Analysis of progression of number and structure of scans performed using PET, PET/ CT and PET/ MRI in the Czech Republic in 2013- 2021.

BACKGROUND: Positron emission tomography (PET) is a state-of-the-art diagnostic method of nuclear medicine, used for diagnostics of many pathological states in the organism, first and foremost in oncological issues. The first analysis of utilization and potential utilization of PET in the Czech Republic was published in 2013. In the following years, there was a sharp increase in a number of PET/CT and PET/MRI scanners in the country; in 2013-2021, it doubled. Simultaneously with the increase in scans performed, the range of available radiopharmaceuticals also broadened. MATERIAL AND METHODS: The study analyses the numbers and structure of PET, PET/CT and PET/MRI scans in the 2013-2021 period, using the pseudonymized data acquired from the General Health Insurance Company of the Czech Republic. The data was evaluated through a series of qualitative and quantitative indicators (number of scans performed, structure of diagnoses, use of different tracers, and availability of a scan for a patient). RESULTS: In the observed interval of time, the number of scans performed practically doubled, both thanks to more scanners installed and more radiopharmaceuticals available. The percentage of oncological and non-oncological scans remains more or less the same. Nevertheless, the regional differences in a number of scans performed persist, as does the availability of the scan for patients. CONCLUSION: PET is still a dynamically developing molecular imaging method in the Czech Republic. The analysis of a number and structure of scans performed offers a priceless overview of the development of the method over the years, in regard to diagnoses, utilization of individual radiopharmaceuticals or geographic distribution of scans performed. The observed findings are a motivation for further analyses.

Retroperitoneal tumour resection in fifteen consecutive cases: Single centre experience.

INTRODUCTION: Retroperitoneal tumours (RTs) in adults are a rare heterogeneous group of neoplasms arising from the retroperitoneal space. RTs'clinical manifestations are nonspecific and depend on their anatomical positioning and relation with bordering structures. Our study aimed to retrospectively evaluate our patients' diagnosis, length of hospital stay, disease-free period and postoperative metastasis occurrence. METHODS: From 2011 to 2019, fifteen suspected RT resections were performed at our centre. Retrospective analysis of patients' hospital stays, follow-up, histological and immunological tumour profile, and metastasis occurrence/ re-occurrence was performed. RESULT: All of the 15 (100%) patients were males. The average age of our patients was 44 years (SD ± 11.2 years), average hospital stay was 7.4 days (SD±3.4 days) (Tab.1). All resected tumours underwent histological and immunological evaluation. Based on histological examination of the resected tumours, nonseminomatous germ cell tumours were present in 12 (80%) patients - including teratoma in 4 (26.6%) patients, seminoma in 2 (13.3%) patients, and malignant B-cell lymphoma in 1 (6.6%) patient. The average patient follow-up was 42.7 months (SD±31.4.9 months). Complete remission after the surgery was achieved in 11 (76.9%) patients, and 2 (13.3%) patients were lost in follow-up. CONCLUSION: RT is a rare heterogeneous group of neoplasm. The patient's prognosis dramatically depends on the type of tumour, metastasis occurrence and re-occurrence, and the surgeons' ability to resect the tumour completely.

Incidence of fatigue associated with immune checkpoint inhibitors in patients with cancer: a meta-analysis.

