Structured testing of genetic association with mixed clinical outcomes.

Genetic factors play a fundamental role in disease development. Studying the genetic association with clinical outcomes is critical for understanding disease biology and devising novel treatment targets. However, the frequencies of genetic variations are often low, making it difficult to examine the variants one-by-one. Moreover, the clinical outcomes are complex, including patients' survival time and other binary or continuous outcomes such as recurrences and lymph node count, and how to effectively analyze genetic association with these outcomes remains unclear. In this article, we proposed a structured test statistic for testing genetic association with mixed types of survival, binary, and continuous outcomes. The structured testing incorporates known biological information of variants while allowing for their heterogeneous effects and is a powerful strategy for analyzing infrequent genetic factors. Simulation studies show that the proposed test statistic has correct type I error and is highly effective in detecting significant genetic variants. We applied our approach to a uterine corpus endometrial carcinoma study and identified several genetic pathways associated with the clinical outcomes.

Survival Outcomes According to NCCN Criteria for Resection Following Neoadjuvant Therapy for Patients with Localized Pancreatic Cancer.

BACKGROUND: This study aimed to assess the prognostic value of the National Comprehensive Cancer Network (NCCN) criteria for resection following neoadjuvant therapy for patients with localized pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective single-center study assessed 193 consecutive patients with localized PDAC (104 males and 89 females; mean age, 61.1 ± 9.4 years) who underwent neoadjuvant therapy followed by surgery between January 2010 and March 2021. Combined resectability and carbohydrate antigen (CA) 19-9 evaluation before and after neoadjuvant therapy was used to determine whether patients were eligible for resection according to the NCCN criteria. Post-surgical overall survival (OS), recurrence free survival (RFS), and pathologic results were evaluated and compared between patients considered eligible according to the NCCN criteria and those considered ineligible. Preoperative factors associated with better OS and RFS also were investigated. RESULTS: Of the 193 patients, 168 (87.0 %) were eligible for resection according to the NCCN criteria. The patients eligible according to the NCCN criteria showed marginally longer OS than those considered ineligible (p = 0.056). After adjustment of variables, meeting the NCCN criteria for resection was an independent predictor of better OS (hazard ratio, 0.57; 95 % confidence interval, 0.34-0.96; p = 0.034). The two groups had similar RFS. Lower T-staging (T2 or less) and less lympho-vascular invasion and peri-neural invasion were noted in the patients who met the NCCN criteria (p ≤ 0.045). CONCLUSIONS: The patients eligible for resection according to the NCCN criteria showed a trend toward longer OS and better pathologic results than the patients considered ineligible.

Impact of treatment interval between neoadjuvant immunochemotherapy and surgery in lung squamous cell carcinoma.

OBJECTIVE: The optimal timing for surgery following neoadjuvant immunochemotherapy for lung squamous cell carcinoma appears to be a topic of limited data. Many clinical studies lack stringent guidelines regarding this timing. The objective of this study is to explore the effect of the interval between neoadjuvant immunochemotherapy and surgery on survival outcomes in patients with lung squamous cell carcinoma. METHODS: This study conducted a retrospective analysis of patients with lung squamous cell carcinoma who underwent neoadjuvant immunochemotherapy between January 2019 and October 2022 at The First Affiliated Hospital, Zhejiang University School of Medicine. Patients were divided into two groups based on the treatment interval: ≤33 days and > 33 days. The primary observational endpoints of the study were Disease-Free Survival (DFS) and Overall Survival (OS). Secondary observational endpoints included Objective response rate (ORR), Major Pathological Response (MPR), and Pathological Complete Remission (pCR). RESULTS: Using the Kaplan-Meier methods, the ≤ 33d group demonstrated a superior DFS curve compared to the > 33d group (p = 0.0015). The median DFS for the two groups was 952 days and 590 days, respectively. There was no statistical difference in the OS curves between the groups (p = 0.66), and the median OS was not reached for either group. The treatment interval did not influence the pathologic response of the tumor or lymph nodes. CONCLUSIONS: The study observed that shorter treatment intervals were associated with improved DFS, without influencing OS, pathologic response, or surgical safety. Patients should avoid having a prolonged treatment interval between neoadjuvant immunochemotherapy and surgery.

