Bronchial washing fluid sequencing is useful in the diagnosis of lung cancer with necrotic tumor.

BACKGROUND: Early-stage lung cancers detected by low-dose computed tomography (CT) often require confirmation through invasive procedures due to the absence of endobronchial lesions. This study assesses the diagnostic utility of bronchial washing fluid (BW) sequencing, a less invasive alternative, aiming to identify patient characteristics most suited for this approach. METHODS: From June 2017 to March 2018, we conducted a prospective cohort study by enrolling patients with incidental lung lesions suspected of early-stage lung cancer at two independent hospitals, and 114 were diagnosed with lung cancer while 50 were diagnosed with benign lesions. BW sequencing was performed using a targeted gene panel, and the clinical characteristics of patients detected with cancer through sequencing were identified. RESULTS: Malignant cells were detected in 33 patients (28.9 %) through BW cytology. By applying specificity-focused mutation criteria, BW sequencing classified 42 patients (36.8 %) as having cancer. Among the cancer patients who were BW sequencing positive and BW cytology negative, 15 patients (75.0 %) showed necrosis on CT. The sensitivity of BW sequencing was particularly enhanced in patients with necrotic tumors, reaching 75 %. CONCLUSIONS: BW sequencing presents a viable, non-invasive diagnostic option for early-stage lung cancer, especially valuable in patients with necrotic lesions. By potentially reducing the reliance on more invasive diagnostic procedures, this method could streamline clinical workflows, decrease patient burden, and improve overall diagnostic efficiency.

New diagnostic and nonsurgical local treatment modalities for early stage lung cancer.

This paper highlights developments in diagnostic and nonsurgical local treatment modalities that have changed the management of early-stage lung cancer. These innovations aim to enhance diagnostic accuracy, minimize invasiveness, and improve patient outcomes. Liquid biopsies are emerging as promising tools for non-invasive diagnosis and monitoring, enabling earlier intervention without being standardized yet as well as not yet anchored in the guidelines. Endobronchial navigation has emerged as an innovative tool. By combining electromagnetic or GPS-like technology with 3D imaging and a steerable catheter, it enables accurate biopsy of small, peripheral lesions that were once challenging to sample, with a very low pneumothorax rate. Regarding nonsurgical treatments, stereotactic body radiotherapy (SBRT) continues to shine as a non-invasive local treatment modality for early-stage lung cancer and is the guideline-recommended standard-of-care for inoperable patients and patients refusing the risk of surgical resection. The low toxicity and excellent local control has made it an attractive alternative to surgery even in fitter patients. Percutaneous ablative techniques utilising energies such as microwave or pulse-field electroporation are options for patients who are not candidates for surgery or SBRT. Bronchoscopic ablation delivers the same energies but with a very lower pneumothorax rate and it is therefore also open to patients with multiple and bilateral lesions.

Patients With Surgically Resectable Lung Cancer Who Opt for Radiation Have Worse Outcomes.

BACKGROUND: Surgery has been the standard procedure for resectable primary LC. Survival after stereotactic body radiation therapy, another treatment, is significantly biased due to preponderance of data from patients deemed unsuitable for surgery. We examined survival of patients refusing surgery in favor of radiation therapy. METHODS: We used the Surveillance, Epidemiology, and End Results database to identify patients with primary Stage I NSCLC diagnosed between 2007 and 2016. Patients were excluded if it was unknown if they were recommended for surgery or if surgery was contraindicated. Multiple predictors were assessed: radiation versus surgery, age at diagnosis, sex, race/ethnicity, health insurance status, marital status, tumor size, and histology. A multivariate analysis was performed to estimate hazard ratios and generate Kaplan-Meier survival curves. RESULTS: When adjusted for confounding variables, survival was greater for patients undergoing surgical resection than those refusing surgery in favor of radiation (HRadj 2.66; 95% CI: 2.27-3.11, p < 0.001) or for those receiving no standardized treatment (HRadj 4.43; 95% CI: 3.57-5.50, p < 0.001). CONCLUSIONS: SBRT is an effective treatment for inoperable early LC but there is limited data comparing outcomes against surgical resection. When eligible for both, patients refusing surgery and choosing radiation had worse survival when adjusting for variables including age, tumor size, and histology, and suggests that surgical resection is a superior treatment modality.