BACKGROUND: Fatigue is one of the most common adverse effects associated with cancer immunotherapy using checkpoint inhibitors (CPIs). Because treatment-related fatigue also frequently occurs in patients treated with non-immunological therapies, our study aimed to compare the incidence of fatigue in CPI-treated patients with that associated with non-immune therapies in randomised trials. METHODS: PubMed and ClinicalTrials.gov were searched for phase III studies using a CPI alone or in combination with chemotherapy or non-immunologic targeted therapy in the experimental arm and control arm using inactive therapies such as placebo or observation, chemotherapy, or non-immunologic targeted therapy. Adverse events listed in the full texts as well as those available from clinicaltrials.gov were reviewed for all identified studies. RESULTS: A total of 60 studies involving 41 435 patients were included in the analysis. All-grade fatigue was reported in 30.4% of patients [95% confidence interval (CI) 29.9% to 31.0%] in the immunotherapy arms of the analysed studies. Using anti-programmed cell death protein 1 agents as reference, the odds ratio (OR) for fatigue was significantly higher both for anti-cytotoxic T lymphocyte-associated antigen 4 agents (OR 1.46, 95% CI 1.04-2.04) and the combination of anti-cytotoxic T lymphocyte-associated antigen 4 and anti-programmed cell death protein agents (OR 1.43, 95% CI 1.12-1.83). Fatigue was significantly less likely to occur in patients treated with CPI compared with patients receiving chemotherapy (OR 0.79, 95% CI 0.73-0.85), but significantly was more common in patients receiving the combination of CPI/chemotherapy compared with patients receiving chemotherapy alone (OR 1.12, 95% CI 1.03-1.22). CONCLUSIONS: Although immunotherapy using CPIs was associated with treatment-related fatigue, the occurrence of all-grade fatigue was significantly higher in patients treated with chemotherapy compared with patients receiving CPIs. The risk of fatigue was higher for CPI/chemotherapy combinations than for chemotherapy alone. These results suggest that although the effects of CPIs and chemotherapy are additive, chemotherapy was the dominant cause of treatment-related fatigue in the analysed trials.

Incidence, mortality and survival of bladder neoplasms in the Czech Republic in the period 1977-2017: a time trend analysis.

BACKGROUND: Bladder neoplasms represent a significant disease burden in the Czech population. This study aimed to perform a complex time trend analysis of incidence, mortality, and survival of 76,505 patients with bladder neoplasms based on the Czech National Cancer Registry for 1977-2017. MATERIALS AND METHODS: The time trends of incidence and mortality were evaluated using the joinpoint regression. The relative survival and Cox proportional hazards model were used for survival analysis. RESULTS: After 2004, a significant annual decrease by 1.9% in the incidence of malignant tumors of the bladder (C67) was observed, accompanied by a sharp annual increase in the incidence of in situ bladder cancer (D090) by 16.9%. For mortality from malignant tumors of the bladder, a significant decrease by 1.4% annually was detected after 1998. The decline in both incidence and mortality was most pronounced in the below-65 years age group and in patients with a localized stage at dia-gnosis. While a significant decline in both incidence and mortality was observed for the first primary malignant tumors of the bladder, both these measures increased for malignant tumors of the bladder as subsequent primary neoplasms. The five-year relative survival of patients with malignant tumors of the bladder increased from 52.1% in 1990-1993 to 62.3% in 2013-2017. However, comparing the periods 2003-2007 and 2013-2017, a decrease has been observed. CONCLUSION: The decrease in the incidence and survival of malignant tumors of the bladder in the recent period is in particular caused by improved detection of in situ bladder cancer and classification changes. Other reasons for the decreasing survival include the increasing age at dia-gnosis, the growing number of subsequent primary neoplasms, and the increasing proportion of smokers among patients.

Cabozantinib in the treatment of metastatic renal cell carcinoma - final data analysis from four oncology centers in the Czech Republic.

BACKGROUND: Current standard treatments for patients with metastatic renal cell carcinoma (mRCC) involve tyrosine kinase inhibitors (TKI) that inhibit angiogenesis. Cabozantinib is a multi TKI used for the treatment of mRCC in the first- and second-line setting. PURPOSE: The aim of this study was the final analysis of treatment outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with cabozantinib after previous targeted therapy. PATIENTS AND METHODS: A total of 54 patients with mRCC from four oncology centers in the Czech Republic were evaluated retrospectively; the median follow-up was 18.5 months. Cabozantinib was administered in a dose of 60mg/day, a subset of patients received an initial dose of 40mg/day. The treatment was administered until the progression. The Kaplan-Meier analysis was used to calculate progression free survival (PFS) and overall survival (OS). We performed a multivariate analysis of risk factors for treatment outcomes (PFS, OS) by regression analysis. All statistics were evaluated at the significance level α = 0.05. RESULTS: The median PFS in all patients was 9.3 months (95% CI 7.2 - 11.4). The median OS in all patients was 21.9 months (95% CI 15.5 - 28.4). The median PFS in patients with bone metastases was not statistically significantly different compared with patients without bone metastases (9.3 vs 8.7 months, P = 0.53). The median OS in patients with bone metastases was statistically significantly shorter compared with patients without bone metastases (17.7 vs 26.8 months, P = 0.021). A treatment response was observed in 40.7 % of cases, including one complete remission. The regression analysis demonstrated a significant effect on OS in patients with the presence of subsequent treatment (P = 0.001), patients with treatment duration of first line therapy 6 months (P = 0.019) and 12 months (P = 0.003) and in patients without bone metastases (P = 0.021). CONCLUSION: Our final analysis of patients with mRCC treated with cabozantinib after previous targeted therapy confirmed its effectiveness.

