Advances in screening, surgical techniques, perioperative care, and multimodality treatment have progressively expanded the population of long-term survivors with early-stage non-small cell lung cancer (NSCLC). However, disease-free survival does not necessarily correspond to complete functional recovery after curative-intent treatment. Many patients continue to experience persistent fatigue, dyspnea, reduced physical activity, impaired exercise tolerance, muscle loss, and deterioration in health-related quality of life despite adequate oncologic control. This narrative review discusses functional recovery as a survivorship endpoint in early-stage NSCLC, focusing on recovery trajectories, physiologic vulnerability, frailty, sarcopenia, rehabilitation, symptom burden, and emerging biologic frameworks such as allostatic load. Increasing evidence suggests that survivorship after NSCLC should not be interpreted exclusively according to recurrence or survival metrics, but also according to the ability to recover physiologic reserve, autonomy, and daily functioning after treatment. Functional recovery appears heterogeneous and influenced by multiple interacting factors, including baseline reserve, systemic inflammation, physical inactivity, behavioral adaptation, and cumulative stress burden. Rehabilitation strategies, structured symptom surveillance, and patient-reported outcomes may help identify vulnerable patients and improve long-term survivorship trajectories. Future survivorship models should probably integrate oncologic outcomes with longitudinal functional assessment to better characterize recovery patterns after treatment.

Pulmonary metastases affect up to 30

Backgrounds: Despite the availability of multimodal strategies, no universally accepted guidelines exist for the management of advanced Thymic Epithelial Tumors (TETs), particularly in locally advanced thymomas. The aim of this study was to evaluate the oncological and surgical outcomes of induction therapy (IT) followed by surgery in patients with Masaoka-Koga stage III-IVA TETs. To this end, we conducted a systematic review and meta-analysis assessing surgical-pathological and survival outcomes. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials was performed. Twenty-four studies published between 2003 and 2023 were included, comprising 749 patients treated with IT before surgical resection. The co-primary endpoints were Overall survival (OS) and Progression-free survival (PFS). Random-effects meta-analysis assessed pooled outcomes, while heterogeneity, publication bias, and meta-regression analyses were performed to explore potential moderators (year, histology, stage). The study was registered in Prospective Register of Systematic Reviews (PROSPERO) (CRD420251026044). Results: Of the included studies, 6 were prospective and 18 retrospective; 9 analyzed thymomas only, while 15 included both thymomas and thymic carcinomas. Regarding stage distribution, 4 studies focused on stage III, 11 on stage III-IV, 3 on stage IV, and 2 also included earlier stages. Response to IT was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) in 11 studies and World Health Organization (WHO) criteria in 4. The pooled rate of radiological response to IT, completeness of resection, 5-year OS, 10-year OS and 5-year PFS were 62.8%, 71.6%, 77.6%, 54.3% and 55.6%, respectively. Meta-regression showed histology significantly influenced 10-year OS (p-value 0.0418) as well as on PFS (p-value 0.0042) and treatment period on PFS (p-value 0.0007). Conclusions: Induction therapy followed by surgery provides acceptable long-term outcomes in advanced TETs. Histology remains a key prognostic factor, but 10-year OS has not improved over the past two decades, underscoring the need for innovative, histology-tailored therapeutic strategies to enhance survival.

