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Abstract The efficacy of pembrolizumab in the treatment-naïve non-small-cell lung cancer (NSCLC) patients was proved in the KEYNOTE-024 randomized trial. The aim of this systematic literature review was to identify and summarize the real world evidence (RWE) of overall survival (OS) in previously untreated patients with NSCLC receiving pembrolizumab monotherapy. A systematic search was conducted in PubMed (MEDLINE®) and EMBASE databases. Analyses were focused on survival data (median OS and survival rates at specific time points). To explore the population comparable with the KEYNOTE-024 study, we focused on studies enrolling at least 50% of patients at stage IV of cancer and ECOG performance status 0–2. A total of 41 RWE studies covering over 7600 advanced NSCLC patients naïve to systemic treatment were identified. Overall, survival outcomes reported in those studies vary considerably (median OS range: 3.0–34.6 months). Most RWE studies reported median OS shorter to that reported in KEYNOTE-024 (26.3 months), but about half of reported OS medians were in range of 95% confidence interval for OS as reported in KEYNOTE-024 trial (18.3–40.4 months). Patients with similar characteristics of stage and performance status to those of KEYNOTE-024 trial benefited the same with pembrolizumab monotherapy as their survival outcomes (18.9–22.8 months) were consistent with those reported in the clinical trial. RWE data showed substantially worse outcomes in patients with ECOG-PS 2+ compared to ECOG-PS 0–1 patients.

Abstract Objective Primary tracheal tumors are very rare and their management is not definitely established. Due to its rarity, providing patient care in terms of optimal management poses a considerable challenge. The purpose of this study was to investigate treatment outcomes in patients with these rare tumors. Methods We carried out a retrospective analysis of 89 patients with primary tracheal tumors treated at the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, over sixteen years. The study assessed patient demographics, tumor characteristics and treatment. Different treatment options were compared in terms of overall survival, disease-free survival, and progression-free survival. Results A total of 89 patients were included in the study. In the group presented, 45 patients underwent primary radical treatment and 44 were qualified for palliative treatment. Surgical resection was performed in 13 patients out of radically treated patients. The 5 year OS rates in the group of patients who underwent radical treatment and in the group of patients who underwent palliative treatment were 45.9% and 2.3%, respectively. In the group of patients who underwent radical surgical treatment, the 5 year OS was 76.9% compared to 35.8% in the group of patients who underwent nonsurgical treatment. Conclusion A multidisciplinary team should decide treatment options, including in-depth consideration of surgical treatment options.

Abstract Background Primary tracheal tumors are very rare and the literature on this subject is limited. The most common histological type of primary tracheal tumors is squamous cell carcinoma (SCC), followed by adenoid cystic carcinoma (ACC). Limited knowledge exists regarding the behavior and outcomes of different histological types of tracheal cancers. The present study aimed to address this gap by assessing the significance of the histological type of primary tracheal tumors based on our own data and to review the literature. Methods We carried out a retrospective analysis of 89 patients with primary tracheal tumors treated at the Maria Sklodowska‐Curie National Research Institute of Oncology in Warsaw, Poland, between 2000 and 2016. The study assessed patient demographics, tumor characteristics and treatment, with a focus on SCC, ACC, and other histological types. Different histological types were compared in terms of overall survival, disease‐free survival, and progression‐free survival. Results SCC was the most frequently diagnosed histological type (56.2%), followed by ACC (21.3%). Patients with SCC were typically older (78% over 60 years), predominantly male (66%), and associated with smoking. In contrast, the ACC had a more balanced gender distribution and did not correlate with smoking. ACC displayed a significantly better prognosis, with a median overall survival of 129.4 months, compared with 9.0 months for SCC. Conclusion Histological type plays a crucial role in the prognosis of primary tracheal tumors. ACC demonstrated a more favorable outcome compared with SCC.

A substantial portion of patients with advanced cancer cannot be cured, regardless of the therapeutic methods employed. Hence, rational palliative causal treatment becomes crucial. Representative studies specifically addressing the exclusive palliative treatment of patients diagnosed with tracheal cancers have not been identified. In most studies, patients treated palliatively constituted a subset of the overall evaluated group. A thorough literature review was conducted, focusing on three types of palliative treatment: palliative radiotherapy, palliative surgical procedures, and systemic treatment for advanced disease. This review uniquely fills a significant gap in the existing literature by providing the first comprehensive and updated clinical practice guidelines specifically focused on the palliative treatment of tracheal tumors. The proposed guidelines emphasize the unique clinical challenges and treatment strategies pertinent to palliative care in tracheal tumors, which are not adequately covered in existing guidelines for other thoracic malignancies.