Association of triple positivity with prognostic parameters and overall survival in a population-based study of 6,122 HER2-positive breast cancer patients: analysis of real-world clinical practice based on a research database.

Triple-positive breast cancer (TPBC), i.e. HER2-positive (HER2+) and hormone receptors-positive breast cancer, is a specific subgroup of breast cancers. TPBC biology is characterized by strong mutual interactions between signaling pathways stimulated by estrogens and HER2 amplification. The present study aims to carry out a population-based analysis of treatment outcomes in a cohort of hormone receptor (HR) positive and negative breast cancer patients who were treated with anti-HER2 therapy in the Czech Republic. The BREAST research database was used as the data source for this retrospective analysis. The database covers approximately 95% of breast cancer patients treated with targeted therapies in the Czech Republic. The analysis included 6,122 HER2-positive patients. The patients were divided into two groups, based on estrogen receptor (ER) or progesterone receptor (PR) positivity: hormone receptor negative (HR-) patients had both ER- and PR-negative tumors (n=2,518), unlike positive (HR+) patients (n=3,604). HR+ patients were more often diagnosed premenopausal at the time of diagnosis, presented more often at stage I or II and their tumors were less commonly poorly differentiated. The overall survival (OS) was significantly higher in subgroups of HR+ patients according to treatment setting. When evaluated by stages, significantly higher OS was observed in HR+ patients diagnosed at stages II, III, and IV and regardless of tumor grade.

Improved survival in patients with FDG-PET/CT-based radiotherapy treatment planning for squamous cell anal cancer.

The aim of this retrospective analysis was to evaluate the impact of FDG-PET/CT-based target volume definition on locoregional control and survival, compared to conventional CT-based target volume definition and dose prescription. One hundred and twenty-two patients with squamous cell anal cancer were treated with curative radiotherapy (RT) alone (27%) or with RT with concurrent chemotherapy (73%) and analyzed. Forty-six percent had the early disease (stage I+II) and 54% were stage III. FDG-PET/CT-based staging was performed in 21% of the patients. The mean follow-up time was 60 months. Other risk factors affecting survival were investigated. According to initial staging in both groups (FDG-PET/CT and conventional CT) were 10% of stage IV disease, and they were excluded from radical radiotherapy and treated with palliative intent. Ninety-two percent of the patients achieved complete remission. Significant favorable factors in univariate analysis associated with disease-free survival (DFS) were PET/CT staging, T1/2 and N0 stage, and clinical stage I and II. Locoregional control (LRC) correlated with the T1/2 stage and initial performance status (PS) 0. There were no significant factors affecting overall survival (neither in univariate nor multivariate analysis). In multivariate analysis, the factor associated with better DFS was PET/CT staging and for LRC, PS 0 and concomitant chemoradiation. Acute toxicity was increased in the concurrent chemo-radiotherapy group. Two-, five- and ten-year overall survival rates were 83%, 69%, and 60%; disease-free survival rates were 76%, 73%, 73%; local control rates were 91%, 90%, and 90% and colostomy-free survival was 89%, 86%, and 81%, respectively. PET/CT staging allowed targeted dose escalation to the primary tumor and nodal metastases while decreasing dose to uninvolved regions, resulting in significantly improved DFS without compromising locoregional control.

Renal Toxicity of Cancer Immunother apy.

