First-line Treatment Strategy Research Articles

Laryngeal NK/T Cell Lymphoma, Nasal Type: Case Report and Literature Review

Extranodal Natural Killer T-cell lymphoma, nasal type represent a rare and aggressive entity of the non-Hodgkin's lymphomas. Laryngeal localization is rare and has a poor prognosis. We report the case of a 66-year-old patient who consulted for dyspnea, dysphonia and dysphagia. Endoscopic examination revealed an endo-laryngeal lesion. Anatomopathological study with immunohistochemistry concluded to a peripheral T NK/T-cell lymphoma nasal type. The extension workup was without abnormalities. Induction chemotherapy without anthracyclines was administered followed by conformal radiotherapy with intensity modulation in arctotherapy. Significant advances have been made over the past decade including better clarification of clinical heterogeneity, more accurate classification using imaging modalities, establishment of new prognostic models, and sequential use of anthracycline-free radiotherapy and chemotherapy in early stages and risk-adapted first-line treatment strategies in advanced stages.

Efficacy of front-line immunochemotherapy for transplant-ineligible mantle cell lymphoma: A network meta-analysis of randomized controlled trials.

There is no standard first-line immunochemotherapy regimen for transplant-ineligible patients with mantle cell lymphoma (MCL) currently, and the efficacy of various treatment remains unclear. We conducted a Bayesian network meta-analysis (NMA) of all eligible randomized controlled trials. Pairwise comparisons and ranking of different first-line treatment options were performed. Nine studies were included in the NMA, involving a total of 2897 MCL patients. The BR-Ibrutinib+R regimen showed the best progression-free survival (PFS), with a surface under the cumulative ranking curve (SUCRA) of 0.89 and probability of being the best treatment (PbBT) of 69%. The VR-CAP regimen was the most potential intervention to improve overall survival (OS), with a SUCRA of 0.89 and PbBT of 63%. Compared with the R-CHOP regimen, the BR regimen achieved a better PFS (hazard ratio [HR] 0.45 [95% credible interval 0.2-0.96]). The BR-Ibrutinib+R regimen (HR 0.14 [0.02-0.99]), BR+R regimen (HR 0.19 [0.034-0.99]), and BR regimen (HR 0.3 [0.08-1.03]) were superior to CHOP regimen with better PFS. The R-FC regimen (HR 2.27 [1.01-5.21]) or FC regimen (HR 3.17 [1.15-8.71]) was inferior to the VR-CAP regimen with a worse OS. Our study presents the most promising first-line treatment strategy for transplant-ineligible MCL patients in terms of PFS and OS, which provides innovative treatment strategy for MCL treatment.

Cost-effectiveness analysis (CEA) of seven treatment regimens in metastatic hormone-sensitive prostate cancer (mHSPC): A public payer perspective using network meta-analysis.

5081 Background: Recently several new drug treatment regimens have been approved in mHSPC state, building on using androgen deprivation therapy (ADT) alone. These include docetaxel + ADT (DA), Abiraterone Acetate + Prednisone + ADT (AAP), Apalutamide + ADT (AAT), Enzalutamide + ADT (ET), Darolutamide + Docetaxel + ADT (DAD) and AAP + ADT + Docetaxel (AAD). At present, there are no predictive biomarkers for choosing a specific drug regimen over the other. The goal of this study was to conduct an economic evaluation of FDA-approved standard of care drug regimens in the current management of mHSPC state to determine a cost-effective optimal treatment from the US public sector (Veterans Affairs-VA) perspective with a 10-year time horizon. Methods: We developed a partitioned survival model in which mHSPC patients (pts) transitioned between three health states (progression free, progressive disease to castrate resistance state, and death) at monthly intervals based on Weibull survival model estimated from published Kaplan-Meier curves using a network meta-analysis. A Bayesian network meta-analysis of seven randomized clinical trials included 7,208 mHSPC pts. The effectiveness outcome in our model was quality-adjusted life-years (QALYs) with utility values obtained from published literature. Costs in our model included those associated with treatment regimens, subsequent therapies, terminal care, and for managing grade 3-4 drug related adverse events. Costs were obtained from the Federal Supply Schedule and published literature. Incremental cost-effectiveness ratios (ICERs) were calculated for nondominated treatments. Results: Average 10-year costs ranged from $32,697 (ADT) to $649,622 (DAD). Mean QALYs ranged from 3.25 (ADT) to 4.57 (ET). Treatment with DAT, EAD, and DAD were eliminated due to dominance (i.e. they were more costly and less effective than other treatments). AAT was the most cost-effective strategy at a willingness-to-pay threshold of $100,000/QALY (ICER = $70,150/QALY). Results from our analysis for all regimens are shown. Conclusions: Our CEA simulation model found AAT is an optimal cost-effective first-line treatment strategy in mHSPC state from a public (VA) payer perspective. [Table: see text]

