Non-progressive Disease Research Articles

Prospective single-arm multicenter interventional study of surgical resection for liver metastasis from gastric cancer; 3-year overall and recurrence-free survival

ObjectivePotential benefit of surgical resection for liver metastasis from gastric cancer (LMGC) remains controversial because most previous studies were retrospective. We evaluated the outcomes of surgical resection following chemotherapy for LMGC in a prospective single-arm multicenter interventional study. MethodsPatients with synchronous or metachronous LMGC received 2–4 cycles of standard chemotherapy and proceeded to surgical resection if restaging showed a non-progressive disease with a chance of R0 resection. The primary endpoint was 3-year OS of R0 patients, with RFS as secondary. Prognostic factors for R0 patients were evaluated by multivariable Cox regression analysis. ResultsSeventy patients were enrolled between 2011 and 2019. Two patients were ineligible, and 20 discontinued treatment before surgery. Of the 48 patients eventually undergoing surgery, 43 accomplished R0 resection of the primary and/or metastatic GC, while 1 ended in R2 resection and 4 were considered ineligible. Median and 3-year OS for R0 patients were 39.8 months (95 % confidence interval [CI], 26.9 to not reached) and 58.1 % (95 % CI, 43.1–71.8), respectively, while median and 3-year RFS were 14.9 months (95 % CI 7.9–34.0) and 34.9 % (95 % CI 22.2–50.1), respectively. On multivariable analysis, both multiple liver metastases and positive nodal status (pN1–3) were negatively associated with OS (multiple liver metastases: hazard ratio [HR] 2.71 (95 % CI, 1.16–6.35), P = 0.022; pN1–3: HR 9.11 (95 % CI, 1.22–68.2), P = 0.031). ConclusionR0 resection following chemotherapy for LMGC yielded promising survival, with multiple liver metastases and positive nodal status being significant indicators of poor prognosis. Clinical trial registration number: UMIN 000011445 (https://www.umin.ac.jp/ctr/).

A real-world study of active vitamin D as a prognostic marker in patients with sarcoma

PurposeThe assessment of sarcoma during clinical practice is primarily based on imaging examination, with no effective biomarkers available. Although it has been established that 1,25(OH)2D3 is abnormally expressed in patients with sarcoma, it remains unclear whether 1,25(OH)2D3 level could be used as an evaluation marker in these patient population.MethodsThis real-world study investigated 1,25(OH)2D3 level and its association with clinical features in sarcoma patients. Data on 1,25(OH)2D3, parathyroid hormone, calcium, and calcitonin were collected from 331 patients with sarcoma, while the imaging results and the variation in 1,25(OH)2D3 among 213 patients with sarcoma before and after treatment was further analyzed.ResultsWe found that the serum 1,25(OH)2D3 level was predominantly decreased in patients with sarcoma, with a mean of 45.68 nmol/L. 1,25(OH)2D3 was significantly correlated with the gender and age of sarcoma patients, with more substantial reductions in women and younger patients. Among sarcoma patients, those with progressive disease exhibited a 7.08 nmol/L (−13.73%) decrease in serum 1,25(OH)2D3 levels compared to baseline, while patients with non-progressive disease showed a 1.11 nmol/L (+ 7.0%) increase.ConclusionThe variation of serum 1,25(OH)2D3 can predict the disease status of patients with sarcoma. Decreased serum 1,25(OH)2D3 levels are indicative of disease progression in sarcoma patients, suggesting its potential for application as a prognostic marker for disease assessment in this patient population.

18F-fluorodeoxyglucose positron emission tomography-computed tomography in the localization of the lesions in the osteogenic region of breast cancer bone metastases after therapy.

