Search Results (734)

The Fernald Feed Materials Production Center (FMPC), located in Fernald, Ohio, USA, released radon (Rn) as a byproduct of the processing of uranium materials during the years from 1951 to 1989. Rn is a colorless, odorless gas that emits charged alpha radiation that interacts with cells in the lung and trachea-bronchial tree, leading to DNA damage, mutations, and tumor initiation. The purpose of this project was to use evidence collected by the Fernald Dosimetry Reconstruction Project and other sources to estimate the outdoor Rn exposure to individuals in the community immediately surrounding the FMPC during the years of plant operation. Using previously tabulated source terms, diffusion and meteorological data, and self-reported detailed residential histories, we estimated radon exposure for approximately 9300 persons who lived at more than 14,000 addresses. The results indicated that a portion of the population cohort experiences mean annual Rn exposure exceeding the U.S. Environmental Protection Agency (EPA) action limit of 4 pCiL⁻¹. These exposure estimates support the analysis of the incidence of lung cancer in the Fernald Community Cohort (FCC). Full article

Pneumonitis is characterized as inflammation of the lung parenchyma, and a potential adverse effect of several anti-cancer therapies. Diagnosing pneumonitis can be particularly challenging in lung cancer patients due to inherent similarities in symptoms and radiological presentation associated with pneumonitis, as well as other common conditions such as infection or disease progression. Furthermore, many lung cancer patients have underlying pulmonary conditions that might render them more susceptible to severe or fatal outcomes from pneumonitis. Novel anti-cancer agents, such as antibody–drug conjugates (ADCs) and bispecific antibodies (BsAbs), are being incorporated into the treatment of lung cancer; therefore, understanding the risk and mechanisms underlying the potential development of pneumonitis with these new therapies is important to ensure continuous improvements in patient care. This narrative review provides an overview of the incidence of pneumonitis observed with novel anti-cancer agents, characterizes potential pathophysiological mechanisms underlying pneumonitis risk and emerging predictive biomarkers, highlights management strategies, and explores future directions for minimizing the risk of pneumonitis for lung cancer patients. Full article

Dark sweet cherries (DSC) phytochemicals have emerged as a promising dietary strategy to combat triple-negative breast cancer (TNBC). This study explored the effects of DSC extract rich in anthocyanins (ACN) as a chemopreventive agent and as a complement to doxorubicin (DOX) in treating TNBC tumors and metastasis using a 4T1 syngeneic animal model. Initiating ACN intake as a chemopreventive one week before 4T1 cell implantation significantly delayed tumor growth without any signs of toxicity. Both DOX treatment and the combination of DOX-ACN effectively delayed tumor growth rate, but DOX-ACN allowed for body weight gain, which was hindered by DOX alone. As a chemopreventive, ACN downregulated metastasis- and immune-suppression-related genes, including STAT3, Snail1, mTOR, SIRT1, TGFβ1, IKKβ, and those unaffected by DOX alone, such as HIF, Cd44, and Rgcc32. Correlations between mRNA levels seen in control and DOX groups were absent in ACN and/or DOX-ACN groups, indicating that Cd44, mTOR, Rgcc32, SIRT1, Snail1, and TGFβ1 may be ACN targets. The DOX-ACN treatment showed a trend toward enhanced efficacy involving CREB, PI3K, Akt-1, and Vim compared to DOX alone. Particularly, ACN significantly suppressed lung metastasis compared to the other groups. ACN also decreased the frequency and incidence of metastasis in the liver, heart, kidneys, and spleen, while their metastatic area (%) and number of breast cancer (BC) metastatic tumor nodules were lowered without reaching significance. Further research is needed to explore the efficacy of combining ACN with drug therapy in the context of drug resistance. Full article

