Event-free Survival Research Articles

Anagrelide and idarubicin combination induces GSDME-mediated pyroptosis as a potential therapy for high-PDE3A acute myeloid leukemia.

Acute myeloid leukemia (AML) is an invasive hematopoietic malignancy requiring novel treatment strategies. In this study, we identified phosphodiesterase 3 A (PDE3A) as a potential new target for drug repositioning in AML. PDE3A was preferentially overexpressed in AML cells than in normal cells, and high expression of PDE3A was correlated with lower event-free survival (EFS) in de novo AML patients. The PDE3A inhibitor anagrelide (ANA) profoundly suppresses the proliferation of high PDE3A-expressing AML cells while exhibiting minimal impact on those with low PDE3A expression. Moreover, synergistic effect of ANA with other chemotherapeutic drugs in high PDE3A expression AML cells was observed. The ANA-idarubicin (IDA) combination showed the most remarkable synergistic effect among all ANA-chemotherapeutic drugs commonly used in AML cell line models. Mechanistically, the synergy between ANA and IDA inhibited the survival of PDE3Ahigh AML cell lines through pyroptosis. This mechanism was initiated by GSDME cleavage triggered by caspase-3 activation. In vivo combination treatment of leukemic animals with high PDE3A expression significantly reduced leukemia burden and prolonged survival time compared with single-drug and vehicle control treatments. Our findings suggest that combined ANA and IDA treatment is an innovative and promising therapeutic strategy for AML patients with high PDE3A expression.

Outcomes of relapsed favorable-histology Wilms tumor in non-clinical trial setting.

The last major North American cooperative group clinical trial for relapsed favorable-histology Wilms tumor (FHWT) was completed in 2002. The outcomes of patients with relapsed Wilms tumor subsequently treated outside of clinical trials are unknown. The aim of this study was to assess the efficacy and toxicity of salvage therapies used for patients with FHWT suffering first relapse. We conducted a retrospective chart review of patients treated for first relapse of FHWT at six large North American institutions from January 2002 through August 2018. Ninety-four patients were identified. Thirty-six patients were classified as standard-risk relapse (SRR), 49 patients as high-risk relapse (HRR), and seven patients as very high-risk relapse (VHRR). Two patients were unable to be classified. Twenty-one patients with SRR were treated with Regimen I. The 4-year event-free survival (EFS) and overall survival (OS) for SRR were 82.4% and 93.3%, respectively, with median follow-up of 72months. Twenty-eight HRR/VHRR patients were treated with ICE therapy, while 13 received National Wilms Tumor Study (5th) (NWTS-5) Stratum C. No patient completed protocol therapy per Stratum C; median maintenance cycles administered were two cycles. The 4-year EFS and OS for HRR/VHRR were 32.6% and 58.3%, respectively, with median follow-up of 33months. Outcomes for all strata of relapsed WT patients treated in a non-clinical setting appear to have similar outcomes to historical cohorts treated on NWTS-5. Improved strategies are urgently needed for HRR and VHRR relapses.

Survival and prognostic factors for relapsed childhood acute lymphoblastic leukemia after treatment with the Chinese children's cancer group ALL-2015 protocol: a single center results.

This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children's Cancer Group ALL-2015 protocol at the Children's Hospital of Chongqing Medical University. The study cohort involving 852 evaluable children with ALL reported a total of 146 relapses during a median follow-up period of 53 months. The primary outcomes measured were the second complete remission (CR2) rates, and 5-year event-free survival (EFS) and overall survival (OS) for patients who received re-treatment post-relapse. Patient data were stratified by ALL subtype (B-ALL vs. T-ALL), age at relapse, site of relapse, and timing of relapse. Univariate and multivariate analyses were performed to identify factors significantly associated with EFS and OS. As of March 31, 2023, 146 relapses were observed, including 128 B-ALL and 18 T-ALL cases. The 8-year CIR was (19.8 ± 1.6)%, with no significant difference between B-ALL and T-ALL (P=0.271). Among the 105 patients who underwent re-treatment, 70 achieved CR2, resulting in a CR2 rate of 67.6%. The 5-year EFS and OS rates for re-treated patients were (45.0 ± 5.4)% and (56.9 ± 5.2)%, respectively. Significant differences in 5-year OS and EFS were found between B-ALL and T-ALL relapses (P < 0.001). The 5-year EFS and OS varied significantly with relapse timing and site of relapse. Factors significantly affecting EFS after relapse included the site of relapse, immunophenotyping, CR2 achievement, and hematopoietic stem cell transplantation (HSCT). Immunophenotyping, CR2 achievement, and HSCT were also identified as significant factors affecting OS after relapse. Despite treatment with the CCCG-ALL-2015 protocol, a significant relapse rate was observed, with 72% of children opting for re-treatment post-relapse. The study highlights the importance of considering specific prognostic factors to inform tailored treatment strategies for relapsed childhood ALL. The findings emphasize the need for further research into improving therapeutic approaches for this patient population. This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children's Cancer Group ALL-2015 protocol at the Children's Hospital of Chongqing Medical University.