Impact of imaging features on selecting limited lymph node resection for cT1N0M0 lung cancer.

Background: Controversy still exists in the medical community regarding the performance of limited mediastinal lymphadenectomy (LML) in early-stage lung cancer. The objective of this study was to identify predictors of mediastinal lymph node (mLN) status and analyze its role in guiding surgical strategy. Methods: A retrospective cohort study was conducted on 2,834 surgical patients with peripheral cT1N0M0 non-small cell lung cancer between 2016 and 2018. Logistic regression was employed to identify predictors of N2 metastasis. Prognosis was compared between groups and independent prognostic factors were identified using Kaplan-Meier and multivariate Cox analysis. Results: There were 2,126 patients with systematic mLN dissection and 708 with LML. The multivariate analysis showed that N2 metastasis were associated with tumor size and consolidation tumor ratio (CTR). Patients in group A, with CTR >0.5 and tumor size ≤1 cm or CTR ≤0.5, had a significantly lower rate of N2 metastasis compared to those in group B, with CTR >0.5 and tumor size >1 cm (14.2% vs. 0.2%, P<0.001). Additionally, LML demonstrated comparable recurrence-free survival (RFS) and overall survival (OS) in group A, but a worse prognosis in group B compared to systematic lymph node dissection (SND). Furthermore, multivariate Cox regression analysis indicated that SND (vs. LML) was a favorable prognostic predictor for patients in group B [RFS: hazard ratio (HR) =0.71, P=0.005; OS: HR =0.66, P=0.01]. But univariate analysis in group A showed no significant difference in prognosis between SND and LML (RFS: P=0.24; OS: P=0.10). Conclusions: The combination of CTR and tumor size can predict mLN metastasis and procedure-specific outcome (SND vs. LML). This information may assist surgeons in identifying suitable candidates for LML.

Preoperative early-stage lung cancer patients and local brain area changes: a cross-sectional observational descriptive study.

Introduction: Lung cancer is a major global health concern. Patients undergo a substantial process of emotional transformation following a lung cancer diagnosis, during which subtle changes in brain function and/or structure may occur. As such, the present study aimed to investigate the neuroplastic changes induced by negative emotions in patients with early-stage lung cancer. Methods: This cross-sectional study recruited 35 patients with early-stage lung cancer and 33 age- and sex-matched healthy control patients. All participants completed the Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), and functional magnetic resonance imaging (fMRI). Amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were used as the fMRI indices. Correlations between the clinical assessments and ALFF and ReHo values were calculated. Results: Our analysis revealed no significant differences in HAMD and HAMA scores between patients and control patients (p > 0.05). However, significant alterations in ALFF and ReHo were observed in multiple brain regions in patients with early-stage lung cancer compared to healthy controls (P FalseDiscoveryRate < 0.05). Specifically, ALFF values were decreased in the right postcentral gyrus, calcarine, and left middle cingulate, while ReHo values increased in the right angular gyrus and decreased in the bilateral postcentral gyrus, insula, left calcarine, putamen, superior temporal gyrus, middle cingulate, and right Rolandic gyrus. The HAMD score was significantly correlated with the ALFF value in the right postcentral gyrus (P = 0.007). Conclusion: This study provides valuable insights into the adaptive responses of the brain following the early diagnosis of lung cancer, revealing potential disturbances in negative emotional processing. Harnessing neuroplasticity may open new avenues for the establishment of personalized treatment strategies and targeted interventions to support the emotional and mental health of patients with lung cancer.

Timeliness of surgery for early-stage lung cancer: Patient factors and predictors.

