conventional post-surgical management. Controls received conventional post-surgical management without CHMs. Studies reported results for Sino-Nasal Outcome Test (SNOT), visual analogue scales (VAS), Lund-Mackay computed tomography score (LM), Lund-Kennedy endoscopic score (LK), mucociliary transport time (MTT), mucociliary transport rate (MTR), mucociliary clearance (MC) or quality of life (QoL). Twenty-one RCTs were included. All used oral CHMs following functional endoscopic sinus surgery (FESS). The pooled results showed no significant difference between groups for SNOT-20 at the end of treatment (EoT) but there was a significant difference at follow up (FU) in favour of additional CHMs. The VAS for total nasal symptoms (VAS-TNS) showed greater improvements in the CHM groups at EoT and FU. Only FU data were reported for LM which showed greater improvement in the CHM groups. LK showed greater improvements at EoT and FU. The measures of mucociliary transport (MTT, MTR, and MC) each showed significantly greater improvement at EoT in the group that received additional CHMs. No study reported QoL. Adverse events were not serious, but reporting was incomplete. The meta-analyses suggested the addition of oral CHMs to conventional management following FESS may improve recovery. However, most studies were not blinded, and substantial heterogeneity was evident in some meta-analyses. Blinded studies are required to further investigate the roles of oral CHMs in post-surgical recovery. Systematic review registration number: The protocol was registered in PROSPERO (CRD42019119586).

Implementation of a Systematic, Digital Oncology Workflow for Patient Distress Screening in a National, Multi-Site Radiotherapy Outpatient Setting.

Distress screening is recommended as standard of care in oncology to improve the quality of personalized care for patients, however previously reported barriers have led to poor uptake and reporting of clinician follow up and interventions. Our purpose was to improve the quality of personalized care for patients with high patient participation rate (>50%), clinical and nurse workflow compliance rate (>70%) and create structured data for practice improvement. To achieve this purpose, an in-house systematic digital screen and templated well-being plan (WBP) workflow was implemented across 33 outpatient Radiation Oncology sites in a multi-institutional center. An in-house digital version of the NCCN Distress Thermometer and Problem Checklist (DT) was built in the integrated web-based portal for patients to complete at home or in a clinic setting. A digital workflow was co-designed with clinicians with automatic integration of the DT PDF document into the Electronic Medical Record (EMR), assigned for doctor review. Nurses subsequently recorded screening actions in the WBP. An extensive engagement, education and support program was completed nationally with phased implementation after an initial pilot at 3 sites. Staff and patient feedback were documented and presented with the collated data for review. The program was successfully implemented at 33 centers across Australia in the multi-site organization between March and October 2022. A total of 7788 distress screening forms were submitted with an uptake rate of 78% at baseline and 53% at end of treatment (EOT). DT document approval rates by doctors varied (41%-98%), and WBP was completed for 48-100% of patients, with variations of rates and use noted between states and individuals for both. Referrals were recorded in the WBP for 3% of patients, however, as up to 52% of documentation was not in a WBP (for some states), true referral numbers require further manual analysis. Pairwise analysis of screening scores between time points saw 42% of scores reduced, 34% increased and 24% with no change. Analysis of a subset of patients with increased or no change in score showed 57% had some change in categories of distress, 22% had complete change and 10% had no change. With an increasing global focus on improving patient centered care, implementation of a systematic digital workflow for distress screening and supportive care was achieved resulting in patient identified stressors being addressed as standard of care. Key barriers reported, include confidence discussing screening results with patients and manual workflows at EOT. The provision of a rich data set can also highlight opportunities for clinical practice improvement, cohort-based focus, clinical quality indicators, benchmarking and reporting.

Predicting diffuse large B-cell lymphoma outcomes with lesion-to-liver maximum standardized uptake value for interim-treatment and end-of-treatment positron emission tomography-computed tomography.

