Progression-free Survival Values Research Articles

Management of Metastatic Renal Cell Carcinoma Following First-Line Immune Checkpoint Therapy Failure: A Systematic Review.

There is a significant gap in the literature concerning the effective management of second-line therapy for patients with metastatic renal cell carcinoma (RCC) who have received immune checkpoint inhibitors (ICIs). Most of the published articles were small multicenter series or phase 2 studies. To our knowledge, a systematic review that comprehensively outlines the range of treatment options available for patients with metastatic RCC who do not respond to first-line ICIs has not yet been conducted. Our aim was to synthesize evidence on second-line therapies for patients with metastatic RCC after initial treatment with ICIs and to offer recommendations on the best treatment regimens based on the current literature. We conducted a search in PubMed, Embase, and the Cochrane Library on 29 February 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We selected articles that met the predetermined inclusion criteria (written in English, retrospective observational studies, prospective series, and randomized trials reporting second-line therapy for metastatic RCC after failure of ICI-based therapy). Relevant articles were identified in the reference lists. The main endpoint was the overall response rate (ORR), with the median progression-free survival (PFS) and overall survival (OS) as secondary endpoints. We included 27 studies reporting the outcomes of 1970 patients. Salvage therapies were classified as targeted therapy (VEGFR TKIs) in 18 studies and ICIs in 8 studies. In studies where TKIs were the second line of choice, the pooled ORR was 34% (95% CI: 30.2-38%). In studies where ICIs, alone or in combination with TKIs, were used as second-line therapies, the ORR was 25.7% (95% CI: 15.7-39.2%). In studies where TKIs and ICIs were the second-line choices, the pooled median PFS values were 11.4 months (95% CI: 9.5-13.6 months) and 9.8 months (95% CI: 7.5-12.7 months), respectively. This systematic review shows that VEGFR TKIs and ICIs are effective second-line therapies following an initial treatment with anti-PD(L)1 alone or in combination. The treatment choice should be personalized, taking into account the patient's response to first-line ICIs, the site of the disease, the type of first-line combination (with or without VEGFR TKIs), and the patient's overall condition.

Omics-imaging signature-based nomogram to predict the progression-free survival of patients with hepatocellular carcinoma after transcatheter arterial chemoembolization

BACKGROUND Enhanced magnetic resonance imaging (MRI) is widely used in the diagnosis, treatment and prognosis of hepatocellular carcinoma (HCC), but it can not effectively reflect the heterogeneity within the tumor and evaluate the effect after treatment. Preoperative imaging analysis of voxel changes can effectively reflect the internal heterogeneity of the tumor and evaluate the progression-free survival (PFS). AIM To predict the PFS of patients with HCC before operation by building a model with enhanced MRI images. METHODS Delineate the regions of interest (ROI) in arterial phase, portal venous phase and delayed phase of enhanced MRI. After extracting the combinatorial features of ROI, the features are fused to obtain deep learning radiomics (DLR)_Sig. DeLong's test was used to evaluate the diagnostic performance of different typological features. K-M analysis was applied to assess PFS in different risk groups, and the discriminative ability of the model was evaluated using the C-index. RESULTS Tumor diameter and diolame were independent factors influencing the prognosis of PFS. Delong's test revealed multi-phase combined radiomic features had significantly greater area under the curve values than did those of the individual phases (P < 0.05).In deep transfer learning (DTL) and DLR, significant differences were observed between the multi-phase and individual phases feature sets (P < 0.05). K-M survival analysis revealed a median survival time of high risk group and low risk group was 12.8 and 14.2 months, respectively, and the predicted probabilities of 6 months, 1 year and 2 years were 92%, 60%, 40% and 98%, 90%,73%, respectively. The C-index was 0.764, indicating relatively good consistency between the predicted and observed results. DTL and DLR have higher predictive value for 2-year PFS in nomogram. CONCLUSION Based on the multi-temporal characteristics of enhanced MRI and the constructed Nomograph, it provides a new strategy for predicting the PFS of transarterial chemoembolization treatment of HCC.

Fetal hemoglobin induction in azacytidine responders enlightens methylation patterns related to blast clearance in higher-risk MDS and CMML

BackgroundAs new treatment options for patients with higher-risk myelodysplastic syndromes are emerging, identification of prognostic markers for hypomethylating agent (HMA) treatment and understanding mechanisms of their delayed and short-term responses are essential. Early fetal hemoglobin (HbF) induction has been suggested as a prognostic indicator for decitabine-treated patients. Although epigenetic mechanisms are assumed, responding patients’ epigenomes have not been thoroughly examined. We aimed to clarify HbF kinetics and prognostic value for azacytidine treated patients, as well as the epigenetic landscape that might influence HbF re-expression and its clinical relevance.ResultsSerial HbF measurements by high-performance liquid chromatography (n = 20) showed induction of HbF only among responders (p = 0.030). Moreover, HbF increase immediately after the first azacytidine cycle demonstrated prognostic value for progression-free survival (PFS) (p = 0.032, HR = 0.19, CI 0.24–1.63). Changes in methylation patterns were revealed with methylated DNA genome-wide sequencing analysis (n = 7) for FOG-1, RCOR-1, ZBTB7A and genes of the NuRD-complex components. Targeted pyrosequencing methodology (n = 28) revealed a strong inverse correlation between the degree of γ-globin gene (HBG2) promoter methylation and baseline HbF levels (p = 0.003, rs = − 0.663). A potential epigenetic mechanism of HbF re-expression in azacytidine responders was enlightened by targeted methylation analysis, through hypomethylation of site -53 of HBG2 promoter (p = 0.039, rs = − 0.504), which corresponds to MBD2-NuRD binding site, and to hypermethylation of the CpG326 island of ZBTB7A (p = 0.05, rs = 0.482), a known HbF repressor. These changes were associated to blast cell clearance (pHBG2 = 0.011, rs = 0.480/pZBTB7A = 0.026, rs = 0.427) and showed prognostic value for PFS (pZBTB7A = 0.037, HR = 1.14, CI 0.34–3.8).ConclusionsEarly HbF induction is featured as an accessible prognostic indicator for HMA treatment and the proposed potential epigenetic mechanism of HbF re-expression in azacytidine responders includes hypomethylation of the γ-globin gene promoter region and hypermethylation of the CpG326 island of ZBTB7A. The association of these methylation patterns with blast clearance and their prognostic value for PFS paves the way to discuss in-depth azacytidine epigenetic mechanism of action.Graphical abstract