Pulmonary benign metastasizing leiomyoma (PBML) is a rare condition characterized by the spread of uterine leiomyomas to the lungs, typically observed in premenopausal women with a history of hysterectomy or myomectomy. This report presents a unique case of a postmenopausal woman, aged 65, that emphasizes the clinical, radiological, histologic, and immunohistochemical aspects of the disease. On presentation, the patient suffered from severe pain. On imaging, a sizable lung tumor was found. Histopathological examination and immunoprofiling confirmed PBML. The patient underwent various treatments, including surgery, radiation therapy, and hormonal therapy, illustrating the challenges in managing PBML. A literature review underscores the rarity of PBML and its diverse clinical manifestations. This study provides valuable insights into the complexities of PBML.

The key association between gut dysbiosis and cancer is already known. Here, we used whole-genome shotgun sequencing (WGS) and gas chromatography/mass spectrometry (GC/MS) to conduct metagenomic and metabolomic analyses to identify common and distinct taxonomic configurations among 40, 45, 71, 34, 50, 60, and 40 patients with colorectal cancer, stomach cancer, breast cancer, lung cancer, melanoma, lymphoid neoplasms and acute myeloid leukemia (AML), respectively, and compared the data with those from sex- and age-matched healthy controls (HC). α-diversity differed only between the lymphoid neoplasm and AML groups and their respective HC, while β-diversity differed between all groups and their HC. Of 203 unique species, 179 and 24 were under- and over-represented, respectively, in the case groups compared with HC. Of these, Faecalibacillus intestinalis was under-represented in each of the seven groups studied, Anaerostipes hadrus was under-represented in all but the stomach cancer group, and 22 species were under-represented in the remaining five case groups. There was a marked reduction in the gut microbiome cancer index in all case groups except the AML group. Of the short-chain fatty acids and amino acids tested, the relative concentration of formic acid was significantly higher in each of the case groups than in HC, and the abundance of seven species of Faecalibacterium correlated negatively with most amino acids and formic acid, and positively with the levels of acetic, propanoic, and butanoic acid. We found more differences than similarities between the studied malignancy groups, with large variations in diversity, taxonomic/metabolomic profiles, and functional assignments. While the results obtained may demonstrate trends rather than objective differences that correlate with different types of malignancy, the newly developed gut microbiota cancer index did distinguish most of the cancer cases from HC. We believe that these data are a promising step forward in the search for new diagnostic and predictive tests to assess intestinal dysbiosis among cancer patients.

IntroductionPembrolizumab combined with chemotherapy has become the standard of care for patients with non-small-cell lung cancer (NSCLC) and the expression of programmed death ligand 1 (PD-L1) in 3 (HR 2.3, 95%CI 1.3-4.2; p=0.04), presence of liver (HR 2.0, 95%CI 1-3.7; p=0. 03) and bone metastases (HR 1.3, 95%CI 1-3; p=0.04), weight loss (HR 1.8, 95%CI 1.1-2.8; p=0.01) and sum of measurable lesions diameters >110 mm (HR 1.7, 95%CI 1-2.9, p=0.049) had a negative impact on OS.ConclusionsIn the real world, patients can clinically benefit from immunochemotherapy, regardless of the expression of PD-L1 and the histological type. Other clinicopathological factors such as performance status, extent, and location of secondary lesions have prognostic significance.

The role of sequential chemoradiotherapy in non-small cell lung cancer (NSCLC) patients who are not eligible for concurrent therapy has not been clearly defined. The aim of this study was to determine the usefulness of Karnofsky performance status (KPS) monitoring and to define the factors determining clinical deterioration during sequential chemoradiotherapy in patients treated from July 2009 to October 2014. The study included 196 patients. The clinical stage was defined as III A in 94 patients (48%) and III B in 102 patients (52%). Reduced KPS was found in 129 patients (65.8%). Baseline KPS had no significant prognostic significance. Deterioration of KPS during chemoradiotherapy was observed in 53 patients (27%) and had a negative predictive value for both worse-progression free survival (HR = 1.44; 95% CI: 1.03–1.99; p = 0.03) and overall survival (HR = 1.42; 95% CI: 1.02–1, 99; p = 0.04). The deterioration of KPS correlated with the disease control rate 6 weeks after the end of chemoradiotherapy (p = 0.0085). The risk of KPS worsening increased with each subsequent day between the end of chemotherapy and the start of radiotherapy (OR = 1.03; 95%CI: 1.01–1.05; p = 0.001), but decreased with each year of older age of patients (OR = 0.94, 95% CI: 0.9–0.98, p = 0.009). The time between the end of chemotherapy and the start of radiotherapy determined the prognosis of NSCLC after chemoradiotherapy. It should be adjusted to the age of patients.