Accurate efficacy evaluation of bone metastases (BMs) from breast cancer (BC) is an intractable issue in clinical practice, for which solutions are urgently needed. This study aimed to investigate the utility of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in the response evaluation of bone metastasis of BC. In total, 22 patients diagnosed with BC and BM were enrolled. These patients underwent repeated 18F-FDG PET/CT evaluations. The patients and each BM site were divided into two groups based on their response to treatment: progressive disease (PD) and nonprogressive disease (non-PD). We analyzed and compared the changes in PET and CT images, as well as the serum concentration of carcinoembryonic antigen (CEA), carbohydrate antigen 153 (CA153), alkaline phosphatase (ALP), and calcium (Ca) over the same time frame. The immunohistochemistry (IHC) of primary lesions between groups and between the primary focus and BM with high 18F-FDG uptake were compared and analyzed. Maximum standard uptake value (SUVmax) after therapy [area under the curve (AUC): 0.932] and Δ-value of SUVmax (AUC: 0.811) on 18F-FDG PET imaging proved significantly valuable for the efficacy of therapy outcomes related to BM lesions (P<0.05). In terms of overall evaluation of BM, age and human epidermal growth factor receptor 2 (HER2) expression were significantly lower in the PD group than in the non-PD group (P<0.05). There were marked differences in CEA after therapy, the changes of CEA, and CA153 (∆-value) between the groups (P<0.05). The SUVmax and Ca concentration after therapy and ∆-value of SUVmax, along with the levels of CA153, CEA, and ALP, were valuable indicators for evaluating the efficacy of individual BMs (P<0.05). IHC of BM in the PD group showed differences compared to primary lesions, with antigen Ki-67 being downregulated in metastatic lesions and HER2 being downregulated in a portion of BMs (2 of 6). Meanwhile, the expression of estrogen receptor (ER) and progesterone receptor (PR) remained relatively unchanged. 18F-FDG PET/CT confers precise assessment of the posttreatment efficacy pertaining to BM in BC. This modality facilitates the identification of poor effect lesions following extant therapies and localization for pathological assessment and may substantially contribute to evaluating therapeutic efficacy, refining treatment strategies, and predicting the disease trajectory of patients with BC and BM.

Serum interleukin-6 levels at the start of the second course of atezolizumab plus bevacizumab therapy predict therapeutic efficacy in patients with advanced hepatocellular carcinoma: a multicenter analysis.

Serum interleukin-6 (IL-6) before the administration of atezolizumab plus bevacizumab (Atez+Bev) is a prognostic biomarker in patients with hepatocellular carcinoma (HCC) treated with Atez+Bev. We previously revealed that the neutrophil-to-lymphocyte ratio and serum chemokine levels during treatment with Atez+Bev were more useful as prognostic biomarkers. Therefore, we examined the predictive ability of serum IL-6 for the efficacy of Atez+Bev in patients with HCC. We enrolled 94 patients with HCC who received treatment with Atez+Bev. Initial responses were assessed through dynamic computed tomography or magnetic resonance imaging. The levels of IL-6 in serum were measured before and at the initiation of the second course of Atez+Bev. Subsequently, the relationship of IL-6 levels with treatment efficacy was evaluated. IL-6 levels at the initiation of the second course tended to be higher in patients with progressive disease versus those with non-progressive disease in the initial evaluation (P=0.054). Moreover, the cutoff value (7.4pg/mL) was useful in stratifying patients by overall survival (i.e. low vs high: not reached vs 21.4months, respectively, P=0.001) and progression-free survival (low vs high: 11.9 vs 5.2months, respectively, P=0.004). This result was reproduced in patients with HCC who received Atez+Bev as first-line therapy. In the multivariate analyses, IL-6 levels at the initiation of the second course were independent predictive factors for progression-free and overall survival. Serum levels of IL-6 at the initiation of the second course of treatment may predict Atez+Bev efficacy and prognosis in HCC.

METRADS-P vs. RECIST/PCWG criteria to detect disease progression in metastatic castration-resistant prostate cancer (mCRPC).

5070 Background: Radiographic Progression-free survival (rPFS) derived from Computer Tomography (CT) and Bone Scan (BS) using Prostate Cancer Working Group (PCWG) criteria is utilized as an intermediate clinical endpoint for overall survival (OS) benefit in mCRPC. Whole Body MRI (WBMRI) is emerging as a potentially superior response biomarker, allowing a more accurate assessment of bone marrow and soft tissue disease. We have now compared the performance of previously reported WBMRI criteria (MET-RADS-P) with PCWG criteria as a response biomarker for mCRPC, and this with overall survival (OS). Methods: We retrospectively analysed imaging data from mCRPC patients that 1) discontinued therapy based on PCWG criteria; 2) had contemporaneous WBMRI, CT, and BS at time-points according to PCWG. Soft tissue lesions were classified according to RECIST1.1 both on CT and WBMRI; bone lesions were classified on BS using PCWG criteria as non-PD (non-progressive disease), PD-U (PD unknown) &amp; PD (progressive disease) and on WBMRI using MET-RADS-P as non–PD (subclassified as partial response-PR &amp; stable disease-SD) &amp; PD, for each imaging time-point. We calculated % agreement between MET-RADS-P and PCWG across all time-points. Median PFS as per PCWG (rPFS) and METRADS-P (mPFS) and median OS according to METRADS-P response at 12 weeks was estimated by Kaplan Meier. Results: 100 cases (91 subjects received 100 lines of treatment, 100 baseline imaging &amp; 216 follow-up imaging assessments). For soft tissue disease, RECIST 1.1 and WBMRI assessments were concordant at 201 of 216 time-points (93.1%); the discordance was related to superior detection of local disease and liver metastases on WBMRI. Bone metastases assessments showed agreement in 37.5% time-points, with details as follows (% over BS category): 1) Negative BS (13 time-points): WBMRI 69.2% negative, 15.4% PR, 15.4% as PD; 2) Non-PD BS (154 time-points): WBMRI non-PD 51% (34.4% PR, 17.5% SD), 48.1% PD; 3) PD-U BS (40 time-points): WBMRI PD 90%; Non-PD 10% (1pt FLARE &amp; 3pt with subsequent concordant PD). At time of PD-U, 30 out of 40 pt (75%) discontinued treatment due to RECIST PD (24/40) &amp; clinical progression (6/40). 4) PD confirmatory BS (9 time-points) : WBMRI 100%PD. Median rPFS by PCWG was 4.9 months (m) (95%CI: 3.8-5.7); the median mPFS by MET-RADS-P was 2.8 months (2.6-3.9), with overall progression rate of 70% and 94% respectively. Non-PD by WBMRI at 12-weeks associated with longer OS when compared with PD by MRI (median OS: 17.9m (14.2-22.6) vs 14.4m (9.6-17.0) (crude log-rank test 0.0059). Conclusions: Regarding soft-tissue disease, MET-RADS-P detects progression earlier than RECIST in 4.2% time-points, while for bone metastases it detects progression earlier than PCWG at 51.9% of timepoints. WBMRI can better classify BS non-PD patients in PR, SD and PD. Response evaluation based on WBMRI is a prognostic factor in mCRPC.