BACKGROUND: Acute renal impairment is a relatively rare complication of anti-tumour immunotherapy. The incidence of renal toxicity due to immuno-oncological therapy is relatively low, approximately 2% in patients treated with PD-1/PD-L1 inhibitors and 4.5% with combination treatments with PD-1/PD-L1 therapy and a CTLA-4 inhibitor. The most common underlying pathology is acute tubulointerstitial nephritis. Autoimmune nephropathy presenting as a electrolyte imbalance may also occur during immuno-oncological therapy. Discontinuation of immunotherapy and corticosteroid therapy are indicated in patients with moderate to severe renal toxicity. CASE: A 61-year-old patient with metastatic renal cell carcinoma was admitted to hospital after 7 months of treatment with nivolumab for general deterioration, severe weakness, nausea, and anorexia. Laboratory examinations showed worsening of the glomerular filtration rate, severe hyperkalaemia, and metabolic acidosis. Thyroid hormone and cortisol levels were within normal ranges. Renal tubular acidosis resulting from immuno-oncological therapy was diagnosed, and treatment with methylprednisolone was initiated. Electrolyte abnormalities and symptoms improved rapidly, after which the dose of prednisone was gradually reduced; however, after a reduction to 5 mg daily, hyperkalaemia recurred and the patient was kept on a maintenance dose of 10 mg prednisone administered orally on a daily basis thereafter. Immunotherapy was not reintroduced. CONCLUSION: Renal toxicity following immuno-oncological therapy usually presents initially as an increase in the serum creatinine level without any clinical signs or symptoms. Electrolyte disturbances, oliguria, anuria, and swelling may develop gradually. Endocrine and metabolic disorders such as new-onset type 1 diabetes mellitus, hypophysitis, adrenal insufficiency, and hypothyroidism should be excluded as possible causes of electrolyte abnormalities. Corticosteroids at the usual immunosuppressive dose are the treatment of choice. The prognosis is generally favourable because renal toxicity responds well to corticosteroid treatment regardless of the underlying pathology.

Sarcopenia in Metastatic Colorectal Carcinoma.

Sarcopenia is the loss of skeletal muscle mass (SMM) and is associated with decreased muscle strength and/or decreased physical performance. Sarcopenia in patients with malignancies is a multifactorial problem, caused by chronic inflammation associated with malignancies, aging, nutritional deficiency, inactivity, and antineoplastic treatment. Sarcopenia is present in approximately 30-60% of patients with metastatic colorectal cancer (mCRC). It is an objective, measurable predictor of survival and systemic toxicity. The detection and quantification of sarcopenia in routine clinical practice does not require any particular test beyond routine imaging. Initial results show that regimens used to treat mCRC can have differential effect on skeletal mass. SMM tends to decrease during intensive regimens. Conversely, SMM tends to increase during low-intensity maintenance therapy or in patients with stable disease. The status of the underlying disease is another determinant of muscle mass changes, and SMM decreases during disease progression. Third-line therapy with regorafenib, a tyrosine kinase inhibitor of the vascular endothelial growth factor receptor, results in more skeletal muscle loss than trifluridine/tipiracil chemotherapy, which may have consequences for the survival or quality of life of patients. Larger prospective studies are needed to elucidate the importance of SMM changes during mCRC treatment. TB received fees for lectures and consultations related to the treatment of colorectal cancer from Merck, Amgen, Eli Lilly, Servier, Roche, Sanofi and Bayer. JH declares she has no potencional conflict of interest. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 15. 9. 2019 Accepted: 25. 10. 2019.

[Pilot Study on MicroRNAs as Biomarkers of Response to Sunitinib Treatment in Patients with Metastatic Renall Cell Carcinoma]. / MikroRNA jako biomarkery odpovedi na lécbu sunitinibem u pacientu s metastatickým karcinomem ledvin - pilotní studie.

BACKGROUND: Renal cell carcinoma (RCC) accounts for 2-3% of all malignant tumours. Metastatic RCC (mRCC) is commonly treated with tyrosine kinase inhibitors (TKI). Effective TKIs administration can be achieved only by accurate prediction of therapeutical response. Therefore, the aim of this study was to analyse papers concerning predictive potential of microRNA (miRNA). MATERIAL AND METHODS: We chose seven candidate miRNAs and analysed their expression on 44 patients divided into cohort with poor and good response to sunitinib treatment. Patients were divided into two groups according to progression-free survival. RNA from tissue samples was isolated and expression of selected miRNAs was measured using quantitative PCR with miRNA-specific TaqMan probes. RESULTS: We successfully validated two miRNAs to be differentially expressed in responding and non-responding patients to sunitinib treatment. Other analysed miRNAs have not shown predictive potential. CONCLUSION: From miRNAs studied so far, two miRNAs had predictive value according to present study.Key words: microRNA - renal cell carcinoma - sunitib The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Supported by Ministry of Health of the Czech Republic, grant No. 15-34678A. All rights reserved.Submitted: 19. 3. 2018Accepted: 20. 3. 2018.

