Ioannis Gkiozos

The pituitary gland is an uncommon site of tumor metastasis and is predominantly associated with malignancies of the lung and breast. Metastatic involvement of the pituitary gland in lung cancer (LC) typically indicates advanced disease and is associated with poor prognosis and pituitary insufficiency, which often remains underdiagnosed and significantly affects quality of life and survival. We present four cases of pituitary metastasis (PM) originating from LC, characterized by distinct histological subtypes, variable timing from initial diagnosis, and diverse clinical manifestations. Clinical presentation was heterogeneous: two patients had involvement of both pituitary lobes with multiple pituitary hormone deficiencies, one had anterior lobe involvement with anterior pituitary deficiency following immune checkpoint inhibitor-associated hypophysitis, and one remained asymptomatic. Therapeutic approaches included partial surgical resection followed by radiotherapy in two patients and radiotherapy alone in the other two; all patients continued systemic antineoplastic therapy and received hormone replacement as indicated. Mean overall survival was 7.5 months. PM can occur across all histological subtypes of LC and typically signifies advanced disease with poor prognosis. Early identification and appropriate management of hypopituitarism may improve quality of life and clinical outcomes.

Background: Lung cancer (LC) is a complex-to-treat disease and remains the leading cause of cancer-related mortality. Methods: Our aim was to investigate the prognostic role of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR) in patients with LC. In this retrospective study, examining the period between 1 June 2020 and 31 May 2024, we recorded consecutive patients who presented to the Department of Respiratory Medicine, University Hospital of Patras, Patras, Greece, and received a first diagnosis of LC. The primary outcome was mortality risk analysis based on NLR, PLR, and MLR at diagnosis. Secondary outcomes included associations of tumor, node, metastasis (TNM) staging, and smoking with NLR, PLR, and MLR at diagnosis. Results: We identified 353 patients with a first diagnosis of LC. The mean age ± SD at the time of diagnosis was 68.1 ± 9.1 years. Most patients were male (77.9%, n = 275) and current or ex-smokers (58.1%, n = 205, and 39.1%, n = 138, respectively). Histological diagnosis was non-small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), and not otherwise specified (NOS) in 67.1% (n = 237), 29.8% (n = 105), and 3.1% (n = 11) of patients, respectively. Adenocarcinoma NSCLC was more common (40.2%, n = 142) compared to squamous NSCLC (25.5%, n = 90). In 12.9% of patients, we identified EGFR, KRAS, ALK, or BRAF molecular driver mutations, while PD-L1 expression was positive in 20.7% of patients. The majority of enrolled patients presented with advanced stage IV LC at diagnosis (63.2%, n = 223). Kaplan–Meier curves showed that patients with higher than the median NLR and PLR at diagnosis were associated with significantly higher mortality risk compared to those with lower than the median [HR: 0.58, (95% CI: 0.42 to 0.81) p = 0.0009 and HR: 0.71, (95% CI: 0.53 to 0.95) p = 0.02, respectively], while no differences in mortality risk were observed between patients with higher versus lower than the median MLR [HR: 0.84, (95% CI: 0.63 to 1.12) p = 0.22]. With regard to secondary outcomes, no associations between higher versus lower than the median NLR, PLR, or MLR values and TNM staging [4.0 (95% CI: 4.0–4.0) vs. 4.0 (95% CI: 4.0–4.0), p = 0.95, 4.0 (95% CI: 4.0–4.0) vs. 4.0 (95% CI: 4.0–4.0), p = 0.09, 4.0 (95% CI: 4.0–4.0) vs. 4.0 (95% CI: 4.0–4.0), p = 0.4, respectively], as well as smoking status [70 (95% CI: 60–80) vs. 80 (95% CI: 60–80), p = 0.10, 70 (95% CI: 60–80) vs. 80 (95% CI: 60–80), p = 0.46, 80 (95% CI: 60–80) vs. 70 (95% CI: 60–80), p = 0.96, respectively] were reported. Conclusions: NLR and PLR could serve as reliable and clinician-friendly prognosticators of clinical outcomes in patients with LC. Further validation cohorts are sorely needed to prove this notion.

Immune checkpoint inhibitors (ICIs) redefined the therapeutics of non-small cell lung cancer (NSCLC), leading to significant survival benefits and unprecedented durable responses. However, the majority of the patients develop resistance to ICIs, either primary or acquired. Establishing a definition of primary resistance to ICIs in different clinical scenarios is challenging and remains a work in progress due to the changing landscape of ICI-based regimens, mainly in the setting of early-stage NSCLC. The mechanisms of primary resistance to ICIs in patients with NSCLC include a plethora of pathways involving a cross-talk of the tumor cells, the tumor microenvironment and the host, leading to the development of an immunosuppressive phenotype. The optimal management of patients with NSCLC following primary resistance to ICIs represents a significant challenge in current thoracic oncology. Research in this field includes exploring other immunotherapeutic approaches, such as cancer vaccines, and investigating novel antibody–drug conjugates in patients with NSCLC.

