Inhibiting Bruton's Tyrosine Kinase to Counteract Chemoresistance and Stem Cell-Like Properties in Osteosarcoma.

Osteosarcoma, a highly aggressive bone cancer, often develops resistance to conventional chemotherapeutics, leading to poor prognosis and survival rates. The malignancy and chemoresistance of osteosarcoma pose significant challenges in its treatment, highlighting the critical need for novel therapeutic approaches. Bruton's tyrosine kinase (BTK) plays a pivotal role in B-cell development and has been linked to various cancers, including breast, lung, and oral cancers, where it contributes to tumor growth and chemoresistance. Despite its established importance in these malignancies, the impact of BTK on osteosarcoma remains unexplored. Our study delves into the expression levels of BTK in osteosarcoma tissues by data from the GEO and TCGA database, revealing a marked increase in BTK expression compared with primary osteoblasts and a potential correlation with primary site progression. Through our investigations, we identified a subset of osteosarcoma cells, named cis-HOS, which exhibited resistance to cisplatin. These cells displayed characteristics of cancer stem cells (CSCs), demonstrated a higher angiogenesis effect, and had an increased migration ability. Notably, an upregulation of BTK was observed in these cisplatin-resistant cells. The application of ibrutinib, a BTK inhibitor, significantly mitigated these aggressive traits. Our study demonstrates that BTK plays a crucial role in conferring chemoresistance in osteosarcoma. The upregulation of BTK in cisplatin-resistant cells was effectively countered by ibrutinib. These findings underscore the potential of targeting BTK as an effective strategy to overcome chemoresistance in osteosarcoma treatment.

Interleukin-11/gp130 upregulates MMP-13 expression and cell migration in OSCC by activating PI3K/Akt and AP-1 signaling.

Oral squamous cell carcinoma (OSCC) is an extremely common head and neck cancer with a poor 5-year survival rate, especially in cases of metastatic disease. Interleukin (IL)-11 reportedly promotes cell growth and the epithelial-mesenchymal transition process in metastasis. However, the molecular mechanisms of IL-11 in OSCC metastasis are unclear. This study found that IL-11 upregulates matrix metalloproteinase 13 (MMP-13) expression in OSCC via the IL-11 receptor alpha subunit/glycoprotein 130 receptors that activate phosphatidyl-inositol 3-kinase, Ak strain transforming, and activator protein 1 signaling, which subsequently enhance MMP-13-induced tumor metastasis. TIMER2.0 analysis revealed a positive correlation between MMP-13 and IL-11 levels (r = 0.454). Moreover, a strong positive association was observed between higher levels of IL-11 expression in OSCC tissue (p < 0.01), lymph node metastasis (p = 0.0154), and clinical disease stage (p = 0.0337). IL-11 knockdown suppressed the migration of OSCC cells (p < 0.05). The evidence indicates that IL-11 can serve as a new molecular therapeutic target in OSCC metastasis.

Rituximab in combination with gemcitabine plus cisplatin in patients with recurrent and metastatic head and neck squamous cell carcinoma: a phase I trial.

BACKGROUND: The treatment of recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC) remains challenging. Preclinical studies revealed that B cell depletion could modulate the microenvironment and overcome chemoresistance. We conducted a phase I study to evaluate the feasibility and safety of B cell depletion using the anti-CD20 antibody rituximab to treat HNSCC. METHODS: Ten patients were enrolled in two protocols. The first four patients treated using protocol 1 received rituximab 1000 mg on days -14 and -7, followed by gemcitabine/cisplatin every 3 weeks, and rituximab was administered every 6 months thereafter. Because of disease hyperprogression, protocol 1 was amended to protocol 2, which consisted of the concomitant administration of rituximab 375 mg/m2 and gemcitabine/cisplatin every 3 weeks. Another six patients were enrolled and treated using protocol 2. RESULTS: Three patients treated using protocol 1 exhibited rapid disease progression, and the remaining patient could not undergo evaluation after rituximab treatment. Conversely, no unpredicted harm was observed in the six patients treated using protocol 2. Among these patients, one achieved complete response, and two had partial responses. The disease-free durations in these patients were 7.0, 6.2, and 7.1 months, respectively. Immune cell analysis revealed a higher ratio of cytotoxic T cells to regulatory T cells in responders than in non-responders. CONCLUSIONS: B cell depletion using rituximab alone in patients with HNSCC can cause hyperprogressive disease. Contrarily, the co-administration of rituximab and cisplatin/gemcitabine was feasible and safe. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04361409 , 24 April 2020, retrospectively registered.