Infection Mortality in Acute Promyelocytic Leukemia in Children

Abstract Background Acute promyelocytic leukemia (APL) is a rare entity in children. The percentage of APL patients is 5-7% of all pediatric acute myeloid leukemia cases; a higher frequency (about 20%) is reported in children of Latino/Hispanic ancestry. The introduction of trans retinoic acid has been crucial for both antileukemic efficacy in APL and for prevention of early deaths. Furthermore, the use of arsenic trioxide (ATO) demonstrated to be highly effective in achieving high cure rates with reduced toxicity. However, there is a paucity of data concerning infection related deaths in APL. The objective was to describe the percentage of infection-related-deaths in APL in children; to describe the event free survival (EFS) and describe other main complications observed. Methods We identified 30 patients, as part of the Hospital Alejandro Posadas registry from a single center. We conducted a retrospective observational descriptive analysis. The patients were treated with the GIMEMA-AIDA 2000 protocol (n=23, 76.7%) and 1-LPA pediatrico-18-GALTA/CLEHOP (n=6, 20%). One patient died before treatment was given. The patients were diagnosed between 2000 to 2022. We used frequencies for descriptive variables, Chi2 /Fisher test for categorical data and time to event techniques for survival analysis. Any cause of mortality was extracted and analyzed. Results There were 66.7% of males; and median age was 12-year (IQR 8-15). PML-Rar alfa was positive (cytogenetics) in 23 (76.7%); Negative 6 (20%) and failed in 1 patient (3.3%). 100% had positive molecular biology for PML-rarAlfa transcript. Median white cells were 3.35x 109 /l (IQR 1.675-13.25). The patients were classified as high-risk (n=10, 33.3%) and standard risk (n=20, 66.7%). Four patients showed molecular relapse, 2 had CNS and one bone marrow involvement. Three patients died (10%), 2 due to endocranial hemorrhage, 1 as a consequence of complications of a hematological relapse. No patient died due to microbiologically documented infection or febrile neutropenia. With a mean estimated survival time (median not achieved) in years of 17.7 years, (CI 95% 14.6-20.7) the event free survival was 79% (SE 0.75), with 6 events. Cumulative competitive incidence of relapse 14% (SE 0.65). Conclusion In patients with APL, we could not find infections as cause of death. The overall results of APL management were very promising. Figure 1. Event Free Survival Acute Promyelocytic Leukemia.

Long-term survival can be achieved in a significant fraction of older patients with core binding factor acute myeloid leukemia treated with intensive chemotherapy.

Acute Myeloid Leukemia is mainly a disease of the elderly: however, the knowledge on the outcomes of treatment in core binding factor AML (CBFAML) in older population, is limited. We retrospectively collected data on 229 patients with CBF- AML followed long-term in the last two decades. A 5-year overall survival (OS) of 44.2% (95%CI, 39.9-47.5) and a 5-year event - free survival (EFS) of 32.9% (95%CI, 25.5-40.1) was observed. In a subgroup of >70-year patients who completed intensive therapy (induction + >3 courses of consolidation including autologous stem cell transplant: 10 patients) the median EFS was 11.8 months (95%CI, 9.4 - 15.2) and OS was 40.0% (95%CI, 36.4 - 44.1) at 5yr. In univariate analysis, age >70 (hazard ratio (HR) 1.78, [95%CI, 1.15 - 2.54], p=.008), failure to achieve remission following induction (HR, 8.96 [95%CI, 5.5 - 13.8], p=<.0001), no consolidation therapy (HR, 0.75 [95%CI, 0.47 - 1.84], p=.04) and less than 3 cycles of consolidation (HR, 1.48 [95%CI, 0.75 - 3.2], p=.0004), predicted poorer EFS. Our study shows that intensive therapy, in selected older CBF-AML patients, leads to longer survival. Achieving a CR seems to be the most important first step and at least 3 cycles of consolidation, an important second one. The analysis suggests that these patients should not be excluded from studies with intensive therapies.

