Recent studies have suggested that bone marrow-derived multipotent mesenchymal stem cells (MSCs) may have therapeutic applications in multiple clinical disorders including myocardial infarction, ...diabetes, sepsis, and hepatic and acute renal failure. Here, we tested the therapeutic capacity of human MSCs to restore alveolar epithelial fluid transport and lung fluid balance from acute lung injury (ALI) in an ex vivo perfused human lung preparation injured by E. coli endotoxin. Intra-bronchial instillation of endotoxin into the distal airspaces resulted in pulmonary edema with the loss of alveolar epithelial fluid transport measured as alveolar fluid clearance. Treatment with allogeneic human MSCs or its conditioned medium given 1 h following endotoxin-induced lung injury reduced extravascular lung water, improved lung endothelial barrier permeability and restored alveolar fluid clearance. Using siRNA knockdown of potential paracrine soluble factors, secretion of keratinocyte growth factor was essential for the beneficial effect of MSCs on alveolar epithelial fluid transport, in part by restoring amiloride-dependent sodium transport. In summary, treatment with allogeneic human MSCs or the conditioned medium restores normal fluid balance in an ex vivo perfused human lung injured by E. coli endotoxin.
The purpose of the review is to summarize the current status of immune checkpoint inhibitors as adjuvant therapy in patients with resected nonsmall cell lung cancer (NSCLC).
The IMpower010 phase 3 ...trial demonstrated improved disease-free survival and, in case of PD-L1 at least 50%, also improved overall survival for atezolizumab compared to best supportive care among patients with completely resected stage II-IIIA NSCLC. The PEARLS/KEYNOTE-091 trial showed increased disease-free survival for pembrolizumab among patients with stage IB-IIIA NSCLC. Trials with nivolumab and durvalumab are ongoing.
Atezolizumab or pembrolizumab have become options for adjuvant therapy in patients with completely resected NSCLC.
Abstract
OBJECTIVES: Early clinical stage (T1 and T2) non-small cell lung cancer (NSCLC) is commonly treated with anatomic lung resection and lymph node sampling or dissection. The aims of this study ...were to evaluate the incidence and the distribution of occult N2 disease according to tumour location and the short- and long-term outcomes.
METHODS: We performed a retrospective review of patients with clinical stage I NSCLC who underwent anatomic lung resection and lymphadenectomy. Mediastinal lymphadenectomy (ML) was defined as resection of at least 2 mediastinal stations, always including station 7 lymph nodes. Patients who had a lobe-specific lymphadenectomy were excluded.
RESULTS: One thousand six hundred and sixty-seven consecutive patients met inclusion criteria and were included. Overall, 9% (146/1667) of the patients had occult pN2 disease. At multivariable analysis, adenocarcinoma histology and vascular invasion were independently associated with greater risk of occult pN2 disease. In left and right upper lobe tumours, station 7 nodes were involved in 5 and 13% of pN2 positive cases, respectively. Station 5 and station 2/4 nodes were involved in 29 and 18% of left and right lower lobe pN2 tumours, respectively. There was no postoperative mortality, and postoperative morbidity was 28%. The median overall survival was 77.4 months. N0 patients had a median overall survival of 83.7 months vs 48.0 months and 37.9 months in N1 and N2 populations, respectively (P < 0.001).
CONCLUSIONS: Sixteen percent of pN2 patients had mediastinal lymph node metastasis beyond the lobe-specific lymphatic drainage. We recommend a complete lymphadenectomy be performed, even in clinical stage I NSCLC.
Spread through air spaces (STAS) is a novel invasive pattern of lung cancer associated with poor prognosis in non-small cell cancer (NSCLC). We aimed to investigate the incidence of STAS in a ...surgical series of adenocarcinomas (ADCs) resected in our thoracic surgery unit and to identify the association of STAS with other clinicopathological characteristics. We retrospectively enrolled patients with stage cT1a-cT2b who underwent resection between 2016 and 2022. For each case, a comprehensive pathologic report was accessible which included histotype, mitoses, pleural invasion, fibrosis, tumor infiltrating lymphocytes, necrosis, inflammation, vascular and perineural invasion, as well as STAS. PD-L1 expression was also investigated. A total of 427 patients with ADCs underwent surgery. Regarding overall survival (OS), no significant difference was observed between the STAS positive (STAS+) and STAS negative (STAS-) groups ( P =0.44). However, vascular invasion (VI) was associated with a poorer survival probability ( P =0.018). STAS+/VI+ patients had tendentially worse survival compared with STAS+/VI- ( P =0.089). ADCs with pathologic evidence of immune system (IS) activation (TILs>10% and PD-L1≥1) demonstrated significantly increased OS compared with ADCs with no IS and VI. In terms of recurrence rate, no statistical differences were found between the STAS+ and STAS- samples ( P =0.2). VI was also linked to a significantly elevated risk of recurrence ( P =0.0048). Our study suggests that in resected early-stage ADCs, STAS+ does not seem to influence recurrence or mortality. VI was instead an adverse pathologic prognostic factor for both survival and recurrence, whereas IS seemed to be protective.
Despite its prognostic importance, poor pathologic nodal staging of lung cancer prevails. We evaluated the impact of 2 interventions to improve pathologic nodal staging.