Consolidative chemotherapy after definitive concurrent chemoradiotherapy for esophageal squamous cell carcinoma patients: a population based cohort study.

BACKGROUND: The role of consolidative chemotherapy (CCT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients treated with definitive concurrent chemoradiotherapy (dCCRT) is unclear. We aimed to compare the overall survival (OS) of those treated with vs without CCT via a population based approach. METHODS: Eligible LA-ESCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between those with vs without CCT. We also evaluated the OS in supplementary analyses via alternative approaches. RESULTS: Our primary analysis consisted of 368 patients in whom covariates were well balanced after PS weighting. The HR of death when CCT was compared to without was 0.67 (95% confidence interval 0.52-0.86, P = 0.002). The HR of IECM was 0.66 (P = 0.04). The HR of OS remained similarly in favor of CCT in supplementary analyses. CONCLUSIONS: We found that CCT was associated with significantly improved OS for LA-ESCC patients treated with dCCRT. Randomized controlled trials were needed to confirm this finding.

Visfatin Polymorphisms, Lifestyle Risk Factors and Risk of Oral Squamous Cell Carcinoma in a Cohort of Taiwanese Males.

Oral cancer is the eighth greatest generally diagnosed cancer amongst males worldwide and the fourth most generally malignancy amongst Taiwanese males. The pro-inflammatory adipocytokine visfatin promotes tumor growth. Elevated plasma visfatin levels have been identified in patients with oral squamous cell carcinoma (OSCC), although the biological mechanisms underlying the involvement of visfatin in the pathogenesis of OSCC are not well understood. Moreover, no information is available regarding associations between visfatin polymorphisms and carcinogenic lifestyle factors with OSCC. This study, therefore, investigated the effects of four visfatin gene polymorphisms (rs11977021, rs61330082, rs2110385, and rs4730153) and carcinogenic lifestyle factors (betel nut chewing, alcohol consumption and cigarette smoking) on the risk of developing OSCC in 1,275 Taiwanese males with OSCC, and 1,195 healthy males (controls). We also examined the associations between these visfatin genotypes and OSCC histopathological prognostic factors (pathological stage, tumor status, lymph node status, and metastasis). We found that compared with subjects with the CC genotype of SNP rs11977021, those with the CT+TT genotype were less likely to progress OSCC. In addition, an association was found between the rs4730153 variant and lymph node metastasis in the OSCC cohort.

Deleterious alterations of DNA damage response and repair genes and clinical benefit to anti-PD-1 therapy in esophageal squamous cell carcinoma.

BACKGROUND: Although DNA damage response and repair (DDR) gene alteration has been demonstrated as a biomarker for anti-PD-1 therapy in several cancer types, its role in esophageal squamous cell carcinoma (ESCC) is unknown. METHODS: Patients with advanced ESCC treated with anti-PD-1-based immunotherapy were enrolled. Tumor response was evaluated according to RECIST 1.1. Archival ESCC tissues were analyzed using FoundationOne CDx. Deleterious alterations, defined by loss of function, of DDR genes were correlated with patient survival by Cox proportional hazards model. The prognostic significance of deleterious alterations of DDR genes in The Cancer Genome Atlas (TCGA)-ESCC cohort was explored. RESULTS: Forty-three patients were enrolled. The objective response rate (ORR) was 19%. The median tumor mutational burden was 4 mutations/Mb (0-20); none of the tumors were microsatellite instable. Compared with patients with wild-type or other alterations of DDR genes (N = 35, 81%), those with deleterious alterations of DDR genes (N = 8, 19%) had a higher ORR (38 vs. 14%), longer median progression-free survival (4.1 vs. 2.0 months), and significantly longer median overall survival (OS; 27.7 vs. 6.1 months, P = 0.011). In multivariate analysis, harboring deleterious alterations of DDR genes was a favorable prognostic factor for OS (HR = 0.31 [95% CI: 0.11-0.91], P = 0.033). In the TCGA-ESCC cohort, the presence of deleterious alterations of DDR genes was not a favorable prognostic factor. CONCLUSIONS: Deleterious alterations of DDR genes may be associated with improved prognosis and efficacy of anti-PD-1 therapy in patients with advanced ESCC.

