Resection For Early-stage Lung Cancer Research Articles

Lung cancer after kidney transplantation: a 50-year experience at a single institution.

To investigate the clinical characteristics of lung cancer that develops after kidney transplantation. The clinical data of patients with lung cancer diagnosed after kidney transplantation were collected retrospectively. The medical records were extracted from our database. All patients underwent routine chest examination after kidney transplantation. In total, 17 lung tumors were detected in 15 (0.6%) of 2593 patients who underwent kidney transplantation at our institution. Eleven lung tumors were completely resected from a collective 10 patients (surgical group). The remaining five patients did not receive surgical treatment (nonsurgical group). The surgical group underwent wedge resection (n = 5), segmentectomy (n = 1), lobectomy (n = 3), and bilobectomy (n = 1). The pathological stages were 0 (n = 1), IA1 (n = 2), IA2 (n = 4), IA3 (n = 2), and IB (n = 1). The surgical group had a significantly better prognosis than the nonsurgical group. There were no perioperative complications related to kidney transplantation in either group. Routine chest examination would be useful for the early diagnosis and treatment of lung cancer after kidney transplantation. Moreover, surgical resection for early-stage lung cancer was associated with a better prognosis for kidney transplantation patients.

Perioperative immunotherapy in stage IB-III non-small cell lung cancer: a critical review of its rationale and considerations.

Lung cancer is a dismal disease as a leading cause of overall cancer death, but the development of immune checkpoint inhibitors (ICIs) in driver gene mutation negative metastatic non-small cell lung cancer (NSCLC) is changing the paradigm of lung cancer treatment. Recently, ICIs are expanding their treatment area to early-stage NSCLC and ICIs have also changed their treatment strategies of such patients. And it is important to appropriately select patients with resectable early-stage lung cancer through a multidisciplinary team approach and decrease the tumor relapse rate in the ICIs era. In this review article, we discuss the recently released neoadjuvant and adjuvant data of ICIs, their treatment rationale, and unmet needs in the treatment of early-stage NSCLC.

Risk factors for loss of pulmonary function after wedge resection for peripheral ground-glass opacity dominant lung cancer.

This study aimed to identify the risk factors for pulmonary functional deterioration after wedge resection for early-stage lung cancer with ground-glass opacity, which remain unclear, particularly in low-risk patients. We analysed 237 patients who underwent wedge resection for peripheral early-stage lung cancer in JCOG0804/WJOG4507L, a phase III, single-arm confirmatory trial. The changes in forced expiratory volume in 1 s were calculated pre- and postoperatively, and a cutoff value of -10%, the previously reported reduction rate after lobectomy, was used to divide the patients into 2 groups: the severely reduced group (≤-10%) and normal group (>-10%). These groups were compared to identify predictors for severe reduction. Thirty-seven (16%) patients experienced severe reduction. Lesions with a total tumour size ≥1 cm were significantly more frequent in the severely reduced group than in the normal group (89.2% vs 71.5%; P = 0.024). A total tumour size of ≥1 cm [odds ratio (OR), 3.287; 95% confidence interval (CI), 1.114-9.699: P = 0.031] and pleural indentation (OR, 2.474; 95% CI, 1.039-5.890: P = 0.041) were significant predictive factors in the univariable analysis. In the multivariable analysis, pleural indentation (OR, 2.667; 95% CI, 1.082-6.574; P = 0.033) was an independent predictive factor, whereas smoking status and total tumour size were marginally significant. Of the low-risk patients who underwent pulmonary wedge resection for early-stage lung cancer, 16% experienced severe reduction in pulmonary function. Pleural indentation may be a risk factor for severely reduced pulmonary function in pulmonary wedge resection.

Sublobar resection is not always superior for early-stage lung cancer in high-risk patients.

The phase III trial, Japan Clinical Oncology Group 0802, illustrated the superiority of sublobar resection for early-stage lung cancer in terms of overall survival, with more non-lung cancer-related deaths after a lobectomy. The advantages of sublobar resection may be more pronounced in high-risk patients. The goal of this study was to elucidate the prognoses of high-risk patients. Patients with a risk of being ineligible for Japan Clinical Oncology Group 0802 for general conditions were classified as the high-risk group, and those who were not at risk of being ineligible were classified as the normal-risk group. Overall survival and prognostic factors were analysed in the high-risk group. There were 254 (19.4%) and 1054 patients in the high- and normal-risk groups, respectively. Five-year survival rates were 94.5% and 79.1% in the normal-risk and high-risk groups, respectively (P < 0.001). More patients in the high-risk group died of lung cancer (P < 0.001) and non-lung cancer deaths (P < 0.001) than patients in the normal-risk group.In the high-risk group, 151 lobectomies and 103 sublobar resections were performed. There was no significant difference in the numbers of lung cancer deaths and of non-lung cancer deaths between the procedures. Stratified survival analyses showed that the diffusing capacity of the lungs for carbon monoxide  < 40% tended to favour sublobar resection; being female and having a high carcinoembryonic antigen level tended to favour a lobectomy. Sublobar resection is not always superior for early-stage lung cancer. Even in such cases, the surgical method should be determined by taking into consideration the patient's background and lung cancer surveillance.