OBJECTIVES:to date, no consensus has been reached on the surgical gold-standard in pleural mesothelioma (PM). We retrospectively reviewed our experience as a tertiary referral centre, to compare short- and long-term survival of PM patients undergoing different types of surgery.METHODS:in retrospective, observational, single-centre study, we analysed all the patients histologically diagnosed with PM undergoing surgical procedures with palliative or curative intent at IRCCS Istituto Nazionale dei Tumori of Milan, Italy, from January 2003 to December 2020. The primary study endpoint was 10-year overall survival (OS) in three different types of resections: extra-pleural-pneumonectomy (EPP), pleurectomy/decortication (P/D), partial-pleurectomy/pleural-biopsy (PP/B). Secondary endpoints were postoperative hospital stay and postoperative 30-day and 90-day mortality rates. The survival function was estimated using Kaplan-Meier, and the Log-rank test was used for testing differences. Univariable and Multivariable Cox regression models were implemented to estimate Hazard Ratio (HR) for all variables of interest.RESULTS:243 consecutive patients were enrolled, EPP was performed in 49 (20.2%), P/D in 58 (23.8%), PP/B in 136 (56.0%) patients. The median follow-up time was 19.8 months. 10-year OS was significantly better for P/D group (16%, Log-Rank test p<0.0001) compared to PP/B (1.8%) and EPP (0%). No statistically significant differences were found among the 3 surgical groups in 30- and 90-day mortality rates. At multivariable analysis, gender (male, HR=1.58), type of resection (P/D, HR=0.55) and surgery date (recent years, HR=0.61) were found to be independent prognostic factors for OS.CONCLUSIONS:in PM, lung-sparing curative approach (e.g. P/D) should be preferred in highly selected patients and in highly experienced centres, whenever appropriate. Anyway, when P/D is not indicated, adopting palliative/conservative management (e.g. PP/B) could ensure comparable results as extremely aggressive surgeries (e.g. EPP). The aim of surgery in PM should not be reaching complete resection, but rather accomplishing significant resection allowing to complete the multimodality treatment in highly selected patients in experienced centers.

Background: Stage III lung cancer (LC) represents a heterogeneous group of diseases, and the optimal management is still a matter of debate. To date, only a few studies have assessed the role of multidisciplinary team (MDT) discussion in impacting survival of stage III LC. Hence, we aimed to reported the impact of the implementation of MDT discussion on long-term survival of stage III LC patients. Methods: This is a retrospective, observational, single-centre cohort study evaluating data of consecutive patients with a clinical and pathological diagnosis of stage III LC treated before [2005-2011] and after [2012-2020] the implementation of MDT. The primary outcome was 5-year overall survival (OS). Results: A total of 983 patients were enrolled with stage III LC, 411 (41.8%) pre-MDT and 572 (58.2%) post-MDT. The 5-year OS rates were 25.3% for the pre-MDT cohort and 33.9% for the post-MDT cohort (P=0.0008). Resected patients (n=670), who underwent trimodality therapy achieved a higher 5-year OS in both pre-MDT and post-MDT groups. An increased 5-year OS was observed in patients who underwent systemic therapy, from 28.2% in pre-MDT to 40.2% in post-MDT cohorts. In non-resected patients, there was an increased in 5-year OS in both systemic and chemoradiotherapy groups. Conclusions: The implementation of an MDT increased the 5-year OS in both resected and non-resected stage III LC patients. Implementing MDT might be useful in improving the management of therapy with less invasive local and surgical strategies personalized for each LC patient.

The aim of this study is to compare the accuracy of Airgo™, a non-invasive wearable device that records breath, with respect to a gold standard. In 21 healthy subjects (10 males, 11 females), four parameters were recorded for four min at rest and in different positions simultaneously by Airgo™ and SensorMedics 2900 metabolic cart. Then, a cardio-pulmonary exercise test was performed using the Erg 800S cycle ergometer in order to test Airgo™'s accuracy during physical effort. The results reveal that the relative error median percentage of respiratory rate was of 0% for all positions at rest and for different exercise intensities, with interquartile ranges between 3.5 (standing position) and 22.4 (low-intensity exercise) breaths per minute. During exercise, normalized amplitude and ventilation relative error medians highlighted the presence of an error proportional to the volume to be estimated. For increasing intensity levels of exercise, Airgo™'s estimate tended to underestimate the values of the gold standard instrument. In conclusion, the Airgo™ device provides good accuracy and precision in the estimate of respiratory rate (especially at rest), an acceptable estimate of tidal volume and minute ventilation at rest and an underestimation for increasing volumes.

Clinical Practice Points Spontaneous regression can occur in metastatic renal cell carcinoma (mRCC). We observed the spontaneous regression of multiple thoracic metastases from renal cell carcinoma after the palliative removal of only one lesion. In highly selected cases, where a relevant clinical benefit might be expected, palliative metastasectomy should be considered for mRCC. Markers of host immune status might help predicting the clinical course of mRCC.

