UNASSIGNED: The aim of the study was to evaluate the efficacy and safety of induction and consolidation with all-trans retinoic acid (ATRA) +arsenic trioxide (ATO) +anthracyclines and maintenance with ATRA +Realgar-Indigo naturalis formula (RIF) for high-risk APL.
UNASSIGNED: Twenty-one patients with high-risk APL treated with ATRA+ATO+ anthracyclines for induction and consolidation and ATRA+RIF for maintenance from 2012 to 2021 were analyzed. Endpoints include morphological complete remission (CR) and complete molecular remission (CMR), early death (ED) and relapse, survival and adverse events (AEs).
UNASSIGNED: After induction treatment, all 21 patients (100%) achieved morphological CR and 14 people (66.7%) achieved CMR. Five of the 21 patients did not undergo immunological minimal residual disease (MRD) examination after induction; however, 14 of the remaining 16 patients were MRD negative (87.5%). The median time to achieve CR and CMR was 26 days (range: 16-44) and 40 days (range: 22-75), respectively. The cumulative probability of achieving CR and CMR in 45 days was 100% and 76.2% (95% CI: 56.9-91.3%), respectively. All patients achieved CMR and MRD negativity after the three courses of consolidation treatment. The median follow-up was 66 months (25-142), with no central nervous system relapse and bone marrow morphological or molecular relapse until now, and all patients survived with 100% overall survival and 100% event-free survival. Grade 4 adverse events (AEs) were observed in 3 patients (14.3%) during the induction period including arrhythmia (n = 1), pulmonary infection (n = 1) and respiratory failure (n = 1); and the most frequent grade 3 AEs were pulmonary infection, accounting for 62.0% and 28.6%, respectively, during induction and consolidation treatment, followed by neutropenia, accounting for 42.9% and 38.1%, respectively.
UNASSIGNED: For newly diagnosed high-risk APL patients, induction and consolidation with ATRA+ATO+anthracyclines and maintenance with ATRA+RIF is a highly curative treatment approach.

OBJECTIVE: The neoadjuvant chemotherapy (NACT) regimen for triple negative breast cancer (TNBC) primarily consists of anthracyclines and taxanes, and the addition of platinum-based drugs can further enhance the efficacy. However, it is also accompanied by more adverse events, and considering the potential severe and irreversible toxicity of anthracyclines, an increasing number of studies are exploring nonanthracycline regimens that combine taxanes and platinum-based drugs.
METHODS: The retrospective study included 273 stage II-III TNBC patients who received NACT. The AT group, consisting of 195 (71.4%) patients, received a combination of anthracyclines and taxanes, while the TCb group, consisting of 78 (28.6%) patients, received a combination of taxanes and carboplatin. Logistic regression analysis was performed to evaluate the factors influencing pathological complete response (pCR) and residual cancer burden (RCB). The log-rank test was used to assess the differences in event-free survival (EFS) and overall survival (OS) among the different treatment groups. Cox regression analysis was conducted to evaluate the factors influencing EFS and OS.
RESULTS: After NACT and surgery, the TCb group had a higher rate of pCR at 44.9%, as compared to the AT group at 31.3%. The difference between the two groups was 13.6% (OR = 0.559, 95% CI 0.326-0.959, P = 0.035). The TCb group had a 57.7% rate of RCB 0-1, which was higher than the AT group\'s rate of 42.6%. The difference between the two groups was 15.1% (OR = 0.543, 95% CI 0.319-0.925, P = 0.024), With a median follow-up time of 40 months, the TCb group had better EFS (log-rank, P = 0.014) and OS (log-rank, P = 0.040) as compared to the AT group. Clinical TNM stage and RCB grade were identified as independent factors influencing EFS and OS, while treatment group was identified as an independent factor influencing EFS, with a close-to-significant impact on OS.
CONCLUSIONS: In stage II-III triple TNBC patients, the NACT regimen combining taxanes and carboplatin yields higher rates of pCR and significant improvements in EFS and OS as compared to the regimen combining anthracyclines and taxanes.