Rapid Discharge After Anatomic Lung Resection: Is Ambulatory Surgery for Early Lung Cancer Possible?

BackgroundGiven resource constraints during the coronavirus disease 2019 pandemic, we explored whether minimally invasive anatomic lung resections for early-stage lung cancer could undergo rapid discharge. MethodsAll patients with clinical stage I-II non–small cell lung cancer from September 2019 to June 2022 who underwent minimally invasive anatomic lung resection at a single institution were included. Patients discharged without a chest tube <18 hours after operation, meeting preset criteria, were considered rapid discharge. Demographics, comorbidities, operative details, and 30-day outcomes were compared between rapid discharge patients and nonrapid discharge “control” patients. Multivariable logistic regression was performed for predictors of nonrapid discharge. ResultsOverall, 430 patients underwent resection (200 lobectomies and 230 segmentectomies); 162 patients (37%) underwent rapid discharge and 268 patients (63%) were controls. The rapid discharge group was younger (66.5 vs 70.0 years; P < .001), was assigned to lower American Society of Anesthesiologists class (P = .02), had more segmentectomies than lobectomies (P = .003), and had smaller tumors (P < .001). There were no differences between groups in distance from home to hospital (P = .335) or readmission rates (P = .39). Increasing age had higher odds for nonrapid discharge (odds ratio, 1.04; 95% CI, 1.02-1.07), whereas segmentectomy had decreased odds (odds ratio, 0.46; 95% CI, 0.28-0.75). ConclusionsApproximately 37% of the patients underwent rapid discharge after operation with similar readmission rate to controls. Increasing age had higher odds for nonrapid discharge; segmentectomy was likely to lead to rapid discharge. Consideration of rapid discharge minimally invasive lung resection for early-stage lung cancer can result in significant reduction in inpatient resources without adverse patient outcomes.

Changes in pulmonary function in lung cancer patients after segmentectomy or lobectomy: a retrospective, non-intervention, observation study.

Pulmonary segmentectomy (SE) became an increasingly popular method for resection of early-stage lung cancer. This study aims to compare the impact of single SE (SSE), multiple SE (MSE) and lobectomy (LE) on postoperative pulmonary function in patients with NSCLC. Medical records of a total of 1284 patients who underwent LE (n = 493), SSE (n = 558) and MSE (n = 233) at Shanghai Pulmonary Hospital from January 2013 to October, 2020 were retrospectively analysed. Pulmonary function tests (PFTs) were performed preoperatively and 12 months after surgery. SSE was associated with a significantly smaller decline in the PFT values compared to MSE and LE. There was a poor consistency between the observed and expected (O/E) loss of pulmonary function in all study groups (P < 0.05). Both LE and SE resulted in similar O/E ratios of all PFT parameters (P > 0.05). Overall loss of pulmonary function was much greater after LE than after both SSE and MSE. MSE was associated with higher postoperative pulmonary function decline compared to SSE but was still beneficial over LE. Both LE and SE groups had similar PFT loss per segment (P > 0.05).

Sublobar resection for early-stage lung cancer: the issue of safety margins.

The article by Akamine et al. [1] published in this issue of the journal comes at a time when the thoracic surgery community is questioning the optimal surgical treatment of early-stage NSCLC, after the final results of the JCOG 0802 trial [2] and the partial results of the CALBG/Alliance 140503 trial. Things seemed pretty clear with the conclusion of the JCOG 0802 trial recommending anatomical segmentectomy over lobectomy because—despite a significantly higher recurrence rate in the segmentectomy group—survival was significantly better than for lobectomies [2]. The CALBG 140503 trial shows equivalent survival between sublobar resection (SLR) and lobectomy but the SLR group includes segmentectomies and wedge resections. However, as there are more wedge resections than segmentectomies in the SLR arm, the temptation is to assume that the results apply to wedges. At the time of writing this commentary, we are awaiting the final results and do not have a subgroup analysis.

