Search

Despite the huge knowledge about the risk factors associated with lung cancer, this disease remains the leading cause of cancer deaths in highly developed countries. The reason for this phenomenon is the increasing pollution of the natural environment and, above all, the difficulties in eliminating the addiction to smoking. In large Polish urban agglomerations, the exposure to particulate matter containing hydrocarbons on its surface, to free hydrocarbons, nitrogen and sulphur oxides is constantly increasing. Moreover, almost 25% of the Polish population smoke cigarettes and the elimination of smoking addiction through psychotherapy, nicotine replacement therapy and pharmacotherapy are sometimes ineffective. This article presents that the use of tobacco-burning products other than cigarettes (e.g., cigars or pipes) and products containing marijuana are as dangerous to health as classical cigarettes. Other nicotine-containing products have also appeared: e-cigarettes and tobacco heating systems. These products are highly addictive to nicotine, but the aerosols, that are produced by them, contain fewer toxic substances than cigarette smoke. Therefore, there are reasons to use these products instead of traditional cigarettes in people who are highly addicted to nicotine (after exhaustion of other treatment options) to reduce health risks, including lung cancer risk. However, it must be evoked that only a complete smoking cessation and the use of nicotine-containing products could be effective in reducing the risk of lung cancer.

Anti-PD-1 or PD-L1 immunotherapy in some patients with non-small cell lung cancer (NSCLC) may not be effective, despite the high percentage of cancer cells with PD-L1 expression (≥ 50%). TMB (tumor mutation burden), smoking status and low intestinal microbiome diversity may be associated with lack of efficacy of immune checkpoints inhibitors treatment in NSCLC patients. The case presented here concerns a non-smoking female patient with lung adenocarcinoma, in whom, despite the high percentage of PD-L1 positive tumor cells (50%), pembrolizumab therapy was ineffective. Next generation sequencing (NGS) was performed using the FOCUS panel allowing the analysis of 52 genes whose damage is associated with various types of solid tumors, including lung cancer. Benign genetic changes clinically irrelevant for patients with non-small cell lung cancer have been observed. In the meantime, profiling of the patient’s intestinal microbiome was performed, due to the fact that the composition of the intestinal microbiome may be a decisive factor in the lack of response to immunotherapy in patients with high PD-L1 expression and no driver mutations. Low diversity of bacteria in the intestines, with a noticeable dysbiosis (dysbacteriosis), was observed. The presence of bacteria Akkermansia, Enterococcaceae, Bifidobacteriaceae or Coriobacteriaceae , especially the presence of Akkermansia mucinifila seems to be a favourable factor of the possibility of obtaining response to immunotherapy and prolongation of progression-free survival (PFS). In the intestinal microbiome of the presented case, no bacteria from the Verrucomicrobia phylum , to which A. mucinifila belongs , were found. In addition, only 0.011% of Enterococcaceae were found. Studies on the intestinal microbiome in cancer patients receiving immunotherapy appear to be necessary to correctly understand the effect of microbiome composition on the effectiveness of this treatment method.