Adjuvant medial versus entire supraclavicular lymph node irradiation in high-risk early breast cancer (SUCLANODE): a protocol for a multicenter, randomized, open-label, phase 3 trial.

BACKGROUND: Supraclavicular nodal (SCL) irradiation is commonly used for patients with high-risk breast cancer after breast surgery. The Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) breast contouring atlases delineate the medial part of the SCL region, while excluding the posterolateral part. However, recent studies have found that a substantial proportion of SCL failures are located in the posterolateral SCL region, outside of the RTOG/ESTRO-defined SCL target volumes. Consequently, many radiation oncologists advocate for enlarging the SCL irradiation target volume to include both the medial and posterolateral SCL regions. Nevertheless, it remains uncertain whether adding the posterolateral SCL irradiation improves survival outcomes for high-risk breast cancer patients. METHODS: The SUCLANODE trial is an open-label, multicenter, randomized, phase 3 trial comparing the efficacy and adverse events of medial SCL irradiation (M-SCLI group) and medial plus posterolateral SCL irradiation (entire SCL irradiation, E-SCLI group) in high-risk breast cancer patients who underwent breast conserving-surgery or mastectomy. Patients with pathological N2-3b disease following initial surgery, or clinical stage III or pathological N1-3b if receiving neoadjuvant systemic therapy, are eligible and randomly assigned (1:1) to M-SCLI group and E-SCLI group. Stratification is by chemotherapy sequence (neoadjuvant vs. adjuvant), T stage (T3-4 vs. T1-2), N stage (N1-2 vs. N3), and ER status (positive vs. negative). Other radiation volumes are identical in the two arms, including breast/chest wall, undissected axillary lymph node, and internal mammary node. Advanced intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), or tomotherapy techniques are recommended. Both hypofractionated and conventional fractionation schedules are permitted. The primary end point is invasive disease-free survival, and secondary end points included overall survival, SCL recurrence, local-regional recurrence, distance recurrence, safety outcome, and patient-reported outcomes. The target sample size is 1650 participants. DISCUSSION: The results of the SUCLANODE trial will provide high-level evidence regarding whether adding posterolateral SCL irradiation to medial SCL target volume provides survival benefit in patients with high-risk breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05059379. Registered 28 September 2021, https://www. CLINICALTRIALS: gov/ct2/show/NCT05059379 .

Treatment patterns, clinical outcomes and gene mutation characteristics of hepatitis B virus-associated mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an uncommon and incurable B-cell lymphoma subtype that has an aggressive course. Hepatitis B virus (HBV) infection has been associated with an increased risk for B-cell lymphomas, and is characterized by distinct clinical and genetic features. Here, we showed that 9.5% of MCL Chinese patients were hepatitis B surface antigen positive (HBsAg+). Compared to HBsAg-negative (HBsAg-) patients, HBsAg+ MCL patients had a greater incidence of elevated lactate dehydrogenase (LDH), but no difference was observed in the other clinical characteristics, including sex, age, ECOG ps, Ann Arbor stage, MIPI, extranodal involvement and Ki-67. The HD-AraC (high-dose cytarabine) regimen was the main first-line induction regimen for younger HBsAg+ patients, and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) were used for elderly patients. HBsAg seropositivity was associated with a significantly shorter PFS than HBsAg seronegativity when patients were treated with rituximab or CHOP-based regimens. Compared with CHOP, the HD-AraC regimen was associated with longer PFS in HBsAg+ patients. Treatment with a Bruton tyrosine kinase inhibitor (BTKi) alone can also cause HBV reactivation. Among the 74 patients who underwent targeted deep sequencing (TDS), the nonsynonymous mutation load of HBsAg+ MCL patients was greater than that of HBsAg- MCL patients. HDAC1, TRAF5, FGFR4, SMAD2, JAK3, SMC1A, ZAP70, BLM, CDK12, PLCG2, SMO, TP63, NF1, PTPR, EPHA2, RPTOR and FIP1L1 were significantly enriched in HBsAg+ MCL patients.

Transformation risk and associated survival outcome of marginal zone lymphoma: A nationwide study.