Background The implementation of next-generation sequencing (NGS) into daily practice allows for the identification of a greater number of molecular abnormalities. We aimed to confirm the benefits of immunotherapy in the group of patients with KRAS aberrations treated within clinical practice. Methods This study was a retrospective analysis of the patients (pts) treated in routine practice within the National Drug Programme in Poland. The NGS was performed using a FusionPlex Comprehensive Thyroid and Lung (CTL) kit (ArcherDx) and sequenced using a MiniSeq (Illumina). The analyses were performed with the R language environment, version 4.1.3. Results A total of 96 pts with chemotherapy-pre-treated advanced NSCLC (CS III–IV) were qualified for nivolumab or atezolizumab treatment following a molecular diagnosis by the NGS and the exclusion of EGFR and ALK gene abnormalities. A mutation in the KRAS gene was found in 26 patients (27%); among them, the variant p.Gly12Cyc (G12C) was the most common (42%). The median PFS and OS for the overall population were 2 months (95% CI: 1.8–2.75) and 10 months (95% CI: 6.9–16.2), respectively. No differences were observed in terms of the mPFS between the KRAS-mutated and KRAS wild-type (WT) patients. A trend toward a longer OS was observed in the group of patients with the KRAS mutation, but the difference was not statistically significant (p = 0.43). In the multivariate analysis, the presence of mutations in the KRAS gene had no prognostic significance, while the occurence of grade 3 toxicity and the neutrophil-to-lymphocyte ratio (NLR) > 3.5 were found as statistically significant factors. Conclusions Immunotherapy in the second-line treatment of advanced NSCLC allows for a benefit regardless of the KRAS gene mutation status. The treatment sequence, including molecularly targeted drugs such as sotorasib and adagrasib, is still discussed. The NGS is a valuable method to identify a variety of molecular abnormalities in patients with NSCLC in daily practice.

Introduction: The combination of immunotherapy and targeted therapy is currently marking a new era in the treatment of renal cancer. The latest clinical guidelines recommend the use of drug combinations for the first-line treatment of advanced renal cancer. The aim of this review is to compare the efficacy of combined cabozantinib + nivolumab therapy with other immune checkpoint inhibitors combined with tyrosine kinase inhibitors or monoclonal antibodies blocking the CTLA-4 (cytotoxic T cell antigen 4) in the first-line treatment of metastatic clear-cell renal cell carcinoma (RCC).Methodology: A systematic literature search was carried out in the PubMed and EMBASE databases. Randomized controlled trials (RCTs) on therapies recommended by the latest EAU and ESMO guidelines for treatment-naïve metastatic RCC (i.e., lenvatinib + pembrolizumab, axitinib + pembrolizumab and nivolumab + ipilimumab) were searched. A network meta-analysis (NMA) was performed for data synthesis. The methodology of included RCTs was assessed using the Cochrane RoB two tool. The data were analyzed in the overall population as well as in risk subgroups defined according to the International Metastatic Database Consortium (IMDC) i.e., patients with a favorable and intermediate or poor prognoses. The most recent cut-off dates from included studies were analyzed.Results: Four RCTs (CheckMate 9 ER, KEYNOTE-426, CLEAR and CheckMate 214) were included in the review. No studies directly comparing cabozantinib + nivolumab with any of the drug combinations included in this review were available. NMA showed that cabozantinib + nivolumab was superior compared to axitinib + pembrolizumab and nivolumab + ipilimumab in all analyzed comparisons (overall population and IMDC risk subgroups), both in terms of overall survival and progression-free survival (PFS). The advantage of cabozantinib + nivolumab was statistically significant only for PFS when compared to nivolumab + ipilimumab in the overall population. The results for the comparison of cabozantinib + nivolumab with lenvatinib + pembrolizumab showed numerical superiority of lenvatinib + pembrolizumab combination in terms of overall survival, but none of the results were statistically significant. The advantage of lenvatinib + pembrolizumab over cabozantinib + nivolumab in terms of PFS was statistically significant in the overall and favorable prognosis population.Conclusion: Inclusion of the most recent cut-off data from CheckMate 9 ER did not affect the role of the cabozantinib + nivolumab combination for treatment-naïve metastatic RCC. Cabozantinib + nivolumab is an effective therapeutic option for the first-line treatment of advanced renal cancer that is recommended both in the latest European and American guidelines for all IMDC risk groups.

