Treatment Response In Patients Research Articles

Sex differences in clinical presentation, treatment response, and side effects of nutritional therapy among patients at nutritional risk: a secondary analysis of the randomized clinical trial EFFORT

BackgroundConsidering sex-specific factors has become an increasingly recognized area for research and practice, in the field of clinical nutrition, there is insufficient evidence regarding differences in clinical presentation, treatment response, and side effects of nutritional therapy among female and male patients. ObjectivesWe hypothesized that the clinical presentation, response to nutritional therapy, and side effects from the intervention would differ in the two sexes. MethodsThis secondary analysis investigated differences among female and male patients at risk for malnutrition regarding initial presentation, clinical outcomes, and treatment response in patients included in the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized controlled trial comparing individualized nutritional support to usual care. ResultsOf 2028 patients included in the trial, 964 were females and 1064 were males. The nutritional history and clinical presentation of female patients was different: they consumed less food and had a greater loss of appetite than the male population. Male patients had higher risk for mortality at 180 d [27% compared with 19%; adjusted hazards ratio (HR): 1.35; 95% CI: 1.12, 1.63] and further adverse clinical outcomes. However, there was no difference in the effect of nutritional support on mortality among female and male patients (HR: 0.76; 95% CI: 0.45, 1.27, compared with HR: 0.81; 95% CI: 0.54, 1.21, respectively; P-interaction = 0.939). ConclusionsResults of this multicenter randomized trial suggest that multimorbid female inpatients have a different clinical presentation and are more prone to loss of appetite and reduced daily dietary intake than male inpatients. Importantly, the favorable response to nutritional interventions was similar in both sexes.This trial was registered at clinicaltrials.gov as NCT02517476.

267P The tumour microenvironment influences long-term tamoxifen treatment response in breast cancer patients

267P The tumour microenvironment influences long-term tamoxifen treatment response in breast cancer patients

Specific Mutation Predict Relapse/Refractory Diffuse Large B-Cell Lymphoma.

The application of rituximab has significantly enhanced the overall survival rates in patients with diffuse large B-cell lymphoma (DLBCL). Regrettably, a significant number of patients still progress to relapse/refractory DLBCL (rrDLBCL). Herein, we employed targeted sequencing of 55 genes to investigate if gene mutations could predict the progression to rrDLBCL. Additionally, we compared the mutation profiles at the time of DLBCL diagnosis with those found in rrDLBCL cases. Our findings highlighted significantly elevated mutation frequencies of TP53, MEF2B and CD58 in diagnostic biopsies from patients who progressed to relapse or refractory disease, with CD58 mutations exclusively observed in the rrDLBCL group. In assessing the predictive power of mutation profiles for treatment responses in primary DLBCL patients, we found that the frequency of CARD11 mutations was substantially higher in non-response group as compared with those who responded to immunochemotherapy. In addition, we revealed mutations in HIST2H2AB, BCL2, NRXN3, FOXO1, HIST1H1C, LYN and TBL1XR1 genes were only detected in initial diagnostic biopsies, mutations in the EBF1 gene were solely detected in the rrDLBCL patients. Collectively, this study elucidates some of the genetic mechanisms contributing to the progression of rrDLBCL and suggests that the presence of CD58 mutations might serve as a powerful predictive marker for relapse/refractory outcomes in primary DLBCL patients.

Leveraging AI technology in sarcoidosis.

Sarcoidosis is a systemic, granulomatous disease of uncertain cause. Diagnosis may be difficult, prognosis uncertain and response to treatment unpredictable. The application of artificial intelligence to sarcoidosis may provide clinical decision support for these challenges. This review will provide an overview of current and potential future applications of artificial intelligence in sarcoidosis. The predominant application of artificial intelligence in sarcoidosis is imaging. Imaging models may differentiate sarcoidosis from other pulmonary disorders. Models, which predict survival and identify key factors relevant to prognosis are also available. The application of cluster analysis to organize sarcoidosis patients into developmental phenotypes is underway. Machine learning algorithms to evaluate the treatment response of sarcoidosis patients do not yet exist but similar models may evaluate patients with other inflammatory disease. The potential applications of artificial intelligence to sarcoidosis is vast, but there are practical limitations that warrant consideration. These include: the accessibility of data, biases in data, cost and privacy. The application of artificial intelligence in medicine is still in its early stages but models are poised to support the diagnostic and prognostic challenges in sarcoidosis patients. The predictive power of these artificial intelligence is likely to come from combining various models, trained on content-rich datasets from phenotypically heterogeneous sarcoidosis patients.