Histological transformation into an aggressive B-cell lymphoma indicates a poor survival outcome for patients with indolent marginal zone lymphoma (MZL), which has been less studied. Large-scale data with long-term follow-up to investigate MZL transformation is limited. Here, by reporting a US-Nationwide cohort of 30,619 MZL patients diagnosed between 2000 and 2019, we found that transformation occurred in 2.08% (N = 624) of MZL cases, with the transformation incidence of 3.1 per 1,000 person-years. Advanced Ann Arbor stage, nodal MZL (NMZL) and splenic MZL (SMZL) were associated with an elevated risk of transformation. Certain subtype-specific characteristics, such as non-gastric extra-nodal MZL (vs. gastric, HR, 1.51, 95%CI 1.13-2.04; p = 0.006), and receiving splenectomy for SMZL (HR, 2.04, 95%CI 1.28-3.26; p = 0.003), also indicated a higher risk of transformation. Besides, transformation independently increased the overall mortality risk (HR, 1.38, 95%CI 1.24-1.53, p < 0.001), especially the higher lymphoma-caused mortality risk (HR, 3.21, 95%CI 2.81-3.67, p < 0.001). Transformation was also associated with a higher percentage of lymphoma-caused deaths. The post-transformation prognostic analyses demonstrated that female gender and age ≥ 65 years independently affected patients' mortalities. These findings, based on the largest cohort to date, contribute to a better understanding of transformed MZL, and provide valuable reference points for guidelines and patient counseling.

Heterogeneous Mediation Analysis for Cox Proportional Hazards Model With Multiple Mediators.

This study proposes a heterogeneous mediation analysis for survival data that accommodates multiple mediators and sparsity of the predictors. We introduce a joint modeling approach that links the mediation regression and proportional hazards models through Bayesian additive regression trees with shared typologies. The shared tree component is motivated by the fact that confounders and effect modifiers on the causal pathways linked by different mediators often overlap. A sparsity-inducing prior is incorporated to capture the most relevant confounders and effect modifiers on different causal pathways. The individual-specific interventional direct and indirect effects are derived on the scale of the logarithm of hazards and survival function. A Bayesian approach with an efficient Markov chain Monte Carlo algorithm is developed to estimate the conditional interventional effects through the Monte Carlo implementation of the mediation formula. Simulation studies are conducted to verify the empirical performance of the proposed method. An application to the ACTG175 study further demonstrates the method's utility in causal discovery and heterogeneity quantification.

Two-stage stratified designs with survival outcomes and adjustment for misclassification in predictive biomarkers.

Biomarker stratified clinical trial designs are versatile tools to assess biomarker clinical utility and address its relationship with clinical endpoints. Due to imperfect assays and/or classification rules, biomarker status is prone to errors. To account for biomarker misclassification, we consider a two-stage stratified design for survival outcomes with an adjustment for misclassification in predictive biomarkers. Compared to continuous and/or binary outcomes, the test statistics for survival outcomes with an adjustment for biomarker misclassification is much more complicated and needs to take special care. We propose to use the information from the observed biomarker status strata to construct adjusted log-rank statistics for true biomarker status strata. These adjusted log-rank statistics are then used to develop sequential tests for the global (composite) hypothesis and component-wise hypothesis. We discuss the power analysis with the control of the type-I error rate by using the correlations between the adjusted log-rank statistics within and between the design stages. Our method is illustrated with examples of the recent successful development of immunotherapy in nonsmall-cell lung cancer.

Robotic gastrectomy is more beneficial for advanced than early-stage gastric cancer: a comparison with laparoscopic gastrectomy using propensity score matching.

