Circulating cell-free and extracellular vesicles-derived microRNA as prognostic biomarkers in patients with early-stage NSCLC: results from RESTING study.

BACKGROUND: Factors to accurately stratify patients with early-stage non-small cell lung cancer (NSCLC) in different prognostic groups are still needed. This study aims to investigate 1) the prognostic potential of circulating cell-free (CF) and extracellular vesicles (EVs)-derived microRNA (miRNAs), and 2) their added value with respect to known prognostic factors (PFs). METHODS: The RESTING study is a multicentre prospective observational cohort study on resected stage IA-IIIA patients with NSCLC. The primary end-point was disease-free survival (DFS), and the main analyses were carried out separately for CF- and EV-miRNAs. CF- and EV-miRNAs were isolated from plasma, and miRNA-specific libraries were prepared and sequenced. To reach the study aims, three statistical models were specified: one using the miRNA data only (Model 1); one using both miRNAs and known PFs (age, gender, and pathological stage) (Model 2), and one using the PFs alone (Model 3). Five-fold cross-validation (CV) was used to assess the predictive performance of each. Standard Cox regression and elastic net regularized Cox regression were used. RESULTS: A total of 222 patients were enrolled. The median follow-up time was 26.3 (95% CI 25.4-27.6) months. From Model 1, three CF-miRNAs and 21 EV-miRNAs were associated with DFS. In Model 2, two CF-miRNAs (miR-29c-3p and miR-877-3p) and five EV-miRNAs (miR-181a-2-3p, miR-182-5p, miR-192-5p, miR-532-3p and miR-589-5p) remained associated with DFS. From pathway enrichment analysis, TGF-beta and NOTCH were the most involved pathways. CONCLUSION: This study identified promising prognostic CF- and EV-miRNAs that could be used as a non-invasive, cost-effective tool to aid clinical decision-making. However, further evaluation of the obtained miRNAs in an external cohort of patients is warranted.

Pathological T3 Non-Small Cell Lung Cancer with satellite nodules: Number or size, what does matter?

BACKGROUND: Non-small Cell Lung Cancer (NSCLC) with intralobar satellite nodule are defined as T3 (T3SN). We investigated the main features of these tumors and analyzed their impact on Overall Survival (OS). METHODS: This was a retrospective multicentric study including all pT3SN NSCLC operated on between 2005 and 2020, excluding patients with multifocal ground-glass opacities; who received induction therapies; N3 or stage IV. The diameter of largest (LgN) and smallest nodule (SmN), the total diameter (sum of diameter of all nodules, TS), and the number of SN were measured. RESULTS: Among 102 patients, 64.7 % were male. 84.3 % of patients had one SN (84.3 %), 9.8 % two SN while 5.9 % more than 2 SN. 63 patients were pN0. LgN (p = 0.001), SN (p = 0.005) and TS (p = 0.014) were significantly related to lymph-node metastasis; the LgN and TS were related to visceral pleural invasion (p < 0.001). Five-year OS was 65.1 %; at univariable analysis more than 2 satellite nodules, LgN and TS were significantly related to worse OS; at multivariable analysis, TS (Hazard Ratio [HR] 1.116 95 % Confidence Interval [CI] 1.008-1.235, p = 0.034) was an independent prognostic factors for OS. No significant prognostic factors were found for DFS at multivariable analysis. In pN0 patients, LgN (HR 1.051, 95 % CI 1.066-1.099, p = 0.027) and non-adenocarcinoma (HR 5.315 CI 95 % 1.494-18.910, p = 0.010) influenced OS. CONCLUSIONS: Tumor size is related to tumor's local invasiveness. TS is an independent prognostic factor for OS. Patients with more than 2 SN seem to be at higher risk for death and recurrence.

Robotic thymectomy in thymic tumours: a multicentre, nation-wide study.