Oral cancer detection and progression prediction using noninvasive cytology-based DNA ploidy approach.

Despite the oral cavity being readily accessible, oral cancer (OC) remains a significant burden. The objective of this study is to develop a DNA ploidy-based cytology test for early detection of high-risk oral lesions. This retrospective study was conducted using 569 oral brushing samples collected from 95 normal and 474 clinically abnormal mucosa with biopsy diagnosis of reactive, low-grade or high-grade precancer or cancers. Brushing cells were processed to characterize DNA ploidy. A two-step DNA ploidy-based algorithm, the DNA ploidy oral cytology (DOC) test, was developed using a training set, and verified in test and validation sets to differentiate high-grade lesions (HGLs) from normal. The prognostic value of the test was evaluated by an independent outcome cohort, including progressed and non-progressing normal, reactive and low-grade lesions. Classification performance was assessed by accuracy, sensitivity, and specificity, while the prognostic value was evaluated by using the Cox proportional hazards analysis on 3-year progression-free survival (PFS). The developed DOC test exhibited high accuracy for detecting HGLs in the test and validation sets, with a sensitivity of 0.97 and 0.96, respectively. Its application to the Outcome cohort demonstrated significant prognostic value for 3-year PFS (log rank, p < 0.001). Multivariate analysis showed that high-grade pathology was the only variable explaining positive DOC test, not age, smoking, or lesional site. Clinical implementation of the DOC test could provide an effective screening method for detecting HGLs for biopsy and lesions at risk of progression.

Effects of lack of access to cancer medication on survival of patients with lung cancer.

e20585 Background: Lung cancer is the leading cause of cancer-related death. The treatment has evolved with the introduction of immunotherapy. During the economic crisis in Lebanon, cancer medications became unavailable forcing oncologists to adjust treatment protocols. This study aims to assess the effect of medication shortage on the progression-free survival (PFS) of lung cancer patients treated at a tertiary care center in Lebanon. Methods: A retrospective analysis of patients with metastatic NSCLC treated during the period of drug shortage (October 2021-December 2022) as compared to those treated in 2019-2020. The primary end point was progression-free survival (PFS) on first line of therapy and its association with dose density ratio (dose density given/standard dose density). Electronic medical records of 117 patients were reviewed and data of 83 eligible patients were collected and analyzed using IBM SPSS software. Results: The mean age at diagnosis was 68 years. Of the total, 63.5% were male. Additionally, 14.4% of the patients received chemotherapy, 39.7% received immunotherapy, and 42.1% received a combination of chemotherapy and immunotherapy. In total, 49 patients were eligible in the 2019/2020 category. 84% of the patients had the opportunity to receive immunotherapy. In contrast, 25 patients were eligible in the 2021/2022 category, and only 73% of them had the opportunity to receive immunotherapy. The median PFS of the 2019/2020 category was 11.2 months, compared to 5.4 months in 2021-2022 (p-value of 0.339). PFS was studied based on the dose density ratio for immunotherapy. Twenty-two patients received a full immunotherapy dose with a ratio of 1, and their PFS was 5.43 months. Twelve patients received a dose density ratio ranging from 0.01 to 0.50 and had a PFS of 10 months. Twenty-nine patients received a dose density ratio of 0.51-0.99 and had PFS of 12.8 months. Contrary to our initial expectations, we did not observe a statistically significant difference between the dose density of immunotherapy and PFS values with a p-value of 0.107. Conclusions: Despite significant shortages in immunotherapy medications, our study suggests that this has no significant detrimental effect on PFS. This unexpected discovery challenges the conventional notion that full immunotherapy doses are necessary and prompts further exploration of the complex relationship between dosage and treatment outcomes in patients.

