Lung Cancer in Women-Sociodemographic, Clinical and Psychological Characteristics with Comparison to Men.

(1) Background: There is a difference in the course of lung cancer between women and men. Therefore, there is a need to evaluate various factors in the patient population treated in daily practice. The purpose of this study was to analyze the clinical, sociodemographic and psychological aspects of female lung cancer. To better express the results, we compared women and men. (2) Methods: Consecutive patients with a history of lung cancer treatment admitted to the outpatient oncology clinic (Department of Lung Cancer and Chest Tumours, Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw) and the Department of Internal Medicine, Pulmonary Diseases and Allergy, were enrolled. We conducted analyses of the clinical, psychological and socioeconomic factors of women with lung cancer treated in everyday practice, including a comparison with a group of men. Demographic data were collected from a self-administered questionnaire. We used the Perceived Stress Scale (PSS-10) and Acceptance of Illness Scale (AIS) questionnaires for psychological evaluation. (3) Results: A total of 100 patients with confirmed primary lung cancer with a history of treatment were enrolled in the study (50 women and 50 men). We found a significantly shorter history of smoking in the group of women; at the same time, there were no differences in the reported incidence of COPD. Despite comparable results to men on the psychological questionnaire (PSS-10, AIS), women more often reported a willingness to be supported by a psychologist or psychiatrist due to lung cancer. However, they did not decide to consult them more often than men. Immunotherapy was a significantly less frequently used method in women. (4) Conclusions: We should be more active in finding out the willingness to consult a psychologist or psychiatrist among women with lung cancer. The diagnosis of COPD should be considered more often among women due to the lack of differences in the reported incidence of COPD between men and women, despite a clear contrast in the number of pack-years.

New developments in the imaging of lung cancer.

Radiological and nuclear medicine methods play a fundamental role in the diagnosis and staging of patients with lung cancer. Imaging is essential in the detection, characterisation, staging and follow-up of lung cancer. Due to the increasing evidence, low-dose chest computed tomography (CT) screening for the early detection of lung cancer is being introduced to the clinical routine in several countries. Radiomics and radiogenomics are emerging fields reliant on artificial intelligence to improve diagnosis and personalised risk stratification. Ultrasound- and CT-guided interventions are minimally invasive methods for the diagnosis and treatment of pulmonary malignancies. In this review, we put more emphasis on the new developments in the imaging of lung cancer.

Clinicopathological characteristics of patients with primary tracheal tumors: Analysis of eighty-nine cases.

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.

Pembrolizumab-combination therapy for NSCLC- effectiveness and predictive factors in real-world practice.

Introduction: Pembrolizumab 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 <50% of tumour cells (TC). Methods: We evaluated the efficacy of the treatment in real-world practice, paying attention to the predictive factors, with a special focus on low level of PD-L1 expression. This study is a multicenter retrospective analysis of patients with stage IV NSCLC. Results: A group of 339 consecutive patients was analysed, among them 51% patients with low PD-L1 expression. In the overall population, the ORR was 40.6%, median PFS and OS were 13 months (95% CI 11.4-15) and 16.8 months (95% CI 13.3-20.3), respectively. In multivariate analysis for the entire study population, performance status - ECOG 1 vs. 0 (HR 2.2, 95%CI 1.1-4.6; p=0.02), neutrophil to lymphocyte ratio (NLR)>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. Conclusions: In 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.

Effectiveness of ALK inhibitors in treatment of CNS metastases in NSCLC patients.

Metastases to the central nervous system (CNS) in patients with non-small cell lung cancer constitute an extremely difficult clinical problem, and their occurrence is associated with a poor prognosis. Due to the existence of the blood-brain barrier (BBB) and the action of proteins responsible for the transport of drugs, e.g. P-glycoprotein (P-gp), the penetration of drugs into the CNS is insufficient. Until recently, the only method of CNS metastases treatment was radiotherapy and neurosurgery. The advancement of molecular biology allowed discover targets for molecularly targeted therapies. One of targets is abnormal anaplastic lymphoma kinase, which results from the rearrangement of the ALK gene in patients with non-small cell lung cancer (NSCLC). ALK rearrangement occurs in only about 4.5% of NSCLC patients, but its presence favors brain metastases. The ALK inhibitors (ALKi) were modified to obtain molecules with high ability to penetrate into the CNS. This was achieved by modifying the structure of individual molecules, which became, inter alia, less substrates for P-gp. These modifications caused that less than 10% of patients experience progression in CNS during new ALK inhibitors treatment. This review summarizes the knowledge about the action of BBB, the pharmacodynamics and pharmacokinetics of ALKi, with particular emphasis on their ability to penetrate the CNS and the intracranial activity of individual drugs from different generations of ALK inhibitors.