OBJECTIVES: Robotic thymectomy has been suggested and considered technically feasible for thymic tumours. However, because of small-sample series and the lack of data on long-term results, controversies still exist on surgical and oncological results with this approach. We performed a large national multicentre study sought to evaluate the early and long-term outcomes after robot-assisted thoracoscopic thymectomy in thymic epithelial tumours. METHODS: All patients with thymic epithelial tumours operated through a robotic thoracoscopic approach between 2002 and 2022 from 15 Italian centres were enrolled. Demographic characteristics, clinical, intraoperative, postoperative, pathological and follow-up data were retrospectively collected and reviewed. RESULTS: There were 669 patients (307 men and 362 women), 312 (46.6%) of whom had associated myasthenia gravis. Complete thymectomy was performed in 657 (98%) cases and in 57 (8.5%) patients resection of other structures was necessary, with a R0 resection in all but 9 patients (98.6%). Twenty-three patients (3.4%) needed open conversion, but no perioperative mortality occurred. Fifty-one patients (7.7%) had postoperative complications. The median diameter of tumour resected was 4 cm (interquartile range 3-5.5 cm), and Masaoka stage was stage I in 39.8% of patients, stage II in 56.1%, stage III in 3.5% and stage IV in 0.6%. Thymoma was observed in 90.2% of patients while thymic carcinoma occurred in 2.8% of cases. At the end of the follow-up, only 2 patients died for tumour-related causes. Five- and ten-year recurrence rates were 7.4% and 8.3%, respectively. CONCLUSIONS: Through the largest collection of robotic thymectomy for thymic epithelial tumours we demonstrated that robot-enhanced thoracoscopic thymectomy is a technically sound and safe procedure with a low complication rate and optimal oncological outcomes.

Modified surgical incision suturing technique in uniportal video-assisted thoracoscopic pulmonary resection.

Background: In recent years, single-hole thoracoscopic surgery technology is widely used in major medical centers and chest-specialized hospitals for the treatment of lung diseases. However, the single-hole minimally invasive surgery method focuses on one incision, and all surgical instruments need to pass through the same hole, resulting in repeated extrusion and tissue damage of the surgical incision. Therefore, we have improved the suture method of conventional surgical incision in order to reduce the probability of wound infection and dehiscence, promote early healing, and reduce the severity of postoperative wound scar, thereby enhancing the postoperative rapid recovery of patients. The purpose of this study is to explore the clinical efficacy of a modified surgical incision suture technique applied to uniportal thoracoscopic pulmonary resection. Methods: This study retrospectively analyzed 151 patients who were admitted to the Department of Thoracic Surgery and underwent pulmonary resection from January 2019 to October 2021 in the North District of Suzhou Municipal Hospital. The patients were divided into two groups according to the different surgical incision suture methods: a modified group and a conventional group. The postoperative general clinical indexes, incision infection rate, secondary suture rate, postoperative incision pain score, and the severity of postoperative incision scar were compared and analyzed between the two groups. Results: There were no statistically significant differences between the two groups in terms of chest tube duration or postoperative drainage and postoperative incision pain scores; the incision infection rate (1.3% vs. 6.7%, P<0.05), secondary suture rate (2.6% vs. 9.4%, P<0.05), and postoperative scar score (4.853 vs. 5.543, P=0.03) were better in the modified group than in the conventional group, and the differences between the two groups were statistically significant. Conclusions: Our modified suture method reduces the chance of infection and splitting and the severity of postoperative incision scar formation, promoting early healing. It can be safely and effectively applied to the incision suture of uniportal thoracoscopic pulmonary resection, enhancing the rapid postoperative recovery of patients.

The future of artificial intelligence in thoracic surgery for non-small cell lung cancer treatment a narrative review.

Objectives: To present a comprehensive review of the current state of artificial intelligence (AI) applications in lung cancer management, spanning the preoperative, intraoperative, and postoperative phases. Methods: A review of the literature was conducted using PubMed, EMBASE and Cochrane, including relevant studies between 2002 and 2023 to identify the latest research on artificial intelligence and lung cancer. Conclusion: While AI holds promise in managing lung cancer, challenges exist. In the preoperative phase, AI can improve diagnostics and predict biomarkers, particularly in cases with limited biopsy materials. During surgery, AI provides real-time guidance. Postoperatively, AI assists in pathology assessment and predictive modeling. Challenges include interpretability issues, training limitations affecting model use and AI's ineffectiveness beyond classification. Overfitting and global generalization, along with high computational costs and ethical frameworks, pose hurdles. Addressing these challenges requires a careful approach, considering ethical, technical, and regulatory factors. Rigorous analysis, external validation, and a robust regulatory framework are crucial for responsible AI implementation in lung surgery, reflecting the evolving synergy between human expertise and technology.