Background: Pseudoprogression is known to occur after immune-checkpoint inhibitor (ICI) therapy in brain metastasis and can complicate clinical decision-making. Still, its incidence, timing, and clinical presentation remain unclear. A retrospective cohort study in melanoma and non-small cell lung cancer brain metastasis patients was conducted to address this. Materials and Methods: Brain metastasis patients showing progression on MRI according to response assessment in neuro-oncology brain metastases criteria after starting ICI therapy were included, irrespective of prior irradiation. Lesions were classified as tumour progression (TP) or pseudoprogression based on three-month radiological follow-up or histopathology. TP was assigned if progression was again shown at three months. Pseudoprogression was assigned if lesions showed stability, partial, or complete response at three months. ‘Non-classified’ lesions were those with new or changed treatment during follow-up. Results: A cohort of 98 patients with 233 lesions was included over a 13-year period; 170 lesions were considered non-classified, and 41 and 22 lesions were classified as TP and pseudoprogression respectively. This resulted in a lesion- and patient-specific incidence for pseudoprogression of 9.4% and 17.3% respectively. Due to the large number of lesions that could not be classified, as is the case in clinical practice, the reported incidence in this study is likely an underestimation and can be seen as a ‘minimum’ incidence rate. Ten pseudoprogression (45.5%) and 13 (31.7%) TP lesions were previously irradiated. Pseudoprogression occurred at a median of 2.7 months after starting ICI therapy. The only clinical feature distinguishing patients with TP from pseudoprogression was that TP patients were more likely to need dexamethasone for neurological symptoms. Conclusions: Pseudoprogression has a lesion-specific incidence rate of at least 9.4% and occurs at a median of 2.7 months after starting ICI therapy. Severe neurological symptoms requiring dexamethasone may be a clinical feature typical for TP. Full article

Background: Lung cancer has the highest morbidity and mortality of all tumors, and the development of TKI drugs targeting EGFR activating mutations has brought lung cancer treatment into the targeted era. In view of their low efficacy and susceptibility to drug resistance, there is an urgent need to find strategies to increase their efficacy and reduce the incidence of drug resistance. Methods: In this study, we examined the distribution and probability of EGFR mutations in non-small cell lung cancer patients in the cBioPortal database and compared the survival prognosis of patients with normal and abnormal EGFR, NSCLC patients treated with and without TKI, and NSCLC patients with different EGFR gene copy numbers. We established a mouse lung cancer model and examined the histomorphological characteristics of lung tissues via hematoxylin and eosin staining. Additionally, changes in the copy number of the EGFR gene and its protein expression levels were detected using RT-qPCR and Western blotting. Furthermore, we quantified the concentration of the EGFR protein using ELISA. Results: We found no significant advantage of EGFR-TKI therapy over first-line chemotherapeutic agents in patients with EGFR-abnormal NSCLC. The reason for this may be related to the abnormal EGFR gene copy number; the higher the copy number increases, the worse the survival prognosis of the patients. In molecular biology experiments, we demonstrated that ginsenoside Rg3 down-regulated the copy number of 18, 19, 20, and 21 exons and protein expression of EGFR in lung adenocarcinoma cells. The results of in vivo pharmacodynamic assays confirmed that sequential administration of ginsenoside Rg3 with TKI drugs could achieve a gainful complementary effect. Conclusions: Ginsenoside Rg3 down-regulates the copy number of EGFR important exons in EGFR-mutant cells of lung adenocarcinoma and reduces EGFR protein expression, thus providing a high gainful complementary effect in combination with EGFR-TKI. Full article