Informing optimal treatment (tx) sequences for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma (la/mUC) in the United States: Results of a clinical simulation modeling exercise.

e13514 Background: Platinum-based chemotherapy (PBT) followed by avelumab (AVE) as first-line (1L) maintenance for patients with nonprogressive disease (PBT ± AVE) is the standard of care in la/mUC. This study compared the overall survival (OS) and cost-effectiveness of the tx sequence of PBT ± AVE followed by enfortumab vedotin (EV) or other therapies, including immuno-oncology (IO), in second line (2L; ie, PBT + 2L EV/IO or PBT + AVE + 2L EV/IO) vs 1L EV + pembrolizumab (PEM) for PBT-eligible patients (PBTp) from a US commercial payer perspective. Methods: A partitioned survival model compared outcomes with PBT ± AVE and EV + PEM among PBTp. Inputs included progression-free survival and OS, time to tx discontinuation, adverse event (AE) incidence, and health utilities and costs. Efficacy inputs were sourced and extrapolated from patient data in JAVELIN Bladder 100 (data cut: Jun 4, 2021), AVENANCE real-world study (1), and published data (EV-302 trial). Safety data were sourced from US prescribing information. Drug, subsequent tx, disease management, and AE management costs (2023 USD) were calculated. The optimal tx sequencing scenario assumed 80% of patients starting PBT were eligible to receive AVE (2023 Flatiron data cut; (2)), 70% of patients progressing on PBT ± AVE would start 2L, and 70% of those would be eligible for EV. Outcomes included life-years (LYs), quality-adjusted LYs (QALYs), costs, and incremental cost-effectiveness ratio (ICER). Scenarios and probabilistic sensitivity analyses (PSAs) were conducted to assess uncertainty. Results: LY, QALY, costs, and ICER modeling outcomes are shown in the Table. Use of EV in 2L after PBT ± AVE is associated with 0.76 lower QALYs, but given the large cost saving, it represents a cost-effective use of resources at the $150,000/QALY willingness to pay (WTP) threshold. PSAs showed that PBT ± AVE is likely to be more cost-effective over a broad and relevant WTP threshold range ($0-500,000/QALY). Results were sensitive to drug acquisition costs and eligibility to receive AVE and 2L EV. Conclusions: Based on this simulation exercise, the use of 2L EV after PBT ± AVE achieves considerable survival benefit at substantially lower costs vs 1L EV + PEM in PBTp with la/mUC. Given the shift toward value-based care in oncology, such analyses are becoming increasingly relevant to guide clinical decision-making. There is a need to assess tx alternatives that balance healthcare costs while optimizing outcomes in patients with la/mUC. 1. Barthélémy et al, J Clin Oncol 2024;42[suppl 4]: Abstract 561. 2. Moon et al, J Clin Oncol 2023;41[suppl 16]: Abstract 4567. [Table: see text]

Outcomes of accelerated corneal cross-linking for pediatric and adult keratoconus: a comparative study.