BACKGROUND: Gastric cancer is the fifth most prevalent malignancy globally and the fourth major contributor to cancer-related mortality. The comparative effectiveness of robotic gastrectomy (RG) versus laparoscopic gastrectomy (LG) at different stages of gastric cancer is unclear regarding surgical and survival outcomes. We compared surgical and survival outcomes between RG and LG in early-stage (cStage I) and advanced (cStage II/III) gastric cancers to elucidate the difference in the efficacy of RG across various stages of gastric cancer. METHODS: We identified 299 patients (LG, 170; RG, 129) with cStage II/III disease and 569 (LG, 455; RG, 114) with cStage I disease who underwent either LG or RG. Following propensity score matching for RG and LG, 118 pairs were selected for cStage II/II and 113 pairs for cStage I. Surgical and survival outcomes of LG and RG were separately compared for cStage II/III and cStage I. RESULTS: In cStage II/III, RG showed significantly fewer intra-abdominal complications of Clavien-Dindo (C.D.) Grade ≥ III in the RG group than in the LG group (LG = 8.5 vs. RG = 1.7%, P = 0.033). Multivariate analysis identified LG as an independent risk factor for intra-abdominal complications of C.D. Grade ≥ III (OR 5.69, 95% CI 1.17-27.70, P = 0.031). However, in cStage I, no difference in surgical outcomes between LG and RG was observed. No differences were observed in survival outcomes between LG and RG in both cStage I or cStage II/III. CONCLUSIONS: The real benefit of RG was demonstrated in surgical outcomes, especially for advanced-stage gastric cancer.

Defining distal splenopancreatectomy by the mesopancreas.

BACKGROUND: The implementation of the pathologic CRM (circumferential resection margin) staging system for pancreatic head ductal adenocarcinomas (hPDAC) resulted in a dramatic increase of R1 resections at the dorsal resection margin, presumably because of the high rate of mesopancreatic fat (MP) infiltration. Therefore, mesopancreatic excision (MPE) during pancreatoduodenectomy has recently been promoted and has demonstrated better local disease control, fueling the discussion of neoadjuvant downsizing regimes in MP + patients. However, it is unknown to what extent the MP is infiltrated in patients with distal pancreatic (tail/body) carcinomas (dPDAC). It is also unknown if the MP infiltration status affects surgical margin control in distal pancreatectomy (DP). The aim of our study was to histopathologically analyze MP infiltration and elucidate the influence of resection margin clearance on recurrence and survival in patients with dPDAC. Furthermore, the results were compared to a collective receiving MPE for hPDAC. METHOD: Clinicopathological and survival parameters of 295 consecutive patients who underwent surgery for PDAC (n = 63 dPDAC and n = 232 hPDAC) were evaluated. The CRM evaluation was performed in a standardized fashion and the specimens were examined according to the Leeds pathology protocol (LEEPP). The MP area was histopathologically evaluated for cancerous infiltration. RESULTS: In 75.4% of dPDAC patients the MP fat was infiltrated by vital tumor cells. The rates of MP infiltration and R0CRM- resections were similar between dPDAC and hPDAC patients (p = 0.497 and 0.453 respectively). MP- infiltration status did not correlate with CRM implemented resection status in dPDAC patients (p = 0.348). In overall survival analysis, resection status and MP status remained prognostic factors for survival. In follow up analysis. surgical margin clearance in dPDAC patients was associated with a significant improvement in local recurrence rates (5.2% in R0CRM- resected vs. 33.3 in R1/R0CRM + resected, p = 0.002). CONCLUSION: While resection margin status was not affected by the MP status in dPDAC patients, the high MP infiltration rate, as well as improved survival in MP- dPDAC patients after R0CRM- resection, justify mesopancreatic excision during splenopancreatectomy. Larger scale studies are urgently needed to validate our results and to study the effect on neoadjuvant treatment in dPDAC patients.

Survival outcome of chemotherapy-naïve castration-resistant prostate cancer treated with new-generation androgen receptor axis-targeted agents in real-world analysis.