(1) Background: Occupational exposure to asbestos remains a significant public health concern due to its association with pleural cancer and other cancers. This cohort study examines the incidence of asbestos-related diseases among railway carriage maintenance workers exposed to asbestos between 1960 and 1979 in Bologna, Italy. (2) Methods: A cohort of 2197 male workers was followed from 1960 onwards, with data collected on asbestos exposure, smoking habits, and mortality outcomes. The association of asbestos exposure and smoking with the risk of pleural cancer and lung cancer was assessed using Cox proportional hazards regression models. (3) Results: This study identified a substantial burden of asbestos-related pleural cancer, with an exponential increase in risk over time since the beginning of exposure. Our results suggest the lack of a multiplicative effect of asbestos exposure and smoking on lung cancer risk. The Cox models showed a significant association between smoking and lung cancer risk, with a hazard ratio of 3.26 (95% CI: 1.10–9.64, p = 0.03), less significant for asbestos exposure, with a hazard ratio of 1.42 (95% CI: 0.66–3.06). (4) Conclusions: This study provides valuable insights into the long-term health effects of occupational asbestos exposure and underscores the complex interaction between asbestos exposure and smoking in the development of lung cancer. Full article

Background: With a high human immunodeficiency virus (HIV) adult prevalence, people living with HIV (PLHIV) in Botswana continue to experience a high burden of comorbid HIV and cancer. We sought to investigate the trends of acquired immunodeficiency syndrome (AIDS) defining cancers (ADCs), non-AIDS defining cancers (NADCs), and associated risk factors in PLHIV compared with those without HIV. Methods: We analyzed data from adults aged ≥18 years reported in Botswana National Cancer Registry and National Data Warehouse. The crude, age-standardized incidence rate (ASIR), standardized incidence ratios (SIRs) of cancers and time trends were computed. Risk factors were determined using the Cox-regression model. Results: Over a 30-year period, 27,726 cases of cancer were documented. Of these, 13,737 (49.5%) were PLHIV and 3505 (12.6%) were people without HIV and 10,484 (37.8%) had an unknown HIV status. Compared to the HIV-uninfected, the PLHIV had higher and increasing trends in the cancer incidence overall during the study period (from 44.2 to 1047.6 per 100,000; p-trend < 0.001) versus (from 1.4 to 27.2 per 100,000; p-trend < 0.001). The ASIRs also increased in PLHIV for overall ADCs, NADCs and other sub-types like cervical, lung, breast, and conjunctiva cancers (p-trend < 0.001). Further, PLHIV had elevated SIRs for cervical cancer, Kaposi sarcoma in males and some NADCs. The most common risk factors were HIV infection and female sex for ADCs incidence and advanced age and being HIV-uninfected for NADCs incidence. Conclusions: Increasing trends of ADCs and NADCs during ART expansion were observed among PLHIV compared to those without HIV highlighting a greater need for targeted effective prevention and screening strategies including the provision of access to timely HIV and cancer treatment. Full article

Lung cancer is one of the most common and deadly forms of cancer worldwide, despite sustained efforts to encourage smoking cessation and raise awareness of the risk factors. In Romania, lung cancer is a significant health challenge, being the leading cause of death caused by cancer, especially amongst men. The incidence of lung cancer in connective tissue disease (CTD) varies in different studies from 4.5% in rheumatoid arthritis (RA), to 4.4% in polymyositis or dermatomyositis, and up to 11.1% in systemic sclerosis. However, older studies have shown an increased risk of cancer in patients with rheumatoid arthritis (RA), ranging from 10% to 30% compared to the general population, particularly in those undergoing methotrexate therapy. Rheumatoid arthritis affects approximately 40 per 100,000 people annually worldwide, with a three- to four-fold higher incidence in women. Non-small cell lung cancer (NSCLC), the most common lung cancer subtype, has been linked to RA, yet the association remains poorly defined, with limited insight into the underlying molecular mechanisms. We present the case of a 61-year-old male with a 49-pack-year smoking history and a known diagnosis of rheumatoid arthritis, currently managed with methotrexate therapy. He was admitted for evaluation due to a progressive decline in general condition, characterized by worsening dyspnea and chest pain, symptoms that had been longstanding but had markedly exacerbated over the past two weeks. Based on a chest CT performed prior to the patient’s admission to our clinic, subsequent diagnostic investigations established the diagnosis of pulmonary adenocarcinoma. The diagnostic process proved to be particularly challenging due to the presence of multiple comorbidities, which significantly impacted both the diagnostic approach and the overall clinical trajectory. Full article