Background: Large cell neuroendocrine carcinoma (LCNEC) presents significant treatment challenges due to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC. Methods: In this non-randomized study, patients with metastatic LCNEC were prospectively enrolled and assigned to receive either standard chemotherapy plus atezolizumab followed by maintenance with atezolizumab or standard chemotherapy alone. The primary outcomes measured were 12- and 24-month survival rates, progression-free survival (PFS), and overall survival (OS) between the two groups. Results: Of the 22 patients screened, 17 met the inclusion criteria and received either atezolizumab plus platinum-based chemotherapy (n = 10) or chemotherapy alone (n = 7). After a median follow-up of 23.3 months, the 12-month survival rate was 57.1% (95% CI: 32.6–100%) and 14.3% (95% CI: 2.33–87.7%) for the atezolizumab and the chemotherapy-only groups, respectively. The survival benefit for the atezolizumab group was sustained at 24 months (45.7% vs. 14.3%). Overall survival was significantly higher for the atezolizumab group, and PFS was non-significantly associated with the addition of atezolizumab (log-rank p = 0.04 and 0.05, respectively). Conclusions: This pilot study suggests that the addition of atezolizumab to standard platinum-based chemotherapy may provide a substantial survival benefit compared with chemotherapy alone in the first-line treatment of metastatic LCNEC.

Background: Lung Cancer Screening (LCS) is an evolving field with variations in its implementation in various countries. There are only scarce data from National LCS programs. Aim: We aim to provide an up-to-date overview of the current evidence regarding the use of biomarkers in LCS. Materials and Methods: A multidisciplinary Task Force experts’ panel collaborated and conducted a systematic literature search, followed by screening, review and synthesis of available evidence. Results: Biomarkers in LCS could be used to improve risk stratification in high-risk participants, improve clarification regarding indeterminate lung nodules and avoid overdiagnosis in suspicious lung findings. Currently, there seem to be promising biomarkers (blood/serum/breath) that have been studied in various trials; however, there is still a lack of solid evidence in clinical validation that would pave the way for their integration into LCS programs. Conclusions: Biomarkers are the next logical step in improving the LCS pathway and its efficiency by playing an adjuvant role in a minimally invasive way. National LCS programs and pilot studies should integrate biomarkers to validate their accuracy in real-life LCS participants.

Conventional cancer clinical trials can be time-consuming and expensive, often yielding results with limited applicability to real-world scenarios and presenting challenges for patient participation. Real-world data (RWD) studies offer a promising solution to address evidence gaps and provide essential information about the effects of cancer treatments in real-world settings. The distinction between RWD and data derived from randomized clinical trials lies in the method of data collection, as RWD by definition are obtained at the point of care. Experimental designs resembling those used in traditional clinical trials can be utilized to generate RWD, thus offering multiple benefits including increased efficiency and a more equitable balance between internal and external validity. Real-world data can be utilized in the field of pharmacovigilance to facilitate the understanding of disease progression and to formulate external control groups. By utilizing prospectively collected RWD, it is feasible to conduct pragmatic clinical trials (PCTs) that can provide evidence to support randomized study designs and extend clinical research to the patient’s point of care. To ensure the quality of real-world studies, it is crucial to implement auditable data abstraction methods and develop new incentives to capture clinically relevant data electronically at the point of care. The treatment landscape is constantly evolving, with the integration of front-line immune checkpoint inhibitors (ICIs), either alone or in combination with chemotherapy, affecting subsequent treatment lines. Real-world effectiveness and safety in underrepresented populations, such as the elderly and patients with poor performance status (PS), hepatitis, or human immunodeficiency virus, are still largely unexplored. Similarly, the cost-effectiveness and sustainability of these innovative agents are important considerations in the real world.

