Pleural Malignancies Research Articles

Unravelling switch/sucrose non-fermentable (SWI-SNF) complex-deficient thoracic tumours: a clinicopathological comparative on undifferentiated tumours and non-small cell lung carcinomas with BRG1 and BRM deficiency

AimsThis study was undertaken to compare and expand the clinicopathological characteristics of SMARCA4-deficient thoracic undifferentiated tumour (SMARCA4-dUT) and switch/sucrose non-fermentable-deficient non-small cell lung carcinomas (SWI/SNF-dNSCLC) and to address cases with...

Postoperative early laboratory changes and follow-up process of patients underwent hyperthermic intrathoracic chemotherapy

BackgroundThe aim of combining hyperthermic intrathoracic chemotherapy (HITHOC) with surgery is to achieve local control in patients with pleural malignancies. Liver and kidney dysfunction resulting from this procedure have been reported in the literature. The objective of the study is to examine whether the laboratory abnormalities observed during the initial period persist until day 30.MethodsThe study conducted a retrospective analysis of the blood glucose levels, renal function markers, and hepatic function markers of 30 patients who underwent pleurectomy-decortication and HITHOC for pleural mesothelioma from January 2010 to April 2022. The measurements were taken in the postoperative period on the first four and 30th days. The study analyzed the initial and final laboratory results caused by the procedure.ResultsOut of the total of 30 patients, 29, 28, 14, and 12 patients had elevated glucose levels on the first four days after the surgery, respectively. There was no association between glucose abnormalities and preoperative-postoperative diabetes mellitus. A minority of patients experienced atypical alterations in kidney and liver functions during the initial postoperative period. There was no apparent relationship between the renal and hepatic functions in the early and late periods after the surgery.ConclusionAlthough there were fluctuations in glucose levels and renal and hepatic functions in the early period after surgery, there were no persistent alterations in these parameters by day 30. Elevated glucose levels during the early period were not associated with the development of newly diagnosed diabetes mellitus after surgery. The findings of our study provide evidence that HITHOC is a favorable and well-tolerated treatment option for mesothelioma.

A common secretomic signature across epithelial cancers metastatic to the pleura supports IL-6 axis therapeutic targeting.

Many cancers metastasize to the pleura, resulting in effusions that cause dyspnea and discomfort. Regardless of the tissue of origin, pleural malignancies are aggressive and uniformly fatal, with no treatment shown to prolong life. The pleural mesothelial monolayer is joined by tight junctions forming a contained bioreactor-like space, concentrating cytokines and chemokines secreted by the mesothelium, tumor, and infiltrating immune cells. This space represents a unique environment that profoundly influences tumor and immune cell behavior. Defining the pleural secretome is an important step in the rational development localized intrapleural immunotherapy. We measured cytokine/chemokine content of 252 malignant pleural effusion (MPE) samples across multiple cancers using a 40-analyte panel and Luminex multiplexing technology. Eleven analytes were consistently present in concentrations ≥ 10.0 pM: CXCL10/IP10 (geometric mean = 672.3 pM), CCL2/MCP1 (562.9 pM), sIL-6Rα (403.1 pM), IL-6 (137.6 pM), CXCL1/GRO (80.3 pM), TGFβ1 (76.8 pM), CCL22/MDC (54.8 pM), CXCL8/IL-8 (29.2 pM), CCL11/Eotaxin (12.6 pM), IL-10 (11.3 pM), and G-CSF (11.0 pM). All are capable of mediating chemotaxis, promotion of epithelial to mesenchymal transition, or immunosuppression, and many of are reportedly downstream of a pro-inflammatory cytokine cascade mediated by cytokine IL-6 and its soluble receptor. The data indicate high concentrations of several cytokines and chemokines across epithelial cancers metastatic to the pleura and support the contention that the pleural environment is the major factor responsible for the clinical course of MPE across cancer types. A sIL-6Rα to IL-6 molar ratio of 2.7 ensures that virtually all epithelial, immune and vascular endothelial cells in the pleural environment are affected by IL-6 signaling. The central role likely played by IL-6 in the pathogenesis of MPE argues in favor of a therapeutic approach targeting the IL-6/IL-6R axis.