National Multicenter Study on the Comparison of Robotic and Open Thymectomy for Thymic Neoplasms in Myasthenic Patients: Surgical, Neurological and Oncological Outcomes.

Thymectomy is the gold standard in the treatment of thymic neoplasm and plays a key role in the therapeutic path of myasthenia gravis. For years, sternotomy has been the traditional approach for removing anterior mediastinal lesions, although the robotic thymectomy is now widely performed. The literature is still lacking in papers comparing the two approaches and evaluating long-term oncological and neurological outcomes. This study aims to analyze the postoperative results of open and robotic thymectomy for thymic neoplasms in myasthenic patients. Surgical, oncological and neurological data of myasthenic patients affected by thymic neoplasms and surgically treated with extended thymectomy, both with the open and the robotic approach, in six Italian Thoracic Centers between 2011 and 2021 were evaluated. A total of 213 patients were enrolled in the study: 110 (51.6%) were treated with the open approach, and 103 (48.4%) were treated with robotic surgery. The open surgery, compared with the robotic, presented a shorter operating time (p < 0.001), a higher number of postoperative complications (p = 0.038) and longer postoperative hospitalization (p = 0.006). No other differences were observed in terms of surgical, oncological or neurological outcomes. The robotic approach can be considered safe and feasible, comparable to the open technique, in terms of surgical, oncological and neurological outcomes.

Are the Efficacy and Safety of Chest Tubes in Uniportal Video-Assisted Thoracic Surgery Related to the Level of Intercostal Space Insertion or to the Drain Type? A Prospective Multicenter Study.

OBJECTIVES: The aim of this study is to evaluate if the efficacy and safety of chest tube placement are influenced by the level of intercostal space insertion (uniportal VATS vs. biportal VATS) or by the type of drain employed (standard vs. smart coaxial drain). METHODS: Data on patients who underwent either uniportal or biportal VATS upper lobectomies with lymphadenectomy were prospectively collected in three European centers. The uniportal VATS group with a 28 Fr standard chest tube (U-VATS standard) was compared with the uniportal VATS group with a 28 Fr smart drain (U-VATS smart), and U-VATS smart was also compared with biportal VATS with a 28 Fr smart drain inserted in the VIII intercostal space (Bi-VATS smart). RESULTS: When comparing the U-VATS standard group with the U-VATS smart, a higher fluid output was recorded in the U-VATS smart (p: 0.004) in the III post-operative day (p.o.) and overall (p: 0.027), with a lower 90-day re-admission in the U-VATS smart (p: 0.04). The Bi-VATS smart group compared to U-VATS smart showed a higher fluid output in the I p.o. (p < 0.001), with no difference in total fluid amount or hospitalization. The Bi-VATS smart recorded a lower incidence (p < 0.001) of residual pleural space or effusion (p: 0.004) at chest X-rays prior to drain removal but a higher level of pain and chronic intercostal neuralgia (p: 0.03). CONCLUSIONS: Chest tube insertion through the same incision space in uniportal VATS seems to be safe and effective. Smart drains can improve the fluid output in uniportal VATS, as if the drainage were inserted in a lower space (i.e., biportal VATS), but with less discomfort.

Unsolved Issues in Thymic Epithelial Tumour Stage Classification: The Role of Tumour Dimension.