PURPOSE: The androgen receptor axis-targeted (ARAT) agents abiraterone and enzalutamide have been introduced against castration-resistant prostate cancer (CRPC). However, determining which of these agents should be used first is a clinical challenge. Therefore, in this study, we compared the efficacy of first-line abiraterone and enzalutamide treatments in chemotherapy-naïve patients with CRPC. METHODS: A total of 242 chemotherapy-naïve CRPC cases treated with first-line ARAT were analyzed. Outcome measures were PSA response, PSA progression-free survival (PSA-PFS), time to treatment failure (TTF), cancer specific survival (CSS), and overall survival (OS). RESULTS: Abiraterone (A) and enzalutamide (E) were administered to 61 and 181 patients, respectively. The median PSA response rate (- 65.4% [A] and - 78.8% [E], p = 0.0341), PSA decline ≥ 30% (55.7% [A] and 72.9% [E], p = 0.0183), PSA-PFS (median 4 months [A] and 8 months [E], p = 0.0126), TTF (median 6 months [A] and 14 months [E], p < 0.0001), CSS (median 45 months [A] and not reached [E], p < 0.0001), and OS (median 28 months [A] and 80 months [E], p < 0.001) were significantly better in the enzalutamide group. In the multivariate analyses for CSS and OS, ALP (p = 0.00376) and ARAT (p < 0.001) (CSS), evidence of metastasis (p = 0.0467), Hb (p = 0.00205), and ARAT (p = 0.00514) (OS) were significant factors, respectively. CONCLUSION: This study showed that PSA response, PSA-PFS, TTF, CSS, and OS were better with first-line enzalutamide administration. Direct inhibition of androgen receptor signaling by enzalutamide is associated with better clinical outcomes.

Improving postoperative survival in cholangiocarcinoma: development of surgical strategies with a screening program in the epidemic region.

BACKGROUND: The Cholangiocarcinoma Screening and Care Program (CASCAP) has been launched since 2013 to detect early-stage cholangiocarcinoma and reduce the disease death. However, the clinical utility of the CASCAP remains unclear. To compare survival outcomes between two time periods: before and after 2013, when significant changes in treatment strategies were implemented, and to evaluate the efficacy of the ultrasound-based screening program, in an Asian region endemic for cholangiocarcinoma. METHODS: A single-center retrospective review was conducted in curative-intended resection cholangiocarcinoma from 2002 to 2021. Patents characteristics and survival outcomes were compared between 2002 and 2013 (early period) and 2014 to 2021 (later period). RESULTS: A total of 1091 patients with intrahepatic (n = 624) or perihilar (n = 467) cholangiocarcinoma was included (early period, n = 658; later period, n = 433). Of 66 (15.2%) patients in the later period were referred by the CASCAP. The incidence of early-staged disease (Stage 0 and 1) was lower in early period compared to later period 16.0% versus 29.1% (p < 0.001); that of positive surgical margin was higher in early period 53.7% versus 40.0% (p < 0.001). A median survival time (MST) was 14 months in early and 40 months in later period (p < 0.001). Subgroup analysis by tumor location, the MST was 13 versus 60 months in early and late periods for intrahepatic tumor (p < 0.001), respectively. While MST in perihilar tumor was 18 versus 31 months in early and late periods(p < 0.001), respectively. By presentation, the MST was 51 vs. 38 months, respectively, with screening and usual presentation (p = 0.06). CONCLUSION: Postoperative survival in CCA patients improved more than doubled during the study period. Moreover, the late period demonstrated enhanced early-stage detection, a higher rate of negative surgical margins, and improved survival outcomes.

Neoadjuvant chemotherapy for organ preservation in sinonasal squamous cell carcinoma.

PURPOSE: In this study, we aimed to evaluate the role of induction chemotherapy (IC) in the treatment of locoregionally advanced sinonasal squamous cell carcinoma (SNSCC). METHODS: 130 patients who accepted IC between 2010 and 2022 were retrospectively reviewed. After IC, all the patients underwent chemoradiotherapy (CRT)/ radiotherapy (RT) or CRT/RT followed by surgery. We investigated the objective response to IC, the optimal treatment strategy, organ preservation, and long-term survival. RESULTS:  Eighty-seven patients (66.9%) achieved a partial response after IC. 86% (27/43) of the patients who did not respond to the IC still presented a sensitive response to radiotherapy (χ2 = 9.26, p = 0.005). Patients who respond to IC could benefit from CRT/RT followed by surgery over other treatment modalities. The 3-year overall survival (OS), progression-free survival (PFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) rates of 61.2%, 51.3%, 52.1%, 58.1% for the IC response group were significantly superior to those of 37.3% (HR = 0.58, 95% CI 0.34-1.01, p = 0.030), 33.5% (HR = 0.49, 95% CI 0.30-0.82, p = 0.002), 35.9% (HR = 0.54, 95% CI 0.32-0.91, p = 0.009), 36.1% (HR = 0.60, 95% CI 0.35-1.03, p = 0.040) for the IC non-response group. Patients who responded to IC had a high rate of organ preservation compared with patients who did not respond to IC (90.8% vs. 74.4%, χ2 = 6.19, p = 0.013). CONCLUSIONS: The results demonstrated a response rate to IC in patients with advanced SNSCC; furthermore, the response to IC indicated better survival. Patients who responded to IC had a high rate of organ preservation.