Association Between Surgical Quality Metric Adherence and Overall Survival Among US Veterans With Early-Stage Non–Small Cell Lung Cancer

Surgical resection remains the preferred treatment for functionally fit patients diagnosed with early-stage non-small cell lung cancer (NSCLC). Process-based intraoperative quality metrics (QMs) are important for optimizing long-term outcomes following curative-intent resection. To develop a practical surgical quality score for patients diagnosed with clinical stage I NSCLC who received definitive surgical treatment. This retrospective cohort study used a uniquely compiled data set of US veterans diagnosed with clinical stage I NSCLC who received definitive surgical treatment from October 2006 through September 2016. The data were analyzed from April 1 to September 1, 2022. Based on contemporary treatment guidelines, 5 surgical QMs were defined: timely surgery, minimally invasive approach, anatomic resection, adequate lymph node sampling, and negative surgical margin. The study developed a surgical quality score reflecting the association between these QMs and overall survival (OS), which was further validated in a cohort of patients using data from the National Cancer Database (NCDB). The study also examined the association between the surgical quality score and recurrence-free survival (RFS). Surgical treatment of early-stage NSCLC. Overall survival and RFS. The study included 9628 veterans who underwent surgical treatment between 2006 and 2016. The cohort consisted of 1446 patients who had a mean (SD) age of 67.6 (7.9) years and included 9278 males (96.4%) and 350 females (3.6%). Among the cohort, 5627 individuals (58.4%) identified as being smokers at the time of surgical treatment. The QMs were met as follows: timely surgery (6633 [68.9%]), minimally invasive approach (3986 [41.4%]), lobectomy (6843 [71.1%]) or segmentectomy (532 [5.5%]), adequate lymph node sampling (3278 [34.0%]), and negative surgical margin (9312 [96.7%]). The median (IQR) follow-up time was 6.2 (2.5-11.4) years. An integer-based score (termed the Veterans Affairs Lung Cancer Operative quality [VALCAN-O] score) from 0 (no QMs met) to 13 (all QMs met) was constructed, with higher scores reflecting progressively better risk-adjusted OS. The median (IQR) OS differed substantially between the score categories (score of 0-5 points, 2.6 [1.0-5.7] years of OS; 6-8 points, 4.3 [1.7-8.6] years; 9-11 points, 6.3 [2.6-11.4] years; and 12-13 points, 7.0 [3.0-12.5] years; P < .001). In addition, risk-adjusted RFS improved in a stepwise manner between the score categories (6-8 vs 0-5 points, multivariable-adjusted hazard ratio [aHR], 0.62; 95% CI, 0.48-0.79; P < .001; 12-13 vs 0-5 points, aHR, 0.39; 95% CI, 0.31-0.49; P < .001). In the validation cohort, which included 107 674 nonveteran patients, the score remained associated with OS. The findings of this study suggest that adherence to intraoperative QMs may be associated with improved OS and RFS. Efforts to improve adherence to surgical QMs may improve patient outcomes following curative-intent resection of early-stage lung cancer.

Tumor-identification method for predicting recurrence of early-stage lung adenocarcinoma using digital pathology images by machine learning

Lung cancer is one of the cancers with the highest morbidity and mortality in the world. Recurrence often occurs even after complete resection of early-stage lung cancer, and prediction of recurrence after resection is clinically important. However, the pathological characteristics of the recurrence of pathological stage IB lung adenocarcinoma (LAIB) have not yet been elucidated. Therefore, the problem is what type of histological image of lung adenocarcinoma recurs, and it is important to examine the histological image of recurrence. We attempted to predict recurrence of early lung adenocarcinoma after resection on the basis of digital pathological images of hematoxylin and eosin-stained specimens and machine learning applying a convolutional neural network. We constructed a model that extracts the features of two-color spaces and a switching model that automatically switches between our extraction model and one that extracts the features of one-color space for each image. We then developed a tumor-identification method for predicting the presence or absence of LAIB recurrence using these models. We conducted an experiment involving 55 patients with LAIB who underwent surgical resection to evaluate the proposed method. The proposed method determined LAIB recurrence with an accuracy of 84.8%. The use of digital pathology and machine learning can be used for highly accurate prediction of LAIB recurrence after surgical resection. The proposed method has the potential for objective postoperative follow-up observation.

Highlights from Recent Cancer Literature.

