Non-metastatic Lung Cancer Patients Research Articles

Role of Symptomatic Management in Understanding Effects of Early Integration of Palliative Care among Nonmetastatic Lung Cancer Patients on Psychological Well-Being

Aim. The impact of early referral to palliative care on quality of life for patients with lung cancer has already been discussed. However, the benefits of early integration of palliative care service (EIPCS) combined with standard oncology care for nonmetastatic lung cancer patients remain unclear. Hence, we designed a study to assess the impact of EIPCS among nonmetastatic cancer patients in India. Methods. In this randomized controlled trial study, we divided the data from 115 patients with diagnosed nonmetastatic lung cancer between age group of >18 years to ≥65 years. Following clinicopathological and radiology diagnosis, patients were referred to pain and palliative medicine department. Patients were randomly assigned by palliative physicians into two groups: Group A (N = 64), those who were receiving standard oncology care (chemotherapy or radiation or both) along with EIPCS, and Group B (N = 51), receiving standard oncology care. Patients were followed up every 3 weeks up to 3 months. Primary outcomes, symptoms’ burden, and psychological well-being were measured by validated tools. To define the impact of EIPCS, appropriate statistics were calculated as the mean ± standard deviation of the score of validated tools. Statistical significance was defined at p<0.005. Results. From the beginning, we had taken 115 patients, and on 42 days’ follow-up, the number of dropout patients for Group A was 3 (due to unable to contact), and for Group B, 9 (due to physical condition). This was followed by a reassessment after 126 days where dropout patients for Group A was 4 (due to unable to contact), and for Group B, 7 (due to physical condition). Following statistical report compliance at 126 days by WEMWBS was 21.16 ± 3.65 in Group A versus 16.1 ± 1.93 versus in Group B and by ESAS 51.84 ± 0.01 in Group A versus 97.64 ± 2.18 in Group B. Conclusion. The findings of this study showed that patients with nonmetastatic lung cancer who received standard oncology care combined with EIPCS had increased the psychological well-being and reduced symptoms burden.

Targeting the KRT16-vimentin axis for metastasis in lung cancer

Lung cancer is the most diagnosed malignant cancer and the leading cause of cancer-related deaths worldwide, with advanced stage and metastasis being a major issue. The mechanism leading to metastasis is not yet understood. Here, we found that KRT16 is upregulated in metastatic lung cancer tissues and correlated with poor overall survival. Knockdown of KRT16 inhibits metastasis of lung cancer both in vitro and in vivo. Mechanistically, KRT16 interacts with vimentin, and depletion of KRT16 leads to downregulation of vimentin. KRT16 acquired its oncogenic ability by stabilizing vimentin, and vimentin is required for KRT16-driven metastasis. FBXO21 mediates the polyubiquitination and degradation of KRT16, and vimentin inhibits KRT16 ubiquitination and degradation by impairing its interaction with FBXO21. Significantly, IL-15 inhibits metastasis of lung cancer in a mouse model through upregulation of FBXO21, and the level of IL-15 in circulating serum was significantly higher in nonmetastatic lung cancer patients than in metastatic patients. Our findings indicate that targeting the FBXO21/KRT16/vimentin axis may benefit lung cancer patients with metastasis.

Identification and clinical implications of circulating cancer associated fibroblasts in lung cancer patients

ObjectivesIn tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) are known to expedite cancer progression (metastasis). CAF-secreted cytokines confer a survival advantage to circulating tumor stem cells (CTSCs) (indicators of residual-disease) facilitating immune system evasion. Collectively, CAFs serve as “bio-incubator" by providing favourable "soil" for their subsequent growth in the circulation during EMT and are thus considered as an important target in diagnostic and therapeutic applications. Thus, the aim of this study was to check the presence of circulating CAF (cCAFs) in blood of lung cancer patients as a liquid biopsy approach. Materials and methodsMononuclear cells isolated from the peripheral blood of non-metastatic lung cancer patients were cultured to confirm the presence of cCAF. CAF-specific marker α-SMA and FAP was used to characterise them using Western blot and real time PCR. Furthermore, correlation between expression of cCAFs and various clinico-pathological parameters were examined. ResultsCultured MNCs showed the presence of cCAFs which was further confirmed by western blotting. All patients were found positive for the presence of cCAFs (α-SMA expression), while healthy individuals lacked this, being α-SMA negative. Moreover, significant trend was observed between different stages of lung cancer patients (p < 0.014), suggesting its probable role in lung cancer progression. ConclusionThus, cCAFs could be companion biomarker for the early detection of tumors as well as it could be efficient biomarker for the prediction of metastasis. However, validation of cCAFs as robust marker is still required to be tested in a more number of patients. This should be done using more than one marker associated with CAFs for their clinical application, as it has a potential implication to monitor the effectiveness of a specific cancer therapy and disease progression.