Plasma 25-hydroxyvitamin D deficiency in the peri-operative period is associated with survival outcome in colorectal cancer patients: a meta-analysis.

AIM: Surgery had a significant impact on 25-hydroxyvitamin D (25-(OH)D) levels. Uncertainty still existed regarding the effects of peri-operative 25(OH)D deficiency on colorectal cancer (CRC) patients' prognosis. The purpose of the present study was to explore the potential association between the peri-operative 25(OH)D deficiency and the survival outcome of CRC. METHODS: Seven electronic databases [including PubMed, EMBASE, Web of Science, The Cochrane Library, OvidMEDLINE(R), China National Knowledge Infrastructure (CNKI) and Wangfang data] were searched without language limitations. The primary outcomes were overall survival and all-cause mortality. Secondary outcomes were the incidence of 25(OH)D deficiency and risk variables for low 25(OH)D level in the peri-operative period. RESULTS: 14 eligible studies were obtained with 9324 patients for meta-analysis. In the peri-operative period, the pooled incidence of blood 25(OH)D deficiency was 59.61% (95% CI: 45.74-73.48). The incidence of blood 25(OH)D deficiency post-operatively (66.60%) was higher than that pre-operatively (52.65%, 95% CI: 32.94-72.36). Male (RR = 1.09, 95% CI: 1.03-1.16), rectum tumor (RR = 1.23, 95% CI: 1.03-1.47), spring and winter sampling (RR = 1.24, 95% CI: 1.02-1.49) were the risk factors for the 25(OH)D deficiency. The association between the low 25(OH)D post-operatively and short-term overall survival (HR = 0.43, 95% CI: 0.24-0.77) was most prominent, while a low 25(OH)D pre-operatively (HR = 0.47, 95% CI: 0.31-0.70) was more significantly associated with long-term all-cause mortality than that after surgery. CONCLUSION: Peri-operative 25(OH)D impacted the CRC patients' prognosis. Due to possible confounding effects of systemic inflammatory response (SIR), simultaneous measurement of vitamin D and SIR is essential for colorectal survival.

Acute invasive fungal rhinosinusitis in post-COVID-19 patients in Vietnam.

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFR) is a potentially lethal infection commonly found in immunocompromised patients. It is considered the most aggressive subtype of fungal sinusitis and can lead to severe morbidity and mortality. There was a significant increase in the incidence of AIFR in post-COVID-19 patients compared to AIFR cases before the COVID-19 pandemic. This study aimed to describe the clinical presentation of AIFR associated with COVID-19 illness. METHODS: A retrospective study included 22 patients diagnosed with AIFR with a recent COVID-19 infection. RESULTS: The most frequent disease associated with AIFR was diabetes mellitus (95.5%). The mycological analysis identified infection caused by Aspergillus species in 72.7% of patients. Along with stabilizing hemodynamic parameters and controlling any comorbidities, all patients in the present study underwent combined surgical debridement followed by antifungal medications. The overall survival rate was 72.7%. The chance of developing a fatal outcome was significantly higher if meningitis presented initially (odds ratio 35.63, p < 0.05). CONCLUSION: The presence of meningitis upon initial diagnosis is related to a significantly higher chance of developing a fatal outcome and should be considered, especially in AIFR patients previously treated for COVID-19 infections. Early diagnosis, early use of antifungal agents, aggressive surgical debridement, and control of comorbid conditions remain crucial in managing AIFR.

Survival outcomes of myeloid leukemia associated with Down syndrome and de novo acute myeloid leukemia in children: Experience from a single tertiary center in Thailand.