[Molecular Pathogenesis of Testicular Germ Cell Tumors]. / Molekulární patogeneze testikulárních germinálních nádoru.

BACKGROUND: Testicular germ cell tumors (TGCT) are the most frequently diagnosed solid tumors in young men and their incidence has been increasing over the past decades. Several factors may combine and play a role in the TGCT etiology, including environmental factors and genetic predispositions at multiple genomic loci that affect both testicular germ cells and stromal cells, and their interactions within the testicular microenvironment. The pathogenesis of TGCT starts prenatally with primordial germ cell arrest, and further proceeds postnatally, giving rise to in situ germ cell neoplasia and, finally, to invasive TGCT with the characteristic 12p chromosome amplification. Apart from the genes localized here, further molecular mechanisms have been linked to TGCT pathogenesis, such as the activation of the KIT/KITL signaling pathway, and aberrations in genes involved in DNA reparation, regulation of cellular differentiation, proliferation, and survival. Despite the relatively good prognosis and known etiopathogenesis of these tumors, neither targeted therapy nor molecular prognostic/predictive factors have yet been implemented in the management of TGCT, because there is not enough information about the molecular pathways or molecules involved in TGCT development that could be used for patient stratification and treatment. Current high-throughput technologies, such as next generation sequencing at the exome or transcriptome level could provide this missing information on genetic predispositions and other factors influencing the clinical course of the disease and treatment response in TGCT. AIM: In this review, we summarize the main molecular characteristics of TGCT and the probable mechanisms participating in tumor initiation and progression.Key words: testicular germ cell tumors - signaling pathways - molecular aberrations - predictive factors - prognostic factors The work was supported by the Czech Ministry of Education, Youth and Sports NPU I nr.LO 1604. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 20. 3. 2017Accepted: 23. 7. 2017.

[Immunotherapy for Bladder Cancer]. / Imunoterapie karcinomu mocového mechýre.

Urothelial carcinoma is the most common urological malignancy. Nonspecific immunotherapy using the Bacillus Calmette-Guerin vaccine has long been the mainstay for the treatment of high-risk superficial bladder carcinoma in an adjuvant setting after transurethral endoscopic resection. In metastatic disease, cisplatin-based chemotherapy remains the main therapeutic modality. In Europe, the standard second-line chemotherapy for patients with cisplatin-refractory tumours is vinflunine. Other systemic treatments with a lower level of evidence include paclitaxel and docetaxel. Studies of tumour microenvironment indicate a significant role for the immune system in the pathogenesis of urothelial tumours and the presence of a CD8 lymphocyte infiltrate is associated with better survival. In urothelial tumours, the correlation between PD-L1 expression in the tumour and the response to PD-1/PD-L1 inhibitors has been repeatedly demonstrated in clinical studies. Several inhibitors of PD-1/PD-L1 pathway are undergoing advanced-phase clinical trials and atezolizumab, nivolumab, pembrolizumab, durvalumab, and avelumab have already have received permanent or temporary registration status in the United States, mostly as second-line treatments for patients progressing on cisplatin-based chemotherapy. Three of these agents are currently registered in Europe: nivolumab for second line treatment and atezolizumab and pembrolizumab for first line treatment in patients not eligible for cisplatin as well as and for second line treatment. These novel immunotherapeutic agents for bladder cancer are relatively well tolerated and therefore potentially useful for patients with contraindications or intolerance to platinum regimens. The main toxicities include asthenia/fatigue, lymphopenia, anaemia, musculoskeletal pain, decreased appetite, and nausea.Key words: bladder cancer - imunotherapy - PD-1 receptor - antibodies - monoclonal This work was supported by the Czech Ministry of Health CR - RVO Thomayer Hospital - TN 0064190. The author declare he has no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 29. 8. 2017Accepted: 3. 10. 2017.