Investigation of the effects of IL-13 and IL-22 cytokine levels on disease activity, prognosis, and treatment response in multiple sclerosis patients treated with fingolimod and glatiramer acetate

Background: Multiple Sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease. In this study, we investigated serum protein levels of Interleukin-13 (IL-13) and Interleukin-22 (IL-22) cytokines. These cytokines play an important role in the generation and regulation of the inflammatory response, which is the pathogenesis of MS, and are potential biomarkers for monitoring therapeutic response. cytokines may play a role in the development of MS lesions. Methods: The study included 66 MS patients and 22 healthy individuals. IL-13 and IL-22 cytokine protein levels were measured by ELISA from peripheral blood serum samples collected from the participants. Patient demographics and treatment history data were also collected. Results: IL-13 and IL-22 parameters were lower in MS patients compared to the control group. There was a significant difference between the patient and control groups in terms of IL-13 (p<0.001). Although the mean IL-22 level of the control group was higher than the patient group, the difference did not reach a significant level (p: 0.257). Conclusion: The results of the study suggest that IL-13 and IL-22 cytokines play an important role in the pathogenesis of MS and are affected by fingolimod and glatiramer acetate treatment.

LBA51 Circulating tumor DNA (ctDNA) dynamics and treatment responses in chemotherapy-ineligible patients (pts) with unresectable stage III NSCLC from the phase II DUART trial

LBA51 Circulating tumor DNA (ctDNA) dynamics and treatment responses in chemotherapy-ineligible patients (pts) with unresectable stage III NSCLC from the phase II DUART trial

Angiogenesis and multiple myeloma: Exploring prognostic potential of adrenomedullin.

Adrenomedullin (AM) is a multifunctional peptide which under basal conditions mainly regulates vasodilation and maintains vascular integrity but is also implicated in the pathogenesis of several malignancies, including multiple myeloma (MM). It has been shown that adrenomedullin is expressed by human myeloma cell lines and that it enhances MM-driven angiogenesis. However, the clinical impact of AM remains unknown. On that basis, we enrolled 32 newly diagnosed multiple myeloma patients (NDMM) and studied the potential of AM as a prognostic biomarker. We report that elevated levels of AM trend with suboptimal treatment response and inferior survival of NDMM patients.

593P Treatment response and survival of patients with early onset colorectal cancer in the Netherlands

593P Treatment response and survival of patients with early onset colorectal cancer in the Netherlands

Machine learning-based cell death marker for predicting prognosis and identifying tumor immune microenvironment in prostate cancer

BackgroundProstate cancer (PCa) incidence and mortality rates are rising, necessitating precise prognostic tools to guide personalized treatment. Dysregulation of programmed cell death pathways in tumor suppression and cancer development has garnered increasing attention, providing a new research direction for identifying biomarkers and potential therapeutic targets. MethodsIntegrating multiple database resources, we constructed and optimized a prognostic signature based on the expression of programmed cell death-related genes (PCDRG) using ten machine learning algorithms. Model performance and prognostic effects were further evaluated. We analyzed the relationships between signature and clinicopathological features, somatic mutations, drug sensitivity, and the tumor immune microenvironment, and constructed a nomogram. The expression level of PCDRGs were evaluated and compared. ResultsOf 1560 PCDRGs, 149 were differentially expressed in PCa, with 34 associated with biochemical recurrence. The PCDRG-derived index (PCDI), constructed using the random forest algorithm, exhibited optimal prognostic performance, successfully stratifying PCa patients into two groups with significant prognostic differences. Patients with high PCDI scores exhibited poorer survival and lower immunotherapy benefit. PCDI was closely associated with the infiltration of specific immune cells, particularly positive correlations with macrophages and T helper cells, and negative correlations with neutrophils, suggesting that PCDI may influence the tumor immune microenvironment, thereby affecting patient prognosis and treatment response. PCDI was associated with age, pathological stage, somatic mutations, and drug sensitivity. The PCDI-based nomogram demonstrated excellent performance in predicting biochemical recurrence in PCa patients. Finally, the differential expression of these PCDRGs was verified based on cell lines and PCa patient expression profile data. ConclusionThis study developed an effective prognostic indicator for prostate cancer, PCDI, using machine learning approaches. PCDI reflects the link between aberrant programmed cell death pathways and disease progression and treatment response.