To compare the visual, refractive, and topographic outcomes of a high irradiance accelerated corneal crosslinking (ACXL) protocol after a 12-month follow-up between pediatric and adult patients with progressive keratoconus (KC). Retrospective, comparative, cohort study. Patients with KC were divided into two groups: pediatric (≤ 18years) and adult (> 18years). All of them were managed with epi-OFF ACXL (30mW/cm2, 8min, pulsed 1:1 on and off = 7.2J/cm2). Visual, refractive, and topographic values were measured preoperatively and at 1, 3, 6, and 12months postoperative. KC progression, defined as a Kmax increase of ≥ 1D during follow-up, was recorded. Eighty-nine eyes (53 patients) were included for analysis; 45 (50.6%) eyes were from pediatric patients and 44 (49.4%) from adults. At one-year follow-up, pediatric patients experienced significantly higher rates of progression (22.2% vs. 4.5%, p = .014). Contrariwise, female gender (Beta = - 3.62, p = .018), a baseline uncorrected visual acuity of Snellen ≥ 20/60 (Beta = - 5.96, p = .007), and being ≥ 15years at ACXL treatment (Beta = - 0.31, p = .021) were associated with non-progressive disease. A significant improvement in best-corrected visual acuity, Kmin, Km, and Kmax was recorded in both groups. Overall, 86.5% of eyes from both groups showed Kmax stabilization or improvement. Despite the similarity in visual, refractive, and topographic outcomes in both groups, younger age was associated with KC progression after ACXL at one year of follow-up.

Demographic analysis of hearing impairment based on various parameters in patients with cochlear implant.

To analyse the demographic and clinical variables in children having undergone cochlear implant surgery because of deafness. The cross-sectional study was conducted from January to November 2022 at the Centre for Research in Experimental and Applied Medicine laboratory of the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, Pakistan, in collaboration with the Ear, Nose and Throat Department of Combined Military Hospital, Rawalpindi, and comprised children of eith gender aged up to 10 years who had received cochlear implant. Data was collected through questionnaire-based detailed interviews. Syndromic Hearing Loss, Non-Syndromic Hearing Loss, and Acquired Hearing Loss were identified among the subjects. Data was analysed using SPSS 22. Of the 250 cases, 147(58.8%) were boys, 146(58.4%) were aged 0-5 years, 219(87.6%) had prelingual onset of disease, and 202(80.8%) had a non-progressive disease course. In 203(81.2%) cases, normal developmental milestones were seen. Parental consanguinity was observed in 219(87.6%) cases. However, 63(25.2%) patients had a first-degree relative who had a history of deafness. In 170(68%) cases, hearing loss was hereditary, whereas in 80(32%) it was acquired. Meningitis was the most commonly identified risk factor 55(68.75%). Acquired risk factors and family history had significant association with hearing loss (p<0.05). Speech perception significantly improved in all 219(100%) patients with prelingual hearing loss who underwent cochlear implantation. Majority of the cases were found to be male, had a prelingual disease onset and a non-progressive disease course. Family history was a significant factor, while meningitis was the most common acquired cause of hearing loss.

Impact of the response to platinum-based chemotherapy on the second-line immune checkpoint inhibitor monotherapy in non-small cell lung cancer with PD-L1 expression ≤49%: a multicenter retrospective study.

The efficacy of second-line immune checkpoint inhibitor (ICI) therapy is limited in non-small cell lung cancer (NSCLC) patients with ≤ 49% PD-L1 expression. Although chemoimmunotherapy is a promising strategy, platinum-based chemotherapy followed by ICI monotherapy is often used to avoid synergistic adverse events. However, predictors of the efficacy of ICI monotherapy after platinum-based chemotherapy in NSCLC with ≤ 49% PD-L1 expression remain scarce. This multicenter retrospective study evaluated 54 advanced or recurrent NSCLC patients with ≤ 49% PD-L1 expression who were treated with second-line ICI monotherapy following disease progression on first-line platinum-based chemotherapy at nine hospitals in Japan. The impact of response to platinum-based chemotherapy on the efficacy of subsequent ICI monotherapy was investigated. The response to first-line platinum-based chemotherapy was divided into two groups: the non-progressive disease (PD) group, which included patients who did not experience disease progression after four cycles of chemotherapy, and the PD group, which included patients who showed initial PD or could not maintain disease control during the four cycles of chemotherapy and switched to second-line ICI monotherapy. Among the 54 patients, 32 and 22 were classified into the non-PD and PD groups, respectively. The non-PD group showed better response rates (p = 0.038) and longer overall survival (OS) with ICI monotherapy (p = 0.023) than the PD group. Multivariate analysis identified that maintaining a non-PD status after four cycles of chemotherapy was an independent prognostic factor for ICI monotherapy (p = 0.046). Moreover, patients with a modified Glasgow Prognostic Score (mGPS) of 0 showed a tendency for longer OS with ICI monotherapy (p = 0.079), and there was a significant correlation between maintaining non-PD after four cycles of chemotherapy and an mGPS of 0 (p = 0.045). Maintaining a non-PD status after four cycles of platinum-based chemotherapy was a predictor of OS after second-line ICI monotherapy. These findings will help physicians select the most suitable treatment option for NSCLC patients who were treated with platinum-based chemotherapy and switched to second-line treatment. Those who experienced early PD during platinum-based chemotherapy should not be treated with ICI monotherapy in the second-line setting.