18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) has been used in response evaluation systems for malignant lymphomas and is an important tool for determining efficacy and prognosis. The Deauville 5-point scale (D-5PS) is an 18F-FDG PET-CT image-interpretation protocol for patients with lymphoma. Nevertheless, a number of limitations in visual image interpretation, such as interobserver disagreement and the increase of false-positive results, suggests that new parameters are needed. In this study, we aimed to evaluate the prognostic values of interim-treatment (I-) and end-of-treatment (EOT) PET-CT by comparing D-5PS to the semiquantitative lesion-to-liver maximum standardized uptake value ratio (RLL). A total of 90 patients with diffuse large B-cell lymphoma (DLBCL) (45 I-PET and 45 EOT-PET) were analyzed, and the RLL was calculated. Patients were additionally evaluated using the D-5PS system. We determined the optimal cutoff value of RLL using receiver operating characteristic (ROC) analysis. Kaplan-Meier survival analysis was used to compare the outcome predictions, while multivariate Cox regression analysis was used to identify the predictive factors. Among the patients examined, 41 (20 I-PET and 21 EOT-PET) experienced progression, and 49 (25 I-PET, 24 EOT-PET) did not. The optimal cutoff values of the RLL for predicting disease progression were 1.37 for I-PET (sensitivity 75%, specificity 88%) and 2.03 for EOT-PET (sensitivity 45.5%, specificity 100%), while the cutoffs of the D-5PS were scores 4 for I-PET (sensitivity 80%, specificity 72%) and 5 for EOT-PET (sensitivity 40.9%, specificity 100%). The prognostic efficacy was higher for the RLL at interim than for the D-5PS [area under the curve (AUC) =0.848 vs. 0.741]. The EOT prognostic efficacy of both evaluation methods was essentially equivalent (AUC =0.785 vs. 0.725). Univariate and multivariate analyses showed that RLL and D-5PS were independent factors affecting DLBCL outcomes for both interim and EOT assessment. RLL and D-5PS have independent predictive values for the interim and EOT evaluation of outcomes in patients with DLBCL. The RLL has better interim predictive ability than does D-5PS and can optimize D-5PS interpretation, thus improving interim outcome prediction.

SCCAg as a Biomarker of Advanced Stage and OS in Limited Resource Setting for Cervical Cancer

Elevated serum squamous cell antigen (SCCAg) has been previously correlated with poor survival, extensive tumor involvement, and recurrence for cervical cancer. Failure of serum SCCAg to normalize after treatment completion has also been studied as a poor prognostic indicator. This is the first study describing the association of SCCAg with stage and outcomes in patients diagnosed with cervical cancer in Botswana, in a population with a majority of women who are living with HIV (WLWH). Patients with histologically confirmed cervical cancer were enrolled in a prospective observational study between August 2016 and April 2020 in Botswana. Among all patients undergoing definitive chemoradiation, serum SCCAg was determined at pre-treatment baseline, end of treatment (EOT), and 3-month follow-up (normal reference range 0.3 -1.9 ng/ml). Normalization of SCCAg was defined as return to the reference range after treatment (SCCAg response), and was measured first at EOT; if EOT values were not available, 3-month values were utilized. Patients were staged according to FIGO 2009 criteria, early stage was defined as Stage I-II; while advanced stage was defined as Stage III-IV. Median follow-up was 44 months. A significant cut-off point for baseline and SCCAg response correlated with overall survival (OS) was calculated utilizing a log-rank test RESULTS: Among 234 patients who were diagnosed with histologically confirmed cervical cancer, 73.5% were WLWH (mean CD4 count 466 cells/mL). 92.9% of all cancers were squamous cell carcinoma. 68.8% of patients had elevated SCCAg at time of diagnosis. There was no significant difference in mean baseline SCCAg between WLWH (13.3 ng/mL) and women living without HIV (9.07 ng/mL), p = 0.1052. There was a significant difference seen in mean SCCAg between early (7.9 ng/mL ± SD 13.4) and advanced (18.9 ng/mL, ± SD 29.8) stage disease at diagnosis, p < 0.0001. Baseline SCCAg > 7.9 ng/mL was found to be associated with worse OS (p < 0.001). 5-year OS was significantly different among patients with SCCAg response < = 2.8 (5-year OS 66.2%), vs. SCCAg >2.8 ng/mL (5-year OS 42.4%). There was no significant difference in average SCCAg values between EOT (p = 0.68) and 3-month follow-up (p = 0.24). There was no difference in the proportion of patients who experienced normalized SCCAg by HIV status (p = 0.67). There was no significant difference in SCCAg among WLWH and women living without HIV. Among patients with elevated SCCAg above normal at baseline, SCCAg was associated with early vs. advanced stage disease. Additionally, there was a significant difference seen in overall survival by two measurement points: baseline SCCAg >7.9 ng/mL and response SCCAg >2.8 ng/mL. SCCAg may be utilized as a biomarker in low-resource settings to refine prognosis. Further studies will be needed to determine utility and validation in predicting recurrence risk and/or lymph node metastases.