Treatment strategy for late-life depression.

With the unprecedented aging of the world's population, the number of elderly patients with depression is expected to increase. However, management and treatment of late-life depression (LLD) is more difficult than in early adults. Prior to treatment, diagnosis must take into account the differentiation from, and comorbidity with, organic brain diseases such as dementia and delirium, as well as depression caused by other physical diseases or medications. As clinical features of LLD, treatment response tends to be poor in older patients and recurrence rates are higher than those in early adult patients, therefore psycho-social interventions on the basis of the patient's background and condition are important for LLD. The first-line treatment strategy generally depends on the severity of the depression. Systematic psychotherapies, including cognitive behavioral therapy and problem-solving therapy, have been reported to reduce depressive symptoms in LLD. Regarding pharmacotherapy, newer antidepressants are recommended for LLD, but careful attention to adverse events is required. Treatment using neuromodulation is also reported to be useful for LLD. In the current review, for further-line treatment, treatment strategies were divided according to the level of first-line treatment response. Evidence indicates that LLD is more heterogeneous than depression in younger adults, therefore when treating LLD patients it is necessary to take various conditions and situations into consideration, and to provide detailed treatment that is tailored to each patient.

Systematic Review of the Management of Acute Type A Aortic Dissection with Mesenteric Malperfusion.

Surgical treatment strategy for acute type A aortic dissection (aTAAD) with mesenteric malperfusion (MMP) is quite challenging as it is often associated with poor patient outcomes, and optimal management strategies remain controversial. We conducted MEDLINE and EMBASE database searches up to December 31, 2021 for studies on aTAAD with MMP. Data on study design, patient demographics, patient management strategy, mortality, complications, and follow-up were extracted, analyzed, and investigated. Our literature search identified 941 potentially relevant studies, of which 19 were deemed eligible for this study. A total of 352 patients, mean age: 58.4 11.9 years, diagnosed with aTAAD complicated with MMP were included with an overall prevalence of 4%. Patients for which MMP was observed preoperatively were also included in this analysis. The overall in-hospital mortality amongst these patients was 43.5%, and bowel necrosis and/or multiorgan failure were the major causes of death. Four management strategies for first-line treatment were recognized and these included central aortic repair (191, 54.3%), reperfusion of superior mesenteric artery (SMA) (121, 34.3%), exclusively endo-intervention (11, 3.1%), and exclusively medical intervention (29, 8.2%). These various first-line strategies showed mortality rates of 40.3%, 33.9%, 72.7% and 93.1%, respectively. There was no significant difference in the mortality rate between central aortic repair and reperfusion of SMA as first-line therapies ( = 1.302, p = 0.254). When compared with central aortic repair and reperfusion of SMA, exclusively medical care exhibited a significantly greater mortality rate (p 0.01). aTAAD complicated with MMP is a rare complication that carries a high mortality rate. Central aortic repair and reperfusion of SMA as first-line treatment strategies appear to be associated with better outcomes compared with exclusively endo-intervention and medical care. Clinical decisions may have introduced biases as no differences were indicated in regards to the way patients were being prioritized for the central aortic repair versus reperfusion of SMA. In regards to variable clinical features and pathology of aTAAD complicated with MMP, an individualized approach is recommended.