Background and Objectives: Immune checkpoint inhibitors (ICIs) have emerged as groundbreaking agents in cancer therapy; however, their immune-related adverse effects, especially pulmonary toxicity, significantly limit their use. This study aimed to determine the incidence and risk factors associated with ICI-induced pulmonary toxicity. Materials and Methods: We conducted a prospective observational study involving 126 patients aged ≥18 years with malignancies treated with ICIs between April 2022 and April 2024. Patients were followed every six months over a two-year period. Clinical, laboratory, and radiological data were collected to assess pulmonary toxicity. Results: The mean age of our patients was 62.93 ± 12.94 years, and 81% were male. The ICI-related pulmonary toxicity rate was 16.7%, and the all-cause mortality rate was 68.3%. In the analysis, the conditions associated with pulmonary toxicity were the type of malignancy, the presence of lung cancer, COPD, long-term ICI use, dyspnea, cough and sputum, the pre-ICI lung nodule mass, and high blood monocyte levels. Our regression analysis results for the determination of risk factors showed a 7.70-fold increase in the presence of cough symptoms, a 4.57-fold increase in the presence of COPD, a 0.998-fold increase for every 1 unit decrease in lymphocyte count, and an 11.75-fold increase in risk for a monocyte count of 130 or less. Conclusions: Our study’s findings suggest that patients with identifiable risk factors for pulmonary toxicity should undergo closer monitoring and early diagnostic evaluation during ICI therapy to reduce morbidity and mortality. Full article

Background/Objectives: Lung cancer remains a major cause of cancer-related mortality, with regional differences in incidence and patient characteristics. This study aimed to verify and quantify a perceived dramatic increase in lung cancer cases at a Romanian center, identify distinct patient phenotypes using unsupervised machine learning, and characterize contributing factors, including demographic shifts, changes in the healthcare system, and geographic patterns. Methods: A comprehensive retrospective analysis of 4206 lung cancer patients admitted between 2013 and 2024 was conducted, with detailed molecular characterization of 398 patients from 2023 to 2024. Temporal trends were analyzed using statistical methods, while k-means clustering on 761 clinical features identified patient phenotypes. The geographic distribution, smoking patterns, respiratory comorbidities, and demographic factors were systematically characterized across the identified clusters. Results: We confirmed an 80.5% increase in lung cancer admissions between pre-pandemic (2013–2020) and post-pandemic (2022–2024) periods, exceeding the 51.1% increase in total hospital admissions and aligning with national Romanian trends. Five distinct patient clusters emerged: elderly never-smokers (28.9%) with the highest metastatic rates (44.3%), heavy-smoking males (27.4%), active smokers with comprehensive molecular testing (31.7%), young mixed-gender cohort (7.3%) with balanced demographics, and extreme heavy smokers (4.8%) concentrated in rural areas (52.6%) with severe comorbidity burden. Clusters demonstrated significant differences in age (p < 0.001), smoking intensity (p < 0.001), geographic distribution (p < 0.001), as well as molecular characteristics. COPD prevalence was exceptionally high (44.8–78.9%) across clusters, while COVID-19 history remained low (3.4–8.3%), suggesting a limited direct association between the pandemic and cancer. Conclusions: This study presents the first comprehensive machine learning-based stratification of lung cancer patients in Romania, confirming genuine epidemiological increases beyond healthcare system artifacts. The identification of five clinically meaningful phenotypes—particularly rural extreme smokers and age-stratified never-smokers—demonstrates the value of unsupervised clustering for regional healthcare planning. These findings establish frameworks for targeted screening programs, personalized treatment approaches, and resource allocation strategies tailored to specific high-risk populations while highlighting the potential of artificial intelligence in identifying actionable clinical patterns for the implementation of precision medicine. Full article