Physician and Patient-Reported Outcomes of a Phase III Trial of Ultra-Hypofractionated vs. Moderate Hypofractionated Radiotherapy to the Whole Breast after Breast-Conserving Surgery

To report a final analysis evaluating physician and patient-reported outcomes of early breast cancer patients receiving moderate hypofractionation or ultra-hypofractionated whole breast radiotherapy (RT). Between April 4, 2018, and February 11, 2020, patients with localized breast cancer (T1-T3, N0-N1, and M0) managed with breast-conserving surgery (BCS) were enrolled. Patients were randomized to receive whole breast RT with moderate hypofractionation to 40 Gy in 15 fractions (Arm A) or ultra-hypofractionation to 25 Gy in 5 fractions (Arm B). An optional concurrent integrated boost to 48 Gy on Arm A or 30 Gy on Arm B was allowed. Early toxicity (<3 months), late toxicity (> 3 months), quality of life (QOL), cosmesis, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and deterioration of cosmesis were analyzed. One hundred and seven patients were randomized to moderate hypofractionation (n = 54) or ultra-hypofractionation (n = 53). With a median follow-up of 36 months, no significant differences in patient characteristics were noted between the two arms. There were no patients with a grade ≥3 or higher toxicity. Grade 2 toxicities were 7.4% in Arm A and 7.5% in Arm B, and primarily consisted of radiation dermatitis (6 patients), fibrosis (1 patient) and lymphedema (1 patient). The average Harvard Cosmesis score and overall QoL were similar between arms at all time points, with no patients developing cosmetic deterioration. Patient-reported moderate to severe radiation skin burns were more commonly reported in Arm A (21.05%) vs. Arm B (6.25%) at the end of treatment (EOT) (p = 0.078). At EOT, patients receiving moderate hypofractionation had higher mean toxicity scores in breast tenderness (2.66 vs. 1.5, p = 0.018), skin flaking or peeling (0.63 vs. 0.06, p = 0.035), blistering (0.74 vs. 0.06, p = 0.028), pruritis (2.53 vs. 0.87, p < 0.001), erythema (4.24 vs. 2.0, p <0.001), telangiectasias (1.0 vs. 0.28, p = 0.021). Additionally, patients receiving moderate hypofractionation reported significantly worse changes from baseline at EOT in breast tenderness (-2.25 vs. -.86, p = 0.02), telangiectasia (-0.81 vs. 0.18, p = 0.012), skin discoloration (-4.31 vs. -1.04, p < 0.001), skin flaking or peeling (-.55 vs. 0.04, p = 0.053), blistering (-0.82 vs. -0.07, p = 0.033), and pruritus (-2.27 vs. -.67, p = 0.002). There was a return to baseline in all patient-reported breast domains by 3 months (p >0.05) in both arms. Ultra-hypofractionated whole breast irradiation, consisting of 25 Gy in 5 fractions, provided comparable provider assessed toxicity and cosmetic outcomes to 40 Gy in 15 fractions. At the EOT assessment, ultra-hypofractionation had a better patient reported toxicity profile. Our findings provide further evidence to support daily ultra-hypofractionated whole breast radiotherapy as an appropriate treatment option for early-stage breast cancer.

