Event-free survival by residual cancer burden with pembrolizumab in early-stage TNBC: exploratory analysis from KEYNOTE-522.

BACKGROUND: KEYNOTE-522 demonstrated statistically significant improvements in pathological complete response (pCR) with neoadjuvant pembrolizumab plus chemotherapy and event-free survival (EFS) with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab in patients with high-risk, early-stage triple-negative breast cancer (TNBC). Prior studies have shown the prognostic value of the residual cancer burden (RCB) index to quantify the extent of residual disease after neoadjuvant chemotherapy. In this preplanned exploratory analysis, we assessed RCB distribution and EFS within RCB categories by treatment group. PATIENTS AND METHODS: A total of 1174 patients with stage T1c/N1-2 or T2-4/N0-2 TNBC were randomized 2 : 1 to pembrolizumab 200 mg or placebo every 3 weeks given with four cycles of paclitaxel + carboplatin, followed by four cycles of doxorubicin or epirubicin + cyclophosphamide. After surgery, patients received pembrolizumab or placebo for nine cycles or until recurrence or unacceptable toxicity. Primary endpoints are pCR and EFS. RCB is a prespecified exploratory endpoint. The association between EFS and RCB was assessed using a Cox regression model. RESULTS: Pembrolizumab shifted patients into lower RCB categories across the entire spectrum compared with placebo. There were more patients in the pembrolizumab group with RCB-0 (pCR), and fewer patients in the pembrolizumab group with RCB-1, RCB-2, and RCB-3. The corresponding hazard ratios (95% confidence intervals) for EFS were 0.70 (0.38-1.31), 0.92 (0.39-2.20), 0.52 (0.32-0.82), and 1.24 (0.69-2.23). The most common first EFS events were distant recurrences, with fewer in the pembrolizumab group across all RCB categories. Among patients with RCB-0/1, more than half [21/38 (55.3%)] of all events were central nervous system recurrences, with 13/22 (59.1%) in the pembrolizumab group and 8/16 (50.0%) in the placebo group. CONCLUSIONS: Addition of pembrolizumab to chemotherapy resulted in fewer EFS events in the RCB-0, RCB-1, and RCB-2 categories, with the greatest benefit in RCB-2. These findings demonstrate that pembrolizumab not only increased pCR rates, but also improved EFS among most patients who do not have a pCR.

Radium-223 in women with hormone receptor-positive bone-metastatic breast cancer receiving endocrine therapy: pooled analysis of two international, phase 2, randomized, double-blind, placebo-controlled trials.

BACKGROUND: Most women with advanced breast cancer have skeletal metastases. Radium-223 is an alpha-emitting radionuclide that selectively targets areas of bone metastases. METHODS: Two double-blind, placebo-controlled studies of radium-223 were conducted in women with hormone receptor-positive (HR+), bone-predominant metastatic breast cancer. All patients received endocrine therapy (ET), as a single agent of the investigator's choice (Study A) or exemestane + everolimus (Study B). Patients were randomized to receive radium-223 (55 kBq/kg) or placebo intravenously every 4 weeks for six doses. Accrual was halted following unblinded interim analyses per protocol amendments, and both studies were terminated. We report pooled analyses of symptomatic skeletal event-free survival (SSE-FS; primary endpoint), radiologic progression-free survival (rPFS) and overall survival (OS; secondary), and time to bone alkaline phosphatase (ALP) progression (exploratory). RESULTS: In total, 382 patients were enrolled, and 196 SSE-FS events (70% planned total) were recorded. Hazard ratios (95% confidence intervals) and nominal p values for radium-223 + ET versus placebo + ET were: SSE-FS 0.809 (0.610-1.072), p = 0.1389; rPFS 0.956 (0.759-1.205), p = 0.7039; OS 0.889 (0.660-1.199), p = 0.4410; and time to bone ALP progression 0.593 (0.379-0.926), p = 0.0195. Radium-223- or placebo-related treatment-emergent adverse events were reported in 50.3% versus 35.1% of patients (grade 3/4: 25.7% vs. 8.5%), with fractures/bone-associated events in 23.5% versus 23.9%. CONCLUSIONS: In patients with HR+ bone-metastatic breast cancer, numeric differences favoring radium-223 + ET over placebo + ET for the primary SSE-FS endpoint were suggestive of efficacy, in line with the primary outcome measure used in the underlying phase 2 studies. No similar evidence of efficacy was observed for secondary progression or survival endpoints. Adverse events were more frequent with radium-223 + ET versus placebo + ET, but the safety profile of the combination was consistent with the safety profiles of the component drugs. Clinical trial registration numbers Study A: NCT02258464, registered October 7, 2014. Study B: NCT02258451, registered October 7, 2014.