ALK gene rearrangement favors the development of central nervous system (CNS) metastases in patients with NSCLC. New generations of ALK inhibitors penetrate the CNS and induce an intracranial response and protect against new brain lesions.

Nivolumab or Atezolizumab in the Second-Line Treatment of Advanced Non-Small Cell Lung Cancer? A Prognostic Index Based on Data from Daily Practice.

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.

Beta Blockers with Statins May Decrease All-Cause Mortality in Patients with Cardiovascular Diseases and Locally Advanced Unresectable Non-Small-Cell Lung Cancer after Chemoradiotherapy.

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.

Targeted Next-Generation Sequencing of Thymic Epithelial Tumours Revealed Pathogenic Variants in KIT, ERBB2, KRAS, and TP53 in 30% of Thymic Carcinomas.

A better understanding of the molecular pathogenesis of thymic epithelial tumours (TETs) could revolutionise their treatment. We evaluated thymomas and thymic carcinomas by next-generation sequencing (NGS) of somatic or germline single nucleotide variants (SNVs) in genes commonly mutated in solid tumours. In total, 19 thymomas and 34 thymic carcinomas were analysed for nonsynonymous SNVs in 15 genes by targeted NGS (reference genome: hg19/GRCh37). Ten SNVs in TP53 (G154V, R158P, L194H, R267fs, R273C, R306 *, Q317 *), ERBB2 (V773M), KIT (L576P), and KRAS (Q61L) considered somatic and pathogenic/likely pathogenic were detected in 10 of 34 (29.4%) thymic carcinomas. No somatic SNVs confirmed as pathogenic/likely pathogenic were found in thymomas. Rare SNVs of uncertain or unknown functional and clinical significance, to our knowledge not reported previously in TETs, were found in ERBB2 (S703R), KIT (I690V), and FOXL2 (P157S) in 3 of 19 (16%) thymomas. The most frequent germline SNVs were TP53 P72R (94% TETs), ERBB2 I655V (40% TETs), and KIT M541L (9% TETs). No significant difference in median disease-free survival (DFS) was found between thymic carcinoma patients with and without pathogenic SNVs (p = 0.190); however, a trend toward a longer DFS was observed in the latter (16.0 vs. 30.0 months, respectively). In summary, NGS analysis of TETs revealed several SNVs in genes related to the p53, AKT, MAPK, and K-Ras signalling pathways. Thymic carcinomas showed greater genetic dysregulation than thymomas. The germline and rare SNVs of uncertain clinical significance reported in this study add to the number of known genetic alterations in TETs, thus extending our molecular understanding of these neoplasms. Druggable KIT alterations in thymic carcinomas have potential as therapeutic targets.

Non-Small-Cell Lung Cancer Patients with Coexistence of High PD-L1 Expression and RET Fusion-Which Path Should We Follow? Case Reports and Literature Review.

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 cases­single-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.

Efficacy of Immunotherapy in Second-Line Treatment of KRAS-Mutated Patients with Non-Small-Cell Lung Cancer-Data from Daily Practice.

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.

Thymic epithelial tumors: Do we know all the prognostic factors?

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 < 0.0001), histological type (P < 0.0001), lymph node involvement (P < 0.001), WHO performance status 2 (P < 0.0001), anemia (Hb <9.5 g/dL; P = 0.0002), leucocytosis (>12.5 G/L; P = 0.0011), LDH level (>185 U/L; P < 0.0001), concomitant diseases (P = 0.0012) and weight loss (P < 0.0001).The strongest independent risk factor for death was stage IV disease (P < 0.001). CONCLUSIONS: The results confirmed a fairly good prognosis for patients with thymic epithelial tumors. Clinical stage was the most important prognostic factor, but, some additional clinical factors may also have prognostic value.