Sensitivity of the PROMIS-10 for Capturing Radiation-Related Quality of Life Changes

Patient reported outcomes (PROs) are becoming more common when assessing the effects of radiotherapy (RT). The aim of this study was to assess the sensitivity of the Mental and Physical domains of the Patient-Reported Outcomes Measurement Information System 10 (PROMIS-10) to radiotherapy and determine what predictors were associated with change in quality of life. Patients, regardless of cancer type, were enrolled on a multi-site prospective registry. Inclusion criteria included curative radiotherapy and completion of the PROMIS-10 prior to treatment (Baseline) and at End of Treatment (EOT). To assess the strongest predictors of change in the T score of mental and physical health, we included 14 demographic characteristics and treatment variables in a multivariable stepwise regression. A total of 7,586 patients were eligible for the analysis. The median age was 65 (range 18-94), 54% were males, and 94% were white. A majority received photons (62.5%) and the others received protons (37.5%) with an average dose of 52.3 Gy (range 20-80 Gy) over an average of 22.6 fractions (range 1-66). Patient disease sites were sub-grouped into 12 categories: Breast (25.5%), GU (23.0%), H&N (11.1%), CNS (8.5%), Pancreas-Biliary (6.7%), Thoracic (5.7%), Soft Tissue/Bone (5.0%), Esophagus-Gastric (4.7%), Colorectal-Anus (4.4%), Heme/Lymph (2.6%), GYN (1.8%), and Skin/Melanoma (1.0%). For both outcomes, the model selected disease group as an important predictor and it explained the most variance in the outcome compared to the rest of the predictors. When probing the effect of disease group, H&N, Esophagus-Gastric, Skin/Melanoma, and Colorectal-Anus had the largest mean decrease in quality of life for both domains. For mental health, the model also selected radiation type. Patients treated with protons indicated a bigger decrease in mental health compared to patients treated with photons (b = 0.43, 95% CI: -0.01, 0.69). For physical health, the model selected total fractions, ethnicity, and T stage. As number of fractions increased, the physical health change scores became more negative, on average (b = -0.03, 95% CI: -0.05, -0.01). Hispanic/Latino patients indicated a smaller decrease in physical health compared to White (b = -1.50, 95% CI: -2.60, -0.40) and Unknown ethnicity patients (b = -1.82, 95% CI: -3.36, -0.27). Finally, patients with a T stage of 3 or greater indicated a smaller decrease in physical health than patients with a T stage less than 3 (b = 0.76, 95% CI: 0.35, 1.16). The PROMIS-10 did not capture significant change for patients undergoing curative radiotherapy except for patients with Head & Neck, Esophagus-Gastric, Skin, and Colorectal-Anus cancer. Further analyses should explore which patients experience the greatest change in quality of life within disease group.

Determining the Minimal Clinically Important Difference of the FACT-E to Evaluate the Change in the Quality of Life of Patients with Esophageal Cancer Treated with Curative Radiotherapy