In order to understand the relationship between the presence of bacteria and cancer prognosis, Ghaddar and colleagues developed a single-cell analysis of host-microbiome interactions (SAHMI) computational pipeline to identify bacteria from single-cell RNA sequencing datasets from patients with pancreatic ductal adenocarcinomas (PDAC). They found that ∼0.6% of total reads could be attributed to microbial species. Using a series of controls to denoise potential contaminants and artifacts, the authors predicted that ∼0.01% of the reads were genuine intracellular-associated microbiota. Using barcodes from scRNA-seq for individual cells, they linked each bacterium to particular cell types. Bacterial reads were most strongly enriched in tumor cells themselves. Specific types of bacteria were associated with specific gene expression patterns, e.g., angiogenesis, differentiation, and metastasis. Tumors with greater bacterial loads exhibited increased fractions of activated T cells and natural killer cells. Finally, they showed that the presence of bacteria in tumors was associated with decreased survival across several cohorts of PDAC patients.Expert Commentary: A subset of pancreatic cancers harbors intracellular bacteria, associated with worse overall survival in patients.Ghaddar B, Biswas A, Harris C, Omary MB, Carpizo DR, Blaser MJ, et al. Tumor microbiome links cellular programs and immunity in pancreatic cancer. Cancer Cell 2022;40:1240-53.e1245. doi: 10.1016/j.ccell.2022.09.009.To discern meningioma risk after treatment for childhood cancer, Withrow and colleagues performed a pooled case-control study of four international cohorts comprising 1011 survivors, 273 of whom developed meningioma. Not surprisingly, meningioma cases occurred most frequently among survivors of central nervous system tumors. Using doses reconstructed to the meningioma site, a fitted linear dose-response model was developed showing that odds of meningioma increased with radiotherapy dose. Risk of meningioma was highest with doses above 24Gy, decreased with age, and was highest in children under age 10. The risk of meningioma remained elevated for 30 years after exposure. Interestingly, methotrexate exposure, both systemic and intrathecal, was associated with a significantly increased risk of meningioma development.Expert Commentary: This study represents the largest analysis of radiation-induced meningiomas to date, powered to clearly identify risk factors. This study supports long-term meningioma surveillance for children radiated under age 10 and recipients of intrathecal or systemic methotrexate.Withrow DR, Anderson H, Armstrong GT, Hawkins M, Journy N, Neglia JP, et al. Pooled analysis of meningioma risk following treatment for childhood cancer. JAMA Oncology; Published online October 6, 2022; doi: 10.1001/jamaoncol.2022.4425.Almost half of patients with resected early-stage lung cancer will experience recurrence, but our ability to predict recurrence is limited. Liu and colleagues identified a recurrent germline SNP in BRMS1, which significantly increased the risk of recurrence. The resulting BRMS1A273V mutant isoform increased migration and metastases through upregulation of the c-fos/CEACAM6 pathway in vitro and in vivo. Remarkably, treatment with a clinical c-fos inhibitor prevented metastases in BRMS1A273V mutant lung cancer.Expert Commentary: This study has not only a identified a recurrent germline SNP as a predictor of recurrence but, in addition, has suggested a novel therapeutic strategy to prevent metastases in BRMS1A273V mutant non-small cell lung cancer.Liu Y, Chudgar N, Mastrogiacomo B, He D, Lankadasari MB, Bapat S, et al. A germline SNP in BRMS1 predisposes patients with lung adenocarcinoma to metastasis and can be ameliorated by targeting c-fos. Science Translational Medicine; Published online October 5, 2022; doi: 10.1126/scitranslmed.abo1050.Checkpoint inhibitors show the highest benefits in triple-negative breast cancer, while luminal, hormone receptor–positive disease is inherently insensitive. Hong and colleagues identified that EZH2, a component of the PRC2 complex, promotes immune escape through epigenetic changes of immune-related genes in either cancer cells or surrounding immune cells. Pharmacological and genetic inhibition of cancer intrinsic EZH2 stimulated antitumor immunity by activating interferon signaling in ERα+ breast cancer. After treatment with EZH2 inhibitors, STAT2 was recruited to the promoters of interferon-stimulated genes and STAT2, rather than STAT1, played a critical role in mediating the immunostimulatory functions of type I interferon signaling. High levels of EZH2, but low levels of STAT2, were associated with worse antitumor immune responses in patients with luminal breast cancer.Expert Commentary: Activation of the type I IFN-STAT2 axis upon EZH2 inhibition serves a pivotal role in establishing an antitumor microenvironment in luminal breast cancer. This provides an opportunity for developing an anticancer strategy by combining EZH2 inhibitors with immunotherapy.Hong J, Lee JH, Zhang Z, Wu Y, Yang M, Liao Y, et al. PRC2-mediated epigenetic suppression of type I IFN-STAT2 signaling impairs antitumor immunity in luminal breast cancer. Cancer Res 2022;82:4624-40.Clear cell kidney cancer (ccRCC) is the most common adult renal tumor. Prognosis is often favorable for localized disease, whereas spread to the skeleton, which occurs in a third of patients, is associated with poor outcome. Alchahin and colleagues collected tumor material (including bone metastases) and nearby normal kidney tissue from the same patient to make matched comparisons and to control for interindividual variation. Using single-cell RNA sequencing, the researchers identified a specific four-gene signature prognostic of the ability of ccRCC cells to form metastases and thus drive poor patient outcome. Notably, they showed that the tumor microenvironment inhibited an immune response. In silico analyses suggested signaling via the ligand receptor axes CXCL9/CXCL10-CXCR3 and CD70-CD27 as putative targets for novel therapies.Expert Commentary: This study sheds light on how knowledge of the relationship between ccRCCs and the tumor microenvironment can be the basis for development of novel cancer medicines.Alchahin AM, Mei S, Tsea J, Hirz T, Kfoury Y, Dahl D, et al. A transcriptional metastatic signature predicts survival in clear cell renal cell carcinoma. Nature Commun 2022; 13:5747. doi: 10.1038/s41467-022-33375-w.The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms separates acute myeloid leukemia (AML) with defining genetic abnormalities from AML defined by differentiation, new, and/or uncommon AML subtypes that await future definitions. A letter by Ryland and colleagues reports a novel subtype of AML characterized by somatic recurrent in-frame insertion mutations in core-binding factor beta (CBFB) leading to an amino acid change at position 87 (called GDXY). These AML mutational cases separate from the classified CBF subgroup in lacking KIT mutations and enriching for FLT3-TKD mutations, showing stemness-related gene expression associated with relapsed or refractory disease and with younger age. The authors provisionally termed this group CBFB-GDXY. Further investigation is required to understand the clinical relevance of this novel entity.Expert Commentary: Functional and clinical investigations are needed to understand the relevance of a novel AML entity, CBFB-GDXY. This subtype would fit in the current WHO classification structure “AML with other defined genetic alterations.”Ryland G, Umeda M, Holmfeldt L, Lehmann S, Herlin MK, Ma JJ, et al. Description of a novel subtype of acute myeloid leukemia defined by recurrent CBFB insertions. Blood; Published online September 30, 2022; doi: 10.1182/blood.2022017874.Note: Breaking Insights are written by Cancer Research editors. Readers are encouraged to consult the articles referred to in each item for full details on the findings described.