The association between phylogenetic lineage and the subclinical phenotype of pulmonary tuberculosis: A retrospective 2-cohort study

Subclinical pulmonary tuberculosis (PTB) is an asymptomatic disease state between established TB infection and symptomatic (clinical) TB disease. It is present in 20-25% of PTB patients in high-income countries. Mycobacterium tuberculosis complex (MTBC) genetic heterogeneity, and differential host immunological responses, have been implicated in its pathogenesis. To determine the association between MTBC lineage and PTB disease phenotype, we used two retrospective cohorts of PTB patients in Canada and two independent lineage attribution methods (DNA fingerprinting and genome sequencing). The first cohort, Cohort 1, consisted of consecutively diagnosed PTB patients between 2014 and 2020. The second, Cohort 2, consisted of newly-arrived foreign-born PTB patients who either were or were not referred for post-landing medical surveillance between 2004 and 2017. Univariable and multivariable logistic regression models were sequentially fitted to both cohorts, adjusting for age, sex, disease type, drug resistance and HIV. Evolution of radiographic features was correlated to lineage in Cohort 2. Cohort 1 and 2 included 874 (209 subclinical) and 111 (44 subclinical) patients, respectively. In both cohorts, subclinical patients were more likely than clinical patients to have relapse/retreatment disease, be smear-negative, have longer times-to-culture positivity and to harbor an ancestral MTBC lineage (Indo-Oceanic or Mycobacterium africanum). Relapse/retreatment disease and ancestral MTBC lineage were independent predictors of subclinical disease (ORs and 95% CIs in Cohort 1, 1.85 [1.07,3.28], p<0.029 and 2.30 [1.66,3.18], p<0.001, respectively, and Cohort 2, 5.74 [1.37-24.06], p<0.017 and 3.21 (1.29,7.97], p<0.012, respectively). The geographic distribution of Indo-Oceanic strains causing subclinical disease was uneven. Non-progressive lung disease was more common in patients infected with ancestral than modern lineages in Cohort 2, 56.0% vs 25.4%, p<0.005. MTBC lineage is a strong predictor of PTB disease phenotype. The genetic drivers of this association, and the relative contribution of other explanatory variables, are unknown.

Immunoglobulin A Nephropathy: A 10-year Analysis in a Single Malaysian Centre

Introduction: Immunoglobulin A nephropathy (IgAN), also referred to as Berger’s disease, is the leading primary glomerular disease cause of end-stage kidney disease (ESKD). Its prevalence, presentation, and progression have been shown to vary between different regions and ethnicities. This study aims to explore the presentation, predictors of disease progression, and outcome in a cohort of Malaysian patients with IgAN. Methods: This study evaluated retrospective data from 82 patients with renal biopsy-proven IgAN. The patients were classified into two categories based on their estimated glomerular filtration rate (eGFR) at the last follow-up: those with progressive disease (50% reduction in eGFR from the time of biopsy and/or eGFR &lt;15 ml/min/1.73 m2) and those with non-progressive disease. Results: The majority of patients (75.6%) were female and, 47.6% were less than 30 years old at the time of the renal biopsy. The most common clinical presentation was proteinuria (86.4%). At the end of a median follow-up of 2.7 (IQR 1.2-5.1) years, 29.3% of patients reached the combined renal outcome. Males were more likely than females to have progressive disease (OR = 2.89). The survival rates without ESKD at five and ten years are 82% and 78%, respectively. Multivariate cox regression analysis showed MAP (HR =1.05 95% CI 1.01-1.10), UPCI (HR=13.67 95%CI 1.06-175.88), and MESTC score &gt;3 (HR=3.95 95%CI 1.09-14.23) as predictors of the combined renal outcome. Conclusion: IgAN is not a benign disease, with a significant progression to ESKD in this cohort. MAP, UPCI, and MESTC &gt;3 are predictors of disease progression.

Characterization of IgA1-Containing Circulating Immune Complexes in Patients with IgA Nephropathy with Progressive vs. Nonprogressive Disease

Characterization of IgA1-Containing Circulating Immune Complexes in Patients with IgA Nephropathy with Progressive vs. Nonprogressive Disease

Optimizing disease progression assessment using blinded central independent review and comparing it with investigator assessment in the PRIMA/ENGOT-ov26/GOG-3012 trial: challenges and solutions

ObjectiveProgression-free survival is an established clinically meaningful endpoint in ovarian cancer trials, but it may be susceptible to bias; therefore, blinded independent centralized radiological review is often included in trial...