UNASSIGNED: Pediatric acute myeloid leukemia (AML) has poor prognosis and high rate of relapse and mortality, and exploration of new treatment options is still critically needed.
UNASSIGNED: To summarize the outcome of our new treatment strategies for pediatric AML, which is characterized by dual induction and acute lymphoblastic leukemia (ALL) elements consolidation.
UNASSIGNED: Retrospective, single-arm study.
UNASSIGNED: From July 2012 to December 2019, an intensive chemotherapy protocol was used for newly diagnosed children with AML, which contains dual induction, three courses of consolidations based on high-dose cytarabine, and two courses of consolidations composed of high-dose methotrexate, vincristine, asparaginase, and mercaptopurine (ALL-like elements). Blasts were monitored by bone marrow smears at intervals, and two lumbar punctures were performed during chemotherapy. We retrospectively analyzed the efficacy and safety of this study. The last follow-up was on 26 May 2023.
UNASSIGNED: A total of 70 pediatric AMLs were included. The median age at diagnosis was 6.7 (0.5-16.0) years. The median initial WBC count was 23.74 × 109/L, 11 of whom ⩾100 × 109/L. After dual induction, there were 62 cases of complete remission (CR), 5 cases of partial remission, and 3 cases of nonremission. The CR rate was 88.57%. The median follow-up time was 5.8 (0.2-9.4) years, the 5-year overall survival was 78.2% ± 5%, the event-free survival (EFS) was 71.2% ± 5.6%, and the cumulative recurrence rate was 27.75%. The 5-year EFS of patients with initial WBC < 100 × 109/L (n = 59) and ⩾100 × 109/L (n = 11) were 76.4% ± 5.7% and 45.5% ± 15% (p = 0.013), respectively. A total of 650 hospital infections occurred. The main causes of infection were respiratory tract infection (26.92%), septicemia (18.46%), stomatitis (11.85%), and skin and soft-tissue infection (10.46%).
UNASSIGNED: This intensive treatment protocol with dual induction and ALL-like elements is effective and safe for childhood AML. Initial WBC ⩾ 100 × 109/L was the only independent risk factor in this cohort.
UNASSIGNED: It is a retrospective study, and no registration on ClinicalTrials.gov.

BACKGROUND: Complete pathological response (pCR) and major pathological response (MPR) have been proven to have a close association with improved event-free survival (EFS) and overall survival (OS) for patients accepting chemotherapy or chemoradiotherapy. However, further study focusing on neoadjuvant immunotherapy is limited. Here we provided an updated and comprehensive evaluation of the association between pathological response and long-term survival outcomes at patient level and trial level for neoadjuvant immunotherapy.
METHODS: We systematically searched and assessed studies in PubMed, Embase, the Cochrane Library and relevant conference abstracts from inception to June 1, 2023. Studies reported EFS/OS results by pCR/MPR status were eligible.
RESULTS: Forty-three studies comprising a total of 4100 patients were eligible for the analysis, which included 39 studies for the patient-level analysis and 5 randomized controlled trials for the trial-level analysis. Our results highlighted that pCR was associated with improved EFS (HR, 0.48 [95 % CI, 0.39-0.60]) and OS (HR, 0.55 [95 % CI, 0.41-0.74]). The magnitude of HRs by MPR status were similar to the results by pCR status (EFS HR, 0.31 [95 % CI, 0.18-0.53]) and OS HR, 0.43 [95 % CI, 0.19-0.96]). However, no association between pCR and EFS at trial level was found (P = 0.8, R2 = 0).
CONCLUSIONS: Our meta-analysis demonstrates a strong association between pathological response and long-term survival outcomes at patient level across studies applying neoadjuvant immunotherapy in most solid tumors but we fail to validate the relationship at trial level. Therefore, an accepted surrogate endpoint applied to both patient and trial levels are waited for further search.