Objectives: Time-to-treatment initiation is an important consideration for patients undergoing thoracic surgery for early-stage lung cancer because delays have the potential to adversely affect outcomes. This study seeks to quantify time-to-treatment initiation for patients with clinical stage I lung cancer, explore patient factors and predictors that lead to an increased time-to-treatment initiation, and compare surgeon perception of appropriate time-to-treatment initiation to the results. Methods: Time-to-treatment initiation was determined for patients enrolled in the Mount Sinai Initiative for Early Lung Cancer Research on Treatment study who underwent surgical resection for clinical stage I lung cancer between March 2016 and December 2021. The following dates were determined: (1) date of first suspicious radiologic imaging, (2) date of first biopsy, and (3) date of surgery. A total of 15 thoracic surgeons who participated in the Mount Sinai Initiative for Early Lung Cancer Research on Treatment were assessed on their perception on time-to-treatment initiation. Results: For 638 patients, median time from first suspicious imaging findings to biopsy was 40 days, biopsy to surgery was 37 days, and suspicious imaging to surgery was 84 days. Significant factors that resulted in longer time-to-treatment initiation in the multivariate analysis were African American or Black race (P = .005), vascular disease (P = .01), and median household income less than $75,000 (P = .04). Although the surgeon's perception was that the average time from biopsy to surgery was 28 days, it was longer for 63.5% of participants; surgeon perception of maximum time between diagnosis and surgery was 84 days and longer for 28.7% of participants. Conclusions: Patient factors such as race, income, and comorbidities were found to have differences in time-to-treatment initiation. Delays to surgery exceeded the expectations of thoracic surgeons.

Indeterminate pulmonary nodules and prior malignancy: survival and recurrence after surgery in newly diagnosed stage I non-small cell lung cancer.

Background: Surgical excision biopsy remains the only reliable option in most cases of indeterminate pulmonary nodules, particularly in cancer survivors for whom surgery provides local control of pulmonary metastasis and the best chance of cure for early-stage lung cancer. Nevertheless, unnecessary surgeries remain a concern and the prognosis of newly diagnosed lung cancer might be influenced by the history of previous malignancy. We aimed to analyze the outcomes of resected indeterminate pulmonary nodules in patients with and without previous malignancy, and the impact of prior cancer history on survival and recurrence in stage I non-small cell lung cancer (NSCLC) patients. Methods: We retrospectively studied 176 resected indeterminate pulmonary nodules from 169 patients (58% with and 42% without previous cancer). Recurrence and overall survival (OS) were analyzed in newly diagnosed stage I NSCLC using the Kaplan-Meier method and Cox proportional hazard models. Results: The rate of benign lesions was 15.3% (9.6% in the previous cancer group and 23.6% in the no previous cancer group). In stage I NSCLC patients (n=86), previous malignancy was associated with recurrence (P<0.001) but not OS (P=0.23). Chronic obstructive pulmonary disease and visceral pleural invasion were associated with impaired OS and recurrence. Mediastinal lymph node removal was associated with better OS. Conclusions: The rate of benign resections among indeterminate pulmonary nodules in the no-previous cancer group more than doubled that of the previous cancer group and, in newly diagnosed stage I NSCLC patients, recurrence was independently associated with prior cancer. Therefore, in this setting, a history of previous malignancy should be taken into consideration when identifying patients at risk of tumor recurrence.

Molecular and immune characterization of Chinese early-stage non-squamous non-small cell lung cancer: a multi-omics cohort study.

Background: Albeit considered with superior survival, around 30% of the early-stage non-squamous non-small cell lung cancer (Ns-NSCLC) patients relapse within 5 years, suggesting unique biology. However, the biological characteristics of early-stage Ns-NSCLC, especially in the Chinese population, are still unclear. Methods: Multi-omics interrogation of early-stage Ns-NSCLC (stage I-III), paired blood samples and normal lung tissues (n=76) by whole-exome sequencing (WES), RNA sequencing, and T-cell receptor (TCR) sequencing were conducted. Results: An average of 128 exonic mutations were identified, and the most frequently mutant gene was EGFR (55%), followed by TP53 (37%) and TTN (26%). Mutations in MUC17, ABCA2, PDE4DIP, and MYO18B predicted significantly unfavorable disease-free survival (DFS). Moreover, cytobands amplifications in 8q24.3, 14q13.1, 14q11.2, and deletion in 3p21.1 were highlighted in recurrent cases. Higher incidence of human leukocyte antigen loss of heterozygosity (HLA-LOH), higher tumor mutational burden (TMB) and tumor neoantigen burden (TNB) were identified in ever-smokers than never-smokers. HLA-LOH also correlated with higher TMB, TNB, intratumoral heterogeneity (ITH), and whole chromosomal instability (wCIN) scores. Interestingly, higher ITH was an independent predictor of better DFS in early-stage Ns-NSCLC. Up-regulation of immune-related genes, including CRABP2, ULBP2, IL31RA, and IL1A, independently portended a dismal prognosis. Enhanced TCR diversity of peripheral blood mononuclear cells (PBMCs) predicted better prognosis, indicative of a noninvasive method for relapse surveillance. Eventually, seven machine-learning (ML) algorithms were employed to evaluate the predictive accuracy of clinical, genomic, transcriptomic, and TCR repertoire data on DFS, showing that clinical and RNA features combination in the random forest (RF) algorithm, with area under the curve (AUC) of 97.5% and 83.3% in the training and testing cohort, respectively, significantly outperformed other methods. Conclusions: This study comprehensively profiled the genomic, transcriptomic, and TCR repertoire spectrums of Chinese early-stage Ns-NSCLC, shedding light on biological underpinnings and candidate biomarkers for prognosis development.