Response to Immune Checkpoint Inhibitors in Recurrent or Metastatic Esophageal Squamous Cell Carcinoma May Be Affected by Tumor Sites.

INTRODUCTION: Heterogeneous tumor response has been reported in cancer patients treated with immune checkpoint inhibitors (ICIs). This study investigated whether the tumor site is associated with the response to ICIs in patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC). METHODS: Patients with ESCC who had measurable tumors in the liver, lung, or lymph node (LN) according to the response evaluation criteria in solid tumors (RECIST) 1.1 and received ICIs at 2 medical centers in Taiwan were enrolled. In addition to RECIST 1.1, tumor responses were determined per individual organ basis according to organ-specific criteria modified from RECIST 1.1. Fisher test or χ2 test was used for statistical analysis. RESULTS: In total, 37 patients were enrolled. The overall response rate per RECIST 1.1 was 13.5%. Measurable tumors in the LN, lung, and liver were observed in 26, 17, and 13 patients, respectively. The organ-specific response rates were 26.9%, 29.4%, and 15.4% for the LN, lung, and liver tumors, respectively (p = 0.05). The organ-specific disease control rates were 69.2%, 52.9%, and 21.1% for the LN, lung, and liver tumors, respectively (p = 0.024). Five (27.8%) among 18 patients harboring at least 2 involved organs had heterogeneous tumor response. CONCLUSION: The response and disease control to ICIs may differ in ESCC tumors located at different metastatic sites, with a lesser likelihood of response and disease control in metastatic liver tumors than in tumors located at the LNs and lung.

CCL4 Stimulates Cell Migration in Human Osteosarcoma via the mir-3927-3p/Integrin αvß3 Axis.

Osteosarcoma is the most common type of primary malignant bone cancer, and it is associated with high rates of pulmonary metastasis. Integrin αvß3 is critical for osteosarcoma cell migratory and invasive abilities. Chemokine (C-C motif) ligand 4 (CCL4) has diverse effects on different cancer cells through its interaction with its specific receptor, C-C chemokine receptor type 5 (CCR5). Analysis of mRNA expression in human osteosarcoma tissue identified upregulated levels of CCL4, integrin αv and ß3 expression. Similarly, an analysis of records from the Gene Expression Omnibus (GEO) dataset showed that CCL4 was upregulated in human osteosarcoma tissue. Importantly, the expression of both CCL4 and integrin αvß3 correlated positively with osteosarcoma clinical stages and lung metastasis. Analysis of osteosarcoma cell lines identified that CCL4 promotes integrin αvß3 expression and cell migration by activating the focal adhesion kinase (FAK), protein kinase B (AKT), and hypoxia inducible factor 1 subunit alpha (HIF-1α) signaling pathways, which can downregulate microRNA-3927-3p expression. Pharmacological inhibition of CCR5 by maraviroc (MVC) prevented increases in integrin αvß3 expression and cell migration. This study is the first to implicate CCL4 as a potential target in the treatment of metastatic osteosarcoma.

Visfatin Promotes the Metastatic Potential of Chondrosarcoma Cells by Stimulating AP-1-Dependent MMP-2 Production in the MAPK Pathway.

