The Advantage of Targeted Next-Generation Sequencing over qPCR in Testing for Druggable EGFR Variants in Non-Small-Cell Lung Cancer.

The emergence of targeted therapies in non-small-cell lung cancer (NSCLC), including inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase, has increased the need for robust companion diagnostic tests. Nowadays, detection of actionable variants in exons 18-21 of the EGFR gene by qPCR and direct DNA sequencing is often replaced by next-generation sequencing (NGS). In this study, we evaluated the diagnostic usefulness of targeted NGS for druggable EGFR variants testing in clinical NSCLC material previously analyzed by the IVD-certified qPCR test with respect to DNA reference material. We tested 59 NSCLC tissue and cytology specimens for EGFR variants using the NGS 'TruSight Tumor 15' assay (Illumina) and the qPCR 'cobas EGFR mutation test v2' (Roche Diagnostics). The sensitivity and specificity of targeted NGS assay were evaluated using the biosynthetic and biological DNA reference material with known allelic frequencies (VAF) of EGFR variants. NGS demonstrated a sufficient lower detection limit for diagnostic applications (VAF < 5%) in DNA reference material; all EGFR variants were correctly identified. NGS showed high repeatability of VAF assessment between runs (CV% from 0.02 to 3.98). In clinical material, the overall concordance between NGS and qPCR was 76.14% (Cohen's Kappa = 0.5933). The majority of discordant results concerned false-positive detection of EGFR exon 20 insertions by qPCR. A total of 9 out of 59 (15%) clinical samples showed discordant results for one or more EGFR variants in both assays. Additionally, we observed TP53 to be a frequently co-mutated gene in EGFR-positive NSCLC patients. In conclusion, targeted NGS showed a number of superior features over qPCR in EGFR variant detection (exact identification of variants, calculation of allelic frequency, high analytical sensitivity), which might enhance the basic diagnostic report.

FGFR1-4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer.

While fibroblast growth factor receptors (FGFRs) are involved in several biological pathways and FGFR inhibitors may be useful in the treatment of squamous non-small cell lung cancer (Sq-NSCLC), FGFR aberrations are not well characterized in Sq-NSCLC. We comprehensively evaluated FGFR expression, fusions, and variants in 40 fresh-frozen primary Sq-NSCLC (stage IA3−IV) samples and tumor-adjacent normal tissues using real-time PCR and next-generation sequencing (NGS). Protein expression of FGFR1−3 and amplification of FGFR1 were also analyzed. FGFR1 and FGFR4 median gene expression was significantly (p < 0.001) decreased in tumors compared with normal tissue. Increased FGFR3 expression enhanced the recurrence risk (hazard ratio 4.72, p = 0.029), while high FGFR4 expression was associated with lymph node metastasis (p = 0.036). Enhanced FGFR1 gene expression was correlated with FGFR1 protein overexpression (r = 0.75, p = 0.0003), but not with FGFR1 amplification. NGS revealed known pathogenic FGFR2,3 variants, an FGFR3::TACC3 fusion, and a novel TACC1::FGFR1 fusion together with FGFR1,2 variants of uncertain significance not previously reported in Sq-NSCLC. These findings expand our knowledge of the Sq-NSCLC molecular background and show that combining different methods increases the rate of FGFR aberrations detection, which may improve patient selection for FGFRi treatment.

The expression of circulating miR-504 in plasma is associated with EGFR mutation status in non-small-cell lung carcinoma patients.

