Nikol Rušarová, Marie Bartoušková
Marie Drösslerová, Libor Havel
Renata Soumarová, Tomáš Blažek, Jan Dvořák
Gabriela Krákorová, Marek Šťastný, Hana Steinbergerová, Jana Důrová, Miloš Pešek, Jan Baxa
Igor Richter, Josef Dvořák, Vladimír Šámal, Jiří Bartoš
New approaches in the treatment of stage II and III melanoma in the context of current research results
The successful journey continues. After success in advanced and metastatic melanoma, melanoma treatment has been transferred to adjuvant therapy. It is essential to determine early stages of melanoma suitable for adjuvant treatment. According to the new classification, the prognosis for stages IIB and IIC is worse than for stage IIIA. This group of patients is currently denied adjuvant therapy and we are awaiting the results of ongoing trials. Because the risk of disease relapse is high, between 40 and 60%, the aims of current research to move adjuvant therapy to the stage II. The Keynote 716 study (MK 3475-716 - NCT03553836) sought to determine whether adjuvant therapy with pembrolizumab at risk stages IIB and IIC would delay the relapse of the disease. The focus of the main studies of targeted treatment of COMBI AD and immunotherapy EORTC 18071, CheckMate-238, Keynote 054 was the stage III. The question is not whether to treat, but what treatment to start especially for melanoma with BRAF V600 mutation. Adjuvant treatment at this stage has shown a clear benefit and its use is undoubted. Unfortunately, we are not clear about subsequent treatment at relapse during or after adjuvant treatment.
The emergence of tumor resistance to targeted therapy represents a significant public health problem. Overcoming these mechanisms would lead to a prolonged effect of this form of treatment, which excels at a significantly higher percentage of therapeutic responses than immunotherapy. The key to the development of new drugs that potentiate the effect of BRAF and MEK inhibitors is a detailed mapping of resistance mechanisms. This work points to some mechanisms of epigenetic, genetic and influence of tumor microenvironment. It also points to the influence of the immune system, which offers one way to potentiate the effect of targeted therapy.
Cancer immunotherapy has become a therapeutic routine in increasing number of diagnoses. Beside the established antitumoral efficacy, a range of specific adverse events is now well-known including the immunological basis of the evolution. The article summarizes the most frequent types of skin toxicity in immunotherapy. Severity assessment is presented according to the new version of CTCAE (Common Terminology Criteria for Adverse Events). Current recommendations of ESMO (European Society for Medical Oncology) and NCCN (National Comprehensive Cancer Network) are taken into account in the treatment management.
Solar keratosis is a frequently occurring epithelial dysplasia where atypical keratinocytes proliferate. It is located in places often exposed to UV radiation, more often in people of phototype I and II. Solar keratosis can develop into squamous cell carcinoma. The treatment is surgical, physical and topical. Ingenol-mebutate gel therapy is new topical treatment now.
Case report describe atypical immune response in patient with high-risk melanoma, stadium III, adjuvantly treated with anti-PD-1 antibody nivolumab, noticed in the first 3 months of therapy. PET/CT (positrom emision tomography) showed the presence of pathological lymph-nodes in mediastinum, suspicion to interstitial lung disease and extensive densifications of the subcutaneous fat of extremities with pathological metabolic activity. In cooperation with pneumo-oncologist the adverse event of immunotherapy (autoimmune pneumonitis) was excluded.
Early breast cancer with human epidermal growth factor receptor 2 (HER2 [EGFR2]) positivity has a better chance of recovery due to the potential of targeted adjuvant and neoadjuvant anti-HER2 treatments. Nevertheless, 25% of patients who still have the disease, despite the treatment, remain mostly in the form of distant metastases. Therefore, it is sensible for patients at risk to enhance anti-HER2 treatment for early HER2 positive cancer. One option is prolonged adjuvant therapy with neratinib.
Several recent clinical studies have shown the benefit of combining checkpoint inhibitors with vascular endothelial growth factor (VEGF) directed agents. JAVELIN Renal 101 was a randomised study comparing the combination of avelumab + axitinib versus sunitinib in the first line therapy for metastatic renal cell carcinoma. A total of 886 patients were enrolled. In patients with programmed cell death ligand 1 (PD-L1) expression, the median progression-free survival was 13.6 months versus 7.2 months favoring avelumab-axitinib. Based on these results, the combination of avelumab and axitinib is a new standard first-line treatment for metastatic renal cell carcinoma.