Prognostic value of baseline and interim [18F]FDG PET metabolic parameters in pediatric Hodgkin's lymphoma.

BACKGROUND: Hodgkin lymphoma (HL) in pediatric populations has a high survival rate but poses risks for long-term morbidities. Although [18F]fluoro­2­deoxy­2­d­glucose positron emission tomography ([18F]FDG PET) scans offer potential for improved risk stratification, the definitive prognostic value of quantitative [18F]FDG PET parameters remains unclear for pediatric HL. METHODS: A single-center, retrospective study included pediatric patients diagnosed with HL between 2016 and 2023 treated according to EuroNet-PHL-C1 and DAL/GPOH-HD protocols. Patients underwent baseline and interim PET/CT scans after two chemotherapy cycles. Event-free survival (EFS) was the primary endpoint, Deauville score was the secondary endpoint. Quantitative [18F]FDG PET parameters included SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) that were evaluated using two segmentation methods (SUV 2.5, 41% SUVmax). Survival outcomes were assessed using Cox regression analysis. RESULTS: A total of 115 patients (50 males, median age 14.2 years) were studied, with a median follow-up period of 35 months. During this period, 16 cases (13.9%) of relapse or progression were noted. Baseline and interim MTV 2.5, MTV 41%, TLG 2.5, and TLG 41%, along with interim SUVmax, were significantly associated with worse EFS and correlated with post-treatment Deauville scores. In multivariable analysis, interim MTV 2.5 > 0 ml (adj. hazard ratio, HR: 3.89, p = 0.009) and interim TLG 41% ≥ 30 g (adj. HR: 7.98, p = 0.006) were independent risk factors for EFS. CONCLUSION: Baseline and interim [18F]FDG PET parameters can serve as significant prognostic indicators for EFS and treatment response in pediatric HL. These quantitative measures could enhance individualized, risk-adapted treatment strategies for children and adolescents with HL.

Patterns and treatment outcomes of primary bone tumors in children treated at tertiary referral hospital, Ethiopia.

BACKGROUND: Bone tumors account for approximately 6% of all cancers in children. Malignant bone tumors, commonly occurring in children and adolescents, are associated with high mortality and morbidity. The overall survival of children with primary malignant bone tumors is affected by the stage of disease, time of diagnosis, and treatment response. Despite advanced treatment modalities with chemotherapy, surgery, and radiotherapy, bone tumor is the third leading cause of death in children with malignancy. Patients with metastatic disease at diagnosis have poor outcomes compared to localized disease at presentation. The 5-year Overall Survival and event-free survival in children with primary malignant bone tumors were 85.2% and 69.2%. The study aimed to assess the clinicopathological profile and treatment outcomes of children with primary malignant bone tumors in our setup. MATERIALS AND METHODS: A hospital-based cross-sectional study was conducted on 95 children who met the inclusion criteria through structured questionnaire. The collected data were analyzed using a statistical package for social sciences (SPSS) version 25. P-value < 0.05 was considered to be statistically significant. Kaplan Meier survival estimate was used for overall and event-free survival analysis. RESULTS: A total of ninety-five patients met the study inclusion criteria and the median age at diagnosis with primary malignant bone tumors was 10 years, with an interquartile range of 8-12 years. The duration of the illness from the onset of symptoms to the oncologic treatment center ranges from three weeks to 2 years with a mean duration of five months. Swelling was the commonest presenting symptom accounting for 95.8% (n = 91). Lower extremity was the commonest primary site of involvement accounting for 55.8% (n = 53) of children with primary malignant bone tumors. Osteosarcoma was the commonest malignant bone tumor constituted 66.3% (n = 63), followed by Ewing sarcoma at 33.7% (n = 32). About 41.2% (n = 39) of children had metastatic disease at presentation and the lung was the commonest site of distant metastasis. The Kaplan Meier survival estimate analysis showed the 1-year and 5-year overall survival probabilities for all pediatric primary malignant bone tumor patients were 65% (95% CI: 0.3-0.56) and 38% (95% CI:0.19-0.47) respectively. The 1-year and 5-year event-free survival probabilities were 55% (95% CI: 0.32-0.73) and 33% (95% CI: 0.10-0.59). The stage of the disease at presentation had a significant association with the outcome (p = 0.023). CONCLUSION: Our study showed the mean duration of the illness from the onset of symptoms to the oncologic treatment center was 5 months ranging from 3 weeks to 2 years. More than one-third of the presented with metastatic disease at presentation. The 1-year and 5-year overall survival (OS) probabilities of children with primary malignant bone tumors were low in our setup compared to other studies.