MicroRNAs (miRNAs), key regulators of gene expression at the post-transcriptional level, are grossly misregulated in some human cancers, including non-small-cell lung carcinoma (NSCLC). The aberrant expression of specific miRNAs results in the abnormal regulation of key components of signalling pathways in tumour cells. MiRNA levels and the activity of the gene targets, including oncogenes and tumour suppressors, produce feedback that changes miRNA expression levels and indicates the cell's genetic activity. In this study, we measured the expression of five circulating miRNAs (miR-195, miR-504, miR-122, miR-10b and miR-21) and evaluated their association with EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) mutation status in 66 NSCLC patients. Moreover, we examined the discriminative power of circulating miRNAs for EGFR mutant-positive and -negative NSCLC patients using two different data normalisation approaches. We extracted total RNA from the plasma of 66 non-squamous NSCLC patients (31 of whom had tumours with EGFR mutations) and measured circulating miRNA levels using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The miRNA expression levels were normalised using two endogenous controls: miR-191 and miR-16. We found significant associations between the expression of circulating miR-504 and EGFR-activating mutations in NSCLC patients regardless of the normalisation approach used (p = 0.0072 and 0.0236 for miR-16 and miR-191 normalisation, respectively). The greatest discriminative power of circulating miR-504 was observed in patients with EGFR exon 19 deletions versus wild-type EGFR normalised to miR-191 (area under the curve (AUC) = 0.81, p < 0.0001). Interestingly, circulating miR-504 levels were significantly reduced in the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated subgroup compared to EGFR-mutated patients (p < 0.0030) and those with EGFR/KRAS wild-type tumours (p < 0.0359). Our study demonstrated the feasibility and potential diagnostic value of plasma miR-504 expression analysis to distinguish between EGFR-mutated and wild-type NSCLC patients. However, quality control and normalisation strategies are very important and have a major impact on the outcomes of circulating miRNA analyses.

Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population.

Non-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13336 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with P-value <3.5 × 10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 non-small cell lung cancer cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis P-value for these two SNPs were 1.24 with 6.96 × 10-7 and 1.37 with 3.49 × 10-7, respectively. In addition, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and P-value of 8.12 × 10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.

Open surgery versus stent placement in failed primary surgical treatment of esophageal perforation - a single institutional experience.

BACKGROUND: Surgical treatment is an accepted method to manage esophageal perforation, but in many cases it may result in failure. This paper compares the efficacy of surgical treatment and stenting in patients after previous surgical intervention for esophageal perforation. METHODS: A single-institution retrospective study was performed in a group of patients treated for esophageal perforation admitted to our centre from 2010 to 2015. Seventy eight patients (76.5%) with esophageal perforation received surgical treatment. In this group of patients, the mean time between perforation and treatment was 80.6 h (24-240 h). Spontaneous and iatrogenic perforation was observed in 33 (42.3%) and 45 (57.7%) patients, respectively. Partial esophageal resection was performed in 11 cases (14.1%). The perforation site was sutured in the remaining 67 patients (85.9%). Surgical treatment failed in 29 cases (37.2%). RESULTS: In patients with failed previous surgical treatment, revision surgery was performed in 14 patients (48.3%) (group A), and a large-diameter self-expandable stent was implanted in 15 cases (51.7%) (group B). Perforation in the thoracic and distal esophagus was observed in 5 (35.7%) and 9 (64.3%) patients from group A, and in 7 (46.7%) and 8 (53.3%) patients from group B, respectively. The mean intubation time in both groups was 30.3 and 12.5 days (p < 0.001), respectively. The mean daily drainage within five days after the intervention was 350 mL in group A, and 500 mL in group B (p < 0.02). In both groups hospitalisation time was 41.5 and 19.4 days, respectively (p < 0.001). Six patients died (42.8%) following revision surgery, and 2 (13.3%) patients died after stent implantation (p < 0.001). CONCLUSIONS: Intubation time, hospitalization, and the rate of fatal complications in patients who underwent stent implantations were significantly lower compared to reoperated patients; however, the rate of prolonged drainage was lower in patients who underwent revision surgery. In conclusion, stent implantation is a significantly superior method to treat persistent leakage following failure of previous surgical treatment.

Use the Lower Limit of Normal, Not 80% Predicted, in Judging Eligibility for Lung Resection.

