Venetoclax Plus Azacitidine as a Bridge Treatment to Allogeneic Stem Cell Transplantation in Unfit Patients with Acute Myeloid Leukemia.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is rarely recommended for unfit patients with newly diagnosed acute myeloid leukemia (AML). Patient survival can improve with venetoclax plus azacitidine (VEN plus AZA). However, the long-term outcome of this treatment strategy is still unsatisfactory. The high response and low treatment toxicity rates of patients receiving VEN plus AZA can provide an opportunity for HSCT among unfit patients. Nevertheless, the outcomes and complications of VEN plus AZA, followed by HSCT, remain unclear. METHODS: This single-center retrospective study aimed to compare patients with newly diagnosed AML receiving VEN plus AZA as induction therapy (n = 27) to those receiving the conventional I3A7 regimen as induction therapy (n = 34). RESULT: The 1-year overall survival, relapse, and non-relapse mortality rates in the two groups were similar. The cytogenetic risks and the hematopoietic cell transplantation-specific comorbidity index are the most significant predictive factors of overall survival. CONCLUSION: In older patients unfit for intensive chemotherapy, a low-intensity regimen with VEN plus AZA is a suitable bridge therapy. Furthermore, allo-HSCT is feasible and can be a curative option.

Prognostic Significance of Oligometastatic Disease Classification by the ESTRO/EORTC of Cancer for Patients With Lung Cancer Treated With Definitive Radical Radiotherapy.

BACKGROUND: Randomized controlled trials had demonstrated local therapy, such as radiotherapy, can improve outcomes of patients with lung cancer with oligometastatic disease (OMD). However, the definition of OMD is not uniform and the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) proposed a new classification in 2020 comprising nine subtypes. Therefore, we aimed to investigate the prognostic significance of this European classification for patients with lung OMD treated with definitive radical radiotherapy. PATIENTS AND METHODS: We identified eligible patients via an in-house database. Patient, disease, and treatment characteristics, as well as outcomes, were obtained via chart review plus peer review. Overall and progression-free survival were estimated via the Kaplan-Meier method. Log-rank test was used in univariate analysis and Cox regression in multivariable analyses to investigate the prognostic significance of the subtypes of OMD. RESULTS: We identified 35 eligible patients with six different OMD subtypes treated from 2011 to 2019. After a median follow-up of 23 (range=2-88) months, the median progression-free and overall survival were 11 and 38 months, respectively. The prognosis for patients with the subtype 'induced oligoprogression' was statistically worse than for those without in both univariate (p=0.02) and multivariate (adjusted hazard ratio for death=4.8, 95% confidence interval=1.4-16.2, p=0.01) analyses. CONCLUSION: We found the subtype with induced oligoprogression in the European classification to be associated with worse survival. Further studies are needed to confirm our finding.

Clinical Outcomes and Prognostic Factors of Patients With Esophageal Squamous Cell Carcinoma With Oligo-recurrence Treated With Radical Re-irradiation.

BACKGROUND: For patients with esophageal squamous cell carcinoma (ESCC) with oligo-recurrence (OR) after previous curative radiotherapy and not eligible for radical resection, the role of radical re-irradiation was not clear. Therefore, we aimed to investigate the outcome and prognostic factors of such patients. PATIENTS AND METHODS: We identified patients with OR of ESCC after previous curative radiotherapy and were treated with radical re-irradiation within 2012-2018 via an in-house prospectively established database. The characteristics of patients, disease, treatment, and outcome were retrospectively obtained via chart review. The first day of re-irradiation was defined as the index date. Overall survival was calculated via the Kaplan-Meier method. Log-rank test was used for univariate analysis and Cox regression method was used for multivariable analysis. RESULTS: We identified thirty patients for analyses. After a median follow-up of 9 (range=2-76) months, the 5-year overall survival rate was 21%. Four patients with possible radiotherapy-related complication in need of inpatient care were identified. Gross tumor volume was the only significant prognostic factor in both univariate and multivariable analyses. CONCLUSION: We found that radical definitive re-irradiation may lead to one-fifth long-term survivors of patients with OR after previous curative radiotherapy for ESCC, and the gross tumor volume was the only significant prognostic factor for these patients. Randomized controlled trials should be considered to compare radical re-irradiation with the current standard of care (systemic therapy) for this population.

Effectiveness of image-guided radiotherapy for locally advanced esophageal squamous cell carcinoma patients treated with definitive concurrent chemoradiotherapy.