OBJECTIVE: It has been demonstrated that neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy was safe and feasible referred to neoadjuvant chemotherapy for patients with non-small cell lung cancer undergoing sleeve lobectomy. Nevertheless, no survival data were reported in the previous researches. Therefore, we conducted this study to compare neoadjuvant ICI plus chemotherapy versus neoadjuvant chemotherapy followed by sleeve lobectomy for long-term survival outcomes.
METHODS: Patients who underwent bronchial sleeve lobectomy following neoadjuvant ICI plus chemotherapy or neoadjuvant chemotherapy were retrospectively identified. Treatment response, perioperative outcomes, event-free survival and overall survival were compared between groups in the overall and the inverse probability of treatment weighting-adjusted cohort.
RESULTS: A total of 139 patients with 39 lung cancer recurrence and 21 death were included. Among them, 83 (59.7%) and 56 (40.3%) patients received neoadjuvant chemotherapy and neoadjuvant ICI plus chemotherapy, respectively. After inverse probability of treatment weighting, more patients achieved complete pathological response in the neoadjuvant ICI plus chemotherapy group (6.0% vs 26.3%, P < 0.001). There was no significant difference regarding overall postoperative complication (23.8% vs 20.2%, P = 0.624) and specific complications (all P > 0.05). Patients receiving neoadjuvant ICI plus chemotherapy had favourable event-free survival (hazard ratio 0.37, 95% confidence interval 0.16-0.85, P = 0.020) and overall survival (hazard ratio 0.23, 95% confidence interval 0.06-0.80, P = 0.021). Multivariable analysis revealed that neoadjuvant ICI plus chemotherapy was an independent predictor for favourable event-free survival (hazard ratio 0.37, 95% confidence interval 0.15-0.86, P = 0.020, adjusted for clinical TNM stage).
CONCLUSIONS: Neoadjuvant ICI plus chemotherapy was correlated with favourable long-term survival in patients with non-small cell lung cancer undergoing sleeve lobectomy.

Accurately quantifying event-free survival after induction of remission in high-risk neuroblastoma can lead to better subsequent treatment decisions, including whether more aggressive therapy or milder treatment is needed to reduce unnecessary treatment side effects, thereby improving patient survival.
To develop and validate a 123I-metaiodobenzylguanidine (MIBG) single-photon emission computed tomography-computed tomography (SPECT-CT)-based radiomics nomogram and evaluate its value in predicting event-free survival after induction of remission in high-risk neuroblastoma.
One hundred and seventy-two patients with high-risk neuroblastoma who underwent an 123I-MIBG SPECT-CT examination were retrospectively reviewed. Eighty-seven patients with high-risk neuroblastoma met the final inclusion and exclusion criteria and were randomized into training and validation cohorts in a 7:3 ratio. The SPECT-CT images of patients were visually analyzed to assess the Curie score. The 3D Slicer software tool was used to outline the region of interest of the lumbar 3-5 vertebral bodies on the SPECT-CT images. Radiomics features were extracted and screened, and a radiomics model was constructed with the selected radiomics features. Univariate and multivariate Cox regression analyses were used to determine clinical risk factors and construct the clinical model. The radiomics nomogram was constructed using multivariate Cox regression analysis by incorporating radiomics features and clinical risk factors. C-index and time-dependent receiver operating characteristic curves were used to evaluate the performance of the different models.
The Curie score had the lowest efficacy for the assessment of event-free survival, with a C-index of 0.576 and 0.553 in the training and validation cohorts, respectively. The radiomics model, constructed from 11 radiomics features, outperformed the clinical model in predicting event-free survival in both the training cohort (C-index, 0.780 vs. 0.653) and validation cohort (C-index, 0.687 vs. 0.667). The nomogram predicted the best prognosis for event-free survival in both the training and validation cohorts, with C-indices of 0.819 and 0.712, and 1-year areas under the curve of 0.899 and 0.748, respectively.
123I-MIBG SPECT-CT-based radiomics can accurately predict the event-free survival of high-risk neuroblastoma after induction of remission The constructed nomogram may enable an individualized assessment of high-risk neuroblastoma prognosis and assist clinicians in optimizing patient treatment and follow-up plans, thereby potentially improving patient survival.