Treatment outcomes of pediatrics acute myeloid leukemia (AML) and associated factors in the country's tertiary referral hospital, Ethiopia.

BACKGROUND: Pediatric Acute Myeloid Leukemia (AML) is a major cause of morbidity and mortality in children with cancer in Africa and other developing continents. Systemic chemotherapy and effective supportive care have significantly contributed to increased survival rates of pediatric AML in developed countries reaching approximately 70%. There is a paucity of contextual data regarding overall and event-free survival outcomes in children with acute myeloid leukemia in developing countries and most centers in Africa provide palliative care. The objective of this study was to assess the overall survival, event-free survival, and associated factors in pediatric AML patients treated in Ethiopia. METHODS: This retrospective study was conducted on Pediatric AML patients treated at Tikur Anbessa Hospital between January 1, 2015, and May 30, 2022. The socio-demographic profile of patients, the clinical characteristics, the biochemical and morphological subtypes of AML were analyzed using SPSS version 25. The Kaplan-Meier survival curve was used to estimate the probabilities of overall and event-free survival. Statistical significance was set at p < 0.05. RESULTS: A total of 92 children with AML were included in this study. The median age at diagnosis was 7 years (interquartile range: 5-10 years) with a slight male predominance. The median duration of symptoms was one month. Neutropenic fever (56, 86.2%) was the most common complication during treatment. About 29.3% of the patients succumbed to early death. The corresponding 1-year and 3-year OS probabilities were 28.2% and 23% respectively. The median event-free survival time for all pediatric AML patients was one-month (95% CI: 0.77-1.23). The determinants of poorer survival outcomes were FAB subtype, type of protocol used, and signs of CNS involvement (p < 0.05). CONCLUSION: The survival rates of children from AML were low in the study setting. More than 25% of AML patients succumbed to early death, and febrile neutropenia was the most common complication. Effective supportive and therapeutic measures should be taken to manage febrile neutropenia and to prevent early death in AML patients.

Clinical significance and predictive risk factors for event-free survival at 24 months in patients with PTCL, NOS.

Peripheral T cell lymphoma, not otherwise specified (PTCL, NOS), is a heterogeneous and aggressive type of non-Hodgkin's lymphoma with a bleak prognosis. This study was designed to assess the value of EFS24 as an alternative clinical endpoint and identify prognosis-related factors in PTCL, NOS. Patients diagnosed with PTCL, NOS were retrospectively collected and slides were reviewed by two hematopathologists. EFS was defined as the time from diagnosis to the occurrence of disease progression after initial treatment, retreatment, or death. Subsequent overall survival (OS) was defined from EFS24 or time of progression, if it occurred within 24 months, to the last follow-up or death. 97 cases with complete follow-up were selected. Approximately 66 patients (68.04%) failed to achieve ES24, with the median OS of 12.17 months, and 5-year OS rate of 15.17%. While patients who reached EFS24 had a median OS of 60.57 months and a 5-year OS rate of 68.77%. Multivariate Cox analysis indicated that bone marrow involvement and elevated ß2 Microglobulin (ß2-MG) were associated with a poor prognosis. B symptoms, extranodal involvement more than one site, and a high Ki67 index were significant factors in predicting the failure of EFS24. EFS24 can help stratify the subsequent outcomes of PTCL, NOS. Patients who achieve EFS24 have a favorable prognosis, although it does not reach that of the general population. On the other hand, patients who do not achieve EFS24 have an extremely poor prognosis. Therefore, EFS24 can be used for patient risk stratification, patient counseling, and study design.