Discussion on how to optimize active surveillance for low-risk papillary thyroid microcarcinoma in China

Active surveillance, as a first-line treatment strategy for low-risk papillary thyroid microcarcinoma, has been recommended by guidelines worldwide. However, active surveillance has not been widely accepted by doctors and patients in China. In view of the huge challenges faced by active surveillance, doctors should improve their understanding of the "low risk" of papillary thyroid micropapillary cancer, identify some intermediate or high-risk cases, be familiar with the criteria and methods of diagnosis for disease progression, and timely turn patients with disease progression into more active treatment strategies. By analyzing the long-term cost-effectiveness of active surveillance, it is clear that medical expense is only one cost form of medical activities, and the health cost (thyroid removal and surgical complications) paid by patients due to"over-diagnosis and over-treatment" is the most important. Moreover, the weakening of the patients' social function caused by surgical procedures is a more hidden and far-reaching cost. The formulation of health economic policies (including medical insurance) should promote the adjustment of diagnosis and treatment behavior to the direction which is conducive to the long-term life and treatment of patients, improving the overall health level of society and reducing the overall cost. At the same time, doctors should stimulate the subjective initiative of patients, help them fully understand the impact of various treatment methods on their psychological and physical status, support patients psychologically, and strengthen their confidence in implementing active surveillance. By strengthening multi-disciplinary treatment team and system support, doctors can achieve risk stratification of papillary thyroid microcarcinoma, accurate judgment of disease progress, timely counseling for psychological problems, and long-term adherence to active surveillance. Improving the treatment level of advanced thyroid cancer is the key point of improve the prognosis. It is important to promote the development of active surveillance for low-risk papillary thyroid microcarcinoma. In the future, it is necessary to carry out multi-center prospective research and accumulate research evidence for promoting the standardization process of active surveillance. Standardized active surveillance will certainly benefit specific papillary thyroid microcarcinoma patients.

Central extracorporeal circulatory life support (cECLS) in selected patients with critical cardiogenic shock.

Percutaneous extracorporeal life support (pECLS) is increasingly applied in cardiogenic shock (CS) despite a lack of evidence from randomized trials. The in-hospital mortality rate of pECLS still reaches up to 60%, while vascular access site complications remain a shortcoming. Surgical approaches with central cannulation for ECLS (cELCS) have emerged as a bail-out option. To date, no systematic approach exists that allows a definition of inclusion or exclusion criteria for cECLS. This single-center, retrospective, case-control study includes all patients fulfilling criteria for CS at the West German Heart and Vascular Center Essen/Germany between 2015 and 2020 who underwent cECLS (n = 58), excluding post-cardiotomy patients. Seventeen patients received cECLS (29.3%) as a first-line treatment strategy and 41 patients as a second-line strategy (70.7%). The main complications leading to the use of cECLS as a second-line strategy were limb ischemia (32.8%) and ongoing insufficient hemodynamic support (27.6%). The first-line cECLS cohort showed a 30-day mortality rate of 53.3% that was constant during follow-up. The 30-day mortality rate of secondary cECLS candidates was 69.8% and the rate at 3 and 6 months was 79.1%. Younger patients (<55 years) were more likely to exhibit survival benefit with cECLS (p = 0.043). Surgical cECLS in CS is a feasible therapy for highly selected patients with hemodynamic instability, vascular complications, or peripheral access site limitations as complementary strategy in experienced centers.

First-line systemic treatment strategies for unresectable hepatocellular carcinoma: A cost-effectiveness analysis.