Anaesthetic and perioperative considerations for extrapleural pneumonectomy and extended pleurectomy/decortication: a scoping review protocol

IntroductionExtrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant pleural tumours such as pleural mesothelioma, non-mesothelioma pleural malignancies such as thymoma...

Update in the Treatment of Pleural Tumors: Robotic Surgery Combined with Hyperthermic Intrathoracic Chemotherapy.

(1) Background. Intracavitary hyperthermic chemotherapy (HITHOC) remains part of the complex mosaic that is the multimodal approach for advanced stage thymoma and pleural malignancies. However, robotic pleurectomy/removal of pleural lesions in combination with intrathoracic chemotherapy is not currently being investigated. The aim of this study is to evaluate the safety of robotic pleurectomy/removal of relapses and HITHOC in patients with pleural recurrence of thymoma or MPM. (2) Methods: The data of nine consecutive patients affected by thymoma relapses or MPM who underwent robotic surgery in combination with HITHOC from February 2017 to November 2022 were collected and analyzed. Surgery performed prior to intrathoracic infusion of high-temperature chemotherapy consisted of removal of recurrences (three patients) or pleurectomy (six patients). All surgeries were performed with a four-port, fully robotic technique. (3) Results: No intraoperative complications occurred. No renal complications related to infusion were recorded. One patient, who underwent pleurectomy for MPM, had a grade II Clavien-Dindo postoperative complication. Oncological follow-up showed results in line with the literature. (4) Conclusions: With the limitation of the small number of patients, robotic surgery in combination with HITHOC seems to be safe in patients with pleural relapses of thymoma and early-stage MPM.

Primary Lung and Pleural Malignancies in Children: Imaging of a Case Series

Primary Lung and Pleural Malignancies in Children: Imaging of a Case Series

Physician-led thoracic ultrasound-guided biopsy; a district general hospital perspective.

Physician-led thoracic ultrasound (TUS)-guided biopsies provide a prompt route to tissue diagnosis in pleural and peripheral lung malignancies. This retrospective study reviews the diagnostic performance and safety of this approach in a UK District General Hospital. Time to biopsy, diagnostic yield and complication rate were analysed in a cohort of 49 patients undergoing ultrasound-guided tissue sampling between September 2019 and December 2022. Fifty-one TUS-guided biopsies were attempted. Mean time from decision to biopsy was 5 days. The overall diagnostic yield was 82%. Complication rate was low; 3 minor adverse effects were reported which led to no change in routine care. This single centre retrospective study shows that physician-led TUS-guided biopsy provides a safe and timely method of obtaining a tissue diagnosis in thoracic malignancy. It offers an alternative to computer tomography (CT)-guided or thoracoscopic biopsies and should be considered in selected patients where local procedural expertise exists.

Anesthetic Aspects of Cytoreductive Surgery and Hyperthermic Intrathoracic Chemotherapy (HITHOC) in Treatment of Pleural Malignancies - Experiences from IORS

Background: Cytoreductive surgery (CRS) with hyperthermic intrathoracic chemotherapy (HITHOC) is a procedure that includes surgical removal of all visible tumor implants and intrathoracic application of gradually heated cytostatic solution. Numerous changes in hemodynamic, respiratory, core body temperature and metabolic parameters are possible during this complex procedure. The aim of this retrospective study was to analyze pathophysiological changes which occur during CRS + HITHOC procedure, and to suggest efficient strategies for perioperative patient care that might reduce complication rate. Methods: The study included 7 patients who underwent CRS + HITHOC in our cancer center. Enhanced Recovery After Surgery (ERAS) guideline for Thoracic Surgery was applied to all patients. Data on intraoperative hemodynamics (mean arterial pressure, stroke volume, heart rate, cardiac output) and temperature variations were collected from medical records and analyzed in three timelines: during the CRS phase, at the beginning, and the end of cytostatic perfusion. Occurrence of respiratory, renal, and cardiac complications was monitored. Results: All patients were respiratory stable during one-lung ventilation, with adequate gas exchange. Hemodynamic stability was compromised at the beginning of cytostatic perfusion, with significant decrease of mean arterial pressure and stroke volume. Two patients required vasopressor support. Average core body temperature was satisfactory in all patients. Coagulation disorders and acute renal failure were not recorded in postoperative period. One patient developed atrial fibrillation which was successfully pharmacologically restored. Conclusion: Our results indicate that goal directed fluid management following ERAS protocol, with maintaining hemodynamic stability and normothermia, could prevent perioperative complications during HITHOC procedure.