Health outcomes of pembrolizumab plus chemotherapy in non-small cell lung cancer.

e20527 Background: Pembrolizumab (PEM) is a standard of treatment for advanced or metastatic non-small cell lung cancer (m-nSCLC) in tumors without biomarker actionable. The clinical practice protocol for m-nSCLC in our hospital includes PEM monotherapy if PD-L1 ≥50% and PEM+chemotherapy (PEM+CT) if PD-L1 1-49% or negative. The aim of this study is to determine the effectiveness results of PEM+CT in m-nSCLC in real clinical practice. Methods: It was designed a single center, observational and retrospective study. We included all patients (pts) treated with PEM+CT as first line of therapy with m-nSCLC of September-2019 to August-2023 at a hospital from south Spain, cut-off date 11/30/2023. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The results were analyzed for population and by subgroups (histology, ECOG, previous localized disease (LD) and other), using Kaplan-Meier method. Results: 103 pts were enrolled (89% men), mean age was 66.2 years, 48.5% of pts had ECOG 0, 40.8% ECOG 1 and the rest ECOG 2-3. The tumors were 64.1 % non-squamous histology. 28.2% pts were treated for previous localized disease and 39.8% pts received radiation therapy at some point during treatment. At start of therapy the mean WBC count with PEM+CT was 10.0 x10(9)/L (sd=6.2). With a median follow-up of 10.8 months (m) the median for treatment duration was 5.7 m [95%CI 4.3-7.2].PFS was 7.2 m [IC95% 5.9-8.6] for all pts, 6.6 m [IC95% 4.6-8.7] for non-squamous and 8.2 m [IC95% 4.6-11.7] for squamous histology, p=0.158. OS was 14.2 m [IC95% 10.2-18.2] for all pts, 13.1 m [IC95% 7.6-18.6] and 14.2 [IC95% 9.3-19.2] by non-squamous and squamous histology, respectively, p=0.396.We found statistically significant difference in OS between: pts with ECOG 0-1 (median 15.1 m [IC95% 11.6-18.7]) vs pts with EOCG 2-3 (median 6.6 m [IC95% 1.6-11.6]), p=0.046 and pts previously treated pts of LD (median 21.7 m [IC95% 2.5-40.8]) vs pts with advanced or metastatic disease at onset (median 10.5 m [IC95% 5.2-15.9]), p=0.025. Another subgroup analysis is shown in table. Conclusions: The effectiveness of PEM+CT was similar in OS and PFS values to that of the pivotal trials. In contrast to these, our results were slightly better in squamous histology. The OS was better in pts with ECOG 0-1 and previously treated of localized disease, highlighting the importance of early diagnosis. [Table: see text]

Anti-PD-L1 antibody TQB2450 combined with tyrosine kinase receptor inhibitor AL2846 for immunotherapy-refractory advanced hepatocellular carcinoma and esophageal squamous cell carcinoma: A prospective phase 1b cohort study.

Effective systemic therapy remains limited for advanced esophageal squamous cell carcinoma (ESCC) and hepatocellular carcinoma (HCC), particularly after prior failed treatment with immune checkpoint inhibitors (ICIs). Theoretically, a combination of tyrosine kinase inhibitors (TKIs) with ICIs may restore immunotherapy sensitivity. In this phase 1b study, patients received AL2846, an antiangiogenic TKI with multiple targets (c-MET, VEGFR1, c-KIT, Axl, RET, KDR, and VEGFR3), in combination with an anti-PD-L1 antibody (TQB2450) until disease progression, intolerable toxicity, death, or discontinuation for any cause. The primary end points included overall response rate (ORR) and safety, with secondary end points encompassing progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response. Between November 2021 and September 2022, 18 patients with ESCC and 15 patients with HCC, whose ORR was 11.1% (95% confidence interval [CI], 3.1%-32.8%) and 0%, respectively, were enrolled. Adverse events (AEs) of any grade and treatment-related AEs were documented in 32 patients (97.0%) and 31 patients (93.9%), respectively. Grade 3 or higher AEs were observed in 10 patients (30.3%), with vomiting (6.1%) and infectious pneumonia (9.1%) being the most prevalent. Median PFS and OS values were 3.22 months (95% CI, 1.35-5.68 months) and 5.98 months (95% CI, 3.71-8.87 months), respectively, in patients with ESCC, and 5.55 months (95% CI, 2.66 months to not evaluable [NE]) and 16.72 months (95% CI, 4.86 months to NE), respectively, in patients with HCC. The DCRs were 66.7% (95% CI, 43.75%-83.72%) in patients with ESCC and 73.3% (95% CI, 48.05%-89.10%) in patients with HCC. Combined TQB2450 and AL2846 therapy exhibited a favorable safety profile in immunotherapy-refractory patients with advanced ESCC and HCC.

Real-world osimertinib pretreatment experience in patients with epidermal growth factor receptor T790M mutation-positive locally advanced or metastatic non-small cell lung cancer.

Osimertinib has demonstrated efficacy in patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC) in clinical trials. However, real-world data on its effectiveness remain scarce. Taiwanese patients with T790M-positive locally advanced or metastatic NSCLC and progressive disease following treatment with at least one EGFR tyrosine kinase inhibitor (TKI) were enrolled from the osimertinib early access program. Of the 419 patients (mean age, 63 years; female, 67%), 53% were heavily pretreated (≥ third-line [3L]), making osimertinib a fourth-line (4L) intervention. The median progression-free survival (PFS) was 10.5 months (95% confidence interval [CI]: 8.95-11.41); the 18-month PFS rate was 26.5%. The median overall survival (OS) was 19.0 months (95% CI: 16.30-20.95); the 24-month OS rate was 40.9%. The objective response rate was 32.46%, and the disease control rate was 86.38%. The median time to treatment discontinuation of osimertinib monotherapy was 11.9 months (95% CI: 10.49-13.11). Subgroup analyses of median PFS and OS in the chemotherapy combination group vs. the osimertinib monotherapy group yielded no difference. Central nervous system (CNS) metastasis, number of prior lines of therapy, and types of initial EGFR-TKIs did not significantly impact outcomes. The median PFS values were 9.0 (95% CI: 5.18-11.34) and 10.9 (95% CI: 9.18-11.90) months with and without CNS metastasis, respectively, and 10.8 (95% CI: 8.59-12.69), 13.6 (95% CI: 10.89-16.3), and 9.2 (95% CI: 7.8-10.62) months for second-line (2L), 3L, and ≥4L therapy, respectively. In patients who received osimertinib as 2L therapy, the median PFS values in response to prior afatinib, erlotinib and gefitinib treatment were 11.2 (95% CI: 4.85-4.79), 10.5 (95% CI: 8.59-20.26) and 8.7 (95% CI: 7.21-16.79) months, respectively. Overall, real-world data from Taiwan support the clinical benefits of osimertinib in EGFR T790M -positive NSCLC.