BACKGROUND: For resectable non-small cell lung cancer (NSCLC), the CheckMate-816 study demonstrated that neoadjuvant chemoimmunotherapy increased the rate of complete pathologic response (pCR) by 21.8% compared with chemotherapy alone and resulted in a significant benefit in event-free survival (EFS). This study aimed to investigate the safety and feasibility of this approach in the real world.
METHODS: Clinical data from patients with NSCLC who underwent surgery after neoadjuvant chemoimmunotherapy or chemotherapy alone in two centers were analyzed retrospectively, and subgroup analyses were performed for the chemoimmunotherapy group according to treatment cycle. The primary study endpoints were EFS and major pathologic response (MPR), and the secondary study endpoints were pCR, overall survival (OS), treatment-related adverse events (TRAEs), and surgery-related metrics.
RESULTS: As of April 2023, 89 patients had been enrolled, including 54 in the chemoimmunotherapy group and 35 in the chemotherapy alone group. MPR was achieved in 31 (57.4%) and 5 (14.3%) patients in the chemoimmunotherapy group and chemotherapy alone group, respectively (OR=8.09, 95%CI: 2.72-24.04, P<0.001); pCR was achieved in 25 (46.3%) patients in the chemoimmunotherapy group and no patient in the chemotherapy alone group (P<0.001). The median follow-up time was 22.1 months. At 24 months, the EFS rates of the chemoimmunotherapy group and the chemotherapy alone group were 77.0% and 56.7%, respectively (P=0.026), and the OS rates were 87.1% and 67.7%, respectively (P=0.020). In the neoadjuvant chemoimmunotherapy group, there was no significant difference between the 1-2 cycles and 3-5 cycles groups in terms of operation time, intraoperative blood loss, and postoperative complications.
CONCLUSIONS: Neoadjuvant chemoimmunotherapy was more effective than chemotherapy alone and did not increase the risk associated with surgery. An increase in the number of cycles of neoadjuvant chemoimmunotherapy had no significant effect on the difficulty of surgery.
【中文题目：新辅助免疫治疗联合化疗
在可切除NSCLC中的应用】 【中文摘要：背景与目的 对于可切除的非小细胞肺癌（non-small cell lung cancer, NSCLC），CheckMate-816研究表明，相比于新辅助化疗，免疫治疗联合化疗可将完全病理缓解率（complete pathologic response, pCR）提高21.8%，且无事件生存期（event-free survival, EFS）可显著获益。本研究旨在探讨真实世界中此方法的安全性及可行性。方法 回顾性分析两中心新辅助免疫治疗联合化疗或单独化疗后接受手术的NSCLC患者的临床数据，并根据治疗周期对免疫治疗联合化疗组进行亚组分析。主要研究终点为EFS及主要病理缓解（major pathologic response, MPR），次要研究终点为pCR、总生存（overall survival, OS）率、治疗相关不良事件（treatment-related adverse events, TRAEs）及手术相关指标。结果 截至2023年4月，共纳入89例患者，其中联合治疗组54例，单独化疗组35例。联合治疗组及单独化疗组分别有31例（57.4%）及5例（14.3%）患者达到MPR（OR=8.09, 95%CI: 2.72-24.04, P<0.001），联合治疗组中有25例（46.3%）患者达到pCR，单独化疗组中无pCR患者（P<0.001）。中位随访时间为22.1个月。24个月时，两组EFS率分别为77.0%及56.7%（P=0.026），OS率分别为87.1%及67.7%（P=0.020）。联合治疗组中，1-2个周期与3-5个周期组在手术时间、术中失血量、术后并发症等方面无统计学差异。结论 术前应用免疫治疗联合化疗较单独化疗更有效且未增加手术风险。新辅助免疫治疗联合化疗用药周期的增加对手术难度无明显影响。
】 【中文关键词：肺肿瘤；新辅助治疗；免疫治疗；治疗周期；无事件生存期；手术】.