According to the different classifications now in use, thymic tumours are staged by the extent of local invasiveness, and tumour size is not included as a major determinant for the T category. The aim of this double-site retrospective study is to analyse the correlation between tumour dimension and overall survival (OS) in patients who underwent surgical treatment. From January 2000 to December 2020, patients with thymic epithelial tumours who underwent surgical resection were included in this study. Data from a total of 332 patients were analysed. Five- and ten-year overall survival (5-10 YOS) was 89.26% and 87.08%, respectively, while five- and ten-year disease-free survival (DFS) was 88.12% and 84.2%, respectively. Univariate analysis showed a significant correlation between male sex (p-value 0.02), older age (p-value < 0.01), absence of myasthenia gravis (p-value < 0.01), increase in pTNM (pathological Tumor Node Metastasis) (p-value 0.03) and increase in the number of infiltrated organs (p-value 0.02) with an increase in tumour dimension. Tumour dimension alone was not effective in the prediction of DFS and OS, both when considered as a continuous variable and when considered with a cut-off of 3 and 5 cm. However, with multivariate analysis, it was effective in predicting OS in the aforementioned conditions (p-value < 0.01). Moreover, multivariate analysis was also used in the thymoma and Masaoka I subgroups. In our experience, the role of tumour dimension as a descriptor of the T parameter of the TNM (Tumor Node Metastasis) staging system seemed to be useful in improving this system.

Giant lung bulla as a late-onset complication of mild SARS-CoV-2 pneumonia.

A 49-year-old Caucasian man was admitted to the Emergency Department for shortness of breath and cough. CT imaging showed bilateral a mild COVID-19 related pneumonia. He was hospitalized in the low-intensity COVID-19 unit where he received O2 therapy and oral corticosteroids (CS). Three weeks after discharge a high-resolution computed tomography (HRCT) find a giant bulla of the inferior lobe. The bulla was resected by video-assisted thoracoscopic surgery (VATS) and the patient recovered completely. In our patient, it is reasonable to suspect that the development of the bulla is a result of SARS-CoV-2 infection, since no bulla was observed in the first HRCT two months before. SARS-CoV-2 related pneumonia may be responsible for lung remodeling due to diffuse alveolar damage and later interstitial myofibroblastic proliferation. Corticosteroids might have played a role in increasing SARS-CoV-2 dystrophic action. COVID-19 leads to pulmonary damages, which are still partially unknown and might result in development of bullae. In fit patient surgical treatment can be carried out safely.

Clinical score for colorectal cancer patients with lung-limited metastases undergoing surgical resection: Meta-Lung Score.

BACKGROUND: Radical resection of isolated lung metastases (LM) from colorectal cancer (CRC) is debated. Like Fong's criteria in liver metastases, our study was meant to assign a clinical prognostic score in patients with LM from CRC, aiming for better surgery selection. METHODS: We retrospectively analyzed data from 260 CRC patients who underwent curative LM resection from December 2002 to January 2022, verifying the impact of different clinicopathological features on the overall survival (OS). RESULTS: At the univariate analysis: higher baseline CEA levels (p = 0.0001), disease-free survival less than or equal to 12 months (m) (p = 0.0043), LM size larger than 2 cm (p = 0.0187), multiple resectable nodules (p = 0.0083), and positive nodal status of the primary tumor (p = 0.0011) were associated with worse prognosis. In a Cox regression model, these characteristics retained their independent role for OS (p < 0.0001) and were chosen as criteria to be assigned one point each for clinical risk score. The 5-year survival rate in patients with 0 points was 88%, while no patients with a 5-point score survived at 2 years. Based on the 0-1 vs. 2-5 score range, we obtained a significant difference in median OS: not reached vs. 40.8 months (95 %CI 36 to 87.5), respectively (p < 0.0001) stratifying patients into good and poor prognosis. The prognostic role of the score was also confirmed in terms of median RFS: not reached in 0-1 scored patients vs. 30.5 months (95 %CI 19.4 to 42) in patients with 2-5 scores (p = 0.0006). CONCLUSIONS: When LM from CRC is resectable, the Meta-Lung Score provides valuable prognostic information. Indeed, while upfront surgery should be considered in patients with scores of 0 to 1, it should be cautiously suggested in patients with scores of 2 to 5, for whom a prognosis comparison between preventive surgery and other treatments should be investigated in prospective randomized clinical trials.

Surgery for Solitary Fibrous Tumors of the Pleura: A Review of the Available Evidence.