Chondrosarcoma is a malignant bone tumor that is characterized by high metastatic potential and marked resistance to radiation and chemotherapy. The knowledge that adipokines facilitate the initiation, progression, metastasis, and treatment resistance of various tumors has driven several in vitro and in vivo investigations into the effects of adipokines resistin, leptin, and adiponectin upon the development and progression of chondrosarcomas. Another adipokine, visfatin, is known to regulate tumor progression and metastasis, although how this molecule may affect chondrosarcoma metastasis is unclear. Here, we found that visfatin facilitated cellular migration via matrix metalloproteinase-2 (MMP-2) production in human chondrosarcoma cells and overexpression of visfatin enhanced lung metastasis in a mouse model of chondrosarcoma. Visfatin-induced stimulation of MMP-2 synthesis and activation of the AP-1 transcription factor facilitated chondrosarcoma cell migration via the ERK, p38, and JNK signaling pathways. This evidence suggests that visfatin is worth targeting in the treatment of metastatic chondrosarcoma.

Impacts of CCL4 gene polymorphisms on hepatocellular carcinoma susceptibility and development.

Hepatocellular carcinoma (HCC) is the sixth most common cancer globally and the third most common cause of cancer mortality. In Taiwan, HCC is the second leading cause of cancer death. CCL4 (C-C chemokine ligand 4), is a macrophage inflammatory protein with a chief effect in inflammation and immune-regulation, and was documented in cancer progression by promoting instability in the tumor environment. Polymorphisms in chemokine genes help to determine host-pathogen interactions that influence chemokine levels. We investigated the effects of CCL4 gene polymorphisms on the risk of hepatocellular carcinoma (HCC) disease progression in a cohort of Taiwanese patients. We recruited total of 1,546 participants in current study, including 1,200 healthy control and 346 patients with HCC. Three single-nucleotide polymorphisms (SNPs) of the CCL4 gene were examined by a real-time PCR. We found that the A/G homozygotes of CCL4 rs10491121 polymorphism reduced the risks for HCC. On the other hand, AG and GA haplotypes of 2 CCL4 SNPs (rs1049112 and rs171915) also reduced the risks for HCC by 0.025 and 0.515 fold, respectively. The present report is the first time to examine the risk factors associated with CCL4 SNPs in HCC progression in Taiwan.

Betel-nut chewing does not influence PD-L1 expression rates in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC): A prospective biomarker prevalence study.

This study explored the relationship between betel-nut chewing and programmed death-ligand 1 (PD-L1) expression in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients in Taiwan. A total 280 R/M HNSCC patients, predominantly male, were evaluated; 75.4 % of whom chewed betel-nut. The prevalence of PD-L1 expression (combined positive score ≥1) was 94.3 % with similar PD-L1 expression rates between betel-nut-exposed and non-exposed groups. PD-L1 prevalence did not differ in those who received prior first-or second-line systemic therapy. In summary, betel-nut exposure did not notably affect PD-L1 expression rates in R/M HNSCC patients in Taiwan.

A Novel Prognostic Model Using Pan-Immune-Inflammation Value and Programmed Death Ligand 1 in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Receiving Immune Checkpoint Inhibitors: A Retrospective Multicenter Analysis.

BACKGROUND: Little is known regarding the prognostication of the Pan-Immune-Inflammation Value (PIV) in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). OBJECTIVES: This study aimed to investigate the prognostic role of PIV in patients with R/M HNSCC receiving immune checkpoint inhibitors (ICI). PATIENTS AND METHODS: Patients who were diagnosed to have R/M HNSCC and treated with ICI were reviewed retrospectively. The cutoff value of PIV was set at the median. Patients were stratified into high PIV and low PIV. Kaplan-Meier curves were estimated for progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 192 patients were included in our study for oncologic outcomes evaluation. For the total population, the median PFS was 5.5 months and OS was 18.2 months. After stratification by PIV, median PFS was 11.7 months in the low PIV and 2.8 months in the high PIV groups (p < 0.001). The median OS was 21.8 months in the low PIV and 11.5 months in the high PIV groups (p < 0.001). Multivariate analysis demonstrated that PIV and PD-L1 were independent predictors associated with survival. A prognostic model using both PIV and PD-L1 was constructed. The median PFS was 12.2, 6.4, and 3.0 months for patients with risk scores of 0, 1, and 2, respectively (p < 0.001). The median OS was 23.7, 18.1, and 11.4 months for patients with risk scores of 0, 1, and 2, respectively (p < 0.001). CONCLUSIONS: PIV is a prognostic biomarker in patients with R/M HNSCC treated with ICI. A prognostic model using PIV and PD-L1 could provide outcome prediction and risk stratification.