Histopathologic fate of resected pulmonary pure ground glass nodule: a systematic review and meta-analysis.

Background: Pure ground glass nodules (GGNs) have been increasingly detected through lung cancer screening programs. However, there were limited reports about pathologic characteristics of pure GGN. Here we presented a meta-analysis of the histologic outcome and proportion analysis of pure GGN. Methods: This study included previous pathological reports of pure GGN published until June 14, 2022 following a systematic search. A meta-analysis estimated the summary effects and between-study heterogeneity for pathologic diagnosis of invasive adenocarcinoma (IA), minimally invasive adenocarcinoma (MIA), adenocarcinoma in situ (AIS), and atypical adenomatous hyperplasia (AAH). Results: This study incorporated 24 studies with 3,845 cases of pure GGN that underwent surgery. Among them, sublobar resection was undertaken in 60% of the patients [95% confidence interval (CI): 38-78%, I2=95%]. The proportion of IA in cases of resected pure GGN was 27% (95% CI: 18-37%, I2=95%), and 50% of IA had non-lepidic predominant patterns (95% CI: 35-65%, I2=91%). The pooled proportions of MIA, AIS, and AAH were 24%, 36%, and 11%, respectively. Among nine studies with available clinical outcomes, no recurrences or metastases was observed other than one study. Conclusions: The portion of IA in cases of pure GGN is significantly larger that expected. More than half of them owned invasiveness components if MIA and IA were combined. Furthermore, there were quite number of lesions with aggressive histologic patterns other than the lepidic subtype. Therefore, further attempts are necessary to differentiate advanced histologic subtype among radiologically favorable pure GGN.

Longitudinal quality of life after sublobar resection and stereotactic body radiation therapy for early-stage non-small cell lung cancer.

BACKGROUND: Many patients with early-stage lung cancer are not candidates for lobectomy because of various factors, with treatment options including sublobar resection or stereotactic body radiation therapy (SBRT). Limited information exists regarding patient-centered outcomes after these treatments. METHODS: Subjects with stage I-IIA non-small cell lung cancer (NSCLC) at high risk for lobectomy who underwent treatment with sublobar resection or SBRT were recruited from five medical centers. Quality of life (QOL) was compared with the Short Form 8 (SF-8) for physical and mental health and Functional Assessment of Cancer Therapy-Lung (FACT-L) surveys at baseline (pretreatment) and 7 days, 30 days, 6 months, and 12 months after treatment. Propensity score methods were used to control for confounders. RESULTS: Of 337 subjects enrolled before treatment, 63% received SBRT. Among patients undergoing resection, 89% underwent minimally invasive video-assisted thoracic surgery or robot-assisted resection. Adjusted analyses showed that SBRT-treated patients had both higher physical health SF-8 scores (difference in differences [DID], 6.42; p = .0008) and FACT-L scores (DID, 2.47; p = .004) at 7 days posttreatment. Mental health SF-8 scores were not different at 7 days (p = .06). There were no significant differences in QOL at other time points, and all QOL scores returned to baseline by 12 months for both groups. CONCLUSIONS: SBRT is associated with better QOL immediately posttreatment compared with sublobar resection. However, both treatment groups reported similar QOL at later time points, with a return to baseline QOL. These findings suggest that sublobar resection and SBRT have a similar impact on the QOL of patients with early-stage lung cancer deemed ineligible for lobectomy.

Detection of circulating tumor DNA with ultradeep sequencing of plasma cell-free DNA for monitoring minimal residual disease and early detection of recurrence in early-stage lung cancer.