Outcome of autologous bone marrow transplant in patients with relapsed and refractory diffuse large B-cell lymphoma in relation with prognostic factor: A single-center experience

Abstract: BACKGROUND Currently, about 50% of diffuse large B-cell lymphoma patients are relapsed following their complete response to first-line therapy. The treatment strategy for fit patients with relapsed refractory diffuse large B-cell lymphoma (R/R DLBCL) has been done with salvage therapy with non-cross resistant combination chemo-immunotherapy regimens followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT). OBJECTIVES: The aim of study was to evaluate the outcome of ASCT for R/R DLBCL in relation to certain prognostic parameters. PATIENTS, MATERIALS AND METHODS: This is retrospective study, conducted from May 2014 to December 2022, at Hematology and BMT Center of Medical City Complex in Baghdad. Thirty-six patients with R/R DLBCL were investigated pre- and post-ASCT; the recorded data included patient disease status pre-transplant, early mortality rate, and type of response at day 100 post-transplant and, survival rate, relapsed rate, and mortality at the end of the study were documented accordingly. RESULTS: The mean age of DLBCL patients in this study was 41.3 (14–65) years, post-ASCT at day 100; there were 33 (91.6%), 2 (5.5%), and 1 (2.7%) patients in complete remission, relapsed progressive disease, and death, respectively, At 3-year posttransplant, the overall survival (OS) was 71%, whereas the event-free survival (EFS) was 59%. According to disease status pre-ASCT, the OS was 62%, 80%, and 66% with P = 0.7, whereas the EFS was 66%, 60%, and 50% with P = 0.5 for CR, UCR, and PR, respectively. CONCLUSION: Iraqi bone marrow transplant center data showed acceptable OS and EFS results in the treatment of R/R DLBCL patients in areas where there is no more option in terms of better OS and EFS but with insignificant relation to the available prognostic factor.

Impact of pre-infusion disease burden on outcomes in pediatric relapsed/refractory B-cell lymphoblastic leukemia following anti-CD19 CAR T-cell therapy

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapies have demonstrated high efficacy in pediatric patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Despite this success, the challenge of post-infusion relapse persists. In our study, we evaluate 116 children with R/R B-ALL who received anti-CD19 CAR T-cell therapy at our center. All patients were included in the response analysis and assessed for survival and toxicity. The CR rate was 98.3%, with 90.5% achieving minimal residual disease negative (MRD)- CR by day 28 (d28). The overall survival (OS) and event-free survival (EFS) were 69.3%±4.5% and 59.0%±4.6%, respectively, with a median follow-up duration of 47.9 months. The patients with pre-infusion MRD ≥ 1% was associated with lower 4-year OS (p = 0.006) and EFS (p = 0.027) comparing to those with MRD < 1%. The incidences of grade ≥ 3 cytokine release syndrome (CRS) and neurotoxicity were21.6 and 5.0%, respectively. Therefore, pre-infusion disease burden is a predictor of long-term outcome following anti-CD19 CAR T-cell therapy for pediatric R/R B-ALL.

Effects of asparaginase-associated pancreatitis in children with haematological tumours.