The clinical significance of protein tyrosine phosphatase nonreceptor type 11 mutation (PTPN11mut ) in acute myeloid leukemia (AML) is underestimated.
We collected the data of AML patients with mutated PTPN11 and wild-type PTPN11 (PTPN11wt ) treated at our hospital and analyzed their clinical characteristics and prognosis.
Fifty-nine PTPN11mut and 124 PTPN11wt AML patients were included. PTPN11mut was more common in myelomonocytic and monocytic leukemia, and was more likely to co-mutate with KRAS, KMT2C, NRAS, U2AF1, NOTCH1, IKZF1, and USH2A mutations than PTPN11wt . The overall survival for AML patients with PTPN11mut was significantly shorter than that for those with PTPN11wt (p = 0.03). The negative impact of PTPN11mut on overall survival was pronounced in the \"favorable\" and \"intermediate\" groups of ELN2017 risk stratification, as well as in the wild-type NPM1 group (p = 0.01, p = 0.01, and p = 0.04).
PTPN11mut is associated with distinct clinical and molecular characteristics, and adverse prognosis in AML patients.

Inconsistent pathological responses of tumor and lymph nodes (LNs) were frequently observed in non-small cell lung cancer (NSCLC) receiving neoadjuvant chemoimmunotherapy. However, there is a lack of studies to report the prognostic significance and the relevant clinicopathological factors of tumor-nodal inconsistent responses after neoadjuvant immunotherapy or chemoimmunotherapy. Therefore, this study aimed to depict the inconsistent pathological combined tumor-nodal responses in NSCLC patients after neoadjuvant chemoimmunotherapy as well as the underlying clinical significance.
A total of 81 node-positive NSCLC patients who underwent neoadjuvant chemoimmunotherapy were eligible for inclusion. Demographic, radiologic, and pathological features of patients were recorded. Patients with pathological complete response of both tumor (ypT(pCR)) and LNs (ypN0) were classified into the combined good responder group and the relevant clinicopathological features were evaluated. The event-free survival (EFS) outcome was analyzed using Kaplan-Meier analysis.
The ypN0 and ypT(pCR) rates were 74.1 % and 42.0 %, respectively. A significant correlation was observed between ypT(pCR) and ypN0 (P = 0.003), but inconsistent responses remained. The combined responses of the primary tumor and LNs demonstrated a significant association with the prognosis outcome (P = 0.005). Notably,patients who received at least twice of their infusions of immune checkpoint inhibitors after 15:30 had a worse prognosis (P = 0.015).
A significant but not absolute correlation was observed between good tumor response and good nodal response in NSCLC patients after neoadjuvant chemoimmunotherapy, but inconsistent responses were also found. The combination of tumor and nodal responses is significantly associated with prognosis and combined good responder can be used as a reliable prognosis predictor.

OBJECTIVE: To develop and validate a nomogram for predicting survival in intermediate- and high-risk neuroblastoma patients and to compare the accuracy of the nomogram in predicting survival with Children\'s Oncology Group (COG) risk stratification.
METHODS: A total of 885 intermediate- and high-risk neuroblastoma patients were enrolled in this study, including 243 patients from our hospital (the training set) and 642 patients from the TARGET database (the validation set). The factors related to event-free survival (EFS) and overall survival (OS) in neuroblastoma were determined to construct the nomogram by Cox regression analysis. The C-index, calibration curves, and area under the time-dependent receiver operating characteristic curves (AUCs) were used to assess the predictive performance of the nomogram.
RESULTS: International Neuroblastoma Staging System stage and Mitosis-karyorrhexis index (MKI) were significant unfavorable factors for EFS, while MKI and MYCN status were significant unfavorable factors for OS. The C-index of the nomogram was 0.621 and 0.586 for predicting EFS, 0.650 and 0.570 for predicting OS in the training and validation sets, respectively. The calibration curves revealed good agreement in the EFS and OS predicted by the nomogram. The AUCs of the nomogram for 1-, 2-, 3-year EFS and OS were 0.633, 0.669, 0.604 and 0.672, 0.670, 0.702 in the training set, respectively. Moreover, the nomogram was able to classify patients into two groups according to risk scores, with the \"high-risk\" group having a lower survival rate than the \"intermediate-risk\" group. And the nomogram performed better than the COG risk stratification, which had a C-index of 0.537, 0.502 and 0.565, 0.572 for predicting EFS, OS in the training and validation sets, respectively.
CONCLUSIONS: We developed and validated a prognostic nomogram for intermediate- and high-risk neuroblastoma patients that clinicians can use to make more informed decisions for individual patients.