Reassessing the chronic lymphocytic leukemia International Prognostic Index in the era of targeted therapies

AbstractWe evaluated the chronic lymphocytic leukemia International Prognostic Index (CLL-IPI) in patients with CLL treated first line with targeted drugs (n = 991) or chemoimmunotherapy (n = 1256). With a median observation time of 40.5 months, the 3-year progression-free survival (PFS) rates for targeted drug–treated patients varied by CLL-IPI risk group: 96.5% (low), 87.6% (intermediate), 82.4% (high), and 78.7% (very high). Differences between consecutive CLL-IPI risk groups were observed for intermediate vs low and high vs intermediate, but not very high vs high. CLL-IPI factors β2-microglobulin, immunoglobulin heavy variable (IGHV) status, and TP53 status each retained prognostic value for PFS. The 3-year overall survival (OS) rates by CLL-IPI risk groups were 100%, 96%, 93.9%, and 89.4%, respectively, with no differences between consecutive risk groups. Age, Binet stage, β2-microglobulin, and TP53 status each retained prognostic value for OS. In chemoimmunotherapy patients (median observation time, 66.9 months), 3-year PFS rates for CLL-IPI risk groups were 78.1%, 51.4%, 40.1%, and 16.5%, respectively; corresponding 3-year OS rates were 97.4%, 93.1%, 81.8%, and 57.3%. In a matched-pair analysis, PFS differences in targeted therapies (n = 812) vs chemoimmunotherapy (n = 812) across all risk groups and OS differences in all but patients at low risk were demonstrated. The CLL-IPI maintains its prognostic value in predicting PFS outcomes with targeted drugs, but its impact in predicting survival appears diminished. Targeted therapies showed enhanced outcomes over chemoimmunotherapy, highlighting their effectiveness across various risk groups. Our findings support ongoing assessment of prognostic tools in CLL treatment evolution. These trials were registered at www.ClinicalTrials.gov as #NCT02345863, #NCT02401503, #NCT02689141, #NCT02445131, #NCT02758665, #NCT02950051, #NCT02242942, #NCT00262782, #NCT00281918, and #NCT01010061.

Utility of Alpha-Fetoprotein and Ultrasound in the Diagnosis and Prognosis of Patients with Hepatocellular Liver Cancer.

To investigate the utility of alpha-fetoprotein (AFP) and ultrasound in the diagnosis and prognosis of patients with hepatocellular liver cancer (HCC). Using retrospective convenience sampling, 401 patients with HCC who underwent transarterial chemoembolisation at the Department of Oncology of The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University between June 2015 and January 2020 were recruited and assigned to the case group. Simultaneously, patients matched to the case group in terms of gender and age but excluded for HCC were enrolled at a 1:1 ratio and classified as the control group. Relevant parameters were collected from both groups for comparison. Both AFP levels and ultrasound results demonstrated diagnostic value for patients with HCC (P < 0.05). Their combined use exhibited the highest diagnostic accuracy for the cancer, with an area under the curve of 0.896 (95% confidence interval [CI]: 0.876, 0.923), a sensitivity of 67.65% and a specificity of 91.22%. In terms of overall survival (OS), statistically significant differences in the OS rates were observed between the low-AFP (L-AFP) group and high-AFP (H-AFP) group as well as between the low-tumour-diameter (LTD) group and high-tumour-diameter (HTD) group (81.31% vs 52.22% and 85.11% vs 63.41%, respectively; P < 0.05). Regarding the progression-free survival (PFS), significant differences in the PFS rates were also noted between the L-AFP and H-AFP groups and between the LTD and HTD groups (81.31% vs 52.22% and 85.11% vs 63.41%, respectively; P < 0.05). Ultrasound and AFP display notable distinctions when used in the diagnosis of HCC. The sensitivity of ultrasound as a standalone diagnostic tool surpasses that of AFP alone. However, their combined use results in much higher specificity than the use of either test individually. In addition, both techniques hold predictive value for patients' OS and PFS, enabling timely prognostic assessment.

Prognostic Strength of CA 19-9, Demographic Parameters, and Maximum Standardized Uptake Value of Baseline 18F-FDG PET/CT in Treatment-naïve Patients with Pancreatic Carcinoma.