Solitary fibrous tumors of the pleura (pSFT) are a relatively rare neoplasms that can arise from either visceral or parietal pleura and may have different aggressive biological behaviors. Surgery is well known to be the cornerstone of the treatment for pSFT. We reviewed the existing literature, focusing on the role of surgery in the management and treatment of pSFT. All English-written literature has been reviewed, focusing on those reporting on the perioperative management and postoperative outcomes. Surgery for pSFT is feasible and safe in all experiences reported in the literature, but surgical approaches and techniques may vary according to the tumor dimensions, localization, and surgeons' skills. Long-term outcomes are good, with a 10-year overall survival rate of more than 70% in most of the reported experiences; on the other hand, recurrence may happen in up to 17% of cases, which occurs mainly in the first two years after surgery, but case reports suggest the need for a longer follow-up to assess the risk of late recurrence. Malignant histology and dimensions are the most recognized risk factors for recurrence. Recurrence might be operated on in select patients. Surgery is the treatment of choice in pSFT, but a radical resection and a careful postoperative follow-up should be carried out.

Lung Transplant Recipients and COVID-19: Report of Two Cases.

Although the WHO has declared the end of the pandemic emergency, COVID-19 still poses a threat to immunocompromised patients. The COVID-19 pandemic has spread throughout the world over the last two years, causing a significant number of deaths. After three years, SARS-CoV-2 has lost its initial lethality but has shown a significantly worse prognosis for immunocompromised patients, especially those who have undergone lung transplantation, compared with the general population. This paper presents two compelling case studies that highlight the complex challenges of COVID-19 infection in lung transplant recipients. The first case involves a patient who received a bilateral lung transplant for pulmonary artery hypertension in 2009, followed by a kidney transplant in 2022. Surprisingly, despite an initially favorable clinical course after contracting COVID-19, the patient deteriorated rapidly and died within a few days due to extensive lung involvement. This case highlights the unpredictable nature of COVID-19 and its potentially devastating impact on lung transplant recipients. The second case involves a patient who underwent bilateral lung transplantation five years earlier for chronic obstructive pulmonary disease (COPD). This individual also contracted COVID-19 and had pre-existing complications, including chronic lung allograft rejection (CLAD) and diffuse bronchial stenosis. Following viral infection, the patient's clinical condition deteriorated rapidly, with worsening bronchial stenosis. This case highlights the ability of COVID-19 to exacerbate pre-existing pulmonary complications in transplant recipients. These cases highlight the urgent need for increased vigilance and tailored management strategies when dealing with COVID-19 in lung transplant recipients. The unpredictable and detrimental course of the disease observed in these patients highlights the importance of implementing stringent preventive measures, such as vaccination and strict adherence to infection control protocols, in this vulnerable population. Further research is essential to gain a full understanding of the unique dynamics of COVID-19 in lung transplant recipients and to develop targeted interventions to improve their outcomes.

Early Postoperative Results after Thymectomy for Thymic Cancer: A Single-Institution Experience.

BACKGROUND: Surgery for thymic cancers is considered the key of curative treatment. Preoperative patients' characteristics and intraoperative features might influence postoperative outcome. We aim to verify short-term outcomes and possible risk factors for complications after thymectomy. METHODS: We retrospectively investigated patients undergoing surgery for thymoma or thymic carcinoma in the period between January 1, 2008, and December 31, 2021, in our department. Preoperative features, surgical technique (open, bilateral VATS, RATS), intraoperative characteristics and incidence of postoperative complications (PC) were analyzed. RESULTS: We included in the study 138 patients. Open surgery was performed in 76 patients (55.1%), in 36 VATS (26.1%) and in 26 RATS (36.1%). Resection of one or more adjacent organs due to neoplastic infiltration was required in 25 patients. PC appeared in 25 patients (52% Clavien-Dindo grade I, 12% grade IVa). Open surgery had a higher incidence of PC (p < 0.001), longer postoperative in-hospital stay (p = 0.045) and larger neoplasm (p = 0.006). PC were significant related to pulmonary resection (p = 0.006), phrenic nerve resection (p = 0.029), resection of more than one organ (p = 0.009) and open surgery (p = 0.001), but only extended surgery of more organs was confirmed as independent prognostic factor for PC (p = 0.0013). Patients with preoperative myasthenia symptoms have a trend toward stage IVa complications (p = 0.065). No differences were observed between outcomes of VATS and RATS. CONCLUSIONS: Extended resections are related to a higher incidence of PC, while VATS and RATS guarantee a lower incidence of PC and shorter postoperative stay even in patients that require extended resections. Symptomatic myasthenia patients might have a higher risk toward more severe complications.