LC-MS/MS-Based Quantitative Proteomics Analysis of Different Stages of Non-Small-Cell Lung Cancer.

Lung cancer has a higher incidence rate and mortality rate than all other cancers. Early diagnosis and treatment of lung cancer remain a major challenge, and the 5-year survival rate of its patients is only 15%. Basic and clinical research, especially the discovery of biomarkers, is crucial for improving the diagnosis and treatment of lung cancer patients. To identify novel biomarkers for lung cancer, we used the iTRAQ8-plex labeling technology combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze the serum and urine of patients with different stages of lung adenocarcinoma and healthy individuals. A total of 441 proteins were identified in the serum, and 1,161 proteins were identified in the urine. The levels of elongation factor 1-alpha 2, proteasome subunit alpha type, and spermatogenesis-associated protein increased significantly in the serum of patients with lung cancer compared with those in healthy controls. The levels of transmembrane protein 143, cadherin 5, fibronectin 1, and collectin-11 decreased significantly in the serum of patients with metastases compared with those of nonmetastatic lung cancer patients. In the urine of stage III and IV lung cancer patients, the prostate-specific antigen and prostatic acid phosphatase decreased significantly, whereas neutrophil defensin 1 increased significantly. The results of LC-MS/MS were confirmed by enzyme-linked immunosorbent assay (ELISA) for transmembrane protein 143, cadherin 5, fibronectin 1, and collectin-11 in the serum. These proteins may be a potential early diagnosis and metastasis biomarkers for lung adenocarcinoma. Furthermore, the relative content of these markers in the serum and urine could be used to determine the progression of lung adenocarcinoma and achieve accurate staging and diagnosis.

Evaluation of Oxidative Stress Biomarkers in Brain Metastatic and Non-Metastatic Lung Cancer Patients with Different Cell Types.

Oxidative stress that leads to an imbalanced prooxidant/antioxidant status can be a critical factor affecting lung cancer etiopathology. The antioxidant system provides primary protection under oxidative stress. The purpose of the study was to investigate the serum antioxidant system status in brain metastatic and non-metastatic lung cancer patients with different cell types. In this prospective study, 33 patients with lung cancer metastasis (metastatic patient group), 36 lung cancer patients (non-metastatic patient group), and 25 healthy control groups were included. Enzymatic (Superoxide Dismutase, SOD; Glutathione Peroxidase, GPX; and Glutathione Reductase, GR) and non-enzymatic (Glutathione, GSH) antioxidant system biomarkers with Thiobarbituric Acid Reactive Substances (TBARS) levels were studied in the serum samples of the control and patient groups. The oxidative stress biomarkers were measured spectrophotometrically. SOD activity increased though TBARS levels and GR activity decreased in both patient groups compared to the control. GPX activity increased only in the non-metastatic group. Antioxidant biomarkers varied between small cell and non-small cell group patients. GR activity and GSH levels were significantly higher in the non-metastatic group compared to the metastatic group. Correlations were also found between antioxidant parameters in the non-metastatic group. It was emphasized the imbalanced antioxidant system in the duration of the disease is related to not only cell type but also the metastatic structure. This is the preliminary study exhibiting the contribution of antioxidant imbalance in different subtypes with varied prognosis and behavior of lung cancer in the presence of brain metastasis. Therefore, oxidative stress biomarkers can serve as a useful tool to get information about the progression of lung cancer. Thus, it may provide fundamental data for further cancer research when considering the diagnosis of the disease.