The significance of clinically insignificant residual fragments after percutaneous nephrolithotomy: an analysis into the relevance of complete stone clearance.

PURPOSE: After treatment for kidney stones, residual fragments with a diameter of ≤ 4 mm are traditionally referred to as 'clinically insignificant residual fragments'. We hypothesize that patients with these fragments are at an increased risk for stone-related morbidity, such as complaints, hydronephrosis, and stone regrowth, when compared to stone-free patients. This study aimed to investigate the relevance of complete stone clearance in surgical treatment of urolithiasis. METHODS: We conducted a single-center retrospective cohort study. Patients who underwent percutaneous nephrolithotomy between 2015 and 2020 were included if a CT-scan was available within 6 months after the procedure, and the follow-up duration was at least 1 year. The stone-free status at the end of the first stone episode during the study period was categorized as fully stone-free, not stone-free with small residual fragments (≤ 4 mm) and not stone-free with large residual fragments (> 4 mm). Follow-up data were collected, including stone-related events and re-intervention rates. RESULTS: A total of 103 subjects were included with a median follow-up of 21.4 months. Stone-related events occurred in 10 (29.4%) of the fully stone-free subjects, 20 (58.8%) of the subjects with small residual fragments and 25 (71.4%) of the subjects with large residual fragments. The stone-related event-free survival per subgroup resulted in a significantly different survival distribution in a log rank test (p = 0.008). CONCLUSION: A complete stone-free status seems to be of fundamental importance for decreasing stone-related morbidity. Further developments and research should focus on optimizing the full clearance of stone material during PCNL.

Improvement of survival after hematopoietic stem cell transplantation and trends at a pediatric transplantation center; a three-decade journey.

BACKGROUND: Advances in stem cell transplantation have resulted in improved outcomes. METHODS: This is a retrospective study aimed to analyze changes in patient profile, transplantation, graft characteristics, and outcome among 241 pediatric patients who received stem cell transplantation in a single center between 1993 and 2019. RESULTS: In the 2010-2019, compared with the 1993-2009 period, a significantly higher 5-year overall survival (60% vs. 44%, p = .022) and an event-free survival (53% vs. 34%, p = .025) were observed. Cumulative incidence of deaths due to relapse or progression between the 1993-2009 and 2010-2019 periods were 33% and 26% respectively (p = .66). Cumulative incidence of non-relapse mortality was significantly higher during the 1993-2009 period compared with the 2010-2019 period for malignant diseases (57.7% vs. 28.3%, p = .007). The overall survival from acute graft-versus-host disease between 1993 and 2009 was 11% versus 46% between 2010 and 2019 (p = .0001). The overall survival from infection in both eras did not show any difference (p = .41). CONCLUSIONS: Development in transplantation technology has led to a decrease in non-relapse mortality and better control of graft-versus-host disease. However, relapse and infection remained as major causes of death. Studies evaluating institutional trends in patients undergoing HSCT and analyzing their mortality profile, can improve the management of patients, leading to a reduction in transplant-related problems.

Association between event-free survival and overall survival in early-stage triple-negative breast cancer.

Aim: This study evaluated event-free survival (EFS) as a surrogate outcome for overall survival (OS) in neoadjuvant therapy for early-stage triple-negative breast cancer (eTNBC). Methods: Meta-regression analyses based on a targeted literature review were used to evaluate the individual- and trial-level associations between EFS and OS. Results: In the individual-level analyses, 3-year EFS was a significant predictor of 5-year OS (p < 0.01; coefficient of determinations [R2]: 0.82 [95% CI: 0.68-0.91]). Additionally, there was a statistically significant association between the treatment effect on EFS and OS at the trial level (p < 0.001; R2: 0.64 [95% CI: 0.45-0.82]). Conclusion: This study demonstrates significant associations between EFS and OS and suggests that EFS is a valid surrogate for OS following neoadjuvant therapy for eTNBC.