Background Thymic epithelial tumors constitute a morphologically and clinically diverse group of rare neoplasm of the anterior mediastinum. Methods Here, we present an analysis of 188 patients diagnosed with primary thymic tumors between 1995 and 2015. The prognostic value of selected clinical and morphological factors was assessed in relation to overall survival and recurrence‐free survival. Results The risk of recurrence increased significantly in thymic carcinoma diagnosis (P = 0.0036), co‐occurrence of other diseases, and weight loss (P = 0.0012 and 0.0348, respectively). Multivariate analysis showed that the most important independent risk factor for disease recurrence was clinical stage IV (P = 0.0036). A total of 63 patients (33.5%) died. In the univariate analysis, the following factors were considered as independent prognostic factors for overall survival: clinical stage (P 12.5 G/L; P = 0.0011), LDH level (>185 U/L; P

Non-small-cell lung cancer (NSCLC) represents 85% of new cases of lung cancer. Over the past two decades, treatment of patients with NSCLC has evolved from the empiric use of chemotherapy to more advanced targeted therapy dedicated to patients with an epidermal growth factor receptor (EGFR) mutation. The multinational REFLECT study analyzed treatment patterns, outcomes, and testing practices among patients with EGFR-mutated advanced NSCLC receiving first-line EGFR tyrosine kinase inhibitor (TKI) therapy across Europe and Israel. The aim of this study is to describe the Polish population of patients from the REFLECT study, focusing on treatment patterns and T790M mutation testing practice. A descriptive, retrospective, non-interventional, medical record-based analysis was performed on the Polish population of patients with locally advanced or metastatic NSCLC with EGFR mutations from the REFLECT study (NCT04031898). A medical chart review with data collection was conducted from May to December 2019.The study involved 110 patients. Afatinib was used as the first-line EGFR-TKI therapy in 45 (40.9%) patients, erlotinib in 41 (37.3%), and gefitinib in 24 (21.8%) patients. The first-line EGFR-TKI therapy was discontinued in 90 (81.8%) patients. The median progression-free survival (PFS) on first-line EGFR-TKI therapy was 12.9 months (95% CI 10.3–15.4). A total of 54 patients started second-line therapy, of whom osimertinib was administered to 31 (57.4%). Among 85 patients progressing on first-line EGFR-TKI therapy, 58 (68.2%) were tested for the T790M mutation. Positive results for the T790M mutation were obtained from 31 (53.4%) tested patients, all of whom received osimertinib in the next lines of therapy. The median overall survival (OS) from the start of first-line EGFR-TKI therapy was 26.2 months (95% CI 18.0–29.7). Among patients with brain metastases, the median OS from the first diagnosis of brain metastases was 15.5 months (95% CI 9.9–18.0). The results of the Polish population from the REFLECT study highlight the need for effective treatment of patients with advanced EGFR-mutated NSCLC. Nearly one-third of patients with disease progression after first-line EGFR-TKI therapy were not tested for the T790M mutation and did not have the opportunity to receive effective treatment. The presence of brain metastases was a negative prognostic factor.