A prognostic score from a multicentric retrospective analysis of patients affected by sarcoma with metachronous lung metastases undergoing metastasectomy.

BACKGROUND: Despite the lack of evidence-based on prospective randomized studies, surgery has become the cornerstone of the treatment in patients with pulmonary oligometastatic sarcomas. Our study aimed to construct a composite prognostic score for metachronous oligometastatic sarcoma patients. METHODS: A retrospective analysis was performed on data patients who underwent radical surgery for metachronous metastases in six research institutes from January 2010 to December 2018. The log-hazard ratio (HR) obtained from the Cox model was used to derive weighting factors for a continuous prognostic index designed to identify differential outcome risks. RESULTS: A total of 251 patients were enrolled in the study. In the multivariate analysis, a longer disease-free interval (DFI) and a lower neutrophil-to-lymphocytes ratio (NLR) were predictive of a better overall survival (OS) and disease-free survival (DFS). A prognostic score was developed based on DFI and NLR data, identifying 2 risk class groups for DFS (3-years DFS 20.2% for the high-risk group [HRG]and 46.4% for the low-risk group [LRG] [<0.0001]) and 3 risk groups for OS (3 years OS 53.9% for the HRG vs. 76.9% for the intermediate-risk group and 100% of the LRG (p < 0.0001)). CONCLUSION: The proposed prognostic score effectively predicts outcomes for patients with lung metachronous oligo-metastases from the surgically treated sarcoma.

Innovative use of Protek Duo during bilateral lung transplant with Veno-Arterial Extracorporeal Membrane Oxygenation assistance.

V-A ECMO during bilateral lung transplantation is routinely used when extracorporeal support is needed, in particular in case of patients affected by pulmonary hypertension. We report the case of a patient successfully transplanted with V-A ECMO assistance using a percutaneous double lumen cannula as venous drainage (Protek Duo, CardiacAssist Inc., Pittsburgh, PA) and central aortic cannulation. The double lumen cannula allowed an optimal drainage of the venous system and effective emptying of right heart chambers.

Validation of Inflammatory Prognostic Biomarkers in Pleural Mesothelioma.

Evoked from asbestos-induced inflammation, pleural mesothelioma represents a fatal diagnosis. Therapy ranges from nihilism to aggressive multimodality regimens. However, it is still unclear who ultimately benefits from which treatment. We aimed to re-challenge inflammatory-related biomarkers' prognostic value in times of modern immune-oncology and lung-sparing surgery. The biomarkers (leukocytes, hemoglobin, platelets, neutrophils, lymphocytes, monocytes, neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), C-reactive protein (CRP)) and clinical characteristics (age, sex, histology, therapy) of 98 PM patients were correlated to overall survival (OS). The median OS was 19.4 months. Significant OS advantages (Log-Rank) were observed in multimodal treatment vs. others (26.1 vs. 7.2 months, p < 0.001), surgery (pleurectomy/decortication) vs. no surgery (25.5 vs. 3.8 months, p < 0.001), a high hemoglobin level (cut-off 12 g/dL, 15 vs. 24.2 months, p = 0.021), a low platelet count (cut-off 280 G/L, 26.1 vs. 11.7 months, p < 0.001), and a low PLR (cut-off 194.5, 25.5 vs. 12.3 months, p = 0.023). Histology (epithelioid vs. non-epithelioid, p = 0.002), surgery (p = 0.004), CRP (cut-off 1 mg/dL, p = 0.039), and platelets (p = 0.025) were identified as independent prognostic variables for this cohort in multivariate analysis (Cox regression, covariates: age, sex, histology, stage, CRP, platelets). Our data verified the previously shown prognostic role of systemic inflammatory parameters in patients treated with lung-sparing surgery within multimodality therapy.