BACKGROUND: Image-guided radiotherapy (IGRT) is an advanced radiotherapy technique to improve the accuracy of treatment delivery. However, a recent randomized controlled trial (RCT) for prostate cancer patients treated with radiotherapy either via IGRT or routine care (no daily IGRT) reported a statistically significant worse overall survival for those treated with IGRT. This raised the concern regarding the effectiveness of IGRT for definitive concurrent chemoradiotherapy (dCCRT) for locally advanced esophageal squamous cell carcinoma (LA-ESqCC). METHODS: Eligible LA-ESqCC patients diagnosed between 2011 and 2015 were identified via the Taiwan Cancer Registry. We estimated propensity scores to construct a 1:1 propensity-score-matched groups and balance observable potential confounders. The hazard ratio (HR) of death as well as other outcomes was compared between IGRT and non-IGRT matched groups during the entire follow-up period. The impact of additional covariables was considered in the sensitivity analysis. RESULTS: Our study population included 590 patients in the primary analysis. The HR for death when IGRT was compared with non-IGRT was 0.92 (95% confidence interval 0.77-1.10, P = 0.35). There were also no significant differences for other outcomes or sensitivity analyses. CONCLUSIONS: In this updated nonrandomized study using real world data, we found that the overall survival of LA-ESqCC patients treated with dCCRT was not statistically different between those treated with IGRT versus those without IGRT, although the hazard ratio was less than unity, ie, in favor of IGRT. The results should be interpreted with caution given the nonrandomized design and RCTs are needed to clarify our findings. KEY POINTS: Significant findings of the study: The OS of LA-ESqCC patients treated with dCCRT was not statistically different between those treated with IGRT versus those without IGRT, although the hazard ratio was less than unity, ie, in favor of IGRT. WHAT THIS STUDY ADDS: In this updated nonrandomized study using real world data with additional potential confounders, our study provided a reasonable tentative evidence of lack of RCT as suggested in the literature.

Effects of HMGB1 Polymorphisms on the Susceptibility and Progression of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a malignancy of liver and a leading cause of cancer mortality worldwide. Its management is compounded by biological and clinical heterogeneity. These interindividual genetic variations can modulate the effects of HCC treatment. High-mobility group box protein 1 (HMGB1) is a well investigated, ubiquitous nuclear protein found in eukaryotic cells that plays a multiple biological roles such as DNA stability, program cell death, immune response, and furthermore in cancer progression. In this report, we examined HMGB1 single nucleotide polymorphisms (SNPs) with multiple risk factors related to HCC susceptibility and clinicopathological characteristics. Four HMGB1 SNPs (rs1412125, rs2249825, rs1045411, and rs1360485) were assessed by using a TaqMan SNPs Genotyping in 324 patients with HCC and in 695 cancer-free controls. The results showed that HMGB1 SNP rs1045411 with CT or at least one T alleles has lower risk of HCC than wild-type (CC) carriers. Moreover, HMGB1 SNP rs1412125 with TT allele has a higher risk of distant metastasis compared with patients carrying at least one C allele. The present study is the first report to discuss the risk factors associated with HMGB1 SNPs in HCC progression in Taiwan.

WISP-1 promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-300 in human oral squamous cell carcinoma cells.

Oral squamous cell carcinoma (OSCC), which accounts for nearly 90% of head and neck cancers, is characterized by a poor prognosis and a low survival rate. Vascular endothelial growth factor-C (VEGF-C) has been implicated in lymphangiogenesis and is correlated with cancer metastasis. WNT1-inducible signaling pathway protein-1 (WISP)-1/CCN4 is an extracellular matrix-related protein that belongs to the CCN family and stimulates many biological functions. Our previous studies showed that WISP-1 plays an important role in OSCC migration and angiogenesis. However, the effect of WISP-1 on VEGF-C regulation and lymphangiogenesis in OSCC is poorly understood. Here, we showed a correlation between WISP-1 and VEGF-C in tissue specimens from patients with OSCC. To examine the lymphangiogenic effect of WISP-1, we used human lymphatic endothelial cells (LECs) to mimic lymphatic vessel formation. The results showed that conditioned media from WISP-1-treated OSCC cells promoted tube formation and cell migration in LECs. We also found that WISP-1-induced VEGF-C is mediated via the integrin αvß3/integrin-linked kinase (ILK)/Akt signaling pathway. In addition, the expression of microRNA-300 (miR-300) was inhibited by WISP-1 via the integrin αvß3/ILK/Akt cascade. Collectively, these results reveal the detailed mechanism by which WISP-1 promotes lymphangiogenesis via upregulation of VEGF-C expression in OSCC. Therefore, WISP-1 could serve as therapeutic target to prevent metastasis and lymphangiogenesis in OSCC.

WISP-1 a novel angiogenic regulator of the CCN family promotes oral squamous cell carcinoma angiogenesis through VEGF-A expression.

Oral squamous cell carcinoma (OSCC), which accounts for nearly 90% of head and neck cancers, is characterized by poor prognosis and a low survival rate. VEGF-A is the most established angiogenic factor involved in the angiogenic-regulated tumor progression. WISP-1/CCN4 is an extracellular matrix-related protein that belongs to the Cyr61, CTGF, Nov (CCN) family and regulates many biological functions, such as angiogenesis. Previous studies indicated the role of WISP-1 in tumor progression. However, the angiogenic property of WISP-1 in the cancer microenvironment has never been discussed. Here, we provide novel insights regarding the role of WISP-1 in the angiogenesis through promoting VEGF-A expression. In this study, the correlation of WISP-1 and VEGF-A was confirmed by IHC staining of specimens from patients with OSCC. In vitro results indicated that WISP-1 induced VEGF-A expression via the integrin αvß3/FAK/c-Src pathway, which transactivates the EGFR/ERK/HIF1-α signaling pathway in OSCC. This pathway in turn induces the recruitment of endothelial progenitor cells and triggers the neovascularization in the tumor microenvironment. Our in vivo data revealed that tumor-secreted WISP-1 promoted the angiogenesis through VRGF expression and increased angiogenesis-related tumor growth. Our study offers new information that highlights WISP-1 as a potential novel therapeutic target for OSCC.