Association of Plasma Cabozantinib Concentration With Treatment Response and Adverse Events in Japanese Patients With Advanced Renal Cell Carcinoma.

Cabozantinib is highly effective against advanced renal cell carcinoma (RCC). However, approximately 60% of the patients require a dose reduction due to severe adverse events. Although associations between trough concentrations of cabozantinib and its efficacy and safety have been reported in other countries, reports on Japanese patients are unavailable. Therefore, we investigated the association of cabozantinib trough concentration with therapeutic efficacy and adverse events in Japanese patients with RCC and evaluated the usefulness of therapeutic drug monitoring. In this prospective observational study, we measured the trough concentrations of cabozantinib in 10 Japanese patients with RCC enrolled between May 2022 and September 2023. The associations of trough concentration with treatment response, as determined by RECIST 1.1, and the occurrence of grade 2 or higher adverse events were assessed. Trough concentration was higher in patients with controlled cancer than in those with progressive cancer (1024 ± 352 versus 457 ± 216 ng/mL, P = 0.035). In addition, patients with grade 2 or higher adverse events showed a significantly higher trough concentration than those without (1560 ± 513 versus 807 ± 319 ng/mL, P = 0.032). In particular, grade 2 or higher dysgeusia, anorexia, fatigue, and dyspepsia significantly correlated with trough concentrations. This is the first clinical study to demonstrate a correlation between cabozantinib trough concentration, therapeutic efficacy, and adverse events in Japanese patients with RCC. The therapeutic drug monitoring of cabozantinib could be useful for improving therapeutic efficacy and avoiding serious adverse events.

Recent advancements in biomarkers, therapeutics, and associated challenges in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a common type of leukemia that has a high mortality rate. The reasons for high mortality in patients with AML are therapeutic resistance, limited ability to predict duration of response, and likelihood of cancer relapse. Biomarkers, such as leukemic stem cell biomarkers, circulatory biomarkers, measurable residual disease biomarkers, and molecular biomarkers, are used for prognosis, diagnosis, and targeted killing to selectively eliminate AML cells. They also play an indispensable role in providing therapeutic resistance to patients with AML. Therefore, targeting these biomarkers will improve the outcome of AML patients. However, identifying biomarkers that can differentiate between treatment-responsive and non-responsive AML patients remains a challenge. This review discusses recent advancements in AML biomarkers, promising therapeutics, and associated challenges in the treatment of AML.

Effects of BRCA variation on prognosis in patients with nonmetastatic breast cancer.

To compare the clinicopathological characteristics of nonmetastatic breast cancer patients with and without BRCA variations and to investigate the impact of BRCA variations on prognosis. This retrospective single-center study involved an analysis of 938 patients with localized or locally advanced breast cancer who underwent BRCA variation testing. The patients were divided into three groups: 757 were without BRCA variation, 64 were with BRCA1 variation, and 117 were with BRCA2 variation. In patients with BRCA1 variation, the Ki67, grade, and frequency of triple-negative breast cancer were significantly higher than in patients without BRCA variation and with BRCA2 variation. The 5-year disease-free survival in patients with BRCA1 variation was significantly worse than the other two groups (without BRCA, BRCA1, and BRCA2; 87.7%, 69.9%, and 95.3%, respectively, p=0.049). Multivariate analysis detected no significant difference between groups. The pathological complete response rates with neoadjuvant therapy were significantly better in patients with BRCA variations than those without BRCA variations (49.2%vs. 29.6%, p=0.024). Patients with BRCA1 variation had more aggressive tumor characteristics, such as higher Ki67 and higher grade. Also, triple-negative breast cancer was more common. The presence of BRCA1 variation may worsen survival outcomes. Neoadjuvant treatment responses of patients with BRCA variations were significantly better, and neoadjuvant treatment may contribute to survival outcomes in nonmetastatic patients with BRCA variations.