The Excretion of Cisplatin after Hyperthermic Intrathoracic Chemotherapy.

Hyperthermic intrathoracic chemotherapy (HITOC) is an additional intraoperative treatment option within the multimodality therapy of pleural malignancies. A chemotherapy perfusion with high-dose cisplatin is performed over a period of 60 min after surgical cytoreduction to improve local tumour control through the eradication of residual tumour cells. Although HITOC is increasingly used, there is only little scientific evidence about the necessary safety measures after HITOC. Therefore, the objective of this study was an analysis of cisplatin excretion via various body fluids after HITOC, with the aim of providing recommendations on occupational health and safety. Five patients undergoing HITOC were included. Before and after the HITOC, as well as during the following days, serum, urine, and bronchial secretion, as well as pleural effusion, were sampled. The platinum levels in the samples were measured using ICP-MS (inductively coupled plasma-mass spectrometry). Immediately after the HITOC, the mean levels of cisplatin increased dramatically in the serum (from 0.79 to 1349 µg/L), urine (from 3.48 to 10,528 µg/g creatinine), and bronchial secretion (from 0.11 to 156 µg/L). Thereafter, the cisplatin levels dropped to 133 µg/L in the serum and 994 µg/g creatinine in the urine within nine days after the HITOC. The AUC ratio shows 59% of the cisplatin being excreted via the urine after 48 h. The sampling of pleural effusion started 24 h after the HITOC, and the cisplatin levels decreased from 618 to 93 µg/L within nine days. Although the cisplatin levels in the body fluids of HITOC patients are much lower compared to patients receiving intravenous chemotherapy, a significant amount of cisplatin is excreted via these body fluids. Consequently, safety precautions must be implemented in the post-HITOC care of patients to avoid occupational exposure to cisplatin.

Hyperthermic intrapleural chemotherapy: an update.

The safety and efficacy of hyperthermic intrathoracic chemotherapy (HITHOC) as an adjunct to cytoreductive surgery (CRS) in pleural malignancies has been well demonstrated. This is most often described in cases of mesothelioma, thymoma, or other secondary pleural metastases. The utilization of a direct cytotoxic agent with increased penetration secondary to a hyperthermic environment is especially beneficial in pleural malignancy as a microscopic resection remains immensely challenging. Despite favorable outcomes with a limited associated risk profile, there persists a variety in utilization and technique of HITHOC described in current literature. National Comprehensive Cancer Network (NCCN) guidelines state that though intraoperative adjuvant therapies such as HITHOC have been studied, they remain of unclear benefit and definitive recommendations do not currently exist. This ambiguity limits the standardization of HITHOC, thus hindering its further application in a patient population with exceedingly poor outcomes within current guideline-based therapy. As the prevalence of pleural malignancies necessitating CRS with adjuvant HITHOC remains quite low, we believe a task force initiative to further investigate the role of HITHOC in surgical management of pleural malignancies would enable wider utility of this promising technique. Additionally, we propose that the creation of a pleural cancer index could aid in standardization of HITHOC in those with pleural malignancy.

Pleural Neoplasms—What Could MRI Change?