The aim of this study was to evaluate the prognostic value of imaging-based variables and tumor marker in predicting the progression-free survival (PFS) in treatment-naïve pancreatic cancer (PC) using baseline 18-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT). This retro-prospective study was conducted at PET/CT imaging facility of JCIA health-care facility of Pakistan. Total 68 patients with PCs were retrospectively included who had 18FDG PET/CT for staging from March 2017 to December 2020. Thirty-two patients had unresectable Stage IV disease on baseline imaging while the remaining 36 underwent Whipple's procedure and both categories were followed by chemotherapy with/without immunotherapy. These patients were followed for a median period of 18 months (1-62 months) for PFS. Logistic regression analysis and receiver operating characteristic (ROC) analysis were used for independent predictors of patients' demographics, tumor characteristics, CA 19-9, and maximum standardized uptake value (SUVmax) in PFS. Kaplan-Meier's survival curves were analyzed to measure PFS using ROC-derived significant cutoff values of CA 19-9 and SUVmax. Median PFS was 18 months (11-45) with 60% (41/68) patients were either died or labelled having metabolic progressive disease (MPD. Using logistic regression analysis, significant correlations were found for Stage IV disease and pancreatic body/tail tumor with disease progression (odd ratio: 7.535 and 4.803, respectively; P < 0.05). Gender, obesity, histological tumor type, and 18FDG-avid regional nodes did not show a significant impact on PFS. On ROC analysis, SUVmax >5.3 of primary tumor and baseline CA 19-9 >197 U/ml were found to have a significant negative correlation with PFS (area under the curve: 0.827 and 0.911, respectively; P < 0.0001) and no association of age and primary tumor size in PFS. Significantly, shorter PFS was found using ROC-derived cutoff values of SUVmax >5.3 versus ≤5.3 of primary tumor (mean and 95% confidence interval [CI]: 16.7 vs. 48.5 and 10-23 vs. 41-56; log-rank = 25.014; P < 0.0001) and baseline CA 19-9 >197 versus ≤197 U/ml (mean and 95% CI: 11.8 vs. 46.9 and 7-16 vs. 39-55; log-rank = 38.217; P < 0.0001). SUVmax >5.3 of primary tumor and baseline CA 19-9 >197 U/ml were found to have a significant negative correlation with PFS in treatment-naïve PC patients. Among demographics, only Stage IV disease and pancreatic tail and body tumors were found to have a negative association with disease progression.

Impact of Sarcopenia on Prognosis in Primary Hepatocellular Carcinoma Patients Treated with Transcatheter Arterial Chemoembolization: A Single Center Retrospective Study.

Objective: This study aimed to investigate the prognostic effect of sarcopenia on primary hepatocellular carcinoma (HCC) patients after transcatheter arterial chemoembolization (TACE). Methods: This retrospective study enrolled 265 patients diagnosed with HCC who underwent TACE between April 2014 and February 2021. The patients were divided into two groups: the sarcopenia group (n=133) and the non-sarcopenia group (n=132). The study analyzed the differences in overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier curves. The independent risk factors for OS and PFS were determined using univariate and multivariate Cox regression analysis. Based on these factors, the study constructed a prognostic risk grading system. Results: At 3 and 6 months post-TACE, the prognoses of the sarcopenia group were worse than that of the non-sarcopenia group according to the mRECIST criteria. Kaplan-Meier curves showed that the cumulative OS and PFS rate in the non-sarcopenia group were significantly higher compared to the sarcopenia group (HR=3.319, 95%CI: 2.283-4.824, Log-rank P < 0.001; HR=0.631, 95%CI: 0.486-0.820, Log-rank P < 0.001). Sarcopenia, maximal tumor diameter, and AFP ≥ 200 ng/mL were independent risk factors for OS and PFS. The prognostic risk grading system based on sarcopenia, AFP ≥ 200 ng/mL, and maximal tumor diameter≥8.9 cm showed significant differences in prognosis between risk groups. Conclusion: Sarcopenia had excellent predictive value for OS and PFS in patients after TACE, and AFP ≥ 200 ng/mL and maximal tumor diameter were also independent risk factors for a poor prognosis. The prognostic risk grading system based on sarcopenia, AFP, and maximal tumor diameter had good guiding value for the prognosis of patients.

Enhancing precision: A predictive model for 177Lu-DOTATATE treatment response in neuroendocrine tumors using quantitative 68Ga-DOTATATE PET and clinicopathological biomarkers.