Few studies have reported the survival outcomes of myeloid leukemia associated with Down syndrome (DS) in resource-limited countries. This study aimed to compare characteristics and survival outcomes of children with acute myeloid leukemia (AML) between those with and without DS in Thailand. The medical records of AML patients aged 0-15 years treated in a major tertiary center in Southern Thailand between October 1978 and December 2019 were reviewed retrospectively. The overall (OS) and event-free survivals (EFS) rates were calculated using the Kaplan-Meier method. A total of 362 AML patients were included, of which 41 (11.3%) had DS. The mean age at diagnosis of the DS patients was 2.5 ± 1.9 years and most of them (90.2%) were under the age of five. The DS patients had lower initial white blood cell counts and peripheral blasts compared to the non-DS patients. The AML-M7 subtype was more common in the DS than in the non-DS patients (80.5% vs. 9.1%, p < 0.01, respectively). The 5-year OS and EFS rates of the DS patients were lower compared to the non-DS patients (12.9% vs. 20.5%, p = 0.05 and 13.7% vs. 18.4%, p = 0.03, respectively). DS patients had a significantly higher rate of early and treatment-related deaths compared to non-DS patients (30.3% vs. 13.5%, p < 0.01 and 39.4% vs. 19.5%, p = 0.02, respectively). Over the study period, there were a decrease in early death rate and an increase in survival rates of DS patients, which suggests that chemotherapy regimens and supportive care have improved over time.

Chromosome-1 abnormalities in Childhood B-Lymphoblastic Leukemia - An analysis with reference to clinical variables and survival outcome.

Background: Chromosome-1 abnormalities (C1As) are common genetic aberrations in hematological malignancies. We sought to evaluate significance of these abnormalities with reference to clinical characteristics and survival outcome in a pediatric B-Lymphoblastic Leukemia (B-ALL) cohort. Methods: This is a retrospective study conducted in cytogenetic section of Indus Hospital and Health Network. Data was retrieved from October 2020 to July 2022 for childhood B-ALL cases exhibiting C1As. Chromosome analysis was performed on Cytovision MB8 using G-banded metaphases derived from unstimulated bone marrow culture. Results were recorded according to the International System for Human Cytogenetic Nomenclature (ISCN-2020). Data analyzed using SPSS, version 24.0. Results: C1As were observed in 60/450 (13.3%) cases of B-ALL. Among C1As, 29 (48%) cases had t(1;19). There were 13 (45%) balanced and 16 (55%) unbalanced translocations. The aberrations without t(1;19) were seen in 31 (52%) cases including 1q duplication with hyperdiploidy in 14 (45%) cases. The median age for C1As with and without t(1;19) was eight years and six years while the median leukocyte count was 32 x 109/L vs. 17 x 109/L. Event-free survival (EFS) for cases with and without t(1;19) was 69% and 74.2% respectively. Conclusion: Despite the fact that the t(1;19) positive group had a higher median age, a higher white cell count and more CNS positives, the difference in EFS is statistically insignificant when compared to the t(1;19) negative cases. Furthermore, we found a survival difference between balanced and unbalanced t(1;19) groups, which is statistically insignificant but warrants large-scale prospective studies for further understanding.

Treatment patterns and clinical outcomes of mantle cell lymphoma: A retrospective cohort study by CHOICE.

Regimens based on Bruton's tyrosine kinase inhibitors (BTKi) have been increasingly used to treat mantle cell lymphoma (MCL). A real-world multicenter study was conducted to characterize treatment patterns and outcomes in patients with newly diagnosed MCL by Chinese Hematologist and Oncologist Innovation Cooperation of the Excellent (CHOICE). The final analysis included 1261 patients. Immunochemotherapy was the most common first-line treatment, including R-CHOP in 34%, cytarabine-containing regimens in 21% and BR in 3% of the patients. Eleven percent (n = 145) of the patients received BTKi-based frontline therapy. Seventeen percent of the patients received maintenance rituximab. Autologous hematopoietic stem cell transplantation (AHCT) was conducted in 12% of the younger (<65 years) patients. In younger patients, propensity score matching analysis did not show significant difference in 2-year progression-free survival and 5-year overall survival rate in patients receiving standard high-dose immunochemotherapy followed by AHCT than induction therapy with BTKi-based regimens without subsequent AHCT (72% vs 70%, P = .476 and 91% vs 84%, P = .255). In older patients, BTKi combined with bendamustine plus rituximab (BR) was associated with the lowest POD24 rate (17%) compared with BR and other BTKi-containing regimens. In patients with resolved hepatitis B at the baseline, HBV reactivation rate was 2.3% vs 5.3% in those receiving anti-HBV prophylaxis vs not; BTKi treatment was not associated with higher risk of HBV reactivation. In conclusion, non-HD-AraC chemotherapy combined with BTKi may be a viable therapeutic strategy for younger patients. Anti-HBV prophylaxis should be implemented in patients with resolved hepatitis B.