[Comparison of RECIST 1.1 and iRECIST for Response Evaluation in Solid Tumours]. / Souhrnné srovnání kritérií RECIST 1.1 a iRECIST pro hodnocení odpovedi na onkologickou lécbu solidních tumoru.

BACKGROUND: Immunotherapy is a relatively new and developing modality in oncological treatment, which may significantly improve treatment results for some patients with malignant tumors. With the increasing number of clinical trials, the demand for a suitable tool to assess and compare treatment responses is growing. Currently, the most common response assessment system for solid tumors is RECIST (response Evaluation Criteria in Solid Tumors) version 1.1. However, in immuno-oncology, a small percentage of patients manifest a new response pattern termed pseudoprogression, in which, after the initial increase in tumor burden or after the discovery of new lesions, a response or at least a prolonged stabilization of the disease can occur. This patient group would be included in the progression category when using RECIST 1.1 and effective treatment would be discontinued. Therefore, iRECIST criteria were established to capture the phenomenon of pseudoprogression, the need for PD confirmation (according to RECIST 1.1) was introduced, and changes were made in the evaluation of new lesions. AIM: The present work introduces criteria for the evaluation of oncological responses in solid tumors using RECIST version 1.1 and iRECIST immunotherapy variant (including a brief overview of previous immune criteria). These criteria are compared in an immuno-oncological context and their potential pitfalls are discussed. CONCLUSION: iRECIST criteria were established by expert consensus; however, sufficient data for final validation has not yet been collected. As a result, RECIST 1.1 should be the primary assessment system in immuno-oncology. The use of iRECIST should be reserved for research purposes (testing and validation). Distinguishing pseudoprogression from true PD in patients treated with immunotherapy remains a major challenge in oncological imaging.Key words: RECIST - response criteria - immunotherapy - measurement - tumor burden The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 24. 9. 2017Accepted: 3. 10. 2017.

[Immunotherapy of Renal Cell Carcinoma]. / Imunoterapie zhoubného nádoru ledviny.

Treatment of renal cell carcinoma is still palliative. Targeted therapy increases response rates and prolongs overall survival and progression-free survival compared with cytokines and chemotherapy. Checkpoint inhibitors constitute the up-date of therapeutic approaches, and anti-PD-1 antibody, one checkpoint inhibitor, is now well established as a second and/or third palliative treatment for patients with renal cell carcinoma. In this study, we present the latest data from current studies on cytokines, cancer vaccines, ipilimumab, and nivolumab. The therapeutic efficacies of combinations such as targeted therapy with immune checkpoint inhibitors and anti-CTLA-4 with anti PD-1 (-L1) have been reported in many studies. Preliminary results are encouraging but the high toxicities and elevated cost are limiting. Treatments with combinations of bevacizumab and atezolizumab, axitinib and pembrolizumab or avelumab, lenvatinib and pembrolizumab, and nivolumab and ipilimumab (results from study phase I, II, and sometimes III) are reported to be highly effective and to result in long-lasting responses with response-rates of 70-100%. So far, valid predictors for these therapies have not been forthcoming, but considerable work is being exerted in this area. Heng and Memorial Sloan Kettering Cancer Center (MSKCC) models are still being used to select patients for immunotherapy. Immunotherapy will definitely continue to play an important role in the treatment of patients with renal cell carcinoma; however, many questions remain.Key words: renal cell carcinoma - immunotherapy - checkpoint inhibitors - target therapy Supported by MH CZ - DRO (MMCI, 00209805) This work was supported by program of the Czech Ministry of Health No. P03-15-34 678A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 16. 8. 2017Accepted: 7. 9. 2017.

[Evaluation of Anti-cancer Therapies with Reimbursement Limited to Comprehensive Cancer Centres Using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale]. / Hodnocení klinického benefitu protinádorových léku limitovaných na komplexní onkologická centra podle metodiky ESMO-MCBS.