BACKGROUND: In early-stage non-small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for recurrence after curative intent therapy. This study aimed to risk stratify patients with early-stage NSCLC via a personalized, tumor-informed multiplex polymerase chain reaction (mPCR) next-generation sequencing assay. METHODS: This retrospective cohort study included patients with stage I-III NSCLC. Recruited patients received standard-of-care management (surgical resection with or without adjuvant chemotherapy, followed by surveillance). Whole-exome sequencing of NSCLC resected tissue and matched germline DNA was used to design patient-specific mPCR assays (Signatera, Natera, Inc) to track up to 16 single-nucleotide variants in plasma samples. RESULTS: The overall cohort with analyzed plasma samples consisted of 57 patients. Stage distribution was 68% for stage I and 16% each for stages II and III. Presurgery (i.e., at baseline), ctDNA was detected in 15 of 57 patients (26%). ctDNA detection presurgery was significantly associated with shorter recurrence-free survival (RFS; hazard ratio [HR], 3.54; 95% confidence interval [CI], 1.00-12.62; p = .009). In the postsurgery setting, ctDNA was detected in seven patients, of whom 100% experienced radiological recurrence. ctDNA positivity preceded radiological findings by a median lead time of 2.8 months (range, 0-12.9 months). Longitudinally, ctDNA detection at any time point was associated with shorter RFS (HR, 16.1; 95% CI, 1.63-158.9; p < .0001). CONCLUSIONS: ctDNA detection before surgical resection was strongly associated with a high risk of relapse in early-stage NSCLC in a large unique Asian cohort. Prospective studies are needed to assess the clinical utility of ctDNA status in this setting.

Incidental pulmonary nodules may lead to a high proportion of early-stage lung cancer: but it requires more than a high CT volume to achieve this.

Background: The management of pulmonary nodules plays a critical role in early detection of lung cancer. Computed tomography (CT) has led to a stage-shift towards early-stage lung cancer, but regional differences in survival rates have been reported in Denmark. This study aimed to evaluate whether variations in nodule management among Danish health regions contributed to these differences. Material and Methods: The Danish Health Data Authority and Danish Lung Cancer Registry provided data on CT usage and lung cancer stage distribution, respectively. Auditing of lung cancer stage IA patient referrals and nodule management of stage IV lung cancer patients was conducted in seven Danish lung cancer investigation centers, covering four of the five Danish health regions. CT scans were performed up to 2 years before the patients' diagnosis from 2019 to 2021. Results: CT usage has increased steadily in Denmark over the past decade, with a simultaneous increase in the proportion of early-stage lung cancers, particularly stage IA. However, one Danish health region, Region Zealand, exhibited lower rates of early-stage lung cancer and overall survival despite a CT usage roughly similar to that of the other health regions. The audit did not find significant differences in pulmonary nodule management or a higher number of missed nodules by radiologists in this region compared to others. Conclusion: This study suggests that a high CT scan volume alone is not sufficient for the early detection of lung cancer. Factors beyond hospital management practices, such as patient-related delays in socioeconomically disadvantaged areas, may contribute to regional differences in survival rates. This has implications for future strategies for reducing these differences.

Consequences of Losing Incidental Pulmonary Nodules to Follow-Up: Unmonitored Nodules Progressing to Stage IV Lung Cancer.

INTRODUCTION: Lung cancer is the leading cause of cancer-related death globally. Incidental pulmonary nodules represent a golden opportunity for early diagnosis, which is critical for improving survival rates. This study explores the impact of missed pulmonary nodules on the progression of lung cancer. METHODS: A total of 4,066 stage IV lung cancer cases from 2019 to 2021 in Danish hospitals were investigated to determine whether a chest computed tomography (CT) had been performed within 2 years before diagnosis. CT reports and images were reviewed to identify nodules that had been missed by radiologists or were not appropriately monitored, despite being mentioned by the radiologist, and to assess whether these nodules had progressed to stage IV lung cancer. RESULTS: Among stage IV lung cancer patients, 13.6% had undergone a chest CT scan before their diagnosis; of these, 44.4% had nodules mentioned. Radiologists missed a nodule in 7.6% of cases. In total, 45.3% of nodules were not appropriately monitored. An estimated 2.5% of stage IV cases could have been detected earlier with proper surveillance. CONCLUSION: This study underlines the significance of monitoring pulmonary nodules and proposes strategies for enhancing detection and surveillance. These strategies include centralized monitoring and the implementation of automated registries to prevent gaps in follow-up.