Purpose: This study aims to elucidate the role of quantitative SSTR-PET metrics and clinicopathological biomarkers in the progression-free survival (PFS) and overall survival (OS) of neuroendocrine tumors (NETs) treated with peptide receptor radionuclide therapy (PRRT). Methods: A retrospective analysis including 91 NET patients (M47/F44; age 66 years, range 34-90 years) who completed four cycles of standard 177Lu-DOTATATE was conducted. SSTR-avid tumors were segmented from pretherapy SSTR-PET images using a semiautomatic workflow with the tumors labeled based on the anatomical regions. Multiple image-based features including total and organ-specific tumor volume and SSTR density along with clinicopathological biomarkers including Ki-67, chromogranin A (CgA) and alkaline phosphatase (ALP) were analyzed with respect to the PRRT response. Results: The median OS was 39.4 months (95% CI: 33.1-NA months), while the median PFS was 23.9 months (95% CI: 19.3-32.4 months). Total SSTR-avid tumor volume (HR = 3.6; P = 0.07) and bone tumor volume (HR = 1.5; P = 0.003) were associated with shorter OS. Also, total tumor volume (HR = 4.3; P = 0.01), liver tumor volume (HR = 1.8; P = 0.05) and bone tumor volume (HR = 1.4; P = 0.01) were associated with shorter PFS. Furthermore, the presence of large lesion volume with low SSTR uptake was correlated with worse OS (HR = 1.4; P = 0.03) and PFS (HR = 1.5; P = 0.003). Among the biomarkers, elevated baseline CgA and ALP showed a negative association with both OS (CgA: HR = 4.9; P = 0.003, ALP: HR = 52.6; P = 0.004) and PFS (CgA: HR = 4.2; P = 0.002, ALP: HR = 9.4; P = 0.06). Similarly, number of prior systemic treatments was associated with shorter OS (HR = 1.4; P = 0.003) and PFS (HR = 1.2; P = 0.05). Additionally, tumors originating from the midgut primary site demonstrated longer PFS, compared to the pancreas (HR = 1.6; P = 0.16), and those categorized as unknown primary (HR = 3.0; P = 0.002). Conclusion: Image-based features such as SSTR-avid tumor volume, bone tumor involvement, and the presence of large tumors with low SSTR expression demonstrated significant predictive value for PFS, suggesting potential clinical utility in NETs management. Moreover, elevated CgA and ALP, along with an increased number of prior systemic treatments, emerged as significant factors associated with worse PRRT outcomes.

Challenges to achieving BMT in the treatment of AML in Brazil

Introduction: Acute myeloid leukemia is a heterogeneous aggressive leukemia with a poor prognosis. The standard remission induction regimen for medically eligible patients consists of a backbone of cytarabine &amp; anthracycline. Objective: This study assessed the efficacy and safety of cytarabine and anthracycline in a public health center in Salvador, Brazil. Methods: It is a retrospective analysis of 45 non-promyelocytic AML patients diagnosed between 2018 and 2022. Subgroups analyzed included patients having FTL3 and NPM1 mutations, leukocyte count (&gt;10,000 or &lt;10,000), platelets count (&gt;20,000 or &lt;20,000), and transplanted patients. Kaplan-Meier methods were used to determine overall survival (OS) and progression-free survival (PFS). Results: The median age at diagnosis was 43 years (16-69 years), and 62% were females. FLT3-ITD and NPM1 mutations were found for 17.8% and 13.3% of patients, respectively. 85% of the patients had a normal karyotype. For efficacy, 52% of patients were eligible for the next treatment after complete remission. Refractory patients were 20%. Early mortality was 28.8%. Median values of PFS and OS were 3.6 and 8.2 months, respectively. Patients presenting FLT3 mutation and stem cell transplantation had PFS and OS of 20 and 43 months, respectively. Conclusion: The outcomes were consistent with the literature. Waiting time was not critical for treatment outcomes.&#x0D;

Pretreatment systemic inflammatory markers predict survival in endometrial cancer: A Japanese Gynecologic Oncology Group 2043 exploratory data analysis

ObjectiveWe investigated whether pretreatment systemic inflammatory markers are associated with survival outcomes in patients with endometrial cancer (EC). MethodsData from the Japanese Gynecologic Oncology Group 2043 were analyzed. Patients who did not receive chemotherapy or were lost to follow-up were excluded. Associations of pretreatment systemic inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and hemoglobin, albumin, lymphocyte, and platelet (HALP) score, with progression-free survival (PFS) and overall survival (OS) were analyzed. The optimal NLR, PLR, and HALP score cutoff values for PFS and OS were determined. Survival estimates were calculated and compared using the Kaplan–Meier method and log-rank test. ResultsWe included 712 patients (median age: 55 [range, 28–74] years; body mass index [BMI]: 21.1 [15.2–38.6] kg/m2). For PFS, optimal NLR, PLR, and HALP score cutoff values were 1.48, 0.017, and 35.52, respectively, and for OS, the values were 1.88, 0.026, and 19.87, respectively. At optimal PFS-related cutoff values, NLR was associated with BMI; PLR with age, BMI, and clinical stage; and HALP score with BMI, clinical stage, and lymph node metastasis. At optimal OS-related cutoff values, NLR was associated with BMI, PLR, and BMI; the HALP score was associated with age and BMI. The HALP score was a prognostic factor for PFS (p = 0.025), while PLR and HALP scores were prognostic factors for OS (both p = 0.028). ConclusionsPretreatment systemic inflammatory markers are associated with survival outcomes in patients with EC, with the HALP score being a prognostic factor for PFS and OS.

An Ensemble Machine Learning Model Using Gradient Boosting Identifies Patients with Disease Progression in Newly Diagnosed Multiple Myeloma