BACKGROUND: The costs of oncology treatments are increasing, due to the rising prevalence of malignant diseases and the introduction of expensive novel anti-cancer agents. The new European Society for Clinical Oncology (ESMO) has recently developed a new parametric system to evaluate the clinical benefit of drugs. The Magnitude of Clinical Benefit Scale (ESMO-MCBS) compares the contribution of a novel drug based on overall and progression-free survival and quality of life with those of current treatment options. MATERIAL AND METHODS: An expert group of the Czech Oncological Society conducted an assessment based on published data and an ESMO-MCBS methodology for antineoplastic agents used for the treatment of solid tumors with limited reimbursement to Comprehensive Cancer Centers. We evaluated drugs categorized as "S" that were eligible for public health insurance as of January 1, 2017. RESULTS AND CONCLUSION: The ESMO-MCBS score is a promising new parameter for the evaluation of new anticancer drugs. The ESMO-MCBS method for assessing the clinical benefit of drugs is simple, robust, and reproducible. The advantage of the assessment is that it is not based on a single index but rather combines several dimensions of drug performance. This parameter will be gradually added to Czech cancer guidelines. Scores obtained in the majority of cases correspond to the observed benefit of a drug in routine clinical practice.Key words: tumors - farmacotherapy - assesment study as a subject - survival - protocols of anti-cancer therapy The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 3. 5. 2017Accepted: 20. 6. 2017.

Durable Complete Response of Colorectal Cancer Metastasis after Biochemotherapy.

BACKGROUND: Resection of the metastatic site is indicated but not always possible in patients with metastatic colorectal cancer (mCRC) who achieve a partial or complete response (CR) to induction systemic treatment. CR after systemic treatment alone is uncommon, and even patients with radiologic CR after induction chemotherapy harbour persistent macroscopic or microscopic residual disease in more than 80% of cases. Occasionally, some metastatic lesions disappear radiologically but others persist after induction systemic treatment. The indication and extent of metastasectomy in these situations is controversial, especially regarding sites with completely regressed metastases. CASE: This case report describes a patient with mCRC who achieved a long-term response after biochemotherapy and incomplete metastasectomy. One of the known liver lesions could not be removed due to its disappearance after induction biochemotherapy with FOLFOX and bevacizumab. Further adjuvant chemotherapy using the FOLFOX regimen was administered postoperatively. The patient has been meticulously followed by radiology including repeated positron emission tomography/computed tomography and magnetic resonance scans, clinical examination and tumour markers. No recurrence of cancer has been detected after a follow-up of 5 years. RESULTS AND CONCLUSION: CR to systemic treatment is uncommon, but this case report demonstrates that it can be durable in patients with colorectal cancer and liver metastases. This case report indicates that some patients with mCRC can be cured with systemic therapy only, challenging the prevailing paradigm of mCRC therapy.Key words: colorectal cancer - metastasis - chemotherapy - molecular targeted therapy - diagnostic imaging.

Prognostic role of serum C-reactive protein in patients with advanced-stage NSCLC treated with pemetrexed.

Pemetrexed is an intravenously administered antifolate cytostatic agent targeting several folate-dependent enzymatic pathways, widely used in the treatment of patients with advanced non-small cell lung cancer (NSCLC). It has been previously demonstrated that the superiority of pemetrexed is limited to patients with non-squamous histology. Aside from the non-squamous histology, there is still no available molecular biomarker predicting treatment efficacy of pemetrexed-based chemotherapy. The aim of our retrospective study was to evaluate the association of baseline serum levels of C-reactive protein (CRP) with outcomes in a large cohort of patients with non-squamous NSCLC treated with pemetrexed. Clinical data of 325 patients were analysed. Serum samples were collected within one week before the initiation of treatment. The median progression-free (PFS) and overall survival (OS) for patients with high CRP was 2.1 and 9.5 compared to 4.2 and 20.5 months for those with normal CRP (p=0.002 and p<0.001, respectively). The multivariable Cox proportional hazards model revealed that serum CRP (HR=1.46, p=0.002) was significantly associated with PFS and also with OS (HR=1.95, p<0.001). In conclusion, the study results suggest that pretreatment serum CRP is associated with poor outcome of non-squamous NSCLC patients treated with pemetrexed.

Wilms tumor gene 1 (WT1), TP53, RAS/BRAF and KIT aberrations in testicular germ cell tumors.