EP02.03-011 Timeliness of Surgery for Early-Stage Lung Cancer: Perspectives from Surgeons and Patients

Surgical resection remains the gold standard for treatment of early-stage lung cancer. There has been extensive research on the association between time to treatment initiation (TTI) and survival for lung cancer, with most studies finding a negative association including a recent systematic review. Nevertheless, there is no widely accepted standard for the appropriate TTI for patients undergoing surgical resection for early-stage lung cancer, though different guidelines exist, ranging from 2-8 weeks.

Intraoperative quality metrics and association with survival following lung cancer resection.

8502 Background: Surgical resection remains the preferred treatment for functionally fit patients with clinical stage I non-small cell lung cancer (NSCLC). Process-based intra-operative quality metrics (QMs) are important for optimizing long-term outcomes following curative-intent resection. We sought to characterize overall survival using a novel surgical quality score. Methods: We performed a retrospective cohort study using a uniquely compiled dataset of US Veterans with clinical stage I NSCLC receiving definitive surgical treatment. Based on contemporary treatment guidelines, we defined five surgical QMs: timely surgery (within 12 weeks of diagnosis), minimally invasive approach, anatomic resection via lobectomy, adequate nodal sampling (≥10 nodes), and negative margin. Using a multivariable Cox proportional hazards model, we developed a surgical quality score reflecting the relationship between these QMs and overall survival (OS). We also examined the relationship between this score and disease-free survival (DFS). Results: The study included 9,628 Veterans undergoing surgical treatment between 2006 and 2016. QMs were met as follows: timely surgery (n=6,633, 68.9%), minimally invasive approach (n=3,986, 41.4%), lobectomy (n=6,843, 71.1%), adequate nodal sampling (n=3,278, 34.1%), and negative surgical margin (n=9,312, 96.7%). The median (IQR) follow-up was 6.2 (2.5-11.4) years. A normalized score from 0 (no QMs met) to 100 (all QMs met) was constructed, with higher scores reflecting progressively improved risk-adjusted OS (Table). The median (IQR) OS was 86.8 (37.8-149.6) months in the highest score quintile versus 25.3 (7.1-45.8) months in the lowest score quintile. Recurrence was detected in 2,268 (23.6%) patients. Higher surgical quality score was associated with improved DFS (multivariable-adjusted hazard ratio, aHR 0.494, 95% CI 0.245-0.997). Conclusions: Adherence to intra-operative QMs is associated with markedly improved overall and disease-free survival. Efforts to improve adherence to surgical QMs can dramatically improve patient outcomes following curative-intent resection of early-stage lung cancer. [Table: see text]