Patients with esophageal cancer (EC) are often treated with radiotherapy (RT). The Functional Assessment of Cancer Therapy-Esophageal (FACT-E) is a health-related quality of life (QOL) instrument validated in patients with EC. The aim of this study was to determine the minimal clinically important difference (MCID) for FACT-E subscales, to allow for meaningful evaluation of the effect of RT on EC patient's QOL. We evaluated patients with EC, treated with curative intent RT, who completed the FACT-E at baseline and end of treatment (EOT). We calculated the MCID for the FACT-E subscales using anchor-based and distribution-based approaches. In the anchor-based approach we determined improvement and deterioration based on the overall health assessment from the PROMIS-10 as the anchor. We modeled the change in domain scores with age-adjusted regressions to determine the difference in classifications. For distribution-based analysis, we considered 0.3 and 0.5 standard deviation (SD). We averaged MCID for improvement and deterioration separately across timepoints, by approach, and we report MCID ranges as the minimum and maximum values across methods. Our cohort included 210 patients with EC, 96.7% white, 85.7% males, and 32.9% treated with photon with a median dose of 50 Gy (IQR 50-50) and a median fraction number of 25(IQR 25,25). The median age at RT was 67.6 years (IQR 60.9,73.7). The social domain had the lowest MCID (deterioration and improvement 0.9-1.9), while the widest MCID range, proportionally to the measure, was associated with the Fact-E total score (2.1-5.6 for improvement, and 3.7-5.6 for deterioration). MCID estimates from 0.3 SD were in exact agreement with the anchor-based deterioration estimates for the physical domain (2.3), and improvement estimates for the Trial Outcome Index (6.1). We determined the MCID for the FACT-E domains, using a combination of anchor- and distribution-based approaches. These findings are critical to determine whether there is meaningful change in the QOL of individuals with EC treated with curative RT.

Empirical cefepime+vancomycin versus ceftazidime+vancomycin versus meropenem+vancomycin in the treatment of healthcare-associated meningitis: results of the multicenter Ephesus study

BackgroundHerein, we analyzed the efficacy of main antibiotic therapy regimens in the treatment of healthcare-associated meningitis (HCAM).Materials/methodsThis retrospective cohort study was conducted in 18 tertiary-care academic hospitals Turkey, India, Egypt and Romania. We extracted data and outcomes of all patients with post-neurosurgical meningitis cases fulfilling the study inclusion criteria and treated with empirical therapy between December 2006-September 2018.ResultsTwenty patients in the cefepime + vancomycin-(CV) group, 31 patients in the ceftazidime + vancomycin-(CFV) group, and 119 patients in the meropenem + vancomycin-(MV) group met the inclusion criteria. The MV subgroup had a significantly higher mean Glasgow Coma Score, a higher rate of admission to the intensive care unit within the previous month, and a higher rate of antibiot herapy within the previous month before the meningitis episode (p < 0.05). Microbiological success on Day 3–5, end of treatment (EOT) clinical success (80% vs. 54.8%% vs 57.9%), and overall success (EOT success followed by one-month survival without relapse or reinfection 65% vs. 51.6% vs. 45.3%), EOT all cause mortality (ACM) and day 30 ACM (15% vs. 22.6% vs. 26%) did not differ significantly (p > 0.05) among the three cohorts. No regimen was effective against carbapenem-resistant bacteria, and vancomycin resulted in an EOT clinical success rate of 60.6% in the methicillin-resistant staphylococci or ampicillin-resistant enterococci subgroup (n = 34).ConclusionsOur study showed no significant difference in terms of clinical success and mortality among the three treatment options. All regimens were ineffective against carbapenem-resistant bacteria. Vancomycin was unsuccessful in approximately 40% of cases involving methicillin-resistant staphylococci or ampicillin-resistant enterococci.

Effects of family-based treatment on adolescent outpatients treated for anorexia nervosa in the Eating Disorder Unit of Helsinki University Hospital