Oral multikinase inhibitors and immune checkpoint inhibitors (ICIs) are effective for treating advanced hepatocellular carcinoma (aHCC) but may increase cost. This study compared the cost-effectiveness of oral multikinase inhibitors and ICIs in the first-line treatment of patients with aHCC. A three-state Markov model was established to study the cost-effectiveness of drug treatment from the perspective of Chinese payers. The key outcomes in this study were total cost, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). The total costs and QALYs of sorafenib, sunitinib, donafenib, lenvatinib, sorafenib plus erlotinib, linifanib, brivanib, sintilimab plus IBI305, and atezolizumab plus bevacizumab were $9070 and 0.25, $9362 and 0.78, $33,814 and 0.45, $49,120 and 0.83, $63,064 and 0.81, $74,814 and 0.82, $81,995 and 0.82, $74083 and 0.85, and $104,188 and 0.84, respectively. The drug regimen with the lowest ICER was sunitinib ($551 per QALY), followed by lenvatinib ($68,869 per QALY). For oral multikinase inhibitors, the ICER of lenvatinib, sorafenib plus erlotinib, linifanib and brivanib compared with sunitinib was $779576, $1534,347, $1768,971, and $1963,064, respectively. For ICIs, sintilimab plus IBI305 is more cost effective than atezolizumab plus bevacizumab. The model was most sensitive to the price of sorafenib, the utility of PD, and the price of second-line drugs. For oral multikinase inhibitors, the order of possible treatment options is sunitinib > lenvatinib > sorafenib plus erlotinib > linifanib > brivanib > donafenib. For ICIs, the order of possible treatment options is sintilimab plus IBI305 > atezolizumab plus bevacizumab.

A Real-world Study on the Expression Characteristics of PD-L1 in Patients with Advanced EGFR Positive NSCLC and Its Relationship with the Therapeutic Efficacy of EGFR-TKIs

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is the first choice for first-line treatment of advanced patients with EGFR positive non-small cell lung cancer (NSCLC). For advanced NSCLC patients with negative drive gene and positive programmed cell death ligand 1 (PD-L1) or highly expressed NSCLC patients, the first-line treatment recommends immune checkpoint inhibitors (ICIs) monotherapy or ICIs combined chemotherapy. Therefore, the first-line treatment strategy for advanced NSCLC patients with EGFR positive at different PD-L1 expression levels is worth further exploring. Many previous studies have suggested that the expression of PD-L1 is obviously affected by EGFR mutation, and the expression of PD-L1 is likely to be related to the mechanism of EGFR-TKIs resistance. The purpose of this study was to analyze the expression characteristics of PD-L1 in patients with advanced EGFR positive NSCLC and its relationship with the efficacy of EGFR-TKIs. 159 patients with newly diagnosed advanced NSCLC with EGFR positive (including 141 patients with EGFR sensitive mutations) were enrolled to analyze the relationship between clinicopathological characteristics and PD-L1 expression. The factors affecting the therapeutic effect of EGFR-TKIs in 141 patients with EGFR sensitive mutations were also explored. The PD-L1 expression of the included patients was classified according to the tumor promotion score (TPS): negative (TPS<1%) accounted for 47.2%, low expression (1%≤TPS<50%) accounted for 32.1%, and high expression (TPS≥50%) accounted for 20.7%. Among them, patients with solid predominant cancer cell pathomorphology classification are more likely to have high expression of PD-L1, accounting for 52.9% (P<0.0001). The median progression-free survival (mPFS) of patients with PD-L1 negative expression, low expression and high expression who received first generation EGFR-TKIs treatment were 12.4 months, 10.5 months and 3.7 months, respectively, with significant statistical difference (P<0.0001). During the EGFR-TKIs treatment, patients with a history of radiotherapy for lung lesions have a longer PFS benefit than those without a history of radiotherapy (mPFS: 17.0 months vs 9.3 months, P<0.0001). The expression level of PD-L1 in advanced EGFR positive NSCLC patients was significantly correlated with the pathomorphology classification of cancer cells. The efficacy of EGFR-TKIs in patients with PD-L1 overexpression NSCLC was significantly poor. PFS can be significantly prolonged during targeted therapy combined with radiotherapy of lung lesions.