PURPOSE: Wilms tumor gene 1 (WT1), a zinc-finger transcription factor essential for testis development and function, along with other genes, was investigated for their role in the pathogenesis of testicular germ cell tumors (TGCT). METHODS: In total, 284 TGCT and 100 control samples were investigated, including qPCR for WT1 expression and BRAF mutation, p53 immunohistochemistry detection, and massively parallel amplicon sequencing. RESULTS: WT1 was significantly (p < 0.0001) under-expressed in TGCT, with an increased ratio of exon 5-lacking isoforms, reaching low levels in chemo-naïve relapsed TGCT patients vs. high levels in chemotherapy-pretreated relapsed patients. BRAF V600E mutation was identified in 1% of patients only. p53 protein was lowly expressed in TGCT metastases compared to the matched primary tumors. Of 9 selected TGCT-linked genes, RAS/BRAF and WT1 mutations were frequent while significant TP53 and KIT variants were not detected (p = 0.0003). CONCLUSIONS: WT1 has been identified as a novel factor involved in TGCT pathogenesis, with a potential prognostic impact. Distinct biologic nature of the two types of relapses occurring in TGCT has been demonstrated. Differential mutation rate of the key TGCT-related genes has been documented.

[Immunotherapy for Renal Cell Carcinoma]. / Imunoterapie renálního karcinomu.

BACKGROUND: Renal cell carcinoma is characterised by chemo and radioresistance. Although drugs targeting angiogenesis and intracellular signaling have become the mainstay of systemic therapy for renal cell carcinoma in the last decade, latest immunotherapeutic approaches have achieved promising results. AIM: To review the development of immunotherapy for renal cell carcinoma, especially the results of published studies using novel immunotherapeutic agents including checkpoint inhibitors. RESULTS: It has long been known that nonspecific immunotherapy may result in long term complete remission in a small number of patients. Advances in immunology have led to the renewal of interest in the use of anticancer immunotherapy for metastatic renal cell carcinoma. Promising results in phase I and II studies have been achieved using monoclonal antibodies against PD 1 receptor and its ligand. Studies comparing immunotherapy to standard targeted therapies are ongoing.

Estimating cancer incidence, prevalence, and the number of cancer patients treated with antitumor therapy in 2015 and 2020 -  analysis of the Czech National Cancer Registry.

BACKGROUND: Cancer burden in the Czech population ranks among the highest worldwide, which introduces a strong need for a prospective modelling of cancer incidence and prevalence rates. Moreover, a prediction of number of cancer patients requiring active antitumor therapy is also an important issue. This paper presents the stage-specific predictions of cancer incidence and prevalence, and the stage- and region-specific patients requiring active antitumor therapy for the most common cancer diagnoses in the Czech Republic for years 2015 and 2020. The stage-specific estimates are also presented with regard to the treatment phase as newly diagnosed patients, patients treated for non-terminal recurrence, and patients treated for terminal recurrence. PATIENTS AND METHODS: Data of the Czech National Cancer Registry from 1977 to 2011 has been used for the analysis, omitting the records of patients diagnosed as death certificate only or at autopsy. In total, 1,777,775 incidences have been considered for the estimation using a statistical model utilizing solely the population-based cancer registry data. All estimates have been calculated with respect to the changing demographic structure of the Czech population and the clinical stage at diagnosis. RESULTS: Considering year 2011 as the baseline, we predict 89%, 15%, 31% and 32% increase in prostate, colorectal, female breast and lung cancer incidence, respectively, in 2020 resulting in 13,153, 9,368, 8,695, and 8,604 newly dia-g--nosed cancer patients in that year, respectively. Regarding cancer prevalence in 2020, the estimated increase is 140%, 40%, 51%, and 17% for prostate, colorectal, female breast and lung cancer, respectively, meaning that more than 100,000 prevalent female breast cancer patients as well as more than 100,000 prevalent prostate cancer patients are expected in the Czech Republic. The estimated numbers of patients requiring active antitumor therapy for prostate, colorectal, female breast and lung cancer in the Czech Republic in 2020 are 23,652, 14,006, 14,759 and 8,272; respectively. CONCLUSIONS: The analysis documents a serious increase in cancer incidence and prevalence in the Czech Republic in years 2015 and 2020 when compared to the situation in 2011. Regarding the estimated numbers of patients requiring active antitumor therapy, the model confirms a continuous increase that must be accounted for in the future planning of health care in the Czech Republic.