OBJECTIVES:Current guidelines recommend preoperative invasive mediastinal staging in centrally located tumours with negative mediastinum on positron emission tomography-computed tomography, based on a 20-30% prevalence of occult mediastinal disease (pN2-3). However, a uniform definition of central tumour location is lacking. Our objective was to determine the best definition in predicting occult pN2-3.METHODS:A single-institution database was queried for patients with (suspected) non-small-cell lung cancer staged cN0 after positron emission tomography-computed tomography and referred to invasive staging and/or primary surgery. We evaluated 5 definitions: inner 1/3, inner 2/3, contact with bronchovascular structures, ≤2 cm from bronchus or endobronchial visualization.RESULTS:Between 2005 and 2015, 813 patients were eligible (cT1: 42%, cT2: 28%, cT3: 17% and cT4: 11%). Invasive mediastinal staging and resection were performed in 30% and 97% of patients, respectively. Any nodal upstaging (pN+) was found in 21% of patients, of whom pN2-3 was found in 8%. Central tumour location demonstrated 4 times higher odds for any pN+ [for inner 1/3 vs outer 2/3, odds ratio 3.90 (95% confidence interval 2.24-6.77), P < 0.001], whereas no significantly different odds was observed for pN2-3. The discriminative ability for pN+ was not significantly different between the several definitions.CONCLUSIONS:The prevalence of occult pN2-3 was only 8% when modern fusion positron emission tomography-computed tomography imaging pointed at clinical N0 non-small-cell lung cancer. None of the 5 verified definitions of centrality was predictive for occult pN2-3. However, each definition of centrality was related to any pN+ at a prevalence of 21%, without significant differences in discriminative ability between definitions. These data question whether indication for preoperative invasive mediastinal staging should be based on centrality alone.

Ex-vivo lung perfusion (EVLP) has become a clinical reality with most reported cases for short-term (<4h) assessment of questionable lungs. To fully explore the EVLP potential, this time window should be safely extended. However, the graft function during longer EVLP largely remains unknown. We studied EVLP graft parameters and recipient outcome in clinical lung transplantation (LuTx) with EVLP time >8h.

Large retrospective series have indicated lower rates of cN0 to pN1 nodal upstaging after video-assisted thoracic surgery (VATS) compared with open resections for Stage I non-small-cell lung cancer (NSCLC). The objective of our multicentre study was to investigate whether the presumed lower rate of N1 upstaging after VATS disappears after correction for central tumour location in a multivariable analysis. Consecutive patients operated for PET-CT based clinical Stage I NSCLC were selected from prospectively managed surgical databases in 11 European centres. Central tumour location was defined as contact with bronchovascular structures on computer tomography and/or visibility on standard bronchoscopy. Eight hundred and ninety-five patients underwent pulmonary resection by VATS (n = 699, 9% conversions) or an open technique (n = 196) in 2014. Incidence of nodal pN1 and pN2 upstaging was 8% and 7% after VATS and 15% and 6% after open surgery, respectively. pN1 was found in 27% of patients with central tumours. Less central tumours were operated on by VATS compared with the open technique (12% vs 28%, P < 0.001). Logistic regression analysis showed that only tumour location had a significant impact on N1 upstaging (OR 6.2, confidence interval 3.6-10.8; P < 0.001) and that the effect of surgical technique (VATS versus open surgery) was no longer significant when accounting for tumour location. A quarter of patients with central clinical Stage I NSCLC was upstaged to pN1 at resection. Central tumour location was the only independent factor associated with N1 upstaging, undermining the evidence for lower N1 upstaging after VATS resections. Studies investigating N1 upstaging after VATS compared with open surgery should be interpreted with caution due to possible selection bias, i.e. relatively more central tumours in the open group with a higher chance of N1 upstaging.