The primary pleural neoplasms constitute around 10% of the pleural tumors. The currently recommended method for their imaging is CT which has been shown to have certain limitations. Strong development of the MRI within the last two decades has provided us with a number of sequences that could potentially be superior to CT when it comes to the pleural malignancies’ detection and characterization. This literature review discusses the possible applications of the MRI as a diagnostic tool in patients with pleural neoplasms. Although selected MRI techniques have been shown to have a number of advantages over CT, further research is required in order to confirm the obtained results, broaden our knowledge on the topic, and pinpoint the sequences most optimal for pleural imaging, as well as the best methods for reading and analysis of the obtained data.

Anatomical Targeting of Anticancer Drugs to Solid Tumors Using Specific Administration Routes: Review.

Despite remarkable recent progress in developing anti-cancer agents, outcomes of patients with solid tumors remain unsatisfactory. In general, anti-cancer drugs are systemically administered through peripheral veins and delivered throughout the body. The major problem with systemic chemotherapy is insufficient uptake of intravenous (IV) drugs by targeted tumor tissue. Although dose escalation and treatment intensification have been attempted in order to increase regional concentrations of anti-tumor drugs, these approaches have produced only marginal benefits in terms of patient outcomes, while often damaging healthy organs. To overcome this problem, local administration of anti-cancer agents can yield markedly higher drug concentrations in tumor tissue with less systemic toxicity. This strategy is most commonly used for liver and brain tumors, as well as pleural or peritoneal malignancies. Although the concept is theoretically reasonable, survival benefits are still limited. This review summarizes clinical results and problems and discusses future directions of regional cancer therapy with local administration of chemotherapeutants.

Racial disparities in utilization of palliative care among inpatients admitted for lung cancer.

e24166 Background: Multiple national database-based studies have shown that Black and Hispanic patients are less likely to receive palliative care options at end-of-life (EOL) inpatient care leading to higher costs and poorer quality of life. To the best of our knowledge, there is no reported data specifically considering lung and pleural malignancies. Methods: We analyzed hospitalizations across the United States in 2019 from the National Inpatient Sample dataset, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. We identified adult non-emergent hospitalizations with ‘malignant neoplasm of the lung and bronchus’ (including mesothelioma) listed as the principal reason for hospitalization using the International Classification of Diseases, 10th revision, clinical modification codes C34.0, C34.1, C34.2, C34.3, C34.8, C34.9, and their sub-branches. StataCorp Stata software was used to extract data and compute mortality and palliative care consult utilization among various demographic factors such as sex, age, race, and payer status. Results: Of 67,425 total hospitalizations, 9.4% resulted in mortality. Of these 6338 patients that died, 73.1% were White, 13% Black, 5.8% Hispanic, 3.9% Asians/Pacific Islanders, 0.6% Native Americans, and 3.3% were other races. Palliative care was consulted in 63% of the patients whose admission resulted in death. 64.9% of the White patients, 58.6% of the Black patients, 62.6% of Hispanic patients, 67.7% of Asians/Pacific Islanders, 60% Native Americans, and 59.6% of other races were offered palliative care prior to their death. The average age among the admissions which resulted in death was 69.03 years. Conclusions: While most admissions resulting in mortality were among the White population, there was still a clear discrepancy in the number of Black patients on whom palliative care was consulted. Possible reasons include poor healthcare literacy, physician mistrust, and cultural preferences. Clinicians should consider and suggest early palliative care consultation in the care of Black patients and other minority racial groups to improve the quality of EOL care.

In vivo spectroscopic evaluation of human tissue optical properties and hemodynamics during HPPH-mediated photodynamic therapy of pleural malignancies.