Background: The efficacy of nivolumab and atezolizumab in advanced pre-treated NSCLC was documented in prospective trials. We aim to confirm the benefits and indicate predictive factors for immunotherapy in daily practice. Methods: This study was a retrospective analysis. The median PFS and OS were estimated using the Kaplan-Meier method. The log-rank test was used for comparisons. Multivariate analyses were performed using the Cox regression method. Results: A total of 260 patients (ECOG 0-1) with advanced NSCLC (CS III-IV) were eligible to receive nivolumab or atezolizumab as second-line treatment. Median PFS and OS were three months (95% confidence interval [CI] 2.57–3.42) and 10 months (95% CI 8.03–11.96), respectively, for the overall population. The median OS for the atezolizumab arm was eight months (95% CI 5.89–10.1), while for the nivolumab group, it was 14 months (95% CI 10.02–17.97) (p = 0.018). The sum of all measurable changes >100.5 mm (p = 0.007; HR = 1.003, 95% CI 1.001–1.005), PLT > 281.5 G/l (p < 0.001; HR = 1.003, 95% CI 1.001–1.003) and bone metastases (p < 0.004; HR = 1.58, 95% CI 1.04–2.38) were independent negative prognostic factors for OS in multivariate analysis. Based on preliminary analyses, a prognostic index was constructed to obtain three prognostic groups. Median OS in the subgroups was 16 months (95% CI 13.3–18.7), seven months (95% CI 4.83–9.17) and four months (95% CI 2.88–5.13), respectively (p < 0.001). Conclusions: Nivolumab and atezolizumab provided clinical benefit in real life. Clinical and laboratory factors may help to identify subgroups likely to benefit. The use of prognostic indices may be valuable in clinical practice.

The study was conducted in the era when maintenance immunotherapy with durvalumab was not available in clinical practice after chemoradiotherapy (CRT) in unresectable non-small-cell lung cancer (NSCLC). The main aim of the study was to check whether the presence of cardiovascular diseases (CVD) and their pharmacotherapy affects the overall survival (OS) in such NSCLC patients undergoing sequential CRT. The group of 196 patients were analyzed: 101 patients with CVD (51.53%) and 95 patients with other reasons of qualification for sequential CRT (decreased performance status, older age, and other non-cardiovascular co-morbidities). Although patients with CVD were more often in older age, and they more often experienced cardiac and nephrological complications (p < 0.05 for all), there was a statistically nonsignificant trend for lower all-cause mortality in patients with CVD. The lowest all-cause mortality was observed in patients treated with beta-blockers and statins after two (HR = 0.31; 95%CI: 0.1–0.98; p = 0.047), three (HR = 0.33; 95%CI: 0.13–0.81; p = 0.015) and even four (HR = 0.45; 95%CI: 0.22–0.97; p = 0.027) years of follow-up. The benefit in OS remained significant in 101 patients with CVD treated with beta-blockers (HR = 0.65; 95%CI: 0.43–0.99; p = 0.045), and eventually statin, throughout the whole follow-up (log-rank p < 0.05). Further prospective studies are necessary to confirm the role of beta-blockers and statins in reduction of mortality in NSCLC patients undergoing radical CRT.

Cancer of unknown primary (CUP) represents a rare oncological and heterogeneous disease in which one or more metastases are present, but the location of the primary site is unknown. Pathological diagnosis, using immunohistochemistry, of such metastatic materials is challenging and frequently does not allow for determining the tissue of origin (ToO). The selection of systemic therapy in patients with CUP is usually based on empiric grounds, and the prognosis is generally unfavourable. New molecular techniques could identify the tissue of origin and be used to select systemic agnostic therapies in various malignancies with specific molecular abnormalities. Targetable driver mutations or gene rearrangements in cancer cells may be identified using various molecular assays, of which particularly valuable are next-generation sequencing techniques. These assays may identify tumour sources and allow personalized treatments. However, current guidelines for CUP management do not recommend routine testing of gene expression and epigenetic factors. This is mainly due to the insufficient evidence supporting the improvement of CUP’s prognosis by virtue of this approach. This review summarizes the advantages and disadvantages of new genetic techniques in CUP diagnostics and proposes updating the recommendations for CUP management.