Programmed Death Ligand-1 and Tumor Burden Score Dictate Treatment Responses in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

BACKGROUND: The significance of tumor burden for survival is unknown for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The purpose of our study was to evaluate the prognostic impact of programmed death ligand-1 (PD-L1) and tumor burden score (TBS) in patients with R/M HNSCC. PATIENTS AND METHODS: R/M HNSCC patients who were treated with cisplatin, 5-fluorouracil plus cetuximab (EPF) or pembrolizumab (PPF) as first-line treatment were included in our study. PD-L1 and TBS were estimated and correlated with treatment responses. Kaplan-Meier curves were plotted for outcomes estimation. RESULTS: A total of 252 R/M HNSCC patients were included, with 126 high tumor burden (HTB) and 126 low tumor burden (LTB) patients. Median progression-free survival (PFS) was 7.1 months in LTB and 3.9 months in HTB (p < 0.001) and median overall survival (OS) was 14.2 months in LTB and 9.2 months in HTB (p = 0.001). Patients with LTB had better PFS and OS than those with HTB independent of PD-L1 status. Subgroup analysis showed HTB patients treated with EPF had better survival than those treated with PPF, regardless of PD-L1 expression. For LTB PD-L1 positive patients, there was a longer survival with PPF than EPF, while for LTB PD-L1 negative patients, survival was similar between PPF and EPF. Multivariate analysis exhibited that tumor burden was significantly correlated with OS. CONCLUSIONS: Tumor burden is significantly correlated with survival in patients with R/M HNSCC. PD-L1 and TBS should be taken into consideration to determine first-line treatment.

Cetuximab Treatment beyond Progression in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Nationwide Population-Based Study (THNS-2021-08).

BACKGROUND: Little is known regarding the association of cetuximab treatment beyond progression (TBP) with survival among patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Although immune checkpoint inhibitors (ICIs) are now considered as first-line treatment, not all patients are suitable for ICIs. OBJECTIVE: We conducted a multicenter, retrospective study to evaluate the role of cetuximab TBP in patients with R/M HNSCC after failure of first-line cetuximab-containing chemotherapy. PATIENTS AND METHODS: Patients with R/M HNSCC who had tumor progression after first-line cetuximab-containing chemotherapy were included into our study. Oncologic outcomes were estimated including time to cetuximab treatment discontinuation (TTD), progression-free survival 2 (PFS2), overall survival (OS), overall response rate (ORR), and disease control rate (DCR). Multivariate cox regression analysis with survival were conducted. Subgroup analysis with P16 and programmed death ligand 1 expression were performed. RESULTS: A total of 498 patients were eligible with 259 patients in the TBP group and 239 patients in the non-TBP group. The most common first-line chemotherapy was the EXTREME regimen in both groups. As for second-line treatment, the most common regimen were TPEx in the TBP group and taxane-based chemotherapy in the non-TBP group. Median TTD was 8.7 months in TBP and 5.5 months in non-TBP (p < 0.001). In terms of survival, median OS1 was significant longer in the TBP group than in the non-TBP group [14.1 months versus 10.9 months (p = 0.016)]. Multivariate analysis demonstrated cetuximab TBP was a factor independently associated with OS. CONCLUSIONS: Our retrospective study suggests cetuximab TBP to be effective and to provide better survival for patients with R/M HNSCC after failure of first-line cetuximab-containing chemotherapy. Further prospective studies are warranted to validate the role of cetuximab TBP in R/M HNSCC.

Clinical outcomes of cetuximab-based treatment for distant metastatic head and neck squamous cell carcinoma: A real-world study using Taiwan Head Neck Society registry database.