BackgroundFamily therapy for adolescent anorexia nervosa (AN) has stronger evidence of efficacy in comparison with individual therapy, and family-based treatment (FBT) is the most evaluated in numerous randomized clinical trials. However, few studies have focused on how FBT performs outside of research settings. The current study is the first to assess clinical outcomes of FBT for adolescent AN in Finland, in a specialized outpatient clinic.AimThe naturalistic outcome of outpatient FBT for adolescent AN was investigated.MethodsFifty-two female patients and their families who received FBT at a tertiary eating disorders unit participated in the study. Data on their pre-treatment parameters, treatment details, and condition at the end of treatment (EOT) was collected from their medical records.ResultsAt EOT, a majority (61.5%) had achieved a full weight restoration [percentage of expected body weight (%EBW) ≥ 95%]. Participants with an %EBW ≥ 95 at EOT had a significantly higher pre-treatment %EBW than those with an EBW < 95% at EOT. Participants with an EBW ≥ 95% at EOT showed significantly higher total weight gain during the treatment period, a higher rate of regular menstrual periods at EOT, significantly lower rates of dietary restrictions, and less cognitive or behavioral symptoms of the eating disorder overall, compared to participants who did not achieve a normal body weight. In 22 cases (42.3%), there was no need for further treatment at the end of FBT. Participants who needed further treatment after FBT, compared to those who did not, showed significantly higher rates of psychiatric comorbidity, history of mental health treatment, and need for psychopharmacological treatment.ConclusionsIn this naturalistic study, and in line with previous studies, FBT for AN appeared to be an effective and sometimes sufficient intervention, especially for patients with milder weight deficit and less severe psychiatric comorbidities. The results show that FBT can be successfully implemented in Finland and suggest that training more ED clinicians in FBT would be beneficial.Trial registration: The study was retrospectively registered on February 8th, 2023, in ClinicalTrials.gov Protocol Registration and Results System, identifier: NCT05734573.

Serum inducible protein 10kDa/C-X-C motif chemokine10 levels predict regression of M2BPGi-based liver fibrosis after hepatitisC virus eradication by direct-acting antiviral agents.

It is desirable to identify predictors of regression of liver fibrosis after achieving sustained virological response by anti-hepatitisC virus (anti-HCV) therapy. We retrospectively investigated the serum interferon-γ inducible protein 10kDa (IP-10) level as a predictive indicator of regression of liver fibrosis after successful hepatitis C virus eradication by direct-acting antiviral agents (DAAs) therapy. The study participants were recruited from a historical cohort of 116 chronically hepatitisC virus-infected patients who had achieved sustained virological response by DAAs therapy and whose serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels at baseline (before DAAs therapy) were ≥2.0 cut-off index. We defined patients with M2BPGi levels <1.76 and ≥1.76 cut-off index at 2years after the end of treatment (EOT) as the regression (n=71) and non-regression (n=45) groups, respectively. Multivariate analyses revealed that the albumin-bilirubin score at baseline, and albumin-bilirubin score, Fibrosis-4 index at 24weeks after the EOT, and serum IP-10 change from baseline to 24weeks after the EOT (IP-10 change) were significantly associated with regression of M2BPGi-based liver fibrosis. In addition, IP-10 change was significantly associated with regression of M2BPGi-based liver fibrosis by a multivariate analysis, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis: M2BPGi levels ≥3.3 cut-off index at baseline. Serum IP-10 change from baseline to 24weeks after the EOT is a feasible predictor of regression of M2BPGi-based liver fibrosis after achieving sustained virological response with DAA therapy.

Patient-Reported Outcomes With Belantamab Mafodotin Treatment in Patients With Triple-Class Refractory Multiple Myeloma.

In the randomized phase II DREAMM-2 study, single-agent belantamab mafodotin demonstrated deep and durable responses and a manageable safety profile in triple-class refractory relapsed/refractory multiple myeloma (RRMM). We present patient-reported outcomes (PROs) from this study for patients treated with the approved dose of belantamab mafodotin (2.5 mg/kg q3w). Disease and treatment-related symptoms, health-related quality of life (HRQOL), functioning, and patient-reported ocular changes were assessed using questionnaires (European Organisation for Research and Treatment of Cancer Quality of Life questionnaires EORTC-QLQ-C30 and EORTC-QLQ-MY20, Ocular Surface Disease Index [OSDI], and the National Eye Institute Visual Functioning Questionnaire 25 [NEI VFQ-25]) at baseline, during treatment (every 3 or 6 weeks), and at the end of treatment (EOT). Eye examinations were conducted at baseline, prior to each treatment cycle, and at EOT. Patients reported ocular symptoms in the OSDI and NEI VFQ-25 questionnaires, with the median time to worst severity of 45 to 64 days depending on symptoms considered. Some limitations in driving and reading were reported. Ocular symptoms were improved and median time to recovery was 23.5 to 44.0 days. EORTC-QLQ-C30 data suggest core MM symptoms (including fatigue and pain), overall HRQOL, and patient functioning were maintained while patients continued belantamab mafodotin treatment, even if meaningful worsening of vision-related symptoms occurred. These PRO results, together with the clinical efficacy of belantamab mafodotin, support its use in patients with RRMM and further evaluation of its use at earlier lines of therapy.