Asparaginase-associated pancreatitis (AAP) is a major challenge for continuing asparaginase therapy. We aimed to investigate the acute and long-term complications and survival rates related to first and second AAP episodes in Chinese children with haematological malignancies. We retrospectively analysed clinical data of children with pancreatitis who received asparaginase chemotherapy for acute lymphoblastic leukaemia (ALL), acute mixed cell leukaemia, and non-Hodgkin's lymphoma at Shanghai Children's Medical Center from November 2013 to November 2023. Of the 76 children included in the study, 12 had local complications (15.79%), with no deaths recorded. Systemic complications manifested in 28 patients (36.84%), resulting in 3 deaths (3.95%). Four patients (5.26%) developed long-term complications (chronic pancreatitis or insulin-dependent diabetes mellitus). No significant differences in local or long-term complications were recorded between children in the asparaginase re-exposed (n=39) and non-re-exposed (n=45) groups. Among the re-exposed patients, eight (25.81%) experienced a second attack without fatalities or complications. Survival analysis of intermediate- to high-risk patients revealed a significantly higher event-free survival (EFS) rate for the re-exposed group than for the non-re-exposed group. The second AAP episode's occurrence and severity had no relation to the first AAP episode's severity, and the second AAP episode was significantly less severe than the first (p<0.001). The second AAP episode's occurrence is unrelated to the first AAP episode's severity, and the second AAP episode's severity is significantly lower than that of the first. Further, asparaginase therapy could improve EFS in children with intermediate and high-risk ALL.

MYC-rearranged mature B-cell lymphomas in children and young adults are molecularly Burkitt Lymphoma

Aggressive B-cell non-Hodgkin lymphomas (NHL) in children, adolescents, and young adults (CAYA) include Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and a subset of high-grade tumors with features intermediate between these entities whose genetic and molecular profiles have not been completely elucidated. In this study, we have characterized 37 aggressive B-NHL in CAYA, 33 with high-grade morphology, and 4 DLBCL with MYC rearrangement (MYC-R), using targeted next-generation sequencing and the aggressive lymphoma gene expression germinal center B-cell-like (GCB), activated B-cell-like (ABC), and dark zone signatures (DZsig). Twenty-two tumors had MYC-R without BCL2 breaks, and two MYC-non-R cases had BCL6 translocations. MYC-R cases, including DLBCL, carried BL-related mutations and copy number alterations. Conversely, MYC-non-R lymphomas had alterations in the B-cell receptor signaling/NF-κB pathway (71%). DZsig was expressed in 12/13 of MYC-R tumors but only in 2/10 of MYC-non-R GCB tumors (P < 0.001). The 3-year event-free survival (EFS) of the whole cohort was 79.6%. TP53 and KMT2C mutations conferred inferior outcome (3-year EFS P < 0.05). Overall, MYC-R lymphomas in CAYA have a molecular profile similar to BL regardless of their high-grade or DLBCL morphology, whereas MYC-non-R has more heterogeneous genetic alterations closer to that of DLBCL.

Neoadjuvant Pembrolizumab Plus Chemotherapy in Early-Stage Triple-Negative Breast Cancer: A Nationwide Retrospective Turkish Oncology Group Study

Background/Objectives: Following the results of the phase 3 KEYNOTE-522 trial, the U.S. Food and Drug Administration approved pembrolizumab, a humanized IgG4 kappa monoclonal antibody, in combination with neoadjuvant chemotherapy as a new standard of care for high-risk early-stage triple-negative breast cancer (TNBC). This retrospective, multicenter study in Türkiye assessed the real-world efficacy and safety of neoadjuvant pembrolizumab combined with chemotherapy in early-stage TNBC. Methods: The study included 108 patients treated between 2021 and 2023 across 14 oncology centers. Three distinct neoadjuvant regimens incorporating pembrolizumab were administered at the discretion of the treating physicians. The primary outcomes were the pathological complete response (pCR) rate after neoadjuvant therapy and the 2-year event-free survival (EFS) and overall survival (OS) rates. Results: The observed pCR rate was 63.9%, closely mirroring the 64.8% reported in the KEYNOTE-522 trial. At the two-year mark, the EFS rate was 87.2% and the OS rate was 92.3%. Multivariable analysis identified pCR as the sole independent predictor of both EFS and OS. The safety profile was consistent with previous clinical trial data, with most adverse events being of grade 1–2 in severity. Conclusions: These findings provide valuable real-world confirmation of the efficacy and safety of neoadjuvant pembrolizumab–chemotherapy in early-stage TNBC, complementing evidence from randomized trials.

Dofetilide for the treatment of premature ventricular complexes and ventricular tachycardia in patients with structural heart disease.