BACKGROUND: For R/M HNSCC, the differences in prognosis and treatment options between distant metastasis (DM) and locoregional recurrence, especially in the DM group, remain unclear. METHODS: From the Taiwan Head Neck Society registry database, patients who were diagnosed with R/M HNSCC and received cetuximab-based frontline therapy were collected for analysis. RESULTS: Among the enrolled patients, 59.3% (491/827) belonged to the DM group. The DM group had less primary site of oral cavity, less betel nut chewing, higher lactate dehydrogenase (LDH) levels, and higher LDH/albumin ratio compared with the non-DM group. For the patients with primary site of oral cavity and current smokers, DM coexisted with poorer outcomes. In the DM group, EXTREME-like regimen was more suitable for older patients, those with elevated LDH, and those with higher LDH/albumin ratio than TPExtreme-like regimen. CONCLUSION: DM coexisted with poorer prognosis in certain groups. LDH-associated biomarkers may aid treatment options for DM patients.

Case reports of management of aplastic anemia after COVID-19 vaccination: a single institute experience in Taiwan.

Global vaccination against the coronavirus disease 2019 (COVID-19) is thought to be the most effective way to end or at least contain the COVID-19 pandemic. However, despite the good safety profiles and effectiveness of the available COVID-19 vaccines, rare but serious hematological complications have emerged, including thromboembolic outcomes with thrombocytopenia following the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and Ad26.COV.2.S (Johnson & Johnson/Janssen) vaccines. Moreover, COVID-19 vaccination may be linked to the development of aplastic anemia (AA). We discuss four cases of AA that arose after COVID-19 vaccination in our hospital and two other such cases identified in our literature review.

The Chemokine CCL4 Stimulates Angiopoietin-2 Expression and Angiogenesis via the MEK/ERK/STAT3 Pathway in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a common malignant tumor with a poor prognosis and is a major public health burden in Taiwan. Angiogenesis, the formation of new blood vessels, promotes tumor proliferation, maintenance, and metastasis. Angiopoietin 2 (Angpt2), a mitogen with a strong angiogenic effect, is highly specific to endothelial cells and a key player in angiogenesis. The inflammatory chemokine (C-C motif) ligand 4 (CCL4) is also important in the pathogenesis and progression of cancer. In this study, an analysis of records from The Cancer Genome Atlas (TCGA) database found higher CCL4 expression in oral cancer tissue than in normal healthy tissue. CCL4 treatment of oral cancer cells upregulated Angpt2 expression and stimulated mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase 1/2 (ERK), and signal transducer and activator of transcription 3 (STAT3) phosphorylation. Transfection of oral cancer cells with MEK, ERK, and STAT3 inhibitors and their small interfering RNAs inhibited CCL4-induced promotion of Angpt2 expression and angiogenesis. In a mouse model of OSCC, CCL4-treated cells promoted neovascularization in implanted Matrigel plugs, whereas inhibiting CCL4 expression suppressed Angpt2 expression and angiogenesis. CCL4 shows promise as a new molecular therapeutic target for inhibiting angiogenesis and metastasis in OSCC.

B Cells in Tumor Microenvironment Associated With The Clinical Benefit to Programmed Cell Death Protein-1 Blockade Therapy in Patients With Advanced Esophageal Squamous Cell Carcinoma.

Background: B cells and B cell-related gene signatures in the tumor microenvironment (TME) are associated with the efficacy of anti-programmed cell death-1 (anti-PD-1) therapy in several cancer types, but not known for esophageal squamous cell carcinoma (ESCC). Patients and Methods: Patients with advanced ESCC receiving anti-PD-1/PD-L1-based therapy were retrospectively included. A targeted RNA profiling of 770 immune-related genes from archival ESCC tissues was performed. Differential immune-related pathways and the levels of infiltrating immune cells were estimated through Gene Set Enrichment Analysis and CIBERSORT, respectively. CD19 and CD138 expression were evaluated through immunohistochemistry (IHC). The markers evaluated were correlated with clinical benefit (CB; defined as either objective response or stable disease for ≥6 months) and survival. Results: A total of 64 patients were enrolled. The transcriptome analysis based on 25 patients revealed that B cell signature was significantly increased in patients with CB (P <.05) and correlated with a longer PFS (P = .032) and OS (P = .013). Multiple genes representative of B cells, B cell functions, and plasma cells were upregulated in patients with CB. On further analysis of B cell subtypes in patients with CB, increase of naïve B cells (P = .057) and plasma cells (P <.01) was found but not memory B cells (P = .27). The CD19 expression in tumor stroma, detected by IHC, was higher in patients with CB (P = .033). Conclusion: B cells in the TME were associated with CB in patients with advanced ESCC receiving anti-PD-1/PD-L1-based therapy.