Prognosis of metastasis based on age and serum analytes after follow-up of non-metastatic lung cancer patients

At the diagnostic stage, metastasis detection is around 75% in the lung cancer patients. Major clinical challenge faced by medical oncologists is the unpredictable metastasis development in non-metastatic patients. The literature regarding the biomarkers/factors prognosticating metastasis in non-metastatic patients during follow-up is very limited. In this pilot study, the levels of serum biomarkers (IL-8, VEGF, MMP-2, MMP-9) were measured at diagnosis stage of non-metastatic lung cancer patients and these observations were evaluated for metastasis development after follow-up of median 29.2 months. After follow-up, ∼40% of these patients developed metastasis. The average age of non-metastatic patients which later developed metastasis, was found to be lower than the patients continued to be non-metastatic. These patients also showed higher levels of IL-8 and MMP-9 than the patients which did not develop metastasis. Analysis of Receiver Operating Characteristic Curves, Youden's Index and positive likelihood ratio values showed better diagnostic ability for IL-8 and MMP-9, which improved when both markers used together. Moreover, patients with age ≤60 years showed higher prognostic ability of metastasis development, which was significantly enhanced when patient age was analysed with IL-8. These results suggest potential of serum analytes (IL-8, MMP-9) and/or patient age in prognosticating the metastasis development in non-metastatic patients.

447P - Hypomagnesaemia: An unnoticed problem in lung cancer patients treated with concurrent chemoradiation

BackgroundHypomagnesaemia is a well-known side-effect in patients receiving cisplatin-containing chemotherapy. However, a small number of patients, who are receiving weekly cisplatin along with radiotherapy, will show symptoms. Till date in Bangladesh no study has been done to find out the incidence of hypomagnesaemia in concurrent chemo-radiotherapy patients. MethodsThis observational study was done between January, 2018 and February, 2019 at the Cancer Care Center of United Hospital Limited, Dhaka, Bangladesh. A total of 100 non-metastatic lung cancer patients were included in this study. Inclusion criteria were: patients treated with concurrent chemo-radiotherapy and weekly cisplatin; no prior chemotherapy; no prior kidney diseases; ECOG PS 1-2. All patients were treated with 40mg/m2 cisplatin weekly with radiotherapy. Radiotherapy doses were range in 60Gy to 70Gy in 2Gy per fraction. During chemotherapy 1000cc 0.9%NaCl saline was used as pre-hydration and post-hydration. Magnesium level was checked at week 1, week 3 and week 6. Events were categorized according common terminology criteria for adverse events v.4.0. In very severe cases IV magnesium was used, and in mild to moderate cases oral supplement has been used. ResultsAmong 100 patients, 63 patients suffered various degrees of hypomagnesaemia. 23 patients were symptomatic for hypomagnesaemia and needed IV correction. And 27 patients were suffering from mild hypomagnesaemia. It has been observed that elderly patients suffer more; 41 patients were above the age of 60 years. ConclusionsAlthough hypomagnesaemia is rarely symptomatic, it should be kept in mind that severe grade of hypomagnesaemia can cause fatal damage especially in elderly patients. As, Bangladesh is a developing country and accordingly to their food habits, people have low amounts of dietary magnesium as usual. This finding drives us, to change our daily practice to add IV magnesium (2.5mg/5ml) during post-hydration along with 20mmol potassium n weekly cisplatin chemotherapy to prevent hypomagnesaemia. This was a practice changing finding in our canter. To validate this observational finding we need large prospective multicenter data. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Relationship between age at diagnosis and treatments received by cancer patients.

Increases in cancer incidence and mortality reflect the larger numbers of elderly in the population. Using a mortality sample of 1891 biopsy-confirmed cancer patients, analyses reveal older breast, prostate, and cervical-uterine cancer victims were more likely to be diagnosed with metastases. Logistic regression analyses of subsamples of breast (N = 224), lung (N = 513), and colorectal (N = 299) cancer patients indicate that age is significantly inversely related to receipt of both subsequent chemotherapy and radiation therapy, controlling for stage of disease and presence of co-morbid disease. Exceptions to this relationship are the use of radiation therapy among nonmetastatic lung cancer patients and all breast cancer patients. The implications of these findings for current cancer control programs are discussed.