Background: Lung cancer is associated with a high incidence of mortality worldwide. Molecular mechanisms governing the disease have been explored by genomic studies; however, several aspects remain elusive. The integration of genomic profiling with in-depth proteomic profiling has introduced a new dimension to lung cancer research, termed proteogenomics. The aim of this review article was to investigate proteogenomic approaches in lung cancer, focusing on how elucidation of proteogenomic features can evoke tangible clinical outcomes. Methods: A strict methodological approach was adopted for study selection and key article features included molecular attributes, tumor biomarkers, and major hallmarks involved in oncogenesis. Results: As a consensus, in all studies it becomes evident that proteogenomics is anticipated to fill significant knowledge gaps and assist in the discovery of novel treatment options. Genomic profiling unravels patient driver mutations, and exploration of downstream effects uncovers great variability in transcript and protein correlation. Also, emphasis is placed on defining proteogenomic traits of tumors of major histological classes, generating a diverse portrait of predictive markers and druggable targets. Conclusions: An up-to-date synthesis of landmark lung cancer proteogenomic studies is herein provided, underpinning the importance of proteogenomics in the landscape of personalized medicine for combating lung cancer.

Background: The widespread use of chest CT has increased the number of detected pulmonary nodules. Nodules with intermediate risk of malignancy warrant further evaluation with PET-CT or sampling. Although sampling with conventional bronchoscopy presents lower complication rates compared to transthoracic needle biopsy (TTNB), it is limited by the inability to reach distal airways. To overcome this shortcoming, a new bronchoscopic technique named robotic bronchoscopy (RB) has emerged. Methods: A literature review was used to clarify the rationale behind RB emergence, describe RB procedure, and summarize data regarding its efficacy and safety. Results: The FDA has approved three RB platforms for clinical use. RB is safe, presenting a mortality and complication rate of 0% and 0–8.1%, respectively. Common complications include pneumothorax (0–5.7%) and minor bleeding (0–3.2%). However, its diagnostic yield remains lower than that of TTNB. Conclusions: RB is a promising bronchoscopic technique that aims to overcome the limitations of conventional bronchoscopy and improve upon the current techniques of guided bronchoscopy for the investigation of pulmonary nodules. Despite the lower complication rate, current evidence suggests a lower diagnostic yield compared to TTNB. Additional studies are required to adequately evaluate the role of RB in the diagnosis of pulmonary nodules.

Background: Large-cell neuroendocrine carcinoma presents significant treatment challenges owing to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC. Methods: In this non-randomized study, patients with metastatic LCNEC were treated with ei-ther standard chemotherapy plus atezolizumab or standard chemotherapy alone. The primary outcomes measured were progression-free survival (PFS) and overall survival (OS), with an ex-ploratory analysis of miR375 in plasma as a potential biomarker. Results: Of the 22 screened patients, 17 met the inclusion criteria and were stratified into the atezolizumab and chemotherapy (n=10) or chemotherapy alone(n=7) groups. After a median follow-up of 23.3 months, the 12-month survival rate for the atezolizumab group was 57.1% (95% CI: 32.6%-100%) and 45.7% at 24 months (95% CI: 22.4%-93.2%). In contrast, the chemotherapy group had a 14.3% survival rate at both 12 and 24 months (95% CI: 2.33%-87.7%). The log-rank test for survival showed a statistically significant difference in the atezolizumab-treated group (chi-squared = 4, df = 1, p = 0.04). A non-significant correlation was found between disease pro-gression and elevated levels of miR375. Conclusions: This pilot study suggests that atezolizumab combined with chemotherapy may be effective in treating metastatic LCNEC. The non-significant correlation between plasma miR375 levels and disease progression suggests its biomarker potential, warranting further validation research.

Conventional cancer clinical trials can be time-consuming and expensive, often yielding results with limited applicability to real-world scenarios and presenting challenges for patient participation. Real-world data (RWD) studies offer a promising solution to address evidence gaps and provide essential information about the effects of cancer treatments in real-world settings. Defining RWD based on its original intent, which is the collection of data at the point of care for clinical purposes, can distinguish it from conventional clinical trial data. RWD can be generated using experimental designs that resemble those used in conventional clinical trials, but with several advantages, such as improved efficiency and a better balance between internal and external validity. RWD can support pharmacovigilance, insights into disease progression, and the development of external control groups. Prospective RWD collection enables evidence generation based on pragmatic clinical trials (PCTs) that support randomized study designs and expand clinical research to the point of care. To ensure the quality of real-world studies, it is crucial to implement auditable data abstraction methods and develop new incentives to capture clinically relevant data electronically at the point of care. The treatment landscape is constantly evolving, with the integration of front-line immune checkpoint inhibitors (ICIs), either alone or in combination with chemotherapy, affecting subsequent treatment lines. Real-world effectiveness and safety in underrepresented populations, such as the elderly, patients with poor performance status (PS), hepatitis, or human immunodeficiency virus-infected patients, are still largely unexplored. Similarly, the cost-effectiveness and sustainability of these innovative agents are important considerations in the real world.