18F-FDG positron emission tomography as a marker of disease activity and treatment response in ankylosing spondylitis and psoriatic arthritis

The ability of 18F-FDG positron emission tomography (PET) to track disease activity and treatment response in patients with Ankylosing Spondylitis (AS) or Psoriatic Arthritis (PsA) remains unclear. Here, we assessed whether 18F-FDG uptake is a marker of disease activity and treatment response in AS or PsA, and explored the ability of 18F-FDG to predict treatment response. Patients with AS (n = 16) or PsA (n = 8) who were scheduled to initiate treatment with biologics were recruited. Participants underwent a clinical evaluation and an 18F-FDG scan prior to therapy initiation. Eleven participants underwent a follow-up 18F-FDG scan 3 months post-treatment. Images were quantified using a composite measure that describes the inflammatory status of the patient. Clinically involved joints/entheses had higher 18F-FDG uptake compared to unaffected areas (median difference > 0.6, p < 0.01). Among patients with AS, pre-treatment 18F-FDG uptake was strongly associated with disease activity (r = 0.65, p = 0.006). Longitudinal 18F-FDG scans demonstrated that decreases in uptake at 3 months were associated to clinical response (βΔgSUVmax > 8.5, p < 0.001). We found no significant association between pre-treatment 18F-FDG uptake and subsequent clinical response. 18F-FDG PET shows potential as a marker of disease activity in AS and PsA, allowing for monitorization of biological treatment efficacy in these patients.

Lymphocyte-to-monocyte, platelet-to-albumin and platelet-to-lymphocyte ratios as prognostic biomarkers for neoadjuvant treatment response in rectal cancer patients

IntroductionSystemic inflammatory response (SIR) indicators are an emerging category of serum biomarkers with significant potential as prognostic and predictive factors in various types of cancers The primary focus of our study was to determine the prognostic value of the lymphocyte-to-monocyte ratio (LMR), platelet-to-albumin ratio (PLR) and platelet-to-albumin ratio (PAR) in evaluating the response to neoadjuvant treatment for patients with rectal cancer. Materials and methodsWe included 99 consecutive patients with rectal cancer which were admitted for surgery in our institution after completing a standard neoadjuvant radio-chemotherapy regimen. Several hematologic parameters, including LMR, PAR and PLR, were calculated by collecting and analyzing blood samples preoperatively. Cases were divided into groups using ROC curve analysis to determine optimal cutoff values for each of the investigated parameters. Treatment response was assessed through histopathological analysis of the resected specimens. ResultsPLR values over 215.2 were correlated with the presence of lymph node metastasis. A similar correlation was observed between PAR values over 41.89 and lymph node positivity. A significant correlation was observed between the presence of tumor budding on histopathological analysis and high-PAR values. A statistically significant correlation between a high PLR and a good response to neoadjuvant treatment was determined. ConclusionsHigh PLR values may be associated with a more favorable treatment response to neoadjuvant radio-chemotherapy. A high PAR may be associated with unfavorable histopathological characteristics. Further studies on these readily available biomarkers are required in order to validate their clinical utility.

Side Shift of Attacks in Cluster Headache: A Prospective Single-center Study

Purpose: Although strict unilaterality is a characteristic of cluster headache (CH), side shift of attacks has been reported. We aimed to assess the prevalence and patterns of side shifts, as well as their correlations with clinical characteristics and treatment response in CH patients. Methods: We prospectively recruited and followed up CH patients at a university hospital. Patients with two or more lifetime CH bouts were interviewed about their side shift history using a structured questionnaire. The demographics and disease characteristics were collected at baseline, and the treatment response at 2- to 4-week follow-up examinations was compared between patients with versus without side shifts. Results: Out of 124 CH patients, 26 (21.0%) experienced side shifts. Sixteen (61.5%) experienced shifts between bouts, 13 (50.0%) within a bout, and four (15.4%) within an attack, with none (0%) reporting bilateral pain during an attack. Among patients who experienced shifts between bouts, six (37.5%) reported a single shift during the entire disease course, while 10 (62.5%) reported multiple shifts between bouts. The demographics, characteristics, and treatment response did not significantly differ according to the history of side shift. Conclusion: In our study, the prevalence and pattern of side shifts were comparable to the results from earlier studies. The presence of side shifts did not show significant association with a specific clinical profile and their incidence did not impact the treatment response. These findings suggest that side-shifting CH is not a distinct entity or migraine variant, but rather within the spectrum of CH.

Exploring and identifying the imaging biomarkers for predicting anti-VEGF treatment response in polypoidal choroidal vasculopathy: aprospective multicenter study.