Significance of Radiomics in Predicting Local Control for Patients with Malignant Liver Tumors Treated Using Stereotactic Body Radiotherapy.

We routinely deliver Stereotactic Body Radiotherapy (SBRT) in malignant liver tumors using planning computed tomography (CT) and Magnetic Resonance Images (MRI) to aid target definition. In this study, we extracted radiomic features from the MR images to predict local control (LC) post-SBRT. We retrospectively analyzed patients with either hepatocellular cancers (HCCs) or liver metastases (Mets) treated with SBRT between Aug 2014 and Aug 2020. All patients had CT simulation followed by 1.5 Tesla planning MRI in treatment position. Contrast enhanced T1 VIBE and T2 Haste MR sequences were registered with planning CT for target definition. Radiomic features were extracted from Gross Tumor Volumes (GTV) masked out of 60 seconds post contrast T1 VIBE MR images using the Radiomics calculator tool RaCaT. The output included 480 (408 textural, 50 intensity and 22 morphological) features for each target. Principal Component Analysis of the outputs obtained from all the targets yielded 20 radiomic feature clusters after computational prioritization. These clusters were correlated to LC outcomes at various time points post-SBRT. LC was defined as non-progressive disease. Accuracy of predictions was measured by area under (AUC) receiver operating characteristic curve. Cox regression analysis was done to find univariate and multivariate clinical [HCCs vs. Mets, single vs. multiple lesions, previous local therapy (yes vs. no), GTV volume (≤40 vs. >40 cc)], radiomic and dosimetric predictors (continuous) of LC. In total, 97 patients received SBRT to 122 lesions. The median dose prescribed was 45 Gy (range, 30-50 Gy). Median age was 69 years (interquartile range, IQR 61-73 yrs.). 59 patients had HCCs and 38 had Mets. 24 lesions had prior ablative therapy. 75 patients had one target, and 22 had multiple targets. Median GTV was 43.5 cc (IQR 23.4-78.6 cc). Median follow up was 16.6 months (IQR 9.7-27.2 mths). Median LC was 13.6 months (IQR 8.0-23.5 mths). On univariate analysis, histology (HCCs vs. Mets; Hazard ratio (HR) 2.9, 95% CI 1.4-6.4; p < 0.006), radiomic clusters (p < 0.006) and the max., mean, and min. doses to GTV and Planning Target Volumes correlated with improved LC (all p-values < 0.05). On multivariate analysis, histology (HCCs vs. Mets; HR 4.4, 95% CI 1.6-12.3; p = 0.004), radiomic clusters (p = 0.034) and prescription dose (p = 0.048) were significant covariates. Specifically, the 20 radiomic clusters were predictive of LC, and the accuracy of predictions showed promise with AUC values of 0.74, 0.80, and 0.81 at 12, 24, and 36 months post-SBRT, respectively. AUC values for LC in HCCs vs. Mets at 12, 24, and 36 months were 0.83, 0.77, and 0.70, and 0.66, 0.77, and 0.88, respectively. MR-based radiomics predict LC post-SBRT in patients with malignant liver tumors. Further research focused on independent validation of the model is required to explore its clinical use.

Disease-modifying therapies in multiple sclerosis: A focused review of rituximab.

Treatment for multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system, has changed drastically in the last 30 years. Several different disease-modifying therapies are now available, with off-label use of the B-cell-depleting antibody rituximab becoming an increasingly popular choice, as more and more studies report on its effectiveness. The objective of this study was to summarize the current state of evidence for rituximab as a treatment for relapsing-remitting MS (RRMS). A structured literature search was conducted in PubMed, focusing on peer-reviewed studies of adult populations with RRMS. Ongoing trials with rituximab in MS were identified through Clinicaltrials.gov and additional references were identified through review articles. Despite promising results for rituximab as a treatment of MS, the market-authorization holder switched focus from rituximab and discontinued the industry-sponsored trials programme. However, several observational studies, smaller clinical trials and one large investigator-initiated randomized-controlled trial have continued to report fewer clinical relapses, fewer contrast-enhancing lesions on magnetic resonance imaging and better drug survival with rituximab, compared with MS-approved alternatives. Rituximab should be considered as both a first- and second-line therapy option for most MS patients with active, non-progressive disease. However, as an off-label therapy for MS, regulatory approval remains a barrier for wider adoption in many countries.

Prognostic Value of End-of-Treatment PSMA PET/CT in Patients Treated with 177Lu-PSMA Radioligand Therapy: A Retrospective, Single-Center Analysis.