Clinical application of Mimics software system to three-dimensional reconstruction to guide thoracoscopic anatomic pulmonary segmentectomy / 中国胸心血管外科临床杂志

@#Objective    To investigate the clinical effect of 3D computed tomography bronchial bronchography and angiography (3D-CTBA) and guidance of thoracoscopic anatomic pulmonary segmentectomy by Mimics software system. Methods    A retrospective analysis was performed on patients who underwent thoracoscopic segmentectomy in the Department of Thoracic Surgery of Affiliated People's Hospital of Jiangsu University from June 2020 to December 2022. The patients who underwent preoperative 3D-CTBA using Materiaise's interactive medical image control system (Mimics) were selected as an observation group, and the patients who did not receive 3D-CTBA were selected as a control group. The relevant clinical indicators were compared between the two groups. Results    A total of 59 patients were included, including 29 males and 30 females, aged 25-79 years. There were 37 patients in the observation group, and 22 patients in the control group. The operation time (163.0±48.7 min vs. 188.8±43.0 min, P=0.044), intraoperative blood loss [10.0 (10.0, 20.0) mL vs. 20.0 (20.0, 35.0) mL, P<0.001], and preoperative puncture localization rate (5.4% vs. 31.8%, P=0.019) in the observation group were better than those in the control group. There was no statistically significant difference in the thoracic tube placement time, thoracic fluid drainage volume, number of intraoperative closure nail bin, postoperative hospital stay, or postoperative air leakage incidence (P>0.05) between the two groups. Conclusion    For patients who need to undergo anatomical pulmonary segmentectomy, using Mimics software to produce 3D-CTBA before surgery can help accurately identify pulmonary arteriovenous anatomy, reduce surgical time and intraoperative blood loss, help to determine the location of nodules and reduce invasive localization before surgery, and alleviate patients' pain, which is worthy of clinical promotion.

Efficacy and safety of cyberknife in the treatment of elderly patients with early stage non-small cell lung cancer / 中国现代医生

@#Objective To investigate the efficacy and safety of Cyberknife in the treatment of elderly patients(aged≥75 years)with early stage non-small cell lung cancer(NSCLC),and to compare the results with those of patients aged<75 years.Methods We retrospectively analyzed 75 patients with early(T1-2N0M0)NSCLC admitted to the 960th Hospital of Jinan People's Liberation Army from January 2013 to October 2019.There were 32(42.7%)patients aged<75 years,and 43(57.3%)patients aged≥75 years.All patients were treated with 45-66Gy/3-8F,60%-85%isodose line as the prescription dose to cover planning target volume(PTV),and irradiation once a day and five times a week.The clinical efficacy,survival status and radiotherapy toxicity of the two groups were compared,and the factors affecting the efficacy of elderly patients were analyzed.Results The disease control rates of patients aged<75 and≥75 years were 96.9%and 93.0%,respectively(P>0.05).The 5-year local control rate(LC),progression-free survival(PFS)and cancer-specific survival(CSS)were 70.9%and 85.4%,58.5%and 54.4%,and 70.4%and 64.5%,respectively(P>0.05).However,the overall survival(OS)of patients aged≥75 years was significantly lower than that of patients aged<75 years,and the 5-year OS was 49.2%and 68.2%,respectively(P<0.05).There was no significant difference in the treatment complications between the two groups(P>0.05).Multivariate analysis showed that biologic effective dose(BED)was an independent factor affecting OS in patients aged≥75 years.Conclusion Stereotactic body radiotherapy with cyberknife is a safe and effective treatment for elderly patients with early stage NSCLC who are not suitable for surgery.

Digital spatial profiling to predict recurrence in grade 3 stage I lung adenocarcinoma.

OBJECTIVE: Early-stage lung adenocarcinoma is treated with local therapy alone, although patients with grade 3 stage I lung adenocarcinoma have a 50% 5-year recurrence rate. Our objective is to determine if analysis of the tumor microenvironment can create a predictive model for recurrence. METHODS: Thirty-four patients with grade 3 stage I lung adenocarcinoma underwent surgical resection. Digital spatial profiling was used to perform genomic (n = 31) and proteomic (n = 34) analyses of pancytokeratin positive and negative tumor cells. K-means clustering was performed on the top 50 differential genes and top 20 differential proteins, with