Dofetilide is a class III antiarrhythmic agent approved for the treatment of atrial fibrillation and atrial flutter. Given the efficacy of other class III agents, it has been used off-label for the treatment of premature ventricular complexes (PVCs) and ventricular tachycardias (VTs). The purpose of this study was to determine the efficacy and safety of dofetilide for ventricular arrythmias (VAs). In this retrospective cohort study, 81 patients (59 men; age = 60 ± 14 years; LVEF = 0.34 ± 0.16) were admitted for dofetilide initiation to treat PVCs (29), VTs (42) or both (10). A ≥ 80% decrease in PVC burden was defined as a satisfactory response. An ICD was present in 72 patients (89%). Another antiarrhythmic was previously used in 50 patients (62%). Prior catheter ablation had been performed in 33 patients (41%). During intitiation, dofetilide was discontinued in 12 patients (15%) due to QT prolongation (8) and inefficacy to suppress VAs (4). Among the 32 patients with PVCs who successfully started dofetilide, the mean PVC burden decreased from 20 ± 10% to 8 ± 8% at a median follow-up of 2.6 months (p < .001). PVC burden was reduced by ≥80% in only 11/32 patients (34%). During 7 ± 1 years of follow-up, 41/69 patients (59%) continued to have VAs and received appropriate ICD therapies for monomorphic VTs (35) and polymorphic VT/VF (6) at a median of 8.0 (IQR 2.6-33.2) months. Dofetilide had to be discontinued in 50/69 patients (72%) due to inefficacy or intolerance. The composite outcome of VT/VF recurrence, heart transplantation, or death occurred in 6/12 patients (50%) without dofetilide and 49/69 patients (71%) with dofetilide. The event free survival was similar between patients treated with and without dofetilide (log-rank p = .55). Treatment with dofetilide was associated with a decrease in PVCs, however clinically significant suppression occurred in a minority of patients. Dofetilide failed to suppress the occurrence of VTs in a majority of patients.

Analysis of predictive effect of European treatment and outcome study long term survival score on survival outcomes in children with chronic myeloid leukemia of chronic phase

Objective: To explore the predictive effect of European treatment and outcome study long term survival (ELTS) score on survival outcomes in chronic myeloid leukemia of chronic phase (CML-CP) children. Methods: A single-center retrospective cohort study was conducted. Clinical data of 216 children with CML-CP in Peking University People's Hospital from January 2010 to December 2023 were analyzed. Children were divided into low, intermediate and high-risk groups according to ELTS score. The survival outcomes and prognostic factors were analyzed. Kaplan-Meier method and Log-Rank test were used for survival analysis.Cox regression model was applied for analysis of prognostic factors. Results: Among the 216 children with CML-CP, there were 122 males and 94 females, with the diagnosis age of 11.0 (8.0, 14.7) years. The follow-up time was 77 (57, 99) months. According to ELTS score, 145, 52, and 19 children were classified as low, intermediate and high-risk group. For the low-risk and intermediate/high-risk groups, the 6-year failure-free survival (FFS) rates were (83.0±3.1)% and (64.6±5.7)%, the 6-year progression-free survival (PFS) rates were (91.4±2.3)% and (78.7±4.8)%, and the 6-year event-free survival (EFS) rates were (80.8±3.3)% and (64.2±5.7)%, with statistically significant difference (χ2=9.45, 7.16, 7.40, P=0.002, 0.007, 0.007), respectively.The 6-year overall survival (OS) rates were (98.5±1.0)% and (95.6±2.4)%, without statistically significant difference (χ2=0.35, P=0.550). Multivariate analysis showed that ELTS score was an independent prognostic factor or tendency for FFS (HR=1.97, 95%CI 1.11-3.49), PFS (HR=2.95, 95%CI 1.18-7.39), and no independent prognostic factor for EFS and OS were found. Conclusions: ELTS score at diagnosis can help stratify the risk of children with CML-CP. The children in intermediate/high-risk group are more likely to have treatment failure, disease progression than those in low-risk group, but the predictive ability of ELTS score for OS is limited.