Breast cancer is the most frequently diagnosed cancer of women (except of skin tumors). In addition, up to 30 percent of women with early-stage, non-metastatic breast cancer at diagnosis will develop distant metastatic disease. Currently due to preventive examinations and mammography examination the incidence of breast cancer is increasing, which was 146 women / 100 000 inhabitants in 2017. But mortality decreases due to new possibilities of treatment and enlargement of the treatment armamentarium. In 2017 the mortality rate was 34.7 women / 100 000 inhabitants.
KRAS (Kirsten rat sarcoma viral oncogene homolog) mutations are the most frequently oncogene aberrations in non-small cell lung cancer (NSCLC). KRAS-mutated NSCLC represents a heterogeneous subgroup because there are different KRAS subtypes, mutations and comutations. It results in different biological behavior of the tumor and its response to treatment. A large majority of patients with KRAS mutations have short-term survival. Trials for targeted treatment have failed. Immunotherapy is the most promising treatment for some patients with KRAS-mutated NSCLC. A very hopeful is an experimental cancer drug AMG 510 which is tested in phase 1/2 clinical trial.
Treatment of inoperable non-small cell lung cancer stage III is based on concomitant chemoradiotherapy. However, most patients experience relapse. Efforts to improve the results have resulted in various combinations of cytostatics administered concurrently with or after radiotherapy, an improvement in the irradiation technique, or an increase in the radiation dose administered. However, only a combination of concomitant chemoradiotherapy with immunotherapy led to a significant improvement in progression-free survival and overall survival. In the PACIFIC study, durvalumab was given as consolidation therapy after chemoradiotherapy was completed. The results of the study are discussed in detail in the article and represent a change in current clinical practice and a new standard in the treatment of patients with non-small cell lung cancer III. stages.
Atypical response to anti‑PD‑1 therapy followed by long‑term survival in non‑small cell lung cancer – case reports
Metastatic non-small cell lung cancer has poor prognosis. In the absence of driving mutations (EGFR, ALK, ROS, BRAF) or high expression of programmed death-ligand 1 (PD-L1), chemotherapy or its combination with bevacizumab is the initial treatment option with respect to reimbursement conditions in the Czech Republic. The second line possibility is the use of immunotherapy with inhibitors of protein 1 of programmed cell death (anti-programmed death-1, anti-PD-1) or inhibitors its ligand, anti-PD-LI. The authors present two case reports of patients, who had an atypical response following immunotherapy. This was the persistent effect of immunotherapy, despite the progression on this treatment. The first patient had no need for another active oncology treatment for further 12 months after immunotherapy and the malignancy had not been significantly progressing. The second patient developed a significant response to chemotherapy following anti-PD-1 immunotherapy. This phenomenon, in the literature referred not quite correctly to as chemosensitization, is repetitively described. Next the authors also consider the possibilities of treatment of the next line after immunotherapy failure.
Clinical dilemma of lung cancer treatment with anti‑PD‑1 therapy (nivolumab) in the discovery of rheumatological problems with joint swelling
Immunotherapy is the use of medicines to stimulate a person's own immune system to recognize and destroy cancer cells more effectively. Nivolumab can be used in people with certain types of advanced NSCLC whose cancer starts growing again after chemotherapy. But immunotherapy drugs can cause side effects, including rare complications that, for some patients, may be life threatening, but most side effects are mild to moderate in severity and respond to treatments such as steroids. It’s very important to report any new side as soon as possible. Although rheumatic immune-related adverse events are rarely life-threatening, patients' quality of life can be considerably restricted due to pain, stiffness and limited mobility.
Prostate cancer is the most common male malignant neoplasm in men worldwide and second cause of cancer related death. During the last decade, the treatment of metastatic castration resistant prostate cancer has dramatically changed with the approval of new agents as cabazitaxel, enzalutamide, abiraterone and radium 223. These new therapeutic options have provided an overall survival increase from 14-18 months to average of 30-36 months. The problem is the absence of the clearly defined predictive marker. In this review we discussing to choose the optimal treatment sequence of this disease.
Good and adequate analgesia is a fundamental right of every patient. Although quality pain management is much more affordable today, the quality of pain management is still dependent on the active interest of healthcare professionals and the organization of acute and chronic pain management in the workplace. The high-quality analgesia has been repeatedly proven to be associated with a reduction in morbidity, faster recovery and discharge from the hospital.