BACKGROUND: Impaired lung function (LF) is a well-known risk factor for perioperative complications in patients qualified for lung resection surgery. The recent European guidelines recommend using values below 80% predicted as indicating abnormal LF rather than the lower limit of normal (LLN). OBJECTIVES: To assess how the choice of a cut-off point (80% predicted vs. LLN at -1.645 SD) affects the incidence of functional disorders and postoperative complications in lung cancer patients referred for lung resection. METHODS: Preoperative spirometry and the transfer factor for carbon monoxide (TL,CO) were retrospectively analysed in 851 consecutive lung cancer patients after resectional surgery. RESULTS: Airway obstruction was diagnosed in 369 (43.4%), and a restrictive pattern in 41 patients (4.8%). The forced expiratory volume in 1 s (FEV1) or TL,CO was below the LLN in 503 patients (59.1%), whereas the FEV1 or TL,CO was <80% predicted in 620 patients (72.9%; χ2 test: p < 0.0001). In all, 117 out of 851 patients had LF indices <80% predicted but not below the LLN. Odds ratios (ORs) for perioperative complications were higher in patients with impaired LF indices defined as below the LLN (1.59, p = 0.0005) with the exception of large resections (>5 segments). In patients with test results above the LLN and <80% predicted, the OR for perioperative complications was not different (1.14, p = 0.5) from that in patients with normal LF. CONCLUSIONS: LF impairments are common in candidates for lung resection. Using the LLN instead of 80% predicted diminishes the prevalence of respiratory impairment by 14% and allows for safe resectional surgery without additional function testing.

Pulmonary artery stenosis due to embryonal carcinoma with primary mediastinal location.

A 29-year old man was admitted to the intensive care unit after losing consciousness. On physical examination, a loud systolic murmur over the heart was found. Echocardiography revealed narrowing of pulmonary artery with high pressure gradient. Computed tomography of the chest revealed the presence of large tumour localised in the upper anterior mediastinum. Due to the risk of total closure of the pulmonary artery, interventional mediastinotomy was performed and diagnosis of carcinoma embryonale was established. Subsequent chemotherapy (BEP regimen) has brought regression of tumour and significant improvement in haemodynamic parameters (relief of pressure gradient in pulmonary artery). During the second surgery, the resection of all accessible tumour mass together with marginal resection of the right upper lobe was performed. No signs of cardiac or great vessels infiltration was found. Histopathologic examination revealed the necrotic masses and neoplastic foci diagnosed as teratoma immaturum. In a four-month follow-up the patient's condition remained good. The patient is still under the care of both oncological and cardiological specialists. Thus far he has not required further chemotherapy. Holter ECG monitoring revealed no arrhythmia, but the patient is still treated with mexiletine. The patient is planning to return to work.

Prognostic value of serum C-reactive protein (CRP) and cytokeratin 19 fragments (Cyfra 21-1) but not carcinoembryonic antigen (CEA) in surgically treated patients with non-small cell lung cancer.

INTRODUCTION: The aim of the study was to assess the prognostic value of cytokeratin 19 fragments (Cyfra 21-1), carcinoembryonic antigen (CEA) and C-reactive protein (CRP) in surgically treated NSCLC patients. MATERIAL AND METHODS: 50 NSCLC patients (25 adenocarcinoma, 21 squamous cell and 4 adenosquamous), clinical stages I and II, age 42-89 years, entered the study. CEA, Cyfra 21-1 and CRP concentrations were measured in serum taken before surgery, CEA and Cyfra 21-1 in 50 patients, CRP - in 46 patients. The survival was calculated from the date of surgical treatment until death or until the end of the observation time. The results were expressed as medians (95%CI). RESULTS: Cyfra 21-1 concentration was 2.1 (0.7-14.5) ng/mL. Survival time in the patients with Cyfra 21-1 ≤ 2 ng/mL, and > 2 ng/ /mL was 79 (14.85-88.2) and 29 (5.7-87.6) months, (p < 0.026). CEA concentration was 2.68 (0.87-72.7) ng/mL, significantly higher in adenocarcinoma than in squamous cell lung cancer - 4.38 ng/mL (1.67-41.35) vs. 2.2 ng/mL (1.0-6.1), p = 0.002. CRP concentration was 5.45 (0-122.6) mg/L. Significant dependence was found between CRP and pathological tumour size (pT). Median CRP values in pT1, pT2 and pT3+4 tumours were: 2.8 mg/L, 6.9 mg/L and 23.5 mg/L, respectively. Survival time of the patients with CRP ≤ 10 mg/L and CRP > 10 mg/L was 79 (14.85-88.2) and 29.5 (5.7-87.6) months, respectively (p = 0.045). CRP > 10 mg/L and Cyfra 21-1 > 2 ng/mL were the only significant preoperative prognostic indicators (HR 2.08 and 2.04, respectively). Among the postoperative parameters, pathological stage of disease (p-stage) and pT were the significant prognostic indicators (HR 2.1 and 2.42, respectively). CONCLUSIONS: In the present study, concerning surgically treated NSCLC patients, preoperative CRP > 10 mg/L and Cyfra 21-1 > 2 ng/mL were the only negative prognostic indicators, while pT and p-stage were significant postoperative prognostic indicators.