What is this article about? Studies of cancer therapies typically use patient survival to understand whether a treatment is helpful, such as overall survival (time from treatment to death) and event-free survival (time from treatment until the cancer progresses). Only using overall survival can slow clinical trials and the ability to assess whether new treatments may be useful. This study examined whether event-free survival was a good surrogate outcome for overall survival in studies of neoadjuvant therapy for early stage, triple-negative breast cancer (eTNBC). Neoadjuvant therapy is used to shrink a tumor before the definitive surgery, and TNBC is a type of breast cancer lacking three common hormone receptors that treatments target. To accomplish this, we first searched for published clinical trials and observational studies that reported overall and event-free survival and extracted their data. Then we tested the association between the two survival outcomes to determine if event-free survival could be used to accurately predict overall survival. Using data from randomized clinical trials, we also tested whether a treatment's effect on event-free survival could predict its effect on overall survival. What did this study find? We found that event-free survival at three years could predict overall survival at 5 years, and that there was a meaningful relationship between a treatment's effect on event-free and overall survival for eTNBC following neoadjuvant treatment. What do the results of the study mean? The results suggest that event-free survival is an accurate and useful surrogate for overall survival following neoadjuvant treatment of eTNBC.

End points in clinical trials in diffuse large B-cell lymphoma: time for more dialogue?

We observed lack of clarity and consistency in end point definitions of large randomized clinical trials in diffuse large B-cell lymphoma. These inconsistencies are such that trials might, in fact, address different clinical questions. They complicate interpretation of results, including comparisons across studies. Problems arise from different ways to account for events occurring after randomization including absence of improvement in disease status, treatment discontinuation or the initiation of new therapy. We call for more dialogue between stakeholders to define with clarity the questions of interest and corresponding end points. We illustrate that assessing different end point rules across a range of plausible patient journeys can be a powerful tool to facilitate such a discussion and contribute to better understanding of patient-relevant end points.

What is this article about? This article talks about the lack of clarity and consistency in the definitions of outcomes used in clinical trials that investigate new treatments for diffuse large B-cell lymphoma. This is mainly due to how these different outcome definitions handle events such as absence of improvement in disease status, treatment discontinuation or initiation of new treatment. The authors discuss how these inconsistencies make it hard to interpret the results of individual clinical trials and to compare results across clinical trials.Why is it important? Defining the above events and consequently defining outcomes affects what we can learn from the trials and can lead to different results. Some approaches may not reflect good and bad outcomes for patients appropriately. This makes it challenging for patients, physicians, health authorities and payors to understand the true benefit of treatments under investigation and which one is better.What are the key take-aways? This article serves as a call-to-action for more dialogue among all stakeholders involved in drug development and the decision-making process related to drug evaluations. There is an urgent need for clinical trials to be designed with more clarity and consistency on what is being measured so that relevant questions for patients and prescribing physicians are addressed. Understanding patient journeys will be key to successfully understand what truly matters to patients and how to measure the benefit of new treatments. Such discussions will contribute toward more clarity and consistency in the evaluation of new treatments.

Predicting event-free survival after induction of remission in high-risk pediatric neuroblastoma: combining 123I-MIBG SPECT-CT radiomics and clinical factors.

BACKGROUND: 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. OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The effectiveness of hematopoietic stem cell transplantation in treating pediatric sickle cell disease: Systematic review and meta-analysis.

Background: Patients with sickle cell disease (SCD) have just one recognized curative therapy option: hematopoietic stem cell transplantation (HSCT), which results in a long-lasting improvement in the clinical phenotype. Here, we assessed the effectiveness of HSCT in treating children with SCD by a systematic review and meta-analysis. Methods: Up until January 2024, a comprehensive search was done using Web of Science, CINAHL, Embase, Google Scholar, Cochrane Library, PubMed/Medline, and Embase. Two reviewers worked separately to extract the data, and Newcastle-Ottawa Quality Assessment tool was used to assess the research's quality. The outcomes analyzed were Overall survival (OS), event-free survival (EFS), graft failure (GF) and mortality. Results: Nineteen papers satisfied our inclusion requirements and were assessed to be of fair quality. The pooled rate of OS was high (92%; 95% CI: 90.3%-93.5%). Similar finding was detected for EFS (85.8%; 95% CI: 83.7%-87.7%). In the other hand, pooled rates of GF and mortality were 6.9% (95% CI: 5.3%-8.9%) and 7.4% (95% CI: 5%-10.7%), respectively. A significant publication bias was detected for OS, EFS and GF outcomes. Subgroups analysis showed that study design was the major source of heterogeneity. Conclusion: Our results show that HSCT is effective and safe, with pooled survival rates above 90%. It is important to assess innovative tactics in light of the alarming GF and mortality rates.