Lung-cancer incidence is projected to rise by 50% by 2035, underscoring the need for accurate yet accessible risk-stratification tools. We trained a Bayesian neural network on 300 annotated chest-CT scans from the public LIDC–IDRI cohort, integrating clinical metadata. Hamiltonian Monte-Carlo sampling (10 000 posterior draws) captured parameter uncertainty; performance was assessed with stratified five-fold cross-validation and on three independent multi-centre cohorts. On the locked internal test set, the model achieved 99.0% accuracy, AUC = 0.990 and macro-F1 = 0.987. External validation across 824 scans yielded a mean AUC of 0.933 and an expected calibration error $<0.034$, while eliminating false positives for benign nodules and providing voxel-level uncertainty maps. Uncertainty-aware Bayesian deep learning delivers state-of-the-art, well-calibrated lung-cancer risk predictions from a single CT scan, supporting personalised screening intervals and safe deployment in clinical workflows. Full article

In recent years, an increasingly important role in the etiopathogenesis of lung cancer has been attributed to genetic predisposition. Current genetic research suggests that the increased risk of this cancer may be due to gene polymorphism within repair genes. In the case of lung cancer, observations about genes involved in the DNA repair system by cutting bases of nitrogen—base excision repair (BER)—seem to be interesting. Most attention has been devoted to the XRCC1 gene, which coordinates the various stages of BER. The aim of this study was to assess the role of the single nucleotide polymorphism Arg399Gln in the XRCC1 gene as a factor influencing the risk of lung cancer. The study involved 118 patients with non-small cell lung cancer (NSCLC). The control group consisted of 60 people who did not have cancer. The study proved that the polymorphism of the XRCC1 gene is characterized by a statistically significant relationship with the onset of cancer. There were no statistically significant differences between the Arg399Gln polymorphism of the XRCC1 gene and risk factors for non-small cell lung cancer, such as age, sex, smoking and its duration, or place of residence, as well as between the histological type of the tumor or its severity. Detailed analysis of three genotypes—Arg/Arg, Arg/Gln, and Gln/Gln—showed that the incidence of particular genotypes in the group of patients was, respectively, 16.10%, 27.12%, and 58.78%. In the case of the Gln/Gln genotype, the most common associated histopathological type was squamous cell carcinoma, and in the case of adenocarcinoma, the most common genotype was Arg/Arg. It was estimated that each Arg allele reduced the chance of tumor occurrence to 0.48 times the reference value, i.e., the Gln/Gln genotype class for the Arg/Gln genotype and the Arg/Gln genotype for the Arg/Arg genotype. The relationship between the male sex and the occurrence of cancer remained insignificant, in contrast to the presence of nicotinism. Studies suggest that the Arg399Gln polymorphism of the XRCC1 gene has limited prognostic significance in non-small cell lung cancer. Full article

Colorectal cancer (CRC) is ranked as the third most lethal of all cancers in the USA, following prostate and lung malignancy in men, and breast and lung malignancy in women, respectively. The risk factors for developing colorectal cancer fall into two categories: modifiable risk factors (obesity and physical inactivity, diet, smoking, alcohol, medications, diabetes, and insulin resistance) and non-modifiable risk factors (race and ethnicity, sex, age, and inflammatory bowel disease). The standard therapeutic approaches to the treatment of colorectal cancer have led to a reduction in the burden of colorectal cancer in the USA, with national statistics revealing a reduction in both the incidence and death rates. At the same time, five-year survival rates have also greatly improved. However, associated with these standard treatments are complications, which have become a burden (physical and emotional, financial, and economic burdens, and disability-adjusted life years), affecting the quality of life of CRC patients. This paper discusses the standard therapeutic approaches to managing colorectal cancer, the associated complications, and their management. In addition, a summary of the newly introduced therapeutic approaches for treating CRC, reported improvement in effectiveness over existing strategies and corresponding reduction in therapeutic complications will be discussed. Full article