Our objective was to evaluate the prognostic value of end-of-treatment prostate-specific membrane antigen (PSMA) PET/CT (PSMA-PET) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA radioligand therapy (PSMA-RLT). Methods: This was a single-center retrospective study. mCRPC patients who underwent PSMA-RLT with available baseline PSMA-PET (bPET) and end-of-treatment PSMA-PET (ePET) within 6 mo of the last PSMA-RLT cycle were eligible. Overall survival (OS) and prostate-specific antigen (PSA) progression status at the time of ePET (by Prostate Cancer Clinical Trials Working Group 3 criteria) were collected. PSMA-PET tumor segmentation was performed to obtain whole-body PSMA tumor volume (PSMA-VOL) and define progressive (≥20% increase) versus nonprogressive disease. Pairs of bPET and ePET were interpreted for appearance of new lesions. Response Evaluation Criteria in PSMA-PET/CT (RECIP) 1.0 were also applied to define progressive versus nonprogressive disease. The associations between changes in PSMA-VOL, new lesions, RECIP 1.0, and PSA progression status at the time of ePET with OS were evaluated by Kaplan-Meier analysis. Results: Twenty mCRPC patients were included. The median number of treatment cycles was 3.5 (interquartile range [IQR], 2-4). The median time between bPET and cycle 1 of PSMA-RLT was 1.0 mo (IQR, 0.7-1.8 mo). The median time between the last cycle of PSMA-RLT and ePET was 1.9 mo (IQR, 1.2-3.5 mo). Twelve of 20 patients (60%) had died at the last follow-up. The median follow-up time from ePET for survivors was 31.2 mo (IQR, 6.8-40.7 mo). The median OS from ePET was 11.4 mo (IQR, 6.8-30.7 mo). Patients with new lesions on ePET had shorter OS than those without new lesions (median OS, 10.7 mo [95% CI, 9.2-12.2] vs. not reached; P = 0.002). Patients with progressive PSMA-VOL had shorter OS than those with nonprogressive PSMA-VOL (median OS, 10.7 mo [95% CI: 9.7-11.7 mo] vs. not reached; P = 0.007). Patients with progressive RECIP had shorter OS than those with nonprogressive RECIP (median OS, 10.7 mo [95% CI, 9.7-11.7 mo] vs. not reached; P = 0.007). PSA progression at the time of ePET was associated with shorter OS (median, 10.9 mo [95% CI, 9.4-12.4 mo] vs. not reached; P = 0.028). Conclusion: In this retrospective study of 20 mCRPC patients treated with PSMA-RLT, progression on ePET by the appearance of new lesions, changes in PSMA-VOL, and RECIP 1.0 was prognostic for OS. Validation in larger, prospective multicentric clinical trials is warranted.

Tyrosine kinase inhibitor therapy in pediatric sarcoma: Prognostic implications of pulmonary metastatic cavitation.

This study aims to ascertain the prevalence of cavitations in pulmonary metastases among pediatric and young adult patients with sarcoma undergoing tyrosine kinase inhibitor (TKI) therapy, and assess whether cavitation can predict clinical response and survival outcomes. In a single-center retrospective analysis, we examined chest computed tomography (CT) scans of 17 patients (median age 16years; age range: 4-25years) with histopathologically confirmed bone (n=10) or soft tissue (n=7) sarcoma who underwent TKI treatment for lung metastases. The interval between TKI initiation and the onset of lung nodule cavitation and tumor regrowth were assessed. The combination of all imaging studies and clinical data served as the reference standard for clinical responses. Progression-free survival (PFS) was compared between patients with cavitating and solid nodules using Kaplan-Meier survival analysis and log-rank test. Five out of 17 patients (29%) exhibited cavitation of pulmonary nodules during TKI therapy. The median time from TKI initiation to the first observed cavitation was 79days (range: 46-261days). At the time of cavitation, all patients demonstrated stable disease. When the cavities began to fill with solid tumor, 60% (3/5) of patients exhibited progression in other pulmonary nodules. The median PFS for patients with cavitated pulmonary nodules after TKI treatment (6.7months) was significantly longer compared to patients without cavitated nodules (3.8months; log-rank p-value=.03). Cavitation of metastatic pulmonary nodules in sarcoma patients undergoing TKI treatment is indicative of non-progressive disease, and significantly correlates with PFS.

Conventional Transarterial Chemo embolization Using Streptozocin in Patients with Unresectable Neuroendocrine Liver Metastases.

