scholarly journals Clinical profile and initial treatment of non-small cell lung cancer: a retrospective cohort study at the Uganda Cancer Institute

2021 ◽  
Vol 21 (4) ◽  
pp. 1739-45
Author(s):  
Solomon Kibudde ◽  
Bruce James Kirenga ◽  
Martin Nabwana ◽  
Fred Okuku ◽  
Victoria Walusansa ◽  
...  

Introduction: Lung cancer is a major global public health burden constituting 11.6% of all new cancer diagnoses and 18.4% of all cancer-related mortality. Purpose: To describe the clinical profile and initial treatment of non-small cell lung cancer in Uganda. Methods: We reviewed charts of a cohort of patients with a histologically confirmed diagnosis of non-small cell lung cancer, treated between January 2013 and November 2015 at the Uganda Cancer Institute. Results: A total of 74 patients met the inclusion criteria. The median age was 56 years (IQR 47-70), with 16.2% below the age 45 years, and 51% were female. Only 10 percent were active smokers and the most frequent histological subtype was adenocarcinoma (71%). The majority (91.9%) had stage IV disease at diagnosis and frequent metastases to contralateral lung, liver, and bones. Twenty-seven (27) patients received platinum-based chemotherapy, while 27 patients received erlotinib, and only 4 patients received palliative thoracic radiotherapy. The median survival time was 12.4 months, and the overall response rate was 32.7%. There was no survival difference by type of systemic treatment, and on multivariate analysis, poor performance status was predictive of adverse outcomes (p < 0.001). Conclusions: Patients with non-small cell lung cancer in Uganda frequently presented with late-stage disease at diagnosis. The majority of patients were female, never-smokers, and had predominantly adenocarcinoma subtype. Keywords: Non-small cell lung cancer; Uganda; erlotinib; lung cancer; Uganda Cancer Institute.

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Katrina Kildey ◽  
Neha S. Gandhi ◽  
Katherine B. Sahin ◽  
Esha T. Shah ◽  
Eric Boittier ◽  
...  

AbstractPlatinum-based chemotherapy remains the cornerstone of treatment for most non-small cell lung cancer (NSCLC) cases either as maintenance therapy or in combination with immunotherapy. However, resistance remains a primary issue. Our findings point to the possibility of exploiting levels of cell division cycle associated protein-3 (CDCA3) to improve response of NSCLC tumours to therapy. We demonstrate that in patients and in vitro analyses, CDCA3 levels correlate with measures of genome instability and platinum sensitivity, whereby CDCA3high tumours are sensitive to cisplatin and carboplatin. In NSCLC, CDCA3 protein levels are regulated by the ubiquitin ligase APC/C and cofactor Cdh1. Here, we identified that the degradation of CDCA3 is modulated by activity of casein kinase 2 (CK2) which promotes an interaction between CDCA3 and Cdh1. Supporting this, pharmacological inhibition of CK2 with CX-4945 disrupts CDCA3 degradation, elevating CDCA3 levels and increasing sensitivity to platinum agents. We propose that combining CK2 inhibitors with platinum-based chemotherapy could enhance platinum efficacy in CDCA3low NSCLC tumours and benefit patients.


2021 ◽  
Vol 10 (5) ◽  
pp. 1126
Author(s):  
Michał Szczyrek ◽  
Radosław Mlak ◽  
Aneta Szudy-Szczyrek ◽  
Karolina Kędziora ◽  
Teresa Małecka-Massalska ◽  
...  

Caspase 8 is a protein involved in the process of cell apoptosis, which may affect the efficacy of anti-cancer treatment. The aim of our study was to determine the impact of polymorphisms in the CASP-8 gene encoding caspase 8 on the prognosis in non-small-cell lung cancer (NSCLC). The study involved 99 patients with newly diagnosed locally advanced or metastatic NSCLC treated with platinum-based chemotherapy. The presence of the GG genotype was associated with distant metastases, smoking, and a family history of cancer. The higher risk of early progression was associated with weight loss and the CASP-8 genotype (GG vs. AG or AA: 20.51% vs. 2.86%). The higher risk of progression-free survival (PFS) shortening was associated with a higher stage of disease (hazard ratio (HR) = 2.50, 95% CI: 1.61–3.89, p < 0.0001), distant metastases (HR = 2.30, 95% CI: 1.42–3.72, p = 0.0016), and the GG genotype (HR = 1.68, 95% CI: 1.10–2.57, p = 0.0152). The influence of the GG genotype on the PFS was confirmed in a multivariate analysis (HR = 1.80, 95% CI: 1.06–3.05, p = 0.0317). We did not confirm the influence of CASP-8 genotypes on the overall survival (OS).


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