Differentiation between staple line granuloma and recurrence after sublobar resection for primary lung cancer.

BackgroundThe use of sublobar resection for early-stage lung cancer or frail cases that cannot tolerate radical surgery for primary lung cancer has been increasing. This study aimed to identify the frequency, shape, and course of staple line thickening and granuloma formation after sublobar resection for primary lung cancer, and to identify factors that help distinguish them from recurrent cancer cases.MethodsThe medical records of 64 patients who underwent sublobar resection for primary lung cancer from January 2012 to December 2017 at our institution were retrospectively reviewed. Computed tomography (CT) images taken every 6 months for at least 3 years after surgery were reviewed, and the postoperative course was examined.ResultsStaple line thickening at the time of the first CT scan after surgery was observed in 43 cases (67.2%). Of them, linear thickening was seen in 31 cases (72.1%), and nodular thickening was seen in 12 cases (27.9%). Of these 43 cases, 25 cases were decreased, 8 cases were unchanged and 10 cases showed a tendency to progress during the follow-up period. Of the 64 cases, 7 (10.9%) had staple line recurrence. Staple line recurrence was significantly correlated with vascular invasion (P=0.015), surgical margin (P=0.013), nodular thickening (P<0.001) and a tendency to show progressive thickening (P<0.001).ConclusionsStaple line thickening was observed in many cases of sublobar resection, and most of them were linear thickening. Staple line recurrence should be suspected if nodular thickening appears and shows a tendency to progress.

Transketolase Serves as a Biomarker for Poor Prognosis in Human Lung Adenocarcinoma.

Despite apparently having completed surgical resection, approximately half of resected early-stage lung cancer patients relapse and die of their disease. Adjuvant chemotherapy reduces this risk by only 5% to 8%. Thus, there is a need for better identifying the drivers of relapse, who benefits from adjuvant therapy, and novel targets in this setting. Although emerging evidence has suggested a strong link between the pentose phosphate pathway (PPP) and cancer, the role of transketolase (TKT), an enzyme in the nonoxidative branch of the PPP that connects PPP and glycolysis, remains obscure in Lung adenocarcinoma (LUAD). In this study, TKT expression was first identified in The Cancer Genome Atlas (TCGA) and then validated with our database. TKT was upregulated at protein levels in cancer compared with normal tissues (P <0.05), and high TKT expression was associated with advanced tumor stage in our cohorts. Besides, TKT inhibitor promotes tumor cell apoptosis and cell cycle blockade. Clearly, TKT plays a critical role in LUAD progression and prognosis and could be a potential biomarker for prediction of recurrence after lung cancer resection.

Genetic and immunologic features of recurrent stage I lung adenocarcinoma

Although surgery for early-stage lung cancer offers the best chance of cure, recurrence still occurs between 30 and 50% of the time. Why patients frequently recur after complete resection of early-stage lung cancer remains unclear. Using a large cohort of stage I lung adenocarcinoma patients, distinct genetic, genomic, epigenetic, and immunologic profiles of recurrent tumors were analyzed using a novel recurrence classifier. To characterize the tumor immune microenvironment of recurrent stage I tumors, unique tumor-infiltrating immune population markers were identified using single cell RNA-seq on a separate cohort of patients undergoing stage I lung adenocarcinoma resection and applied to a large study cohort using digital cytometry. Recurrent stage I lung adenocarcinomas demonstrated higher mutation and lower methylation burden than non-recurrent tumors, as well as widespread activation of known cancer and cell cycle pathways. Simultaneously, recurrent tumors displayed downregulation of immune response pathways including antigen presentation and Th1/Th2 activation. Recurrent tumors were depleted in adaptive immune populations, and depletion of adaptive immune populations and low cytolytic activity were prognostic of stage I recurrence. Genomic instability and impaired adaptive immune responses are key features of stage I lung adenocarcinoma immunosurveillance escape and recurrence after surgery.