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.

[The role of systemic therapies of non-small cell lung cancer and malignant pleural mesothelioma: updated expert recommendations]. / Rola systemowych metod leczenia u chorych na niedrobnokomórkowego raka pluca i zlosliwego miedzybloniaka oplucnej: uaktualnione zalecenia ekspertów.

Lung cancer is the leading cause of cancer related death in Poland. About 85% of all lung cancer constitutes non-small cancer (NSCLC), in which the role of cytotoxic and molecularly targeted drugs is increasing. This article presents the current evidence- based recommendations for the use of these methods in clinical practice in NSCLC and malignant pleural mesothelioma.

Clinically important pulmonary vascular variations: a narrative review.

Background and Objective: Pulmonary vascular variations are a major factor in thoracic surgeries. Minimally invasive techniques, such as video-assisted thoracic surgery (VATS) used in non-small lung cancer treatment, have a limited field of view and no haptic feedback. Additionally, new studies suggest that segmentectomies are beneficial for patients. Accurate knowledge of vascular patterns and variants is crucial for conducting such procedures safely. The aim of this review was to systematize data in a useful manner from studies and case reports concerning pulmonary vascular variations and patterns. Methods: We conducted a search on the PubMed and Embase databases. We used classifications of Nagashima, Yamashita, Boyden, Maciejewski, and Shimizu. Key Content and Findings: The analysis showed that more data on the incidence rate and vascular patterns of certain bronchopulmonary segments are needed. Venous variations are a major factor in segmental resections, but additional data regarding incidence and pattern types are needed. Surgeons need to be aware of vascular variations as they can influence procedures in seemingly unrelated areas. The majority of studies emphasize the use of three-dimensional (3D) reconstruction of computed tomography (CT) for accurate planning of any thoracic procedures. Conclusions: Abnormal vessels pose a risk in various procedures performed within the thorax, and the data in this review could be valuable in different medical areas in this regard.

Reliable detection of rare mutations in EGFR gene codon L858 by PNA-LNA PCR clamp in non-small cell lung cancer.

PNA-LNA PCR clamp real-time PCR method represents allele-specific approach to mutation analysis of EGFR gene in NSCLC. Due to its unique design, it is characterized by exceptionally high specificity and sensitivity but also allows detection of rare or not specifically-targeted EGFR mutations within examined exons, otherwise undetectable by other mutation-specific fluorescent probes. We herein present two cases of rare mutations revealed by PNA-LNA PCR clamping of NSCLC samples referred for routine EGFR gene molecular diagnostics. In one, the EGFR gene L858 codon mutation was detected by standard PNA-LNA PCR clamping, subsequently reconfirmed and characterized by direct sequencing of allele specific amplification products as the missense mutation c.2572C>A (p.L858M) paired with L861Q mutation on the same allele (in cis). In the second sample, low quality FFPE material from pleural biopsy, c.2573C>T missense mutation (p.L858P) was revealed. Still, repeated DNA analysis by PNA-LNA PCR clamp and direct sequencing demonstrated low level of mutant allele existing in a total allele pool suggesting rather artifactual c.2572C>T transition, a phenomenon quite frequent in low-volume FFPE samples upon fixation procedures. In conclusion, superior sensitivity and unique design of PNA-LNA PCR clamping are crucial for its excellent diagnostic effectiveness. As we demonstrated, the method allows detecting rare EGFR mutations, although it increases the risk of detection of a very low signal, e.g., generated by a small pool of mutated allele. Therefore, applicability of PNA-LNA PCR clamp product for the direct sequencing reevaluation is of key importance enabling reliable validation of results.

The absence of lymph nodes removed (pNx status) impacts survival in patients with lung cancer treated surgically.