The purpose of this study was to evaluate the clinical, biological and radiological responses to, and tolerability of, conventional transarterial chemoembolization (cTACE) using streptozocin for unresectable neuroendocrine liver metastases. A total of 52 patients with predominant liver disease were treated with cTACE using an emulsion of streptozocin, Lipiodol and embolization particles. A sequential approach was favored in patients with high liver tumor burden. Clinical, biological and radiological responses were evaluated using carcinoid symptoms, biomarkers and mRecist criteria, respectively. A total of 127 procedures were performed with a sequential approach in 65% of patients. All patients received streptozocin and Lipiodol. Carcinoid syndrome was improved in 69% of patients after treatment (p = 0.01). Post-embolization syndrome was reported in 78% of patients. At the end of all cTACE, objective response and non-progressive disease were 32% and 70%, respectively. Progression-free survival was 18.3 ± 13.3 months (median 14.9) and median overall survival (OS) from start of treatment was 74 months. The OS at 1 year, 2 years, 3 years and 5 years was 91% (IC = 84-99%), 84% (CI = 72-95%), 69% (CI = 53-84%) and 63% (C = 46-81%), respectively. cTACE using streptozocin is an effective and well-tolerated palliative option for patients with neuroendocrine liver metastases, associated with prolonged survival and delayed time to progression.

Prognostic utility of RECIP 1.0 with manual and AI-based segmentations in biochemically recurrent prostate cancer from [68Ga]Ga-PSMA-11 PET images

PurposeThis study aimed to (i) validate the Response Evaluation Criteria in PSMA (RECIP 1.0) criteria in a cohort of biochemically recurrent (BCR) prostate cancer (PCa) patients and (ii) determine if this classification could be performed fully automatically using a trained artificial intelligence (AI) model.MethodsOne hundred ninety-nine patients were imaged with [68Ga]Ga-PSMA-11 PET/CT once at the time of biochemical recurrence and then a second time a median of 6.0 months later to assess disease progression. Standard-of-care treatments were administered to patients in the interim. Whole-body tumour volume was quantified semi-automatically (TTVman) in all patients and using a novel AI method (TTVAI) in a subset (n = 74, the remainder were used in the training process of the model). Patients were classified as having progressive disease (RECIP-PD), or non-progressive disease (non RECIP-PD). Association of RECIP classifications with patient overall survival (OS) was assessed using the Kaplan-Meier method with the log rank test and univariate Cox regression analysis with derivation of hazard ratios (HRs). Concordance of manual and AI response classifications was evaluated using the Cohen’s kappa statistic.ResultsTwenty-six patients (26/199 = 13.1%) presented with RECIP-PD according to semi-automated delineations, which was associated with a significantly lower survival probability (log rank p < 0.005) and higher risk of death (HR = 3.78 (1.96–7.28), p < 0.005). Twelve patients (12/74 = 16.2%) presented with RECIP-PD according to AI-based segmentations, which was also associated with a significantly lower survival (log rank p = 0.013) and higher risk of death (HR = 3.75 (1.23–11.47), p = 0.02). Overall, semi-automated and AI-based RECIP classifications were in fair agreement (Cohen’s k = 0.31).ConclusionRECIP 1.0 was demonstrated to be prognostic in a BCR PCa population and is robust to two different segmentation methods, including a novel AI-based method. RECIP 1.0 can be used to assess disease progression in PCa patients with less advanced disease.This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000608561) on 11 June 2015.

Evaluating Real-World Characteristics of Patients With Advanced Urothelial Carcinoma Eligible for Avelumab Maintenance Therapy: A Multicountry Retrospective Medical Chart Review.

Urothelial carcinoma (UC) is a malignancy of the urothelium that encompasses the renal pelvis, bladder, and urethra. Current treatment guidelines for advanced (ie, locally advanced or metastatic) UC recommend using avelumab maintenance therapy in patients with nonprogressive disease following first-line platinum-based chemotherapy. This study aimed to assess the representativeness of the patient population in the JAVELIN Bladder 100 (JB-100) trial, which examined the efficacy and safety of avelumab first-line maintenance, vs. real-world patients with advanced UC that had not progressed with first-line platinum-based chemotherapy treated between 2015 and 2018 by reviewing demographic and clinical characteristics. A medical chart review (MCR) study collected demographics and treatment characteristics for patients with advanced UC in the United States, the United Kingdom, and France. Data were analyzed descriptively for review with data collected from patients enrolled in JB-100. Clinical characteristics were consistent between JB-100 and the MCR. Most patients were male, received 4 to 6 cycles of platinum-based chemotherapy, and had an Eastern Cooperative Oncology Group performance status of 0 or 1. All patients in the MCR had either stable disease or a response with platinum-based chemotherapy (∼75% achieved a complete or partial response). Fewer than half (42.5%) of all patients in the MCR received subsequent therapy. Patient demographics, clinical characteristics, and treatment patterns from a MCR of patients with advanced UC that had not progressed following first-line platinum-based chemotherapy appeared similar to data from patients enrolled in JB-100. Future studies should examine whether real-world outcomes are consistent with findings from JB-100. NCT02603432.