Polypoidal choroidal vasculopathy (PCV) is a hemorrhagic fundus disease that can lead to permanent vision loss. Predicting the treatment response to anti-VEGF monotherapy in PCV is consistently challenging. We aimed to conduct a prospective multicenter study to explore and identify the imaging biomarkers for predicting the anti-VEGF treatment response in PCV patients, establish predictive model, and undergo multicenter validation. This prospective multicenter study utilized clinical characteristics and images of treatment naïve PCV patients from 15 ophthalmic centers nationwide to screen biomarkers, develop model, and validate its performance. Patients from Peking Union Medical College Hospital were randomly divided into a training set and an internal validation set. A nomogram was established by univariate, LASSO regression, and multivariate regression analysis. Patients from the other 14 centers served as an external test set. Area under the curve (AUC), sensitivity, specificity, and accuracy were calculated. Decision curve analysis (DCA) and clinical impact curve (CIC) were utilized to evaluate the practical utility in clinical decision-making. The eye distribution for the training set, internal validation set, and external test set were 66, 31, and 71, respectively. The 'Good responder' exhibited a thinner subfoveal choroidal thickness (SFCT) (230.67 ± 61.96 vs. 314.42 ± 88.00 μm, p < 0.001), lower choroidal vascularity index (CVI) (0.31 ± 0.08 vs. 0.36 ± 0.05, p = 0.006), fewer choroidal vascular hyperpermeability (CVH) (31.0 vs. 62.2%, p = 0.012), and more intraretinal fluid (IRF) (58.6 vs. 29.7%, p = 0.018). SFCT (OR 0.990; 95% CI 0.981-0.999; p = 0.033) and CVI (OR 0.844; 95% CI 0.732-0.971; p = 0.018) were ultimately included as the optimal predictive biomarkers and presented in the form of a nomogram. The model demonstrated AUC of 0.837 (95% CI 0.738-0.936), 0.891 (95% CI 0.765-1.000), and 0.901 (95% CI 0.824-0.978) for predicting 'Good responder' in the training set, internal validation set, and external test set, respectively, with excellent sensitivity, specificity, and practical utility. Thinner SFCT and lower CVI can serve as imaging biomarkers for predicting good treatment response to anti-VEGF monotherapy in PCV patients. The nomogram based on these biomarkers exhibited satisfactory performances.

Electrophysiological predictors of early response to antidepressants in major depressive disorder

BackgroundPsychomotor retardation (PMR) is a core feature of major depressive disorder (MDD), which is characterized by abnormalities in motor control and cognitive processes. PMR in MDD can predict a poor antidepressant response, suggesting that PMR may serve as a marker of the antidepressant response. However, the neuropathological relationship between treatment outcomes and PMR remains uncertain. Thus, this study examined electrophysiological biomarkers associated with poor antidepressant response in MDD. MethodsA total of 142 subjects were enrolled in this study, including 49 healthy controls (HCs) and 93 MDD patients. All participants performed a simple right-hand visuomotor task during magnetoencephalography (MEG) scanning. Patients who exhibited at least a 50 % reduction in disorder severity at the endpoint (>2 weeks) were considered to be responders. Motor-related beta desynchronization (MRBD) and inter- and intra-hemispheric functional connectivity were measured in the bilateral motor network. ResultsAn increased MRBD and decreased inter- and intra-hemispheric functional connectivity in the motor network during movement were observed in non-responders, relative to responders and HCs. This dysregulation predicted the potential antidepressant response. ConclusionAbnormal local activity and functional connectivity in the motor network indicate poor psychomotor function, which might cause insensitivity to antidepressant treatment. This could be regarded as a potential neural mechanism for the prediction of a patient's treatment response.

Exploratory Analyses of Circulating Neoplastic-Immune Hybrid Cells as Prognostic Biomarkers in Advanced Intrahepatic Cholangiocarcinoma.