Introduction: In many cases, treatment decisions for multiple myeloma patients must be made in the absence of high quality randomized controlled clinical trials. As a result, many clinicians lean on prognostic models to drive treatment selection. The most widely used of these models incorporate a limited number of patient related factors that reflect tumor burden, cytogenetic features, or gene expression profiling. These prediction scores are derived from regression models that incorporate these variables at the time of diagnosis. They do not account for variables that change dynamically over time, do not explore the relationship between treatment selection and progression, and imperfectly predict survival outcomes. We designed a prognostic model based on an ensemble machine learning platform to predict progression in NDMM using Extreme Gradient Boosting Machine (XGBoost) combined with accelerated failure time modeling for survival analysis. Methods: We utilized a large retrospective data set containing treatment and response information for 1127 patients with newly diagnosed multiple myeloma (NDMM) treated at the Cleveland Clinic Foundation between 2000 and 2023. Following data preprocessing based on data completeness, 953 patient records were included in our training, testing, and cross validation datasets. For the purposes of our analysis, the initial dataset was randomly split into training (70%), testing (15%) and validation (15%) subsets at the patient level. We also defined the lower and upper bounds for each subset, which is critical due to the right-censored nature of survival data. Hyperparameters for XGBoost were optimized using Bayesian search, minimizing the negative log-likelihood. A random forest method was applied for the imputation of missing data (MissForest). We then trained the XGBoost model using GPU acceleration for enhanced computational efficiency. Finally, a log-rank test on predicted survival times was used to test the model's performance on patients with and without known progression. Results: Our preprocessed data set had 953 patients with a mean age at disease onset of 65 years and a slight male predominance (55%). Approximately 27% of patients harbored high cytogenetic risk disease and 3.5% of the cohort presented with extramedullary disease a diagnosis. At a median follow up of 35 months, 47% of patients had experienced disease progression or death. Induction therapy included an immunomodulatory drug in 40% of patients and proteasome inhibitors in 22%. Frontline autologous stem cell transplantation followed induction in 28% of patients. Median progression free survival in the overall data set was 44 months. These features were consistent across the randomly assigned training, testing, and validation cohorts. Following data preprocessing, 34 independent clinical and genomic variables including selection of first line treatment were assessed as model inputs each available record. Under optimized parameters, the model was trained with a maximum tree depth = 7 and a learning rate ~ 0.22 for the desired output of progression free survival (PFS). We then queried PFS for both the training and validation sets and divided patients into those known to have progressed and those without a progression event. Survival analysis was undertaken using predicted PFS values for patients known to have progressed and those who remained progression free. For the validation data set, our model successfully discerned between progressed and non-progressed cases (log-rank test statistic = 22.07, p &amp;lt; 0.005) (Figure 1). Discussion: We present a machine learning approach based on regularized gradient boosting that accurately discerns between patients who experience progression and those who remain progression free at a median ~35 months of follow-up in a large retrospective data set in patients presenting with NDMM. Further elaboration of our model will allow for the incorporation of large amounts data to predict survival outcomes on the basis of dynamic variables such as depth of response and treatment selection. With the ability to parse outcomes among multiple myeloma patients at high resolution, future clinicians and clinical trialists may be able to overcome limitations in trial design and patient-level therapy selection for both newly diagnosed and relapsed patients.

Pretreatment MR-based radiomics in patients with glioblastoma: A systematic review and meta-analysis of prognostic endpoints

PurposeRecent studies have shown promise of MR-based radiomics in predicting the survival of patients with untreated glioblastoma. This study aimed to comprehensively collate evidence to assess the prognostic value of radiomics in glioblastoma. MethodsPubMed-MEDLINE, Embase, and Web of Science were searched to find original articles investigating the prognostic value of MR-based radiomics in glioblastoma published up to July 14, 2023. Concordance indexes (C-indexes) and Cox proportional hazards ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were pooled via random-effects modeling. For studies aimed at classifying long-term and short-term PFS, a hierarchical regression model was used to calculate pooled sensitivity and specificity. Between-study heterogeneity was assessed using the Higgin inconsistency index (I2). Subgroup regression analysis was performed to find potential factors contributing to heterogeneity. Publication bias was assessed via funnel plots and the Egger test. ResultsAmong 1371 abstracts, 18 and 17 studies were included for qualitative and quantitative data synthesis, respectively. Respective pooled C-indexes and HRs for OS were 0.65 (95 % confidence interval [CI], 0.58–0.72) and 2.88 (95 % CI, 2.28–3.64), whereas those for PFS were 0.61 (95 % CI, 0.55–0.66) and 2.78 (95 % CI, 1.91–4.03). Among 4 studies that predicted short-term PFS, the pooled sensitivity and specificity were 0.77 (95 % CI, 0.58–0.89) and 0.60 (95 % CI, 0.45–0.73), respectively. There was a substantial between-study heterogeneity among studies with the survival endpoint of OS C-index (n = 9, I2 = 83.8 %). Publication bias was not observed overall. ConclusionPretreatment MR-based radiomics provided modest prognostic value in both OS and PFS in patients with glioblastoma.

Impact of Minimal Residual Disease on Progression-Free Survival Outcomes After Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study.