We implemented a lymph node ...specimen collection kit to improve intraoperative lymph node collection (surgical intervention) and a novel gross dissection method for intrapulmonary node retrieval (pathology intervention) in nonrandomized stepped-wedge fashion, involving 12 hospitals and 7 pathology groups. We used standard statistical methods to compare surgical quality and survival of patients who had neither intervention (group 1), pathology intervention only (group 2), surgical intervention only (group 3), and both interventions (group 4).
Of 4019 patients from 2009 to 2021, 50%, 5%, 21%, and 24%, respectively, were in groups 1 to 4. Rates of nonexamination of lymph nodes were 11%, 9%, 0%, and 0% and rates of nonexamination of mediastinal lymph nodes were 29%, 35%, 2%, and 2%, respectively, in groups 1 to 4 (P < .0001). Rates of attainment of American College of Surgeons Operative Standard 5.8 were 22%, 29%, 72%, and 85%; and rates of International Association for the Study of Lung Cancer complete resection were 14%, 21%, 53%, and 61% (P < .0001).
Compared with group 1, adjusted hazard ratios for death were as follows: group 2, 0.93 (95% CI, 0.76-1.15); group 3, 0.91 (0.78-1.03); and group 4, 0.75 (0.64-0.87). Compared with group 2, group 4 adjusted hazard ratio was 0.72 (0.57-0.91); compared with group 3, it was 0.83 (0.69-0.99). These relationships remained after exclusion of wedge resections.
Combining a lymph node collection kit with a novel gross dissection method significantly improved pathologic nodal evaluation and survival.
Background
Patient-reported outcomes are critical for obtaining valuable patient insight into different surgical treatment options with comparable clinical outcomes. This study aimed to compare early ...postoperative patient-reported symptoms and functioning between thoracoscopic segmentectomy and lobectomy for small-sized (≤ 2 cm) peripheral non-small-cell lung cancer (NSCLC).
Patients and Methods
This study included 110 patients who underwent thoracoscopic segmentectomy or lobectomy for peripheral NSCLC ≤ 2 cm in a multicenter prospective longitudinal study (CN-PRO-Lung 1). Symptom severity, functional status, and short-term clinical outcomes were compared between the groups. Symptom severity and functional status were measured using the MD Anderson Symptom Inventory−Lung Cancer at baseline, daily post-surgery, and weekly post-discharge for up to 4 weeks. Both the proportion of moderate-to-severe scores and mean scores on a 0–10 scale were compared between the groups.
Results
Overall, 48 and 62 patients underwent thoracoscopic segmentectomy and lobectomy, respectively. No significant between-group differences were found in the severity of the top five symptoms (coughing, shortness of breath, pain, fatigue, and disturbed sleep) or in the impairment of all six function items (work, walking, general activity, enjoyment of life, mood, and relations with others) during both the 6-day postoperative hospitalization and the 4-week post-discharge (all
p
> 0.05). Short-term clinical outcomes of postoperative hospital stay, operative time, drainage time, postoperative in-hospital oral morphine equivalent dose, and complication rate were also comparable (all
p
> 0.05).
Conclusions
In patients with peripheral NSCLC ≤ 2 cm, thoracoscopic segmentectomy and lobectomy might produce comparable symptom burden and functional impairment during the early postoperative period.
Approximately two-thirds of patients with early-stage non-small-cell lung cancer (NSCLC) in The Netherlands currently undergo surgical resection. As an increasing number of fit patients have elected ...to undergo stereotactic ablative radiotherapy (SABR) in recent years, we studied outcomes after SABR in patients with potentially operable stage I NSCLC.
In an institutional prospective database collected since 2003, 25% of lung SABR cases (n = 177 patients) were found to be potentially operable when the following patients were excluded: those with (1) synchronous lung tumors or other malignancy, (2) prior high-dose radiotherapy/pneumonectomy, (3) chronic obstructive pulmonary disease with a severity score of 3-4 according to the Global initiative for Obstructive Lung Disease classification. (4) a performance score of ≥3, and (5) other comorbidity precluding surgery. Study patients included 101 males and 76 females, with a median age of 76 years old, 60% of whom were staged as T1 and 40% of whom were T2. Median Charlson comorbidity score was 2 (range, 0-5). A SABR dose of 60 Gy was delivered using a risk-adapted scheme in 3, 5, or 8 fractions, depending on tumor size and location. Follow-up chest computed tomography scans were obtained at 3, 6, and 12 months and yearly thereafter.
Median follow-up was 31.5 months; and median overall survival (OS) was 61.5 months, with 1- and 3-year survival rates of 94.7% and 84.7%, respectively. OS rates at 3 years in patients with (n = 59) and without (n = 118) histological diagnosis did not differ significantly (96% versus 81%, respectively, p = 0.39). Post-SABR 30-day mortality was 0%, while predicted 30-day mortality for a lobectomy, derived using the Thoracoscore predictive model (Falcoz PE et al. J Thorac Cardiovasc Surg 2007;133:325-332), would have been 2.6%. Local control rates at 1 and 3 years were 98% and 93%, respectively. Regional and distant failure rates at 3 years were each 9.7%. Toxicity was mild, with grade ≥3 radiation pneumonitis and rib fractures in 2% and 3%, respectively.
Patients with potentially operable disease who underwent primary SABR had a median OS that exceeded 5 years. This finding supports ongoing randomized clinical trials comparing surgery and SABR in cases of operable stage I NSCLC.
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