Outcomes and experience of anatomical partial lobectomy

ObjectiveThe use of limited anatomic resection for early-stage lung cancer is widely practiced worldwide. However, most studies have focused on standard segmentectomy or subsegmentectomy, and data on the short-term outcomes after anatomic sublobar resection in China are lacking. MethodsIn 2014, the use of anatomic partial lobectomy (APL), which is defined as lesion-centered resection of anatomical sublobular parts, was proposed by the National Cancer Center in China. We retrospectively evaluated all consecutive patients who underwent APL between November 2013 and October 2019 from our database, and the operative techniques and short-term outcomes were analyzed. ResultsA total of 3336 patients with a median age of 56 years underwent APL during the study period. Benign lesions were present in 8.5% of all patients and decreased across time. The mean total operation time was 127.3 minutes, the mean overall number of nodal sampling/dissections was 13, and the mean number of stations sampled was 4. Postoperative complications (grade ≥2) developed in 359 patients (10.8%), and no mortality occurred in the 30 days after surgery. Multivariate analysis showed that smoking, surgeon's early experience, thoracotomy or unplanned conversion to thoracotomy, and complex cases were risk factors for the occurrence of postoperative complications. ConclusionsDespite the increasing proportion of complex cases treated with APL, the incidence of postoperative complications decreased as our center accumulated surgical experience. APL procedures are safe and feasible when conducted in a specialized center.

Gut microbiome functionality might be associated with exercise tolerance and recurrence of resected early-stage lung cancer patients

Impaired exercise tolerance and lung function is a marker for increased mortality in lung cancer patients undergoing lung resection surgery. Recent data suggest that the gut-lung axis regulates systemic metabolic and immune functions, and microbiota might alter exercise tolerance. Here, we aimed to evaluate the associations between gut microbiota and outcomes in lung cancer patients who underwent lung resection surgery. We analysed stool samples, from 15 early-stage lung cancer patients, collected before and after surgical resection using shotgun metagenomic and Internal Transcribed Spacer (ITS) sequencing. We analysed microbiome and mycobiome associations with post-surgery lung function and cardiopulmonary exercise testing (CPET) to assess the maximum level of work achieved. There was a significant difference, between pre- and post-surgical resection samples, in microbial community functional profiles and several species from Alistipes and Bacteroides genus, associated with the production of SCFAs, increased significantly in abundance. Interestingly, an increase in VO2 coincides with an increase in certain species and the "GABA shunt" pathway, suggesting that treatment outcome might improve by enriching butyrate-producing species. Here, we revealed associations between specific gut bacteria, fungi, and their metabolic pathways with the recovery of lung function and exercise capacity.

Benefit of Three-dimensional Image Simulation in Surgical Resection of Early-stage Lung Cancer

BackgroundThe present study investigated the oncologic outcomes of clinical stage IA2 non-small cell lung cancer (NSCLC) treated using preoperative simulation and surgical resection. MethodsData of patients who underwent surgical resection for clinical stage IA2 NSCLC between January 2002 and June 2018 were reviewed. Preoperative simulations were indicated for patients with centrally located tumors who could undergo anatomic resection. Clinical features, imaging characteristics of the tumors, surgical approaches, and outcomes were analyzed. ResultsOf the 1086 identified patients, 281 patients with clinical stage IA2 NSCLC were enrolled and categorized into 2 groups, with and without preoperative simulation. Tumor location, maximum standard uptake value, histologic grade, disease-free survival, and disease recurrence were significantly different between the 2 groups. For patients with preoperative simulations, 70.7% underwent anatomic resection, whereas for patients without preoperative simulations, 79.7% underwent anatomic resection (P < .001). Patients with preoperative simulations had fewer relapses (2%) than patients without preoperative simulations (11.5%, P < .01). ConclusionsPreoperative simulation confirmed the relationship between the tumor and surrounding blood vessels and bronchus and ensured an oncologic safety margin. Three-dimensional simulations are a useful and feasible tool for planar operative procedures and satisfy the requirements for early-stage NSCLC. These results are promising but preliminary, and more extended follow-up is needed.