A120 ENDOSCOPIC CLOSURE TECHNIQUES FOLLOWING ACUTE IATROGENIC PERFORATION -- AN UPDATED SYSTEMATIC REVIEW

Abstract Background Iatrogenic perforation is arguably the most feared adverse event associated with endoscopy. Current American Society for Gastrointestinal Endoscopy (ASGE) and European Society of Gastroenterology Endoscopy (ESGE) guidelines recommend endoscopic closure as the first-line treatment strategy. Historically, this has been achieved using through-the-scope clips (TTSC). Given the emergence of alternative endoscopic closure techniques including over-the-scope clips (OTSC) and endoscopic suturing, we sought to provide an updated review of the literature. Purpose To review endoscopic closure techniques following iatrogenic perforation during screening or therapeutic endoscopy. Method Based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Guidelines, an electronic search of MEDLINE and EMBASE from June 1st, 1946 – Oct 10th, 2022 was performed. Inclusion criteria was limited to English full-text original citations, with case reports, and cohorts with &amp;lt; 3 patients excluded. Our primary objective was to assess complete defect closure after attempted endoscopic treatment. Outcomes were stratified by modality (TTSC, OTSC, endoscopic suturing) and chronologically based on a previous well received systematic review. Result(s) A total of 2549 citations were identified in our electronic search, of which 34 were included representing 830 perforations. Overall, successful endoscopic closure was achieved in 763 cases (91.9%). When stratified by endoscopic closure techniques, range estimates for successful endoscopic closure was 71% – 100%, 57% - 100%, and 100% for TTSC, OTSC and endoscopic suturing respectively. When stratifying chronologically, an improvement in TTSC closure was identified. Conclusion(s) Endoscopic defect closure, including TTSC, OTSC and endoscopic suturing, are effective in the management of iatrogenic perforations with increasing TTSC performance over time. It remains the primary treatment strategy for iatrogenic perforation. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Korean Medication Algorithm Project for Bipolar Disorder 2022: Comparisons with Other Treatment Guidelines.

The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2022 (KMAP-BP 2022) with other recently published guidelines for treating bipolar disorder. We reviewed a total of six recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2022 with those of other guidelines. For initial treatment of mania, there were no significant differences across treatment guidelines. All guidelines recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or a combination of an MS with an AAP as a first-line treatment strategy in a same degree for mania. However, the KMAP-BP 2022 recommended MS + AAP combination therapy for psychotic mania, mixed mania and psychotic depression as treatment of choice. Aripiprazole, quetiapine and olanzapine were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Some guideline suggested olanzapine is a second-line options during maintenance treatment, related to concern about long-term tolerability. Most guidelines advocated newer AAPs (asenapine, cariprazine, long-acting injectable risperidone, and aripiprazole once monthly) as first-line treatment options for all phases while lamotrigine was recommended for depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. KMAP-BP 2022 guidelines were similar to other guidelines, reflecting current changes in prescription patterns for bipolar disorder based on accumulated research data. Strong preference for combination therapy was characteristic of KMAP-BP 2022, predominantly in the treatment of psychotic mania, mixed mania and psychotic depression.

The effects of exercise therapy feedback on subjective treatment outcome and patient satisfaction: study protocol for a mono-centric, randomized, controlled trial in orthopedic rehabilitation (FeedYou)