OBJECTIVES: We aimed to study the clinical significance of the lack of lymph node assessment (pNx status) and its impact on survival in non-small-cell lung cancer patients. METHODS: We retrospectively analysed the Polish Lung Cancer Study Group database. pNx status was defined as 0 lymph nodes removed. We included 17,192 patients. RESULTS: A total of 1080 patients (6%) had pNx status. pNx patients were more likely to be younger, be female, have a different pT distribution, have squamous cell carcinoma, undergo open thoracotomy, be operated on in non-academic hospitals, and have a lower rate of some comorbidities. pNx was more likely to be cN0 than pN1 and pN2 but less likely than pN0 (p < 0.001). pNx patients were less likely to undergo preoperative invasive mediastinal diagnostics than pN1 and pN2 patients but more likely than pN0 patients (p < 0.001). Overall, the five-year overall survival rates were 64%, 45%, 32% and 50% for pN0, pN1, pN2 and pNx, respectively. In pairwise comparisons, all pN descriptors differed significantly from each other (all p < 0.0001 but pNx vs. pN1 p = 0.016). The placement of the pNx survival curve and survival rate depended on histopathology, surgical approach and pT status. In multivariable analysis, pNx was an independent prognostic risk factor (HR = 1.37, 95%CI: 1.23-1.51, p < 0.01). CONCLUSION: The resection of lymph nodes in lung cancer remains a crucial step in the surgical treatment of this disease. The survival of pNx patients is similar to that of pN1 patients. pNx survival curve placement depends on the other variables which could be useful in clinical decisions.

The effectiveness of surgical treatment of lung cancer in Polish academic and nonacademic centers.

Background: The theoretical advantage of academic hospitals over nonacademic are: more qualified surgeons, adequate diagnostic facilities and infrastructure, including intensive care units. The aim of the study was to compare the effectiveness of surgical lung cancer treatment in academic (ACA) and nonacademic (non-ACA) centers. Methods: This was a retrospective analysis of data from 31,777 patients surgically-treated for lung cancer during the period from 2007 to 2020 in 9 ACA and 21 non-ACA centers. The analysis considered the clinical data of patients, the effectiveness of preoperative diagnostics, the type of procedures performed, the complications, the postoperative mortality and the long-term survival. Results: The median number of anatomical lung resection procedures was 1,218 for ACA and 550 for non-ACA centers. In the ACA group, resection using the video-assisted thoracic surgery (VATS) technique was performed significantly more often than in the non-ACA group (23.6% vs. 14.2%, P<0.001). The pN feature analysis showed significantly lower proportions of pNX (9.2%) in the ACA group than those in the non-ACA group (17.1%) (P<0.001). The rates of postoperative complications in the ACA and non-ACA groups were 30.7% and 33.8%, respectively (P<0.001). There were no significant differences in 5-year survival between the ACA and non-ACA groups (56% and 56%, respectively) (P=0.2). Conclusions: The present study showed that ACA centers are characterized by better preoperative diagnostics, a higher percentage of VATS lobectomies, a lower percentage of postoperative complications and a shorter hospitalization period than non-ACA centers, but there was no impact on 5-year survival.

Ninety-Day Mortality of Thoracoscopic vs Open Lobectomy: A Large Multicenter Cohort Study.

BACKGROUND: Studies have demonstrated a lower incidence of complications after video-assisted thoracoscopic surgery (VATS) lobectomy compared with thoracotomy, but the data on in-hospital and 90-day mortality are inconclusive. This study analyzed whether surgical approach, VATS or thoracotomy, was related to early mortality of lobectomy in lung cancer and determined the differences between in-hospital and 90-day mortality. METHODS: Data of all patients with non-small cell lung cancer who underwent lobectomy between January 1, 2007, and July 30, 2018, were retrieved from Polish National Lung Cancer Registry. Included were 31 433 patients who met all study criteria. After propensity score matching, 4946 patients in the VATS group were compared with 4946 patients in the thoracotomy group. RESULTS: Compared with thoracotomy, VATS lobectomy was related to lower in-hospital (1.5% vs 0.9%, P = .004) and 90-day mortality (3.4% vs 1.8%, P < .001). Mortality at 90 days was twice as high as in-hospital mortality in both the VATS (1.8% vs 0.9%, P < .001) and thoracotomy groups (3.4% vs 1.5%, P < .001). Postoperative complications were less common after VATS compared with thoracotomy (23.6% vs 31.8%, P < .001). CONCLUSIONS: VATS lobectomy is associated with lower in-hospital and 90-day mortality compared with thoracotomy and should be recommended for lung cancer treatment, if feasible. Patients should also be closely monitored after discharge from the hospital, because 90-day mortality is significant higher than in-hospital mortality.