IntroductionExpression of PD-L1 protein on tumor cells, which is so far the only validated predictive factor for immunotherapy, is regulated by epigenetic and genetic factors. Among the most important ones that regulate gene expression are microRNAs.Materials and MethodsThe study included 60 patients with NSCLC who underwent first or second line immunotherapy with pembrolizumab or nivolumab. FFPE materials were collected before the start of immunotherapy. We examined relative expression of microRNAs (miR-141, miR-200a, miR-200b, miR-200c, miR-429, miR-508-3p, miR-1184, miR-1255a) and PD-L1 mRNA expression. Copy number variation (CNV) of PD-L1 gene by qPCR and FISH methods were assessed. Two single nucleotide polymorphisms (SNPs) in promoter region of PD-L1 gene (rs822335 and rs822336) were examined. Expression of PD-L1 protein on tumor cells was assessed by immunohistochemistry (IHC). The response rate to immunotherapy and progression free survival (PFS) measured in weeks and overall survival (OS) measured in months from the start of immunotherapy were evaluated.ResultsResponse to immunotherapy was observed in nine patients (15%, including one complete response), disease stabilization in 22 patients (36.7%), and progression in 29 patients (48.3%). Significantly higher (p=0.015) expression of miR-200b and significantly lower (p=0.043) expression of miR-429 were observed in responders compared to patients who did not respond to immunotherapy. The median PFS in the whole group of patients was 16 weeks, and the median OS was 10.5 month. In univariate analysis, the median PFS was significantly higher in patients with high miR-200b expression (HR=0.4253, 95%CI: 0.1737–1.0417, p=0.05) and high miR-508 expression (HR=0.4401, 95%CI: 0.1903–1.0178, p=0.05) and with low expression of miR-429 (HR=0.1288, 95%CI: 0.01727–0.9606, p=0.0456) compared to patients with low and high expression of these molecules, respectively. The median OS was higher in patients with low expression of miR-429 (HR=0,6288, 95%CI: 0,3053–1,2949, p=0.06) compared with patients with high expression of this microRNA. In multivariate analysis, we found that patients with PD-L1 expression on ≥1% of tumor cells compared to patients without PD-L1 expression on cancer cells had a significantly lower risk of progression (HR=0.3857, 95%CI: 0.1612–0.9226, p=0.0323) and death (HR=0.377, 95%CI: 0.1636–0.8688, p=0.022).ConclusionThe miR-200b and miR-429 molecules in tumor cells seem to have greatest impact on the effectiveness of immunotherapy in NSCLC patients.

Pembrolizumab is widely used in first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC) with high PD-L1 expression. The activity of pembrolizumab in NSCLC patients with rare molecular alterations is poorly characterised. RET gene rearrangements are identified in 1–2% of lung cancer patients. Here, we present two cases of RET-rearranged NSCLC patients with high PD-L1 expression (>50%), treated with pembrolizumab within routine clinical practice. Pembrolizumab was ineffective in both cases—single-agent immunotherapy seems to be of limited value in this group of patients. Selective RET-inhibitors, if available, are the optimal treatment for patients with RET fusion nowadays. The best sequence of the therapy is still not defined.

Due to the low incidence of primary tracheal neoplasms, there is no uniform system for staging of this disease. Our retrospective analysis based on registry data included 89 patients diagnosed with primary tracheal cancer at the National Research Institute of Oncology in Warsaw, Poland, between January 2000 and December 2016. We analyzed demographic, clinical, pathological, therapeutic, and survival data. The staging—for the purpose of our analysis—was performed retrospectively on the basis of imaging results. Tumor (T) category was defined as a disease confined to the trachea or lesion derived from the trachea and spreading to adjacent structures and organs. Node (N) and metastases (M) categories were divided into absence/presence of metastasis in regional lymph nodes and the absence/presence of distant metastasis. Survival analysis was performed depending on the clinical presentation of these features. There was a significant difference in overall survival depending on the T, N, M categories in the entire group. In the group of patients undergoing radical treatment, the T and N categories had a statistically significant impact on overall survival. In the group of patients treated with palliative aim, only the T category had an impact on overall survival. Multivariate analysis showed statistical significance for the T category in patients undergoing radical and those receiving palliative treatment. The assessment of the anatomical extent of lesions may help decide about treatment options and prognosis.

Concurrent chemoradiotherapy is recommended for locally advanced and unresectable non-small-cell lung cancer (NSCLC), but radiotherapy alone may be used in patients that are ineligible for combined-modality therapy due to poor performance status or comorbidities, which may concern elderly patients in particular. The best candidates for sequential chemoradiotherapy remain undefined. The purpose of the study was to determine the importance of a patients’ age during qualification for sequential chemoradiotherapy. The study enrolled 196 patients. Older patients (age > 65years) more often had above the median Charlson Comorbidity Index CCI > 4 (p < 0.01) and Simplified Charlson Comorbidity Index SCCI > 8 (p = 0.03), and less frequently the optimal Karnofsky Performance Score KPS = 100 (p < 0.01). There were no significant differences in histological diagnoses, frequency of stage IIIA/IIIB, weight loss, or severity of smoking between older and younger patients. Older patients experienced complete response more often (p = 0.01) and distant metastases less frequently (p = 0.03). Univariable analysis revealed as significant for overall survival: age > 65years (HR = 0.66; p = 0.02), stage IIIA (HR = 0.68; p = 0.01), weight loss > 10% (HR = 1.61; p = 0.04). Multivariable analysis confirmed age > 65years as a uniquely favorable prognostic factor (HR = 0.54; p < 0.01) independent of lung cancer disease characteristics, KPS = 100, CCI > 4, SCCI > 8. Sequential chemoradiotherapy may be considered as favorable in elderly populations.