Prognostic factors of childhood acute lymphoblastic leukemia with TCF3::PBX1 in CCCG-ALL-2015: A multicenter study.

BACKGROUND: Contemporary risk-directed treatment has improved the outcome of patients with acute lymphoblastic leukemia (ALL) and TCF3::PBX1 fusion. In this study, the authors seek to identify prognostic factors that can be used to further improve outcome. METHODS: The authors studied 384 patients with this genotype treated on Chinese Children's Cancer Group ALL-2015 protocol between January 1, 2015 and December 31, 2019. All patients provisionally received intensified chemotherapy in the intermediate-risk arm without prophylactic cranial irradiation; those with high minimal residual disease (MRD) ≥1% at day 46 (end) of remission induction were candidates for hematopoietic cell transplantation. RESULTS: The overall 5-year event-free survival was 84.4% (95% confidence interval [CI], 80.6-88.3) and 5-year overall survival 88.9% (95% CI, 85.5-92.4). Independent factors associated with lower 5-year event-free survival were male sex (80.4%, [95% CI, 74.8-86.4] vs. 88.9%, [95% CI, 84.1-93.9] in female, p = .03) and positive day 46 MRD (≥0.01%) (62.1%, [95% CI, 44.2-87.4] vs. 87.1%, [95% CI, 83.4-90.9] in patients with negative MRD, p < .001). The presence of testicular leukemia at diagnosis (n = 10) was associated with particularly dismal 5-year event-free survival (33.3% [95% CI, 11.6-96.1] vs. 83.0% [95% CI, 77.5-88.9] in the other 192 male patients, p < .001) and was an independent risk factor (hazard ratio [HR], 5.7; [95% CI, 2.2-14.5], p < .001). CONCLUSIONS: These data suggest that the presence of positive MRD after intensive remission induction and testicular leukemia at diagnosis are indicators for new molecular therapeutics or immunotherapy in patients with TCF3::PBX1 ALL.

Outcomes in progressive systemic sclerosis treated with autologous hematopoietic stem cell transplantation compared with combination therapy.

OBJECTIVES: Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to improve long-term survival for early diffuse progressive systemic sclerosis (SSc) compared with cyclophosphamide. Cyclophosphamide, however, does not provide a long-term benefit in SSc. The combination of mycophenolate mofetil (MMF) and rituximab is a potent alternative regimen. We aimed to retrospectively compare the outcomes of SSc patients who underwent AHSCT to patients who met the eligibility criteria for AHSCT but received upfront combination therapy with MMF and rituximab. METHODS: Repeated assessments of modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), and diffusing capacity (DLCO) values were conducted. Clinical improvement was defined as an mRSS decrease > 25% or an FVC increase > 10%. Event-free survival (EFS) was defined in the absence of persistent major organ failure or death. RESULTS: Twenty-one SSc patients in the combination therapy group were compared with sixteen in the AHSCT group. Age, sex and disease duration were similar between the two groups. Clinical improvement at 12 months was seen in 18 (86%) patients in the combination group compared with 13 (81%) in the AHSCT group (p= 0.7). The hazard ratio for EFS at 24 months favored the combination group (HR = 0.09, P= 0.04). During follow-up, both groups exhibited a significant and comparable reduction in mRSS and an increase in FVC values at each time interval up to 24 months. CONCLUSION: MMF and rituximab compared with AHSCT in SSc patients eligible for AHSCT resulted in similar skin and lung clinical improvement with a better safety profile at 24 months.

One year overall survival of wilms tumor cases and its predictors, among children diagnosed at a teaching hospital in South Western Uganda: a retrospective cohort study.