The usefulness of progression-free survival in surgical treatment of lung metastases.

Introduction: The history of the treatment of neoplastic metastases and its evolution over more than one hundred years has raised many doubts as to the purposefulness of such management. The main problem that made it difficult to draw certain statistically confirmed conclusions was the inability to conduct prospective studies. Over the years, based on the experience gained and the multicenter analyses carried out, it was determined which elements of the surgical treatment affect the prognosis. Some doubts are raised by the issue of the progression of secondary proliferative disease, which results in a greater number of metastasectomies. Aim: To investigate the factors influencing progression-free survival (PFS) after surgical treatment of secondary proliferative disease with lung involvement. This parameter is directly related to the overall survival time. Material and methods: Five hundred and seventy-seven patients treated surgically due to secondary neoplastic disease with lung involvement were included. One-, three- and five-year PFS was examined. PFS was defined as the time from the first to the next metastasectomy or death from any other cause. One-factor and multi-factor statistical analysis was used. Results: Longer PFS was found in patients over 60 years of age, after unilateral and radical metastasectomies, with a longer time from primary tumor resection to secondary lesions (disease-free interval, DFI). The longest PFS was found for colorectal cancer, the shortest for sarcoma. The presence of nodal metastases and gender did not differentiate PFS. Conclusions: The greatest probability of longer relapse-free survival, and thus longer overall survival, occurs in patients after radical unilateral metastasectomy. Another parameter that positively influences PFS is longer DFI. Histological type differentiates PFS.

Effect of 3A lymph node resection on survival in patients with right-sided NSCLC: a retrospective, multicentre, propensity-score matching study.

Background: We aimed to assess the clinical significance and impact on survival of prevascular mediastinal lymph nodes (3A) in patients with right-sided lung cancer. Methods: Prospective data of 6,348 patients, who underwent lung resection from 2005 to 2015, were retrospectively analysed. There were 221 patients who underwent 3A dissection (3ALN+), while 6,127 did not (3ALN-). We performed propensity score matching (PSM) to decrease selection bias (221 vs. 221). Results: The incidence of 3A metastasis was 8%, and it elevated with pT stage. Between pT1c and pT2a, there was a significant increase in the 3A metastasis incidence, which doubled from 4% to 9%. For pT4, the incidence was 15%. The highest incidence was found among patients undergoing pneumonectomy (10%) and in the N2b1 and N2b2 subgroups (33% and 64%). In univariable analysis, we found no differences in 5-year survival between 3ALN+ and 3ALN- (51% vs. 51%, P=0.74). But, non-metastatic 3ALN+, 3ALN-, and metastatic 3ALN+ differed significantly (P<0.0001). pN2 subgroups (pN2a1, pN2a2, pN2b1, pN2b2) within PSM analysis did not differ significantly in terms of survival. 3A metastasis failed to be an independent prognostic factor in the multivariable analysis of matched pN2 subgroups. Conclusions: Regardless of 3A lymph nodes failing to be an independent prognostic factor in our cohort, the incidence of metastases in lymph nodes increases notably in advanced stages. 3A metastasis rate is comparable to other lymph node stations. Therefore, superior mediastinal lymphadenectomy in advanced cancers may improve from resections of the 3A lymph node station.

Sex differences in clinico-pathologic characteristics and long-term survival among 17,192 surgically treated NSCLC patients: Nationwide population-based propensity score-matching study.