A thymoma or not a thymoma-that is the question: a case report.

Thymomas are malignant, epithelial tumors of the thymus of diverse morphology that may metastasize or relapse after resection. The WHO histological classification includes five main subtypes A, AB, B1, B2 and B3. Types A and AB usually harbour a specific GTF2I gene mutation. Thymolipomas are very rare, benign tumors composed of thymic parenchyma and adipose tissue. We present the case of a 37-year-old male with an incidentally found mediastinal tumor that shared morphological features of a thymoma of unknown histological type and a thymolipoma-like tumor. Microscopically the tumor contained three components: (I) a highly organoid component that reproduced the thymic parenchyma with numerous Hassall corpuscles; (II) a lymphocyte-poor, epithelial component; (III) mature adipose tissue. A wide panel of immunohistochemical tests was used, but the results were not decisive for differential diagnosis. Genetic analysis of GTF2I, BRAF and NRAS genes revealed no mutations. The tumor was completely resected. The patient did not receive adjuvant radiotherapy. A 1.5 years after resection there was no evidence of tumor recurrence. Based on our case we carefully analyse and compare the microscopic features of thymoma vs. thymolipoma. The differentiation between these tumors is crucial due to their distinct clinical course and required therapeutic approach.

Nivolumab for Previously Treated Patients with Non-Small-Cell Lung Cancer-Daily Practice versus Clinical Trials.

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.

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland.

INTRODUCTION: Osimertinib is a third-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated efficacy in the treatment of EGFR-mutant non-small-cell lung cancer (NSCLC) in prospective clinical trials. MATERIAL AND METHODS: This retrospective analysis evaluated the outcomes of 32 pretreated patients with EGFR T790M mutation who received osimertinib in clinical practice at seven centers in Poland within the Expanded Drug Access Program. Osimertinib was used in the second line in 59% of patients and in later lines in 41%. RESULTS: Objective response was attained in 16 patients (50%), and 12 subjects (38%) had stable disease. Median progression -free survival was 11.3 months in the overall population, 12.6 months in patients with EGFR exon 19 mutation and 7.5 months in patients with EGFR exon 21 mutation (p = 0.045). Median overall survival (OS) was 18.3 months. Overall, 58.4% and 45.6% of patients remained in follow-up after 12 and 24 months, respectively. Median OS appeared longer for patients without cerebral metastases than for those with cerebral metastases (27.4 vs 9.4 months, respectively; p = 0.078), and for patients with the Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 than those with ECOG PS 2 (27.4 vs 11.8 months, respectively; p = 0.189), although neither result reached statistical significance. Median OS of patients with partial response, stable disease and progressive disease was 27.4, 12.7 and 4.5 months, respectively (p < 0.001). Age, comorbidities, line of treatment with osimertinib, and type of activating EGFR mutation did not impact on OS. Adverse events of any grade or grade 3/4 were reported in 38% and 9% of patients, respectively. One person discontinued due to interstitial pneumonia. CONCLUSION: These results confirm the value of osimertinib in patients with previously treated EGFR T790M-mutant NSCLC. Clinical benefit was evident in patients with cerebral metastases and moderate performance status.

The Effectiveness of Pemetrexed Monotherapy Depending on Polymorphisms in TS and MTHFR Genes as Well as Clinical Factors in Advanced NSCLC Patients.

In NSCLC, second-line chemotherapy using pemetrexed or docetaxel has limited efficacy and should be dedicated to selected groups of patients. Pemetrexed is an antifolate compound with the ability to inhibit enzymes (TS, DHFR and GARFT) involved in pyrimidine and purine synthesis. The objective of this study was to evaluate the association between polymorphisms of TS and MHFR genes and clinical outcomes in NSCLC patients treated with pemetrexed monotherapy. DNA was isolated from peripheral blood of 72 non-squamous NSCLC patients treated with pemetrexed. Using PCR and RFLP methods, the variable number of tandem repeats (VNTR), the G > C SNP in these repeats and insertion/deletion polymorphism of TS gene as well as 677C > T SNP in MTHFR gene were analyzed and correlated with disease control rate, progression-free survival and overall survival (OS) of NSCLC patients. Carriers of 2R/3R(G), 3R(C)/3R(G), 3R(G)/3R(G) genotypes showed significantly more frequent early progression than carriers of 2R/2R, 2R/3R(C), 3R(C)/3R(C) genotypes of TS gene (p < 0.05). Among carriers of triple 28 bp tandem repeats (3R) in TS gene and C/C genotype of MTHFR gene a significantly shorter OS was observed (HR = 3.07; p = 0.003). In multivariate analysis, significantly higher risk of death was observed in carriers of both 3R/3R genotype in TS and C/C genotype in 677C > T SNP in MTHFR (HR = 3.85; p < 0.005) as well as in patients with short duration of response to first-line chemotherapy (HR = 2.09; p < 0.005). Results of our study suggested that genetic factors may have a high predictive and prognostic value (even greater than clinical factors) for patients treated with pemetrexed monotherapy.