Safety and efficacy of immunotherapy rechallenge following checkpoint inhibitor-related pneumonitis in advanced lung cancer patients: a retrospective multi-center cohort study.

Background: Checkpoint inhibitor-related pneumonitis (CIP) induced by immune checkpoint inhibitors (ICIs) is one of the most fatal immune-related adverse events (irAE). However, only limited data are available on rechallenge with ICIs after CIP. We evaluated the efficacy and safety of rechallenge after CIP in patients with advanced lung cancer to identify the potential populations that would benefit. Methods: We conducted a multicenter retrospective study of advanced lung cancer patients who received further ICI treatment (rechallenge) or did not undergo re-administration after grade ≥1 CIP between May 2017 and May 2021. Progression-free survival (PFS) and overall survival (OS) were estimated from first or second ICI initiation to disease progression (PFS1 and PFS2, respectively), death, or last follow-up (OS1 and OS2, respectively). The recurrence of CIP and new irAEs in these patients after ICI rechallenge were calculated. Results: Among 107 patients afflicted with CIP, 45 (42.1%) received ICI rechallenge. Multivariate analysis showed that severe grade (grades ≥3) and ground-glass opacity of pneumonitis lesions were negatively associated with rechallenge. Following rechallenge, 9 (20.0%) patients developed recurrent pneumonitis, and 11 (24.4%) developed a new irAE. Severe grade of CIP and poor performance status at initial CIP as well as levels of interleukin (IL)-6 and C-reactive protein (CRP), and absolute white blood cell and neutrophil counts at the time of ICI rechallenge were associated with a higher recurrence rate. The median (95% confidence interval) PFS1 and PFS2 were 17.9 (9.9-24.2) and 15.5 (5.5-25.6) months, respectively. The median (95% confidence interval) OS1 and OS2 were 23.5 (16.5-30.5) and 18.4 (10.1-26.7) months, respectively. Lower OS2 was observed in patients with severe grade of CIP and poor performance status at the initial CIP, recurrence of CIP, and in patients with high levels of CRP and IL-6 at rechallenge. Only IL-6 was found to affect OS2 on multivariate analysis. Conclusions: ICI rechallenge following CIP may be a promising treatment for patients with advanced lung cancer, particularly in those with low-grade of CIP and good performance status at initial CIP, and low levels of IL-6 and CRP at the time of initial challenge. Prospective studies are needed for further verification.

Impact of High-Grade Patterns in Early-Stage Lung Adenocarcinoma: A Multicentric Analysis.

OBJECTIVE: The presence of micropapillary and solid adenocarcinoma patterns leads to a worse survival and a significantly higher tendency to recur. This study aims to assess the impact of pT descriptor combined with the presence of high-grade components on long-term outcomes in early-stage lung adenocarcinomas. METHODS: We retrospectively collected data of consecutive resected pT1-T3N0 lung adenocarcinoma from nine European Thoracic Centers. All patients who underwent a radical resection with lymph-node dissection between 2014 and 2017 were included. Differences in Overall Survival (OS) and Disease-Free Survival (DFS) and possible prognostic factors associated with outcomes were evaluated also after performing a propensity score matching to compare tumors containing non-high-grade and high-grade patterns. RESULTS: Among 607 patients, the majority were male and received a lobectomy. At least one high-grade histological pattern was seen in 230 cases (37.9%), of which 169 solid and 75 micropapillary. T1a-b-c without high-grade pattern had a significant better prognosis compared to T1a-b-c with high-grade pattern (p = 0.020), but the latter had similar OS compared to T2a (p = 0.277). Concurrently, T1a-b-c without micropapillary or solid patterns had a significantly better DFS compared to those with high-grade patterns (p = 0.034), and it was similar to T2a (p = 0.839). Multivariable analysis confirms the role of T descriptor according to high-grade pattern both for OS (p = 0.024; HR 1.285 95% CI 1.033-1.599) and DFS (p = 0.003; HR 1.196, 95% CI 1.054-1.344, respectively). These results were confirmed after the propensity score matching analysis. CONCLUSIONS: pT1 lung adenocarcinomas with a high-grade component have similar prognosis of pT2a tumors.