BackgroundThe disease burden of musculoskeletal disorders necessitates multidisciplinary and patient-centered models of care. Exercise therapy represents a first-line treatment strategy and a central component of medical rehabilitation. In order to realize the goals of long-term physical activity and participation as proposed by the ICF, exercise therapy can be supplemented by interventional techniques from the field of psychotherapy. Although psychotherapist feedback has been shown to improve therapeutic outcome and patient satisfaction, feedback use in exercise therapy is mostly limited to motor learning and exercise instruction. The present paper therefore describes the use of multidimensional exercise therapy feedback in medical rehabilitation. The aims of the trial presented in this study protocol are to evaluate the effects of this novel feedback approach on rehabilitation outcomes in comparison to usual care.MethodsThe study is designed as a prospective, mono-centric, randomized controlled, superiority trial (RCT) with two parallel groups and three measuring points: T0 = start of three-week inpatient rehabilitation, T1 = end of three-week inpatient rehabilitation, T2 = 12-week follow-up. In total, 132 patients suffering from chronic neck, shoulder and/or lumbar spine disorders will be recruited. The intervention involves multidimensional exercise therapy feedbacks during the initial and final physical therapist examination, as well as short exercise therapy feedbacks during the course units of the mandatory group-based exercise therapy program. Primary outcomes are the subjective treatment outcome, assessed by BPI and indication-specific questionnaires, as well as patient satisfaction, assessed by ZUF-8 and an intervention-specific questionnaire. The final data collection is expected by May 2023.DiscussionThis study may provide a valuable insight into the effectiveness of multidimensional exercise therapy feedback to improve treatment outcomes and patient satisfaction in medical rehabilitation. This could contribute to rehabilitation quality assurance and the long-term physical activity behavior of rehabilitation patients.Trial registration The trial has been registered with the German Clinical Trial Register (DRKS) under the Registration Number DRKS00027263.

Cost-effectiveness analysis of anlotinib versus sunitinib as first-line treatment for metastatic renal cell carcinoma in China.

Sunitinib was approved several years ago as a first-line drug for treating metastatic renal cell carcinoma (mRCC); however, its high price and broad side effects when administered at the standard dose have limited its clinical use. A clinical trial (NCT02072031) confirmed that anlotinib could be used as the first-line treatment for mRCC. This study was conducted to evaluate the cost-effectiveness of anlotinib as a first-line treatment for mRCC compared to that of sunitinib in China. A Markov model was established to compare the cost-effectiveness of anlotinib with that of sunitinib. Clinical data were obtained from a multi-center phase II trial (clinical trial information: NCT02072031). Utility values were obtained from the literature. Total costs were calculated from a Chinese societal perspective. A sensitivity analysis was conducted to assess the model uncertainty. The life-year (LY), quality-adjusted life-year (QALY), and incremental cost-effectiveness ratio were calculated. The base-case analysis over a lifetime horizon of 10 years showed that the anlotinib group had 2.196 LYs and 1.487 QALYs at a total cost of $68,597.84. The sunitinib group had 2.194 LYs and 1.432 QALYs at a total cost of $88,060.02. This resulted in incremental cost-effectiveness ratios (ICER) of anlotinib versus sunitinib of $-9,210,858.93 per LYs and $-354,117.07 per QALYs, suggesting that anlotinib is a more effective and less costly strategy than sunitinib. Anlotinib may be a more cost-effective first-line treatment strategy for mRCC than sunitinib in China.

Superior mesenteric artery embolism after radiofrequency ablation in regularly anticoagulated patients with paroxysmal atrial fibrillation: a case report

BackgroundSuperior mesenteric artery embolism (SMAE) is a rare cause of acute abdomen, and the fatality rate is extremely high if it is not diagnosed and treated in time. Due to the lack of knowledge and experience of nonspecialist physicians, it is easy to misdiagnose. Radiofrequency ablation (RFA) has become the first-line treatment strategy for atrial fibrillation (AF). Thromboembolic events are some of the major complications after RFA, whereas SMAE is rarely reported.Case presentationA 70 year-old woman with paroxysmal AF who regularly took anticoagulant drugs for 3 months experienced abdominal pain after RFA. At the outset, she was misdiagnosed as mechanical intestinal obstruction. When the patient presented with blood in the stool, abdominal enhancement computed tomography was conducted and showed a small bowel perforation. Immediate laparotomy was performed, and the final diagnosis was SMAE.ConclusionIt is suggested that for unexplained abdominal pain after RFA of AF, the possibility of SMAE should be considered, and a targeted examination should be carried out in time to confirm the diagnosis and give appropriate treatment.

Biomarkers for predicting response to corticosteroid therapy for immune thrombocytopenic purpura.