Perioperative management of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high thrombotic risk undergoing non-deferrable surgery remains poorly defined. Cangrelor represents a potential bridging treatment option. However, there is limited data in this

Introduction: Standard functional respiratory tests require patient cooperation and do not allow continuous and accurate assessment of respiratory function under natural physiological conditions. Aims and objectives: To validate the accuracy of the AirGo™ device comparing its performance in terms of respiratory parameters, with respect to gold standard methods. Methods: AirGo™ is a non-invasive device that continuously records breath dynamics during sleep and daily activity. It measures lower thoracic circumference changes with a wearable elastic band. In a population of 21 healthy subjects [median age 38 (range 24-51), 10 males, median body mass index 22.1 (range 17.7–30.0)], tidal volume (Vt) and respiratory rate (RR) have been recorded for four minutes at rest and in different body positions (standing, seated, supine, right and left side) simultaneously by AirGo™ and SensorMedics Vmax 2900 metabolic cart spirometer. Results: In term of RR we calculated a percentage error medians of 0% for all subjects and regardless of body positions, whereas results for Vt were dependent on body posture as indicated in Table 1. Table 1: percentage error medians (interquartile range mean). Conclusions: The AirGo™ device provides an acceptable estimate of respiratory parameters at rest and could be a helpful tool for management of lung disease, sleep respiratory disorders and early detection of worsening respiratory conditions.

We read with interest the results of the prospective study by Hopkins et al. (1) which collected data on quality of life (QOL), including pain and mood disorders, after thoracotomy versus VATS resection. The authors conclude that VATS and thoracotomy patients had similar late QOL outcomes.

AIM:To systematically review reports on deceased-donor-lobar lung transplantation (ddLLTx) and uniformly describe size matching using the donor-to-recipient predicted-total lung-capacity (pTLC) ratio.METHODS:We set out to systematically review reports on ddLLTx and uniformly describe size matching using the donor-to-recipient pTLC ratio and to summarize reported one-year survival data of ddLLTx and conventional-LTx. We searched in PubMed, CINAHL via EBSCO, Cochrane Database of Systematic Reviews via Wiley (CDSR), Database of Abstracts of Reviews of Effects via Wiley (DARE), Cochrane Central Register of Controlled Trials via Wiley (CENTRAL), Scopus (which includes EMBASE abstracts), and Web of Science for original reports on ddLLTx.RESULTS:Nine observational cohort studies reporting on 301 ddLLTx met our inclusion criteria for systematic review of size matching, and eight for describing one-year-survival. The ddLLTx-group was often characterized by high acuity; however there was heterogeneity in transplant indications and pre-operative characteristics between studies. Data to calculate the pTLC ratio was available for 242 ddLLTx (80%). The mean pTLCratio before lobar resection was 1.25 ± 0.3 and the transplanted pTLCratio after lobar resection was 0.76 ± 0.2. One-year survival in the ddLLTx-group ranged from 50%-100%, compared to 72%-88% in the conventional-LTx group. In the largest study ddLLTx (n = 138) was associated with a lower one-year-survival compared to conventional-LTx (n = 539) (65.1% vs 84.1%, P < 0.001).CONCLUSION:Further investigations of optimal donor-to-recipient size matching parameters for ddLLTx could improve outcomes of this important surgical option.

INTRODUCTION:VATS wedge resection can require conversion to thoracotomy when pulmonary lesions cannot be identified. Hybrid operating rooms (HORs) provide real-time image acquisition capabilities allowing the intraoperative placement of markers to facilitate the removal of non-palpable nodules during VATS. OBJECTIVES:To present our workflow based on the alternative use of two different markers according to the location of the lung lesion and report our initial results. METHODS:All consecutive patients with non-palpable lesions requiring VATS wedge resection underwent localization of the targets in HOR. Lesions were considered non-palpable if they were small (<1 cm), deep (>1 cm from surface), subsolid, or located within a dystrophic area. Anesthetized patients were placed in lateral decubitus. Cone-beam CT (CBCT) was performed, and the needle trajectory was planned using Syngo iGuide Needle Guidance. Metal hook-wire or coil was placed, according to our workflow, close to the lesion and their position was verified by CBCT or fluoroscopy. RESULTS:Eleven VATS wedge resections were performed in 10 patients with 12 non-palpable lesions. The localization was performed with seven hook-wires and four coils in 30 minutes (range 17-56 minutes). The median estimated total effective dose was 11.6 mSv (range 1.9-24.7 mSv). Eleven lesions were removed by VATS, and one deep nodule required a thoracotomy. No complications were observed. CONCLUSIONS:Our experience confirms that HOR is suitable for simultaneous localization and VATS resection of 'difficult' pulmonary lesions. A versatile approach, using different devices, seems advisable for the removal of targets in every clinical scenario, reducing the VATS conversion rate.