Preoperative Maximum Standardized Uptake Value Associated With Recurrence Risk in Early Lung Cancer

BackgroundThis study aimed to investigate the maximum standardized uptake value (SUVmax) as a predictor of recurrence and timing of recurrence after resection of early-stage non-small cell lung cancer. MethodsThe study retrospectively reviewed patients from a single institution who underwent lobectomy for stage I to IIa non-small cell lung cancer from 2013 to 2018. Exclusion criteria included preoperative therapy and neuroendocrine histologic type. The study investigators collected recurrence and follow-up data, as well as preoperative SUVmax. A receiver operating characteristic curve was used to identify the optimal SUVmax for predicting recurrence. Kaplan-Meier curves and Cox regression analyses were used to identify predictors of freedom from recurrence (FFR). ResultsThe study included 238 patients, 30 (12.6%) of whom had disease recurrence. The receiver operating characteristic curve had an area under the curve of 0.671 and identified 4.93 as the optimal SUVmax cutoff. Patients were stratified into groups on the basis of this value; each group included 119 patients. High SUVmax was associated with larger tumor size, poor differentiation, lymphovascular invasion, and shorter FFR. The proportion of patients without recurrence at 5 years in the low- and high-SUVmax groups were 92.4% and 73.4%, respectively (P < .001). On univariate analysis, poor differentiation (hazard ratio [HR],2.35; 95% confidence interval [CI], 1.04 to 5.31; P = .04), lymphovascular invasion (HR, 3.19; 95% CI, 1.37 to 7.44; P = .007), visceral pleural invasion (HR, 2.33; 95% CI, 1.05 to 5.20; P = .04), and SUVmax 4.93 or greater (HR, 4.51; 95% CI, 1.84 to 11.03; P = .001) predicted FFR. On multivariable analysis, only SUVmax 4.93 or greater remained significant (HR, 5.36; 95% CI, 1.50 to 19.17; P = .01). ConclusionsSUVmax is independently associated with a risk of recurrence after resection of early-stage lung cancer. SUVmax may be a valuable tool for stratifying patients with early-stage lung cancer for adjuvant therapy and surveillance frequency.

A narrative review of invasive diagnostics and treatment of early lung cancer.

The diagnosis and treatment of early-stage lung cancer remains a clinical challenge. The broadening implementation of lung cancer screening has resulted in positive findings in numerous patients that are mostly non-malignant. Many other patients have indeterminate nodules that are difficult to assess through simple observation. The critical interpretation of such screening results remains a challenge for radiologists and multidisciplinary teams involved in screening for lung cancer. The evaluation and diagnosis of each participant suspected for malignancy should be based on the basic clinical principles such as a carefully collected medical history, physical examination, and detailed analysis of all imaging tests performed. Indeed, the decision to go ahead with more invasive diagnostics requires consideration of the both the risks and benefits, with reflection upon the complete clinical and radiological picture. Although transthoracic needle aspiration biopsy remains the first-choice method of diagnosis, several newer technologies have slowly begun to emerge as potential replacements. The guiding strategy for method selection is to choose the least harmful approach that offers the most relevant potential insights. Transthoracic biopsy is an effective method that allows the collection of cytological and tissue material from small, peripheral tumors, but it carries a moderate risk of complications. Bronchofiberoscopy, especially in combination with electromagnetic navigation, fluoroscopy or radial EBUS, also allows effective diagnosis of the peripheral pulmonary nodules. One of the most important diagnostic methods is the EBUS examination, which allows determining of staging in addition to diagnosis. Anatomical lung lobe resection and lymphadenectomy or sampling of the hilar and mediastinal lymph nodes is currently the treatment of choice for patients with stage I and II non-small cell lung cancer (NSCLC), but sublobar resections are recommended when a patient has limited pulmonary function or other significant comorbidities. Notably, several studies have highlighted the potential utility of more limited resections in small malignant lesions less than 2cm in diameter, with pure AIS histology, when more than 50% of the diameter of pulmonary nodule has ground-glass opacity (GGO) attenuation on CT, or long volume doubling time (VDT). Videothoracoscopy is the preferred surgical approach for resection of early-stage lung cancer. Patients who are not candidates for surgery or do not agree to surgery can be offered radical radiotherapy. Stereotactic body radiation therapy (SBRT) is a type of radical radiotherapy with proven effectiveness, a high rate of local control and an acceptable risk of the development of later complications. Future trials are expected to define the role of SBRT in the treatment of early lung cancer in healthy subjects.