The Significance of Radiotherapy in Ovarian Clear Cell Carcinoma: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess the response rate and survival effect of adjuvant radiotherapy (RT) or chemoradiotherapy (CRT) during ovarian clear cell carcinoma (OCCC). METHODS: We searched Web of Science, PubMed, Cochrane library electronic databases, Clinical Trials, WanFang Data and Chinese National Knowledge Infrastructure (CNKI) up to October 2022. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. RESULTS: We identified a total of 4259 patients from 14 studies met the inclusion criteria. The pooled response rate of residual tumors for RT/CRT was 80.0%, the pooled 5-year progression-free survival (PFS) ratio during RT/CRT group was 61.0%, and the pooled 5-year overall survival (OS) ratio during RT/CRT group was 68.0%; heterogeneity tests demonstrated significant difference between studies (I2 >50%). Cumulative results suggested adjuvant RT/CRT improved 5-year PFS ratio of OCCC patients (OR: 0.51 (95% CI: 0.42-.88), I2 = 22%, P = .009), had no impact on 5-year OS ratio (OR: 0.52 (95% CI: 0.19-1.44), I2 = 87%, P = .21); meta-regression of studies before and after 2000 found consistent results. Sub-analysis observed that adjuvant RT/CRT had no impact on 5-year OS ratio of early-stage (stage I + II) OCCC patients (OR: 0.67 (95% CI: 0.25-1.83), I2 = 85%, P = .44), but might improve 5-year OS ratio of advanced and recurrent OCCC patients (OR: 0.13(95% CI: 0.04-.44), P = .001). CONCLUSION: This analysis suggested that adjuvant RT/CRT might improve oncologic outcomes of OCCC, especially for advanced and recurrent cases. Due to the inherent selective biases of retrospective studies enrolled in the meta-analysis, more convincing evidences based on prospective randomized controlled trials (RCTs) are urgently needed.

Impact of donor ventricular function on heart transplantation outcomes.

BACKGROUND: Some heart transplant (HTx) centers have expanded their donor eligibility criteria in response to the organ shortage; one area of active interest involves utilizing hearts with ventricular dysfunction. Our study seeks to identify if a relationship exists between donor left ventricular ejection fraction (LVEF) and ischemic time or donor age on HTx outcomes. METHODS: We performed a retrospective analysis on adult patients who had a HTx between 1996 and 2021 (n = 46,936). Donor LVEF (dLVEF) values were categorized into three groups: <50%, 50%-70%, and >70%. Ischemic time and donor age were stratified into four groups: ≤2.0, 2.1-3.0, 3.1-4.0, >4.0 h, and ≤30, 31-40, 41-50, >50 years, respectively. The outcome of interest was long-term survival. RESULTS: Multivariable survival analysis found a slight increase in overall mortality risk for patients with donor ejection fractions <50% (HR = 1.16, p = .013). However, subsequent subgroup investigation discovered that this elevated hazard was only applicable when ischemic time was prolonged to >3.0 h (3.1-4.0 h: HR = 1.23, p = .024; > 4.0 h: HR = 1.52, p < .001). There was no significant difference in survival between dLVEF groups when ischemic time was limited to ≤3.0 h or when stratified by donor age. CONCLUSION: HTx patients with a low donor ejection fraction have comparable survival to recipients with a normal dLVEF when ischemic time is limited to ≤3.0 h. Reduced dLVEF does not appear to be sensitive to advanced donor age. The clinical implications of our study may encourage the recruitment of more donor hearts for transplantation.