INTRODUCTION: More information is needed on gender differences in lung cancer surgery. Thus, we conducted a retrospective study on thoracic treatment of non-small cell lung cancer (NSCLC) patients between 2007 and 2020 in Poland. The aim was to characterize sex differences in survival after complete surgical resection and to compare postoperative complications between Polish men and women. The main aspects that were compared between women and men were as follows: type of surgery and postoperative staging, morbidity and mortality, thoracic surgery complications, comorbidities, and overall survival based on a univariate analysis including propensity score matching (PSM) and a multivariate analysis. MATERIALS AND METHODS: Data were collected retrospectively from the Polish Lung Cancer Study Group database. Patients who were surgically treated for NSCLC between 2007 and 2020 (n = 17,192) were included in the study. RESULTS: The univariate analysis showed significantly better survival in women than in men. Women had better 5-year survival compared to men both for adenocarcinoma and squamous cell carcinoma (66% vs. 53%, p < 0.0001 and 65% vs. 51%, p<0.0001%, respectively), for both smokers and non-smokers (65% vs. 52%, p < 0.0001 and 65% vs. 51%, p < 0.0001, respectively), all age groups, and all stages (IA1 to III B). In the PSM analysis, statistically significant differences in favor of women were found for lower lobectomy (67% vs. 50%, p < 0.0001) and upper lobectomy (67% vs. 56%, p < 0.0001). Overall, postoperative complications occurred in 33.1% of patients and were observed more often in men than in women (35.8% vs. 28.6%, p < 0.001). CONCLUSIONS: Women with NSCLC who were treated surgically had a better long-term outcome compared to men, with no significant difference in disease severity. In addition to gender, the histological type, comorbidities, and type of surgery and surgical approach are also important.

The clinico-pathological characteristics of surgically treated young women with NSCLC.

Background: Non-small cell lung cancer diagnosed in young patients is rare. Younger patients with lung cancer are mostly female and have a more advanced stage at initial diagnosis. To our knowledge, no studies have compared single-surgical treatment in different age groups among women. Our study aimed to elucidate the clinicopathological characteristics and the best strategies for surgically treating young women with non-small-cell lung cancer. Methods: The data were collected retrospectively from the Polish Lung Cancer Study Group database. Women who were surgically treated for non-small-cell lung cancer between 2007 and 2020 were included in the study. The participants (n=11,460) were divided into two subgroups: aged ≤55 and >55 years. Results: Statistically significant differences were found for grades IB, IIA, IIIA, and IIIB (22.8% vs. 24.5%, 5.3% vs. 7.5%, 19.3% vs. 15.8%, 5.8% vs. 3.2%, for younger and older women, respectively, all P<0.001). The univariate analysis showed a higher percentage of 5-year survival in the group of younger women than in older women (0.67 vs. 0.64, P=0.00076). Regarding the stage of advancement, statistically significant differences in survival were found for stages IA1, IA2, and IIIA (0.95 vs. 0.86, P=0.047; 0.88 vs. 0.79, P=0.003; 0.5 vs. 0.42, for younger and older women, respectively, all P=0.01). Postoperative complications were more common in older than younger women (27.6% vs. 23.1%, P<0.001). However, there were no statistically significant differences in the number of hospitalization days since surgery and postoperative 30-day mortality. Conclusions: Younger women treated surgically were characterized by a lower percentage of comorbidities, were treated in a more advanced stage of the disease and had a lower percentage of postoperative complications, which, however, did not affect the hospitalization time. Despite the more advanced stage of the disease, survival in selected stages was much better than in the group of older women.

[Reexpansion pulmonary edema and pleural bleeding after suction drainage of pneumothorax]. / Rozprezeniowy obrzek pluca i krwawienie oplucnowe po leczeniu drenazem ssacym odmy oplucnowej.

We present a case of 26 years old man with large spontaneous pneumothorax of about 5 days duration. Application of suction drainage was complicated by unilateral reexpansion pulmonary edema (REPE) and hemothorax developed during first 24 hours of treatment. On thoracotomy multifocal superficial pleural bleeding was seen which was probably attributed to the pathomechanisms similar to suggested in reexpansion pulmonary edema. The patient received supplemental oxygen therapy and completely recovered during next few days. The patient presented typical risk factors of REPE including: young age, large and prolonged pneumothorax. In such cases chest tube should be initially left off suction to prevent REPE.