Patients with immune thrombocytopenic purpura (ITP) often receive corticosteroids as a first-line treatment strategy. The ability to predict the therapeutic response to corticosteroids before initiating treatment would reduce the risk of adverse events, but biomarkers of this parameter have not yet been established. Here, in a single-centre, retrospective, cohort study of 127 ITP patients who received corticosteroids as first-line treatment, we compared several characteristics and test results between those patients with a favourable response to corticosteroids (responder cohort, n= 68) and those with a poor response to corticosteroids (non-responder cohort, n= 59) to identify potential biomarkers that were predictive of corticosteroid response. We extracted six factors as indicative of poor response to corticosteroid therapy for ITP: old age (≥81 years) (odds ratio [OR], 2.44; p= 0.02); low platelet count (<9 × 109 /L) (OR, 2.25; p= 0.02); high level of platelet-associated IgG (≥445 ng/107 cells) (OR, 3.95; p< 0.01), high platelet distribution width (≥ 14.0g/dL) (OR, 2.00; p= 0.03), high lymphocyte-to-monocyte ratio (≥ 3.52) (OR, 1.40, p= 0.04), and low megakaryocyte count in bone marrow (< 85.5/μl) (OR, 1.72; p= 0.04). Thus, our present data support the fact that these six factors are useful biomarkers for predicting corticosteroid response in patients with ITP.

Emerging predictive biomarkers for novel therapeutics in peripheral T-cell and natural killer/T-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) and natural killer/T-cell lymphoma (NKTCL) are rare subtypes of non-Hodgkin's lymphoma that are typically associated with poor treatment outcomes. Contemporary first-line treatment strategies generally involve the use of combination chemoimmunotherapy, radiation and/or stem cell transplant. Salvage options incorporate a number of novel agents including epigenetic therapies (e.g. HDAC inhibitors, DNMT inhibitors) as well as immune checkpoint inhibitors. However, validated biomarkers to select patients for individualized precision therapy are presently lacking, resulting in high treatment failure rates, unnecessary exposure to drug toxicities, and missed treatment opportunities. Recent advances in research on the tumor and microenvironmental factors of PTCL and NKTCL, including alterations in specific molecular features and immune signatures, have improved our understanding of these diseases, though several issues continue to impede progress in clinical translation. In this Review, we summarize the progress and development of the current predictive biomarker landscape, highlight potential knowledge gaps, and discuss the implications on novel therapeutics development in PTCL and NKTCL.

Immunotherapy or targeted therapy as the first-line strategies for unresectable hepatocellular carcinoma: A network meta-analysis and cost-effectiveness analysis.

The existence of many phase III randomized controlled trials (RCTs) of first-line treatment for unresectable hepatocellular carcinoma (HCC) puzzle doctors and patients in choosing the most effective treatment strategies. We aimed to assess the efficacy, safety, and cost-effectiveness of immunotherapy or targeted therapy as the first-line strategy for unresectable HCC. The included clinical trials were retrieved from PubMed, Embase, the Cochrane library, and Web of Science databases, in which immunotherapy or targeted therapy was regarded as the first-line treatment for unresectable HCC, published in English between January 1, 2010, and September 20, 2022. We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) from the Chinese payer's perspective. Overall survival (OS), progression-free survival (PFS), the ranks of different treatments using P-score, and adverse events (AEs) were evaluated by NMA. Total costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-benefit ratio (ICER) were estimated from 15-year Markov models developed by CEA. We identified 2,825 records, including 11,796 patients, from 15 RCTs. The NMA revealed that sintilimab plus a bevacizumab biosimilar (HR, 0.57; 95% CI, 0.43 to 0.75; P = 0.96) and camrelizumab plus rivoceranib (HR, 0.56; 95% CI, 0.41 to 0.66; P = 0.94) could lead to great improvements in OS and PFS compared with sorafenib-related survival. The CEA indicated that tislelizumab increased by 0.220 QALYs (0.312 LYs) and decreased by $1,938 compared with sorafenib, which yielded ICERs of -$8,809/QALY (-$2,612/LY). Sensitivity analysis showed that the model was stable. Sintilimab plus a bevacizumab biosimilar and camrelizumab plus rivoceranib significantly prolonged OS and PFS, respectively. Further considering the pharmacoeconomics factors, tislelizumab is the most cost-effective first-line treatment strategy for unresectable HCC in China.