Tumor Volume Reduction Rate to Induction Chemotherapy is a Prognostic Factor for Locally Advanced Head and Neck Squamous Cell Carcinoma: A Retrospective Cohort Study.

Introduction: Aim of this retrospective cohort study is to evaluate the prognostic value of tumor volume reduction rate status post-induction chemotherapy in locally advanced head and neck squamous cell carcinoma. Methods: Patients newly diagnosed from year 2007 to 2016 at a single center were included in this retrospective study. All patients had received induction Taxotere, Platinum, Fluorouracil followed by daily definitive intensity-modulated radiotherapy for 70 Gy in 35 fractions concurrent with or without cisplatin-based chemotherapy. Tumor volume reduction rate was measured and calculated by contrast-enhanced computed tomography images at diagnosis, and after at least 1 cycle of induction chemotherapy, and analyzed though a univariate and multivariate Cox regression model. Results: Ninety patients of the primary cancer sites at hypopharynx (31/90, 34.4%), oropharynx (29/90, 32.2%), oral cavity (19/90, 21.1%), and larynx (11/90, 12.2%) were included in this study, with a median follow-up time interval of 3.9 years. In multivariate Cox regression analysis, the tumor volume reduction rate of the primary tumor (TVRR-T) was also an independently significant prognostic factor for disease-free survival (DFS) (hazard ratio 0.77, 95% confidence interval 0.62-0.97; P-value = .02). Other factors including patient's age at diagnosis, the primary cancer site, and RECIST (Response Evaluation Criteria in Solid Tumors), were not significantly related. At a cutoff value using 50% in Kaplan-Meier survival analysis, the DFS was higher with TVRR-T ≥ 50% group (log-rank test, P = .024), and a trend of improved overall survival. (log-rank test, P = .069). Conclusion: TVRR-T is a probable prognostic factor for DFS. With a cut-off point of 50%, TVRR-T may indicate better DFS.

Outcomes of Different Haploidentical Transplantation Strategies from the Taiwan Blood and Marrow Transplantation Registry.

BACKGROUND: The two most noteworthy strategies for haploidentical stem cell transplantation (haplo-HSCT) are posttransplantation cyclophosphamide (PTCy) with or without thymoglobulin (ATG) and granulocyte colony stimulating factor-primed bone marrow plus peripheral blood stem cells (GIAC). We aimed to compare these approaches in patients with hematological malignancies. METHODS: We enrolled 178 patients undergoing haplo-HSCT, including modified GIAC (mGIAC), PTCy without ATG, and PTCy with ATG. RESULTS: The patients in the mGIAC group had the most favorable platelet and neutrophil engraftment kinetics. Although the grade III-IV acute graft-versus-host-disease (GvHD) rates were similar, those receiving mGIAC had a significantly higher extensive chronic GvHD rate. The patients receiving mGIAC had a similar cumulative incidence of relapse (CIR) to that in the patients receiving PTCy with ATG, but this was lower than that in the patients receiving PTCy without ATG. The patients receiving mGIAC had the lowest nonrelapse mortality (NRM) and the highest overall survival (OS) rates. The differences in CIR, NRM, and OS remained significant when focusing on patients with low/intermediate-risk diseases before haplo-HSCT. Intriguingly, among patients with high/very-high-risk diseases before haplo-HSCT, no differences were observed in the CIR, NRM, OS, or GvHD/relapse-free survival. CONCLUSION: the mGIAC approach may yield a better outcome in Taiwanese patients with hematologic malignancies, especially for those with low/intermediate-risk diseases.