Dosimetry for photodynamic therapy is dependent on multiple parameters. Critically, in vivo tissue optical properties and hemodynamics must be determined carefully to calculate the total delivered light dose. Spectroscopic analysis of diffuse reflectance measurements of tissues taken during a clinical trial of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a-mediated photodynamic therapy for pleural malignancies. Diffuse reflectance measurements were taken immediately before and after photodynamic therapy. Measurements were analyzed with a nonlinearly constrained multiwavelength, multi-distance algorithm to extract tissue optical properties, tissue oxygen saturation, StO2, and total hemoglobin concentration (THC). A total of 25 patients were measured, 23 of which produced reliable fits for optical property extraction. For all tissue types, StO2 ranged through [24, 100]% and [22, 97]% for pre-photodynamic therapy (PDT) and post-PDT conditions, respectively. Mean THC ranged through [ 69,152 ] μM and [ 48,111 ] μM, for pre-PDT and post-PDT, respectively. Absorption coefficients, μa, ranged through [ 0.024 , 3.5 ] cm - 1 and [ 0.039 , 3 ] cm - 1 for pre-PDT and post-PDT conditions, respectively. Reduced scattering coefficients, μs', ranged through [ 1.4 , 73.4 ] cm - 1 and [ 1.2 , 64 ] cm - 1 for pre-PDT and post-PDT conditions, respectively. There were similar pre- and post-PDT tissue optical properties and hemodynamics. The high variability in each parameter for all tissue types emphasizes the importance of these measurements for accurate PDT dosimetry.

Assessment of the value of mesothelin in differentiating between different pleural malignancies by different interventional modalities

Abstract Context Malignant mesothelioma is an insidious neoplasm, with malignant pleural mesothelioma as the most common type, which is characterized by poor prognosis in most patients owing to late presentation. The use of noninvasive markers for early diagnosis of malignant pleural mesothelioma is of great importance in decreasing the incidence of associated morbidity and mortality. Aims To evaluate the value of soluble mesothelin level in serum and pleural fluid as a diagnostic marker in patients with pleural malignancies and in differentiation of different causes of pleural effusion. Patients and methods We included 48 patients who were classified into three groups: group A (mesothelioma), group B (metastatic malignancy), and group C (transudative effusion). History taking, clinical examination, and laboratory assessment were performed in all groups, in addition to measuring mesothelin level in serum and pleural fluid. Histopathological examination of pleural biopsies was performed in groups A and B. Results Mesothelin levels in serum and pleural fluid demonstrated a statistically significant increase in group A as compared with the cases in groups B and C (P<0.001). Moreover, mesothelin levels in serum and pleural fluid demonstrated a statistically significant increase in the samples taken from the cases in group B as compared with the cases in group C (P<0.001). Conclusion Soluble mesothelin-related peptides (SMRP) could be used as a valuable marker in diagnosis of different causes of pleural effusion. The diagnostic accuracy of pleural fluid SMRP was higher as compared with the serum SMRP.

Direct and indirect impacts of the COVID-19 pandemic on patients with pulmonary and pleural malignancies – a retrospective analysis of patient outcomes treated at Department of Respiratory Diseases, University Hospital Brno, during the 2nd and 3rd coronavirus waves

The pandemic of COVID-19 has significantly influenced the dia-gnostics and treatment of patients with lung and pleural malignancies. This group of patients is the riskiest, compared to patients with other cancers, both in morbidity and mortality.The data of patients with lung/pleural malignancies and proved COVID-19 positivity were analyzed at the Department of Respiratory Diseases and Tuberculosis, University Hospital Brno, during the period from October 2020 to May 2021. Demographic data, information about the course of SARS-CoV-2 infection and oncological disease as well as mortality were monitored. Together with the data from the study population, three case reports are also presented.Fifty-three patients were found (79% males), mean age 69.4 years, mainly with adenocarcinoma histology. A total of 47.1% patients experienced mild course of SARS-CoV-2 infection, 56.6% needed hospitalization, 24.5% died. Active anticancer treatment was delayed in 62.4% cases due to SARS-CoV-2 infection; the mean time of the delay reached 14.5 days.Patients with lung and pleural malignancies have a high risk of severe course of SARS-CoV-2 infection and mortality. Moreover, the ongoing SARS-CoV-2 infection as well as postcovid changes can complicate the anticancer treatment itself.

Management of Malignant Pleural Effusion: Where Are We Now?