Immune checkpoint inhibitors as first-line therapy for non-small cell lung cancer: A systematic evaluation and meta-analysis

ABSTRACT Recently, immune checkpoint inhibitors (ICIs) present promising application prospects in treating non-small cell lung cancer (NSCLC). This study aimed to investigate optimal treatment strategy by comparing the first-line treatment strategies with ICIs in NSCLC. We retrieved relevant studies on first-line therapy of NSCLC with ICIs. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were treatment-related serious adverse events (tr-SAEs) with grade 3 or higher and objective response rate (ORR). We also conducted a Bayesian network meta-analysis. We included 14 studies involving 7,823 patients and compared seven different interventions. In PD-L1 nonselective NSCLC, nivolumab+ipilimumab had good PFS and ORR, pembrolizumab significantly prolonged OS, and nivolumab had the fewest adverse events (AEs). For PD-L1-positive patients, nivolumab remarkably prolonged OS. For those with negative PD-L1, nivolumab+ipilimumab also showed an advantage. In addition, nivolumab+ipilimumab significantly prolonged the PFS in both PD-L1-negative and -positive patients. For patients with PD-L1 tumor proportion score (TPS) within 1–49%, atezolizumab+chemotherapy remarkably prolonged PFS and OS. For those with PD-L1 TPS ≥50%, pembrolizumab prolonged OS and atezolizumab+chemotherapy significantly prolonged PFS. Nivolumab combined with ipilimumab showed advantages in OS, PFS and ORR in most patients. Nivolumab+ipilimumab may be the optimal first-line therapy for NSCLC.

First-line Systemic Treatment Strategies in Patients with Initially Unresectable Colorectal Liver Metastases: Phase III CAIRO5 Study of the Dutch Colorectal Cancer Group

First-line Systemic Treatment Strategies in Patients with Initially Unresectable Colorectal Liver Metastases: Phase III CAIRO5 Study of the Dutch Colorectal Cancer Group

Curcumin nano-prodrug induces multi-phase cell cycle arrest in colorectal cancer through suppression of CDKs and specific down-regulation of PLK1

Aberrant activation of cell cycle proteins leads to tumor progression in most cancer types. While 5-fluorouracil (5-Fu)-based chemotherapy remains the first-line treatment strategy for colorectal cancer (CRC), more than 40% of patients with advanced CRC do not benefit from the regimen. Herein, a chemically modified curcumin (mCur) was developed to explore its curative effect on CRC and reveal its potential role in cell cycle regulation. Amphiphilic mCur could self-assemble into positively charged nano-micelles, hence facilitating high cellular uptake and anticancer activity. Multi-phase cell cycle arrest, induced by both mCur and Cur, was first observed in HCT 116 ​cells. This phenomenon was mainly attributed to the Cur/mCur mediated downregulation of cyclin-dependent kinases (CDKs) and their direct interactions. Moreover, mCur and Cur treatments generated distinct phenotypic signatures. In particular, mCur induced distinct dynamic fluctuations in cell cycle and a relatively higher proportion of cells in the G2/M phase than Cur, and specifically triggered the impaired expression of polo-like kinase 1 (PLK1). An in vivo evaluation using a CRC patient-derived tumor xenograft (PDX) model indicated that mCur exhibited better antitumor effects via more significant downregulation of PLK1 in PLK1high PDX, with no obvious systemic toxicity. Collectively, our study revealed a unique multi-phase cell cycle arrest effect of Cur-based antitumor agents and highlighted the potential of mCur as a PLK1-targeted inhibitor for CRC therapy.