Introduction. The rearrangement of the gene encoding ROS protooncogene (ROS1) is observed in a very small percentage (1–2%) of patients with non-small cell lung cancer (NSCLC). The clinical characteristics of ROS1-positive patients are similar to those observed in the group of patients with ALK gene rearrangement. Detection of ROS1 gene rearrangement is an extremely important predictive factor enabling the use of crizotinib in the 1st line of NSCLC patients with stage IIIB or IV. Due to the addition of crizotinib to the list of reimbursed drugs from January 2019, the analysis of this genetic change should be part of a molecular tests panel performed in patients with locally advanced and advanced NSCLC in the qualification for molecularly targeted treatment. Aim of the study. Analysis of ROS1 gene rearrangement incidence among NSCLC patients in stage IIIB or IV qualified for molecularly targeted therapies. Presentation of methodological difficulties with fluorescent in situ hybridization (FISH) technique which is used to detect ROS1 genetic abnormality. Materials and methods. The analysis of ROS1 gene rearrangement was carried out using fluorescent in situ hybridization technique in tissue samples taken from 573 NSCLC patients of non-squamous cell type during routine pathomorphological diagnostics. Results. The material obtained from the tumor was fixed in formalin and archived in paraffin. Histological material was obtained from 408 patients, and 165 — cytological (cytoblock). A reliable (diagnostic) result of the ROS1 gene rearrangement was obtained in 439 patients (76.61%). The main difficulties for ROS1 gene analysis were low number of cancer cells, as well as high background fluorescence interference and fragmentation of cell nuclei. ROS1 gene rearrangement was detected in 9 patients with adenocarcinoma (1.57% among all patients), including 5 men and 4 women. In 19 patients, other abnormalities regarding the ROS1 gene were observed, primarily the polysomy of the examined ROS1 gene fragment (3.32%). Polysomy did not coexist with the ROS1 rearrangement. Conclusion. Fluorescent in situ hybridization is a useful tool in detecting ROS1 gene rearrangement. The test can be performed in both histological and cytological material (cytoblock). However, the correct fixation of the material and the appropriate number of tumor cells in the tested samples is extremely important for obtaining a reliable result.

We report a case of patient with non-small-cell lung cancer with expression of PD-L1 molecule on 1% of cancer cells, who was treated with chemotherapy, radiotherapy, and, during disease progression, with nivolumab immunotherapy. In the course of immunotherapy our patient developed symptoms of multi-axis hypopituitarism. Pituitary macroadenoma was diagnosed. In differential diagnosis, autoimmune inflammation of the pituitary gland in the course of nivolumab therapy was considered. After pituitary failure symptoms resolved, the immunotherapy was continued, with two-year remission of the disease.

Small cell lung cancer (SCLC) currently comprises 15–20% of all lung cancers. It is characterised by rapid growth and early appearance of distant metastases. It is closely related to smoking. A characteristic feature of this type of cancer is the frequent coexistence of paraneoplastic syndromes (about 50% of patients). Paraneoplastic syndromes are clinically important because they can be the first sign of cancer. Early diagnosis of disturbing symptoms is an important factor in increasing the effectiveness of treatment and the patient’s chance for longer survival. The most frequent and important paraneoplastic syndromes in the course of SCLC are primarily the syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), paraneoplastic cerebellar degeneration, and Lambert-Eaton syndrome. This paper presents the case of a patient who came to the hospital with symptoms of hyponatraemia. Looking for the causes of hyponatraemia, the syndrome of abnormal secretion of antidiuretic hormone (Schwartz-Bartter syndrome) in the course of small cell lung cancer was confirmed. The fact that the patient was genetically burdened with the family history of breast cancer and was a carrier of the BRCA2 gene mutation was also significant. According to the latest research, mutation in the BRCA2 gene significantly affects the chemosensitivity of cancer cells, and thus increases the body’s response to treatment. The patient received chemotherapy with carboplatin and etoposide, resulting in partial remission of cancer after two treatment cycles.

Inhibitors of immune checkpoints (anti-PD-1 or anti-PD-L1 monoclonal antibodies) are effective in non-small cell lung cancer treatment, significantly extending the overall survival of some patients. However, there are no predictive factors, which could allow precise qualification of cancer patients to immunotherapy. The best evaluated in this regard is the expression of PD-L1 molecule on tumour cells, the occurrence of which is associated with higher response rate and prolonged time to progression in patients undergoing immunotherapy. Some recent reports indicate that the composition of the patient’s intestinal microflora, the presence of inflammation, and antibiotic therapy used before or during immunotherapy may affect the effectiveness of anti-PD-1 or anti-PD-L1 antibodies. Disturbance of the body’s natural balance, e.g. due to the use of antibiotics, may reduce the effectiveness of immunotherapy. This may be due to a lack of stimulation of the immune system by antigens from bacteria found naturally in the gut. On the other hand, supplementing the microflora with the necessary ingredients can improve the effectiveness of immunotherapy. The future goal is to develop so-called “immunotherapeutic probiotics”, the use of which could enhance the effect of cancer immunotherapy.