BACKGROUND: Wilms tumor (WT) is the second most common solid tumor in Africa with both low overall survival (OS) and event-free survival (EFS) rates. However, no known factors are predicting this poor overall survival. OBJECTIVE: The study was to determine the one-year overall survival of WT cases and its predictors among children diagnosed in the pediatric oncology and surgical units of Mbarara regional referral hospital (MRRH), western Uganda. METHODOLOGY: Children's treatment charts and files diagnosed and managed for WT were retrospectively followed up for the period between January 2017 to January 2021. Charts of children with histologically confirmed diagnoses were reviewed for demographics, clinical and histological characteristics, as well as treatment modalities. RESULTS: One-year overall survival was found to be 59.3% (95% CI: 40.7-73.3), with tumor size greater than 15 cm (p 0.021) and unfavorable WT type (p 0.012) being the predominant predictors. CONCLUSION: Overall survival (OS) of WT at MRRH was found to be 59.3%, and predictive factors noted were unfavorable histology and tumor size greater than 115 cm.

Training and external validation of pre-treatment FDG PET-CT-based models for outcome prediction in anal squamous cell carcinoma.

OBJECTIVES: The incidence of anal squamous cell carcinoma (ASCC) is increasing worldwide, with a significant proportion of patients treated with curative intent having recurrence. The ability to accurately predict progression-free survival (PFS) and overall survival (OS) would allow for development of personalised treatment strategies. The aim of the study was to train and external test radiomic/clinical feature derived time-to-event prediction models. METHODS: Consecutive patients with ASCC treated with curative intent at two large tertiary referral centres with baseline FDG PET-CT were included. Radiomic feature extraction was performed using LIFEx software on the pre-treatment PET-CT. Two distinct predictive models for PFS and OS were trained and tuned at each of the centres, with the best performing models externally tested on the other centres' patient cohort. RESULTS: A total of 187 patients were included from centre 1 (mean age 61.6 ± 11.5 years, median follow up 30 months, PFS events = 57/187, OS events = 46/187) and 257 patients were included from centre 2 (mean age 62.6 ± 12.3 years, median follow up 35 months, PFS events = 70/257, OS events = 54/257). The best performing model for PFS and OS was achieved using a Cox regression model based on age and metabolic tumour volume (MTV) with a training c-index of 0.7 and an external testing c-index of 0.7 (standard error = 0.4). CONCLUSIONS: A combination of patient age and MTV has been demonstrated using external validation to have the potential to predict OS and PFS in ASCC patients. CLINICAL RELEVANCE STATEMENT: A Cox regression model using patients' age and metabolic tumour volume showed good predictive potential for progression-free survival in external testing. The benefits of a previous radiomics model published by our group could not be confirmed on external testing. KEY POINTS: • A predictive model based on patient age and metabolic tumour volume showed potential to predict overall survival and progression-free survival and was validated on an external test cohort. • The methodology used to create a predictive model from age and metabolic tumour volume was repeatable using external cohort data. • The predictive ability of positron emission tomography-computed tomography-derived radiomic features diminished when the influence of metabolic tumour volume was accounted for.

Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study.

AIM: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting. METHODS: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR. RESULTS: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR. CONCLUSIONS: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.

Real-world relationship of early end points to survival end points in patients with resectable non-small-cell lung cancer.

Aim: Pathologic response has been shown to be a promising surrogate for survival in non-small-cell lung cancer. We examined the real-world relationship between these end  points in patients with resectable stage IB-IIIA non-small-cell lung cancer receiving neoadjuvant chemotherapy/chemoradiotherapy (CT/CRT). Methods: Electronic health records/medical charts were analyzed. Overall and event-free survival (OS/EFS) were assessed by Kaplan-Meier stratified by pathologic response. Associations between the end  points were assessed by Cox analyses. Results: A total of 425 patients were selected for the study; 147 and 278 received CT and CRT, respectively. Pathologic complete response (pCR) was associated with longer OS (adjusted HR = 0.50; 95% CI: 0.29-0.85) and EFS (adjusted HR = 0.44; 95% CI: 0.28-0.68) versus no pCR, and EFS was associated with OS (HR = 0.51, 95% CI: 0.38, 0.69). Conclusion: In patients receiving neoadjuvant CT/CRT, pCR and EFS were associated with improved survival in this real-world dataset.