Correlation between TS, MTHFR, and ERCC1 gene polymorphisms and the efficacy of platinum in combination with pemetrexed first-line chemotherapy in mesothelioma patients.

INTRODUCTION: The combination of pemetrexed and platinum compound represents the standard regimen for first-line chemotherapy in malignant pleural mesothelioma patients. Pemetrexed is a multitarget antifolate agent that inhibits folate-dependent enzymes (eg, thymidylate synthase [TS]) and thus synthesis of nucleotides and DNA. Expression of TS and folate availability, regulated by gene polymorphisms, have implications for effectiveness of chemotherapy and the outcome of mesothelioma patients. The aim of this retrospective multicenter study was to assess the correlation between TS, 5,10-methylenetetrahydrofolate reductase (MTHFR) and excision repair cross-complementing group 1 (ERCC1) gene polymorphisms and the efficacy of pemetrexed-based first-line chemotherapy of mesothelioma patients. PATIENTS AND METHODS: Fifty-nine mesothelioma patients (31 men with a median age of 62 years) treated in first-line chemotherapy with platinum in combination with pemetrexed or pemetrexed monotherapy were enrolled. Genomic DNA was isolated from peripheral blood. Using polymerase chain reaction and high resolution melt methods, the variable number of tandem repeat, the G>C single nucleotide polymorphism (SNP) in these repeats, and 6-base pair (bp) insertion/deletion polymorphism of the TS gene, the SNP of 677C>T in MTHFR, and 19007C>T in the ERCC1 gene were analyzed and correlated with disease control rate, progression-free survival (PFS), and overall survival (OS) of mesothelioma patients. RESULTS: Greater risk of early disease progression (PD), and shortening of PFS and OS were associated with several clinical factors (eg, anemia for early PD and OS), weight loss (for PFS and OS), and previous surgical treatment (for early PD, PFS, and OS). Insertion of 6-bp in both alleles of the TS gene (1494del6) was the only genetic factor that increased the incidence of early progression (P = .028) and shortening of median PFS (P = .06) in patients treated with pemetrexed-based chemotherapy. In multivariate analysis, the 1494del6 in the 3' untranslated region (UTR) of the TS gene also had a predictive role for PFS (P = .0185; hazard ratio, 2.3258 for +6/+6 homozygotes) in analyzed mesothelioma patients. CONCLUSION: Most analyzed polymorphisms in TS, MTHFR, and ERCC1 genes failed to predict outcome in mesothelioma patients treated with pemetrexed-based chemotherapy. However, different variants of 1494del6 in the 3' UTR of the TS gene were associated with differences in disease control rate and PFS of our patients.

Polymorphisms in TS, MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients.