Post-treatment HBsAg decline predicts high rate of HBsAg loss after stopping entecavir or tenofovir in HBeAg-negative patients without retreatment.

Little is known about the role of post-treatment HBsAg decline in HBsAg loss following nucleos(t)ide analogues cessation. HBeAg-negative patients without cirrhosis who previously received entecavir or tenofovir disoproxil fumarate (TDF) were enrolled (n=530). All patients were followed-up post-treatment for >24 months. Of the 530 patients, 126 achieved sustained response (Group I), 85 experienced virological relapse without clinical relapse and retreatment (Group II), 67 suffered clinical relapse without retreatment (Group III) and 252 received retreatment (Group IV). The cumulative incidence of HBsAg loss at 8 years was 57.3% in Group I, 24.1% in Group II, 35.9% in Group III and 7.3% in Group IV. Cox regression analysis showed that nucleos(t)ide analogue experience, lower HBsAg levels at end-of-treatment (EOT) and higher HBsAg decline at 6 months after EOT were independently associated with HBsAg loss in Group I and Groups II+III. The rates of HBsAg loss at 6 years in patients with HBsAg decline >0.2 log IU/mL in Group I and HBsAg decline >0.15 log IU/mL in Group II+III at 6 months after EOT were 87.7% and 47.1%, respectively. The HBsAg loss rate was high and post-treatment HBsAg decline could predict high HBsAg loss rate among HBeAg-negative patients who discontinued entecavir or TDF and did not need retreatment.

IP10 and Anti-HBc can Predict Virological Relapse and HBsAg Loss in Chronic Hepatitis B Patients after Nucleos(t)ide Analog Discontinuation

Introduction: To assess predictive ability of serum interferon-inducible protein 10 (IP10) and hepatitis B core antibody (anti-HBc) levels for virological relapse (VR) and hepatitis B surface antigen (HBsAg) loss after nucleos(t)ide analog (NA) discontinuation. Methods: In this multicenter prospective study, overall 139 patients were followed up for 24 months after NA discontinuation. Results: End of treatment (EOT) IP10 and anti-HBc were 29.2 (5.1–66.4) pg/mL and 193.6 (136.9–221.4) IU/mL. EOT IP10 and anti-HBc were independent predictors for VR and HBsAg loss in Cox regression analysis. Cumulative rates of VR in patients with EOT IP10 > 26.99 pg/mL was 31.9% (vs. 70.1%, hazard ratio [HR] 2.998, p < 0.001). Cumulative incidences of VR in patients with EOT anti-HBc ≤141.35 IU/mL was 49.1% (vs. 60.6%, HR 2.99, p < 0.001). Cumulative probabilities of VR was 16.7% in patients with EOT IP10 > 26.99 pg/mL plus anti-HBc ≤141.35 IU/mL (vs. 73.6%, HR 6.464, p < 0.001). Cumulative probabilities of HBsAg loss in patients with EOT IP10 > 93.5 pg/mL was 46.2% (vs. 4.7%, HR 10.94, p < 0.001). Cumulative probabilities of HBsAg loss in patients with EOT anti-HBc ≤78.42 IU/mL were 47.1% (vs. 5%, HR 12.27, p < 0.001). Patients with EOT IP10 > 93.5 pg/mL plus anti-HBc ≤78.42 IU/mL had the highest 24-month cumulative HBsAg loss rate (53.8% vs. 4%, HR 16.83, p < 0.001). Conclusion: High EOT IP10 and low EOT anti-HBc levels were related to both lower risk of VR and higher probability of HBsAg loss.