A multicenter study on effect of delayed chemotherapy on prognosis of Burkitt lymphoma in children

Objective: To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis. Methods: Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups. Results: Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old (OR=0.54,95%CI 0.30-0.93), tumor lysis syndrome before chemotherapy (OR=0.48,95%CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy (OR=0.55,95%CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions: The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Improved Event-Free Survival After Complete or Major Pathologic Response in Patients With Resectable NSCLC Treated With Neoadjuvant Chemoimmunotherapy Regardless of Adjuvant Treatment: A Systematic Review and Individual Patient Data Meta-Analysis

IntroductionNeoadjuvant chemoimmunotherapy has reshaped the treatment landscape for resectable NSCLC, yet the prognostic significance of pathologic response remains unclear. We conducted a systematic review and individual patient data (IPD) meta-analysis to evaluate the impact of achieving pathologic complete response (pCR) or major pathologic response (MPR) on event-free survival (EFS) and assessed the influence of adjuvant immunotherapy. MethodsWe performed an IPD meta-analysis of prospective clinical trials on neoadjuvant or perioperative anti–programmed death-ligand 1 in combination with platinum-based chemotherapy in patients with resectable NSCLC. The IPD was extracted from Kaplan-Meier curves for pCR and/or MPR from the included studies. Survival outcomes were compared between patients achieving pCR or MPR and those who did not, considering both intention-to-treat and resected populations. ResultsAchieving pCR or MPR was associated with improved EFS in the intention-to-treat population (pCR, hazard ratio = 0.13; MPR, hazard ratio = 0.18, respectively) with a 24 months EFS rate of 94% and 88% for patients who achieved pCR and MPR, respectively. Independently from pCR status, patients who were treated in an experimental arm that included adjuvant immunotherapy had similar EFS. ConclusionsOur study reported a strong EFS improvement in patients who achieved either pCR or MPR after neoadjuvant chemoimmunotherapy. The use of adjuvant immunotherapy after tumor resection was not associated with improved EFS.

Comparison of zuberitamab plus CHOP versus rituximab plus CHOP for the treatment of drug-naïve patients diagnosed with CD20-positive diffuse large B-cell lymphoma: a phase 3 trial

BackgroundIn patients with untreated CD20-positive diffuse large B-cell lymphoma (DLBCL), a phase 3 trial was carried out to evaluate the efficacy and safety of zuberitamab plus CHOP (cyclophosphamide, doxorubicin, vincristine,...

Mechanism of Drug Resistance to First-Line Chemotherapeutics Mediated by TXNDC17 in Neuroblastomas.

The prognosis of high-risk neuroblastomas (NB) that are resistant to first-line induction chemotherapy is relatively poor. This study explored the mechanism of resistance to first-line chemotherapeutics mediated by TXNDC17 and its potential solutions in NB. The genetic and clinical data of patients with NB were obtained from the Therapeutically Applicable Research to Generate Effective Treatments dataset. TXNDC17 and BECN1 expressions in NB cells were up- and downregulated by transfection with plasmids and shRNA, respectively. Autophagy-related proteins were detected by western blot. Cell viability was determined using cell proliferation and toxicity experiments. Apoptotic cells were detected using flow cytometry. Overall, 1076 pediatric and adolescent patients with NB were enrolled in this study. The 10-year overall survival (OS) rates and event-free survival (EFS) rates for the patients with a mutation of BECN1 were 37.4 ± 9.1% and 34.5 ± 8.8%, respectively. For patients with a mutation of TXNDC17, the 10-year OS and EFS were 41.4 ± 5.9% and 24.3 ± 5.1%, respectively, which were significantly lower than those in the unaltered group. The overexpression of BECN1 and TXNDC17 reduced NB sensitivity to cisplatin (DDP), etoposide (VP16), and cyclophosphamide (CTX). Autophagy mediated by BECN1 was regulated by TXNDC17, and this process was involved in the resistance to DDP, VP16, and CTX in NB. Suberoylanilide hydroxamic acid (SAHA) can enhance the sensitivity and apoptosis of NB cells to chemotherapeutics by inhibiting TXNDC17, ultimately decreasing autophagy-mediated chemoresistance. Acquired resistance to first-line chemotherapeutics was associated with autophagy mediated by BECN1 and regulated by TXNDC17, which can be reversed by SAHA.

PET/CT Response Assessment in Pediatric Hodgkin Lymphoma: Does Deauville Score 3 Reflect Negativity?