Existing clinical biomarkers do not reliably predict treatment response or disease progression in patients with advanced intrahepatic cholangiocarcinoma (ICC). Circulating neoplastic-immune hybrid cells (CHCs) have great promise as a blood-based biomarker for patients with advanced ICC. Peripheral blood specimens were longitudinally collected from patients with advanced ICC enrolled in the HELIX-1 phase II clinical trial (NCT04251715). CHCs were identified by co-expression of pan-cytokeratin (CK) and CD45, and levels were correlated to patient clinical disease course. Unsupervised machine learning was then performed to extract their morphological features to compare them across disease courses. Five patients were included in this study, with a median of nine specimens collected per patient. A median of 13.5 CHCs per 50,000 peripheral blood mononuclear cells were identified at baseline, and levels decreased to zero following the initiation of treatment in all patients. Counts remained undetectable in three patients who demonstrated end-of-trial clinical treatment response and conversely increased in two patients with evidence of therapeutic resistance. In the post-trial surveillance period, interval counts increased prior to or at the time of clinical progression in three patients and remain undetectable in one patient with continued long-term disease stability. Using our machine learning platform, treatment-resistant CHCs exhibited upregulation of CK and downregulation of CD45 relative to treatment-responsive CHCs. CHCs represent a promising blood-based biomarker to supplement traditional radiographic and biochemical measures.

Nevus Spilus, Partial Unilateral Lentiginosis, and Linear and Whorled Nevoid Hypermelanosis: A Comparison of Clinical Features, Course, and Treatment Response.

Skin diseases manifesting as agminated pigmented lesions have overlapping clinical manifestations. Therefore, accurate differentiation is challenging. The clinical characteristics, histopathological findings, and treatment response of patients diagnosed with partial unilateral lentiginosis, nevus spilus, or linear and whorled nevoid hypermelanosis were retrospectively analysed. Each disease demonstrated distinct demographic and clinical characteristics, and the responses to laser treatment varied. The median age at onset varied significantly among the groups: 0.1, 6.6, and 0.5 years in patients with nevus spilus, partial unilateral lentiginosis, and linear and whorled nevoid hypermelanosis, respectively. Regarding the locations of the skin lesions, partial unilateral lentiginosis occurred predominantly on the head and neck, while approximately half of nevus spilus and linear and whorled nevoid hypermelanosis were observed on the extremities. Although linear and whorled nevoid hypermelanosis and partial unilateral lentiginosis share a similar histological feature of basal hyperpigmentation, patients with linear and whorled nevoid hypermelanosis showed the best response to laser treatment, while patients with partial unilateral lentiginosis demonstrated a poor treatment response. The study's data may provide important clues for the differential diagnosis and clinical decision-making regarding the treatment of these agminated pigmented lesions.

First line therapy in stage IV BRAF mutated colorectal cancer

IntroductionThe molecular profile of colorectal cancer (CRC) plays a crucial role in understanding patient prognosis and treatment response. Within CRC, a distinct subgroup can be identified by the presence of the BRAF V600E mutation. This specific mutation, classified as Class I of BRAF mutations, is known to be associated with a poor prognosis and resistance to standard therapy. To determine the most effective treatment approach for this specific subgroup of CRC, we conducted a network meta-analysis (NMA) to compare various pharmacological interventions and evaluate their relative effectiveness in BRAF-mutated CRCs. Materials and methodsOn July 31, 2023, we conducted a systematic search of PubMed, Cochrane Central Register of Controlled Trials, and Embase. The inclusion criteria were as follows: 1) reporting of outcomes in patients with BRAF-mutated CRC who underwent first-line chemotherapy; 2) reporting of survival information as hazard ratios (HR); and 3) publication in English. The data were combined using HRs for overall and progression-free survival (OS and PFS) using random-effects models. NMA was performed under the Bayesian framework, utilizing the GeMTC package. The relative rankings of the treatments were determined using SUCRA scores. ResultsA total of 16 studies were included. When compared to standard chemotherapy (CT) doublets (such as FOLFOX or FOLFIRI), none of the comparison arms demonstrated a gain in OS. CT doublet + bevacizumab did not show significant superiority over either CT doublet alone or 5FU/capecitabine + bevacizumab. FOLFOXIRI and FOLFOXIRI + bevacizumab did not show superiority over any other treatment schedule that was compared. CT doublets + bevacizumab had the highest SUCRA score (0.87), followed by single-agent fluoropyrimidines + bevacizumab (0.61), and FOLFOXIRI (0.56). Regarding PFS, no regimen was found to be superior to the combination of CT doublet plus bevacizumab. However, FOLFOXIRI + bevacizumab + atezolizumab showed a tendency towards better results (HR = 0.26, 95 % CI 0.05–1.1). ConclusionsOur review suggests that a CT doublet with bevacizumab is the most favorable option for OS. However, a reasonable alternative could be a triplet CT without bevacizumab.