Circular RNA SPI1 expression before and after induction therapy and its correlation with clinical features, treatment response, and survival of acute myeloid leukemia patients.

BACKGROUND: Circular RNA spi-1 proto-oncogene (circ-SPI1) regulates cell proliferation, apoptosis, and bone marrow differentiation in acute myeloid leukemia (AML). This study aimed to assess the relationship of circ-SPI1 expression with the clinical features, induction therapy response, and survival of AML patients. METHODS: In total, 80 AML patients were included with bone marrow (BM) samples collected at baseline and after induction therapy. Additionally, 20 healthy donors (HDs) and 20 disease controls (DCs) were enrolled with BM samples collected after enrollment. BM circ-SPI1 expression was detected by reverse-transcription quantitative polymerase chain reaction assay. RESULTS: Circ-SPI1 expression was highest in AML patients, moderate in DCs, and lowest in HDs (median (interquartile range): 3.01 [2.02-4.14] versus 1.71 [1.01-2.85] versus 0.98 [0.74-1.71]) (p < 0.001). Moreover, lower circ-SPI1 expression was related to its decreased located gene SPI1 expression (p = 0.029), white blood cells (WBC) < 18.8 × 109 /L (p = 0.010), trisomy 8 (p = 0.025), and more favorable risk stratification (p = 0.014) in AML patients. Additionally, circ-SPI1 expression was reduced in AML patients after induction therapy (p < 0.001), and its low expression after induction therapy was correlated with the achievement of complete remission (p < 0.001). Furthermore, circ-SPI1 decline ≥30% during therapy (versus <30%) was independently related to longer event-free survival (EFS) (hazard ratio (HR): 0.445, p = 0.028) and overall survival (OS) (HR: 0.319, p = 0.025) in AML patients. CONCLUSION: Decreased circ-SPI1 expression is related to lower WBC, favorable risk stratification, and better therapy response; moreover, its decline during therapy is an independent factor to predict longer EFS and OS in AML patients.

Outcomes linked to eligibility for stem cell transplantation trials in diffuse cutaneous systemic sclerosis.

OBJECTIVES: The aim of this study was to explore outcomes in a cohort of dcSSc patients fulfilling eligibility criteria for stem cell transplantation (SCT) studies but receiving standard immunosuppression. METHODS: From a large single-centre dcSSc cohort (n = 636), patients were identified using the published SCT trials' inclusion criteria. Patients meeting the trials' exclusion criteria were excluded. RESULTS: Of the 227 eligible patients, 214 met the inclusion criteria for ASTIS (Autologous Stem Cell Transplantation International Scleroderma), 82 for SCOT (Scleroderma: Cyclophosphamide Or Transplantation) and 185 for the UPSIDE (UPfront autologous haematopoietic Stem cell transplantation vs Immunosuppressive medication in early DiffusE cutaneous systemic sclerosis) trial, and 66 were excluded based on age >65 years, low diffusing capacity of the lungs for carbon monoxide (DLco), pulmonary hypertension or creatinine clearance <40 ml/min. The mean follow-up time was 12 years (s.d. 7). Among the eligible patients, 103 (45.4%) died. Survival was 96% at 2 years, 88% at 5 years, 73% at 10 years and 43% at 20 years. Compared with this 'SCT-eligible' cohort, those patients who would have been excluded from SCT trials had a worse long-term survival (97% at 2 years, 77% at 5 years, 52% at 10 years and 15% at 20 years, log rank P < 0.001). Excluded patients also had a significantly worse long-term event-free survival. Hazard of death was higher in patients with higher age at onset [hazard ratio (HR) 1.05, P < 0.001], higher ESR at baseline (HR 1.01, P = 0.025) and males (HR 2.12, P = 0.008). CONCLUSION: SCT inclusion criteria identify patients with poor outcome despite current best practice treatment. Patients meeting the inclusion criteria for SCT but who would have been excluded from the trials because of age, pulmonary hypertension, poor kidney function or DLco <40% had worse outcomes.