In GLOW, fixed-duration ibrutinib + venetoclax showed superior progression-free survival (PFS) versus chlorambucil + obinutuzumab in older/comorbid patients with previously untreated chronic lymphocytic leukemia (CLL). The current analysis describes minimal residual disease (MRD) kinetics and any potential predictive value for PFS, as it has not yet been evaluated for ibrutinib + venetoclax treatment. Undetectable MRD (uMRD) was assessed by next-generation sequencing at <1 CLL cell per 10,000 (<10-4) and <1 CLL cell per 100,000 (<10-5) leukocytes. PFS was analyzed by MRD status at 3 months after treatment (EOT+3). Ibrutinib + venetoclax achieved deeper uMRD (<10-5) rates in bone marrow (BM) and peripheral blood (PB), respectively, in 40.6% and 43.4% of patients at EOT+3 versus 7.6% and 18.1% of patients receiving chlorambucil + obinutuzumab. Of these patients, uMRD (<10-5) in PB was sustained during the first year post-treatment (EOT+12) in 80.4% of patients receiving ibrutinib + venetoclax and 26.3% receiving chlorambucil + obinutuzumab. Patients with detectable MRD (dMRD; ≥10-4) in PB at EOT+3 were more likely to sustain MRD levels through EOT+12 with ibrutinib + venetoclax versus chlorambucil + obinutuzumab. PFS rates at EOT+12 were high among patients treated with ibrutinib + venetoclax regardless of MRD status at EOT+3: 96.3% and 93.3% in patients with uMRD (<10-4) and dMRD (≥10-4) in BM, respectively, versus 83.3% and 58.7% for patients receiving chlorambucil + obinutuzumab. PFS rates at EOT+12 also remained high in patients with unmutated immunoglobulin heavy-chain variable region (IGHV) receiving ibrutinib + venetoclax, independent of MRD status in BM. Molecular and clinical relapses were less frequent during the first year post-treatment with ibrutinib + venetoclax versus chlorambucil + obinutuzumab regardless of MRD status at EOT+3 and IGHV status. Even for patients not achieving uMRD (<10-4), PFS rates remained high with ibrutinib + venetoclax; this is a novel finding and requires additional follow-up to confirm its persistence over time.

Prognostic Value of Pre-treatment Albumin/Fibrinogen Ratio in Patients with Diffuse Large B-cell Lymphoma

To investigate the value of pre-treatment albumin/fibrinogen ratio (AFR) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). The data of DLBCL patients in the Affiliated Hospital of North Sichuan Medical College from April 2014 to March 2021 were retrieved, and 111 newly diagnosed patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with complete data were included in the study. The clinical, laboratory examination and follow-up data of the patients were collected, and the receiver operating characteristic curve (ROC) was drawn according to patients' AFR before treatment and the survival status at the end of the follow-up, which could be used to preliminarily evaluate the predictive value of AFR for disease progression and patients' survival outcome. Furthermore, the correlation of AFR with the clinical and laboratory characteristics, progression-free survival (PFS) and overall survival (OS) was analyzed, and finally, univariate and multivariate Cox proportional hazard regression models were used to analyze factors affecting PFS and OS of DLBCL patients. The ROC curve indicated that AFR level had a moderate predictive value for PFS and OS in DLBCL patients, with the area under the curve (AUC) of 0.616 (P =0.039) and 0.666 (P =0.004), respectively, and the optimal cut-off values were both 9.06 for PFS and OS. Compared with high-AFR (≥9.06) group, the low-AFR (<9.06) group had a higher proportion of patients with Lugano III-IV stage ( P <0.001), elevated lactate dehydrogenase (P =0.007) and B symptoms (P =0.038). The interim analysis of response showed that the overall response rate (ORR) in the high-AFR group was 89.7%, which was significantly higher than 62.8% in the low-AFR group (P =0.001). With a median follow-up of 18.5 (3-77) months, the median PFS of the high-AFR group was not reached, which was significantly superior to 17 months of the low-AFR group (P =0.009). Similarly, the median OS of high-AFR group was not reached, either, which was significantly superior to 48 months of the low-AFR group (P < 0.001). In multivariate Cox regression analysis, AFR <9.06 was an independent risk factor both for PFS and OS (HR PFS=2.047, P =0.039; HR OS=4.854, P =0.001). Pre-treatment AFR has a significant value for the prognosis evaluation in newly diagnosed DLBCL patients.

Validation of a novel and rapid reagent free assay to predict outcomes for adjuvant therapy decision making in hormone receptor-positive breast cancer.

545 Background: Digistain is a mid-infrared imaging technology that assesses aneuploidy by measuring the nuclear-to-cytoplasmic chemical ratio in the cellular content of tissues to generate the Digistain Index (DI). DI correlates with tumor grade and shows promise for risk stratification. Here we investigated whether DI could predict clinical outcomes in patients with early breast cancer to guide decision making regarding subsequent adjuvant chemotherapy. Methods: Infrared spectrometry was performed on existing tissue microarrays to determine the DI of 801 patients with hormone receptor-positive, HER 2-negative primary breast cancer with ≤3 positive lymph nodes who had received systemic endocrine therapy only. Multivariate logistic modelling incorporated the DI with pathological features to generate the Digistain Prognostic Score (DPS). Receiver operator characteristics curves were used to assess the ability of DPS to predict 5- and 10-year progression-free survival (PFS), recurrence and overall survival (OS). Results: In a Cox-regression analysis, the hazard ratio (HR) of DI to predict OS was 4.49 (95% CI 1.08–18.67; P=0.039) compared with HRs in the range of 1.04–1.81 (all P &lt; 0.001) for age, tumor grade, tumor size and lymph node stage. In multivariate modelling analysis, DPS was consistently highly accurate and had negative predictive values for PFS, recurrence, and OS at 5 and 10 years that were similar, if not superior, to existing genomic-based tests. Using the DPS, the HRs for Kaplan-Meier curves for low- vs. high-risk classification were statistically significant (P&lt;0.001) for PFS, recurrence and OS (1.80, 1.83 and 2.49, respectively). Conclusions: In patients with early breast cancer, DPS showed high accuracy and predictive performance, and was able to stratify patients into low or high risk. Considering its low cost and ability to provide almost immediate prognostic information, DPS has the potential to offer clinical utility to reduce the use of unnecessary chemotherapy.