High-dose methotrexate and zanubrutinib combination therapy for primary central nervous system lymphoma

In this editorial I comment on the article,published in the current issue of the World Journal of Clinical Oncology.Primary central nervous system lymphoma(PCNSL)is a disease of elderly and immunocompromised patients.The authors reported clinical results of 19 patients with PCNSL treated with zanubrutinib/high dose methotrexate(HD-MTX)until disease progression.They demonstrated that the combination of zanubrutinib with HD-MTX led to a marked clinical response and tolerability among these patients.They also observed that cerebrospinal fluid liquid biopsy to detect circulating tumor DNA may be a good option for evaluating treatment response and tumor burden in patients with PCNSL.PCNSL is a challenging disease for treatment as these patients present with different neurological states and comorbidities.Treatment has evolved over the years from whole brain radiotherapy to HD-MTX followed by autologous stem cell transplant.Gradually,treatment of patients with PCNSL is going to become individualized.

Systemic treatment strategies for triple-negative breast cancer

Triple-negative breast cancer(TNBC) is defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2(EGFR2). Most TNBC has a basal-like molecular phenotype by gene expression profiling and shares clinical and pathological features with hereditary BRCA1 related breast cancers. This review evaluates the activity of available chemotherapy and targeted agents in TNBC. A systematic review of PubM ed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBC treated with chemotherapy and targeted agents. Our review identified TNBC studies of chemotherapy and targeted agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth and survival pathways. TNBC is sensitive to taxanes and anthracyclins. Platinum agents are effective in TNBC patients with BRCA1 mutation, either alone or in combination with poly adenosine diphosphate polymerase 1 inhibitors. Combinations of ixabepilone and capecitabine have added to progression-free survival(PFS) without survival benefit in metastatic TNBC. Antiangiogenic agents, tyrosine kinase inhibitors and EGFR inhibitorsin combination with chemotherapy produced only modest gains in PFS and had little impact on survival. TNBC subgroups respond differentially to specific targeted agents. In future, the treatment needs to be tailored for a specific patient, depending on the molecular characteristics of their malignancy. TNBC being a chemosensitive entity, combination with targeted agents have not produced substantial improvements in outcomes. Appropriate patient selection with rationale combinations of targeted agents is needed for success.

A phase II study of neoadjuvant chemotherapy followed by organ preservation in patients with muscle-invasive bladder cancer

Objective:Conservative approaches in muscle-invasive bladder cancer(MIBC)have been evolved to avoid aggressive surgery,but are limited to elderly,frail,and patients medically unfit for surgery.Our study aimed to assess the response rate of neoadjuvant chemotherapy(NACT)before radiotherapy(RT)in MIBC patients.Methods:Forty patients with urothelial carcinoma of stage T2-T4a,N0,M0 were enrolled between November 2013 and November 2015,and treated with three cycles of NACT with gemcitabine-cisplatin.Post-NACT response was assessed using Response Evaluation Criteria in Solid Tumors(RECIST)criteria.Patients who achieved complete response(CR)and partial response(PR)>50%were treated with radical RT,and those who had PR<50%,stable disease(SD),and progressive disease(PD)underwent radical cystectomy(RC).Survival analysis was done with Kaplan-Meier method and point-to-time events were analyzed with Cox-proportional hazards regression model.Results:After NACT,35(87.5%)patients achieved either PR>50%or CR,and were treated with RT.Five(12.5%)patients who had PR<50%,SD,or PD underwent RC.All patients who received radiation showed CR after 6 weeks.Median follow-up was 43 months(range:10-66 months)and median overall survival(OS)was not reached.Three-year OS,local control,and disease-free survival were 70.1%,60.9%,50.6%,respectively,and 50%of patients preserved their functioning bladder.Three-year OS rate was 88.9%in patients who achieved CR to NACT,73.1%in patients with PR≥50%and 40%in patients with PR<50%.Conclusion:NACT followed by RT provides a high probability of local response with bladder preservation in CR patients.Appropriate use of this treatment regimen in carefully selected patients may omit the need for morbid surgery.

Understanding the role of transmembrane 9 superfamily member 1 in bladder cancer pathogenesis

In this editorial we comment on the article by Wei et al,published in the recent issue of the World Journal of Clinical Oncology.The authors investigated the role of Transmembrane 9 superfamily member 1(TM9SF1)protein in bladder cancer(BC)carcinogenesis.Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines.These cell lines were then subject to cell counting kit 8,wound-healing assay,transwell assay,and flow cytometry.Proliferation,migration,and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression.TM9SF1 silencing inhibited proliferation,migration and invasion of BC cells.The authors conclude that TM9SF1 may be an oncogene in bladder cancer pathogenesis.