PURPOSE: We presented retrospective analysis of up to five polymorphisms in TS, MTHFR and ERCC1 genes as molecular predictive markers for homogeneous Caucasian, non-squamous NSCLC patients treated with pemetrexed and platinum front-line chemotherapy. METHODS: The following polymorphisms in DNA isolated from 115 patients were analyzed: various number of 28-bp tandem repeats in 5'-UTR region of TS gene, single nucleotide polymorphism (SNP) within the second tandem repeat of TS gene (G>C); 6-bp deletion in 3'-UTR region of the TS (1494del6); 677C>T SNP in MTHFR; 19007C>T SNP in ERCC1. Molecular examinations' results were correlated with disease control rate, progression-free survival (PFS) and overall survival. RESULTS: Polymorphic tandem repeat sequence (2R, 3R) in the enhancer region of TS gene and G>C SNP within the second repeat of 3R allele seem to be important for the effectiveness of platinum and pemetrexed in first-line chemotherapy. The insignificant shortening of PFS in 3R/3R homozygotes as compared to 2R/2R and 2R/3R genotypes were observed, while it was significantly shorter in patients carrying synchronous 3R allele and G nucleotide. The combined analysis of TS VNTR and MTHFR 677C>T SNP revealed shortening of PFS in synchronous carriers of 3R allele in TS and two C alleles in MTHFR. The strongest factors increased the risk of progression were poor PS, weight loss, anemia and synchronous presence of 3R allele and G nucleotide in the second repeat of 3R allele in TS. Moreover, lack of application of second-line chemotherapy, weight loss and poor performance status and above-mentioned genotype of TS gene increased risk of early mortality. CONCLUSION: The examined polymorphisms should be accounted as molecular predictor factors for pemetrexed- and platinum-based front-line chemotherapy in non-squamous NSCLC patients.

Analysis of treatment results in primary germ cell tumours with mediastinal location: own experience.

INTRODUCTION: Primary germ cell tumours with mediastinal location comprise 1-6% of mediastinal tumours and 2-5% of all germ cell tumours occurring in adults. They are identified mostly in the 3rd decade of life, in 90% of cases in men. The most common symptoms are dyspnea, chest pain, cough, fever and weight loss. The aim of the present study was the analysis of our own results of treatment of primary germ cell tumours with mediastinal location, and a review of the literature concerning this subject. MATERIAL AND METHODS: Five patients (4 males, 1 female) median age 27.8 years (range 23-30 years) treated in the period from 1999 to 2009 in Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Lung Cancer and Chest Tumours in Warsaw, due to germinal tumours with primary mediastinal location, entered the study. RESULTS: All patients received chemotherapy according to the BEP regimen. All patients achieved an objective response to treatment. Two patients died due to disease progression in spite of II- and III-line treatment. Three patients are still in follow-up. The median survival time was 55.8 months (range 8.0-120.0 months). CONCLUSIONS: Primary mediastinal germ cell tumours have worse prognosis than do those with gonadal location. Based on our observations and review of the literature, it can be concluded that the results of treatment of non-seminoma type germ cell tumours with primary mediastinal location remain poor. Patients who develop early recurrence or progression during first-line chemotherapy are particularly at risk of unfavourable outcome. Identification of new standards of treatment in tumours resistant to cisplatin require further studies evaluating the effectiveness of new generation cytostatic drugs.

[Gefitinib in patients with advanced non-small-cell lung cancer]. / Gefitynib u chorych na niedrobnokomórkowego raka pluca w zaawansowanym stadium.

INTRODUCTION: Patients with advanced non-small cell lung cancer (NSCLC) have a very poor prognosis. Individualization of treatment and identification of therapeutic molecular targets may improve outcomes. Gefitinib was introduced recently among several other molecular-targeted drugs of activity in NSCLC. Gefitinib is indicated for patients diagnosed with advanced or disseminated NSCLC with an activating mutation in the EGFR (epidermal growth factor receptor) gene. The paper summarize experience with gefitinib in the Department of Lung and Thoracic Tumors of Maria Sklodowska-Curie Memorial Cancer Centre and Institute in Warsaw. MATERIAL AND METHODS: The group of 11 patients diagnosed with advanced NSCLC and activating mutations in the EGFR gene was analyzed. Patients were treated from April 2010 to April 2011. Tolerability, objective response rate (ORR) and progression free survival (PFS), which was calculated by the Kaplan-Meier method, were assessed. RESULTS: Median observation time from the start of gefitinib treatment was 14 months (range 4,8-19 months). The rate of one-year survival in this group of patients was 91% (10 patients) with 54% of patients (6 patients) surviving one year without progression of disease. The ORR rate of 82% and median PFS 11.4 months were reached. No treatment-related deaths were reported. Among the complications skin toxicity (82%) and diarrhea (45%) were most frequently observed, in most cases the Common Toxicity Criteria for Adverse Events (CTCAE) first grade. CONCLUSIONS: The results confirm the literature data on the efficacy and safety profile of gefitinib in the treatment of patients with the diagnosis of advanced NSCLC and activating mutation in the EGFR gene.