Pleural malignancies are among the most common causes of pleural disease and form the basis of our daily pleural practice. There has been significant research and increase in both diagnostic and therapeutic management of malignant pleural diseases in the last decade. Good-quality data have led to a paradigm shift in the management options of pleural malignancies, and indwelling pleural catheter is now recommended and widely used as first-line intervention. Several trials compared different treatment modalities for pleural malignancies and continue to emphasize the need to reduce hospital length of stay and unnecessary pleural intervention, and the importance of patient choice in clinical decision making. This practical review aims to summarize the current knowledge for the management of pleural malignancies, and the understanding of the steps that we still have to climb to optimize management and reduce morbidity.

Results of screening in early and advanced thoracic malignancies in the EORTC pan-European SPECTAlung platform

Access to a comprehensive molecular alteration screening is patchy in Europe and quality of the molecular analysis varies. SPECTAlung was created in 2015 as a pan-European screening platform for patients with thoracic malignancies. Here we report the results of almost 4 years of prospective molecular screening of patients with thoracic malignancies, in terms of quality of the program and molecular alterations identified. Patients with thoracic malignancies at any stage of disease were recruited in SPECTAlung, from June 2015 to May 2019, in 7 different countries. Molecular tumour boards were organised monthly to discuss patients’ molecular and clinical profile and possible biomarker-driven treatments, including clinical trial options. FFPE material was collected and analysed for 576 patients with diagnosis of pleural, lung, or thymic malignancies. Ultimately, 539 patients were eligible (93.6%) and 528 patients were assessable (91.7%). The turn-around time for report generation and molecular tumour board was 214 days (median). Targetable molecular alterations were observed in almost 20% of cases, but treatment adaptation was low (3% of patients). SPECTAlung showed the feasibility of a pan-European screening platform. One fifth of the patients had a targetable molecular alteration. Some operational issues were discovered and adapted to improve efficiency.

Image-guided interventional radiological delivery of chimeric antigen receptor (CAR) T cells for pleural malignancies in a phase I/II clinical trial

ObjectivesWe describe techniques and results of image-guided delivery of mesothelin-targeted chimeric antigen receptor (CAR) T cells in patients with pleural malignancies in a phase I/II trial (ClinicalTrials.gov: NCT02414269). Materials and methodsPatients without a pleural catheter or who lack effusion for insertion of a catheter (31 of 41) were administered intrapleural CAR T cells by interventional radiologists under image guidance by computed tomography or ultrasound. CAR T cells were administered through a needle in an accessible pleural loculation (intracavitary) or following an induced loculated artificial pneumothorax. In patients where intracavitary infusion was not feasible, CAR T cells were injected via percutaneous approach either surrounding and/or in the pleural nodule/thickening (intratumoral). Pre- and post-procedural clinical, laboratory, and imaging findings were assessed. ResultsCAR T cells were administered intrapleurally in 31 patients (33 procedures, 2 patients were administered a second dose) with successful delivery of planned dose (10–186 mL); 14/33 (42%) intracavitary and 19/33 (58%) intratumoral. All procedures were completed within 2 h of T-cell thawing. There were no procedure-related adverse events greater than grade 1 (1 in 3 patients had prior ipsilateral pleural fusion procedures). The most common imaging finding was ground glass opacities with interlobular septal thickening and/or consolidation, observed in 12/33 (36%) procedures. There was no difference in the incidence of fever, CRP, IL-6, and peak vector copy number in the peripheral blood between infusion methods. ConclusionImage-guided intrapleural delivery of CAR T cells using intracavitary or intratumoral routes is feasible, repeatable and safe across anatomically variable pleural cancers.

Molecular cytology of the respiratory tract and pleura.

There is growing evidence that molecular testing is feasible on all types of cytological preparation, which is fortunate as more diagnostic markers and biomarkers for targeted therapies are discovered for use in pulmonary and pleural malignancies. In this article we will discuss the pre-analytic, analytic, and post-analytic (interpretive) considerations for successful implementation of molecular tests for diagnostic and predictive markers in respiratory and pleural cytology. The vast majority of laboratories are familiar with, and have validated their molecular protocols for, formalin-fixed paraffin-embedded surgical specimens, which are not directly applicable to cytology specimens. Thus, rigorous validation must be performed for each type of fixative and cytology preparation before it is implemented in the clinical setting.