Introduction: Computed tomography-guided biopsies (CTGB) are essential in diagnosing various conditions, particularly in respiratory medicine, with lung cancer being a primary focus. A significant complication associated with CTGB is pneumothorax, which can occur in up to 26% of cases. At Northumbria Healthcare NHS Foundation Trust, a large interventional service collaborates closely with radiologists and respiratory physicians. This study aims to evaluate the incidence of pneumothorax following CTGB. Methods: A retrospective service review was conducted on all lung parenchymal CTGBs performed between April 2011 and July 2023, with approval from the local information governance. Demographic data and clinical outcomes were analyzed using descriptive statistics. Continuous variables are presented as medians with interquartile ranges (IQR), while categorical variables are reported as frequencies and percentages. Results: A total of 1492 CT-guided lung biopsies were analyzed. The median age of patients was 72 years (IQR 10.5), and 50.9% were male. Pneumothorax occurred in 23.8% (n = 355) of cases. Of these, 159 (44.8%) were detected on post-biopsy CT scans. The average number of pleural passes was 1.8 (range 1–4). Among those with pneumothorax, 53.6% had radiologically evident emphysema. The median forced expiratory volume in 1 s (FEV1) was 1.97 L (IQR 1.04). Sixty-seven percent (n = 234) of patients had no pleural contact, and the median lesion size was 26 mm (IQR 24). Seventy-two percent (n = 255) of lesions with pneumothoraces were less than 3 cm deep. Forty-four percent of biopsies were performed using 18 French gauge tru-cut needles. Of the 355 pneumothoraces, 89% (n = 315) were managed conservatively, with 42 requiring pleural intervention (41 small-bore 12 Fr intercostal chest drains and one pleural vent). Symptoms were initially present in 40 cases, and two cases developed symptoms up to 7 days post-procedure. Conclusions: The incidence of pneumothorax is consistent with expected rates, with more occurrences observed in biopsies of smaller lesions lacking pleural contact, lesions with surrounding emphysema, and cases requiring multiple pleural passes. FEV1 does not appear to influence the risk of pneumothorax. Conservative management is generally effective, without significant complications. Full article

Background/Objectives: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases, with an increasing incidence in patients over 65 years. Although immune-checkpoint inhibitors (ICIs) have transformed the treatment landscape, elderly patients remain underrepresented in pivotal clinical trials, highlighting the need for real-world evidence on their efficacy and tolerability in this population. Methods: We conducted a multicenter, retrospective study of advanced NSCLC patients treated with ICI alone or in combination with chemotherapy between April 2017 and December 2023. Patients were categorized into three age groups: ≤65 (younger group, YG), 66–79 (older group, OG), and ≥80 years (advanced older group, AOG). Efficacy and safety outcomes were compared across groups. Results: Among 452 patients, 221 (48.9%) were in the OG and 36 (8%) in the AOG. Median progression-free survival (PFS) was similar across groups: 8.3 months (YG), 8.4 months (OG; p = 0.872 vs. YG), and 10.5 months (AOG; p = 0.628 vs. YG). Median overall survival (OS) showed a non-significant trend favoring younger patients: 15.1 months (YG), 10.3 months (OG; p = 0.076 vs. YG), and 12.5 months (AOG; p = 0.070 vs. YG). Grade ≥ 3 immune-related adverse events (irAEs) occurred in 9.7% (YG), 5.9% (OG), and 8.3% (AOG). In patients ≥ 66 years, irAEs were associated with longer PFS (18.1 vs. 6 months; p < 0.001). Conclusions: ICIs demonstrated comparable PFS and OS across age groups, including patients aged ≥ 80 years. Chronological age did not increase irAE incidence. The development of irAEs may serve as a favorable prognostic factor in elderly patients. Full article