Dermoscopy is currently the standard method for clinical differential diagnosis of cutaneous melanoma and for qualifying a lesion for excisional biopsy. Full thickness excisional biopsy of suspicious melanomatous skin lesions likely to be diagnosed as early melanomas is crucial in establishing the diagnosis and defining prognostic factors. Early diagnosis and surgical removal of cutaneous melanoma not only improves patients’ prognosis but is also associated with approximately 90% likelihood of cure. The next steps in the therapeutic management of cutaneous melanoma following excisional biopsy are radical scar excision with adequate margins and sentinel lymph node biopsy. Radical lymph node dissection is recommended in the case of regional lymph node metastases. High-risk patients (lymph node involvement and/or ulcerated primary lesion) should be advised to participate in prospective clinical trials on adjuvant therapy. Melanoma patients with distant metastases are still characterized by poor outcomes. In patients with metastatic disease testing for the presence of BRAF gene mutation is mandatory. Patients with metastatic disease should be considered for participation in clinical trials. Long-term survival is confined to a selected group of patients undergoing resection of isolated metastatic lesions. In systemic – mainly first-line – therapy of patients with BRAF V600 mutation the BRAF inhibitor vemurafenib or dabrafenib (preferentially in combination with a MEK inhibitor) may be employed and independently of mutational status immunotherapy with anti-PD-1 antibodies (nivolumab or pembrolizumab) and eventually ipilimumab (anti-CTLA4 antibody) may be used.

Based on the results of the CheckMate 017 and CheckMate 057 studies, nivolumab therapy has become a new standard treatment for both squamous and non-squamous non-small-cell lung cancer (NSCLC). However, due to the specific inclusion criteria of these clinical trials, the efficacy and safety of nivolumab in real-world practice were not certain. In general, the real-world results of nivolumab treatment have been consistent with those obtained in clinical trials. Additional analyses of the real-world data have made the identification of prognostic factors possible. Good performance status is the most significant predictor of clinical benefit. Brain metastases, liver metastases, EGFR mutation, malignant pleural effusion, and a high number of metastatic sites were identified as negative prognostic factors. By contrast, a longer time to disease progression (>6 months) from the beginning of prior chemotherapy and an objective response to chemotherapy seem to have positive prognostic value in the case of nivolumab treatment. In terms of patient age, the data are inconclusive. Some blood biomarkers can also be considered significant prognostic factors.

Cardiovascular diseases may determine therapy outcomes of non-small-cell lung cancer (NSCLC). The evidence for how iatrogenic cardiovascular complications contribute to ceasing anticancer treatment, decreasing the quality of life or even premature death, is unclear. Older patients and smokers are at risk of atherosclerosis and arterial thromboembolic events (TE), such as myocardial infarction or stroke. Venous TE can be observed in up to 15% of NSCLC patients, but the risk increases three to five times in ALK (anaplastic lymphoma kinase)-rearranged NSCLC. ALK inhibitors are associated with electrophysiological disorders. Cytotoxic agents and anti-VEGF inhibitors mainly cause vascular complications, including venous or arterial TE. Cardiac dysfunction and arrhythmias seem to be less frequent. Chemotherapy is often administered in two-drug regimens. Clinical events can be triggered by different mechanisms. Among epidermal growth factor inhibitors, erlotinib and gefitinib can lead to coronary artery events; however, afatinib and osimertinib can be associated with the development of heart failure. During anti-PD1/anti-PDL1 therapy, myocarditis is possible, which must be differentiated from acute coronary syndrome and heart failure. Awareness of all possible cardiovascular complications in NSCLC encourages vigilance in early diagnostics and treatment.