FDG PET is required for the staging and response evaluation of pediatric Hodgkin lymphoma. This study aimed to evaluate the outcomes of pediatric patients with Hodgkin's lymphoma based on interim PET CT assessments of early response following second-cycle chemotherapy using the Deauville score (DS). It also determines whether DS-3 is providing an adequate or inadequate response. We conducted a retrospective cohort study including 504 pediatric patients with classic Hodgkin lymphoma who were treated with chemotherapy based on the Euro-Net protocol at the Children Cancer Hospital Egypt from March 2019 till the end of October 2022. Patients with adequate response DS 1/2 and DS 3 showed nearly the same 3-year event-free survival (EFS) of 91.9% and 91.5%, respectively, compared with those patients with inadequate response DS 4/5, who showed an EFS of 80.4% ( P =0.001). Patients with a DS 3 at interim PET evaluation were considered negative as DS 1/2. Patients of DS 3 group who did not receive radiotherapy had a much worse 3-year EFS by the existence of positive B symptoms, an ESR>30, or an advanced stage. Radiation therapy did not improve the 3-year EFS in patients with an inadequate response (DS4/5) and poor prognostic characteristics. They still need more advanced treatment. DS 1/2 and DS 3 had about the same 3-year EFS, which is better than the 3-year EFS of patients with DS 4/5. Therefore, we can classify DS 3 as having negative FDG PET CT uptake.

A subset of image-defined risk factors predict completeness of resection in children with high-risk neuroblastoma: An international multicenter study.

Image-defined risk factors (IDRFs) were promulgated for predicting the feasibility and safety of complete primary tumor resection in children with neuroblastoma (NB). There is limited understanding of the impact of individual IDRFs on resectability of the primary tumor or patient outcomes. A multicenter database of patients with high-risk NB was interrogated to answer this question. Patients with high-risk NB (age <20years) were eligible if cross-sectional imaging was performed at least twice prior to resection. IDRFs and primary tumor measurements were recorded for each imaging study. Extent of resection was determined from operative reports. There were 211 of 229 patients with IDRFs at diagnosis, and 171 patients with IDRFs present pre-surgery. A ≥90% resection was significantly more likely in the absence of tumor invading or encasing the porta hepatis, hepatoduodenal ligament, superior mesenteric artery (SMA), renal pedicles, abdominal aorta/inferior vena cava (IVC), iliac vessels, and/or diaphragm at diagnosis or an overlapping subset of IDRFs (except diaphragm) at pre-surgery. There were no significant differences in event-free survival (EFS) and overall survival (OS) when patients were stratified by the presence versus absence of any IDRF either at diagnosis or pre-surgery. Two distinct but overlapping subsets of IDRFs present either at diagnosis or after induction chemotherapy significantly influence the probability of a complete resection in children with high-risk NB. The presence of IDRFs was not associated with significant differences in OS or EFS in this cohort.

TCT-844 Symptom-Associated Comorbidities Negatively Affect Symptom Improvement and Event Free Survival After TAVI

TCT-844 Symptom-Associated Comorbidities Negatively Affect Symptom Improvement and Event Free Survival After TAVI

L’immunothérapie péri-opératoire des cancers bronchiques non à petites cellules (CBNPC) : standards actuels et perspectives

Surgery is the cornerstone of the treatment for stage I to IIIA NSCLC. Perioperative platinum-based chemotherapy has long been combined with surgery for patients with resectable stage II-IIIA disease, although the benefits are modest, with an increase in overall survival of approximately 5 %. Recently, immunotherapy has been integrated into neo-adjuvant, adjuvant, and perioperative treatment regimens based on data demonstrating improved event-free survival (EFS) and disease-free survival (DFS), respectively, for localized or locally advanced resectable NSCLC, without activating mutation. Two phase 3 trials have shown an adjuvant benefit and have been approved in Europe but are not supported in France. Four phase III trials Checkmate-816, Checkmate-77T, AEGEAN and KEYNOTE-671 showed a benefit from the combination of an immune checkpoint inhibitor with chemotherapy in the neoadjuvant or in perioperative setting. The results of Checkmate-816 enabled the early access authorization of Nivolumab, in combination with platinum-based chemotherapy in the neoadjuvant treatment of adult patients with resectable NSCLC at high risk of recurrence, including tumors express PD-L1 at the threshold ≥ 1 %, not EGFR mutated, nor ALK translocated.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.