Based on a 20-30% prevalence of occult mediastinal disease, current guidelines recommend preoperative invasive mediastinal staging in patients with central tumor location and negative mediastinum on PET-CT. A uniform definition of central tumor location is lacking. Our objective was to determine the best definition in predicting occult mediastinal disease. A single institution prospective database was queried for patients with (suspected) NSCLC staged cN0 after PET-CT and referred to invasive staging and/or primary surgery. We evaluated 5 definitions of central tumor location (Table 1). Between 2005 and 2015, 822 patients were eligible. Radio-occult lesions were excluded from analysis (n=9). Preoperative histology was NSCLC in 49% and unknown in 51%. The lesion was subsolid in 7%. Tumor stage was cT1, cT2, cT3 and cT4 in 43%, 28% 17% and 11%, respectively. Invasive mediastinal staging (EBUS and/or mediastinoscopy) was performed in 31%. Surgical resection was performed in 97%, a median of 5 (IQR 3-6) nodal stations were examined. The final pathology was squamous NSCLC, non-squamous NSCLC, or other in 38%, 54% and 7%, respectively. Any nodal upstaging was found in 21% (13% pN1 and 8% pN2-3). Central tumor location demonstrated, compared to peripheral location, a 4 times higher risk for any nodal upstaging but not for N2-3 upstaging (table 1). When modern PET-CT fusion imaging points at clinical N0 NSCLC, the prevalence of occult mediastinal nodal disease was only 8% in our patient cohort. None of the five definitions of centrality we studied was predictive for occult pN2-N3. Overall nodal upstaging was 21%, however, and all definitions of centrality then had discriminatory value. These data question whether the indication of preoperative invasive mediastinal staging should be based on centrality alone.

OBJECTIVESNodal upstaging is a quality indicator for oncological thoracic surgery and is found in up to 25% of patients with clinical stage I (cStage-I) non-small-cell lung cancer (NSCLC). In large retrospective series, lower N1 upstaging was reported after video-assisted thoracic surgery (VATS) resections. We studied the impact of central primary tumour location on nodal upstaging in cStage-I NSCLC.METHODSConsecutive patients operated for cStage-I NSCLC were selected from a prospectively managed surgical database. Tumour location was classified as central if the lesion was visible during standard video bronchoscopy. A nodal station mapping was drawn for each patient based on final pathological examination. Univariable and additive multivariable binary logistic regression analyses were performed.RESULTSBetween 2007-2014, 334 patients underwent anatomical resection for cStage-I NSCLC, either by open thoracotomy (n = 158) or by VATS (n = 176; conversion rate 1.7%). All patients underwent imaging with [(18)F]-fluorodeoxyglucose positron emission tomography and computer tomography. Invasive mediastinal staging was performed in 24.6% of patients. There were more central tumours in the open group (24.1%, n = 38) compared with the VATS group (4.5%, n = 8). There was no significant difference between the number (mean ± standard deviation) of nodal stations examined (open 5 ± 1.9 vs VATS 5 ± 1.7, P = 0.99). Pathological nodal upstaging was found in 15.9% (n = 53) of cStage-I patients. Nodal pN1 and pN2 upstaging were 13.3 and 8.2%, respectively, for the open group, and 6.3 and 4.5%, respectively, for the VATS group. In 32.6% (n = 15/46) of patients with a central cStage-I tumour pN1, upstaging was found. A binary logistic regression model (including tumour location, technique, tumour size, gender and histology) showed that only tumour location had a significant impact on pN1 upstaging [peripheral versus central; odds ratio (OR) 5.07 (confidence interval, CI: 1.89-13.60), P = 0.001], while surgical technique had no significant impact [VATS versus open; OR 0.74 (CI: 0.31-1.78), P = 0.50].CONCLUSIONSThe number of lymph node stations examined during VATS resections is similar to open resections for cStage-I NSCLC. Almost one-third of the patients with a central cStage-I NSCLC were upstaged to pN1. Tumour location was the only independent variable for pN1 upstaging in logistic regression analysis. It is a potential bias in retrospective studies and should therefore be accounted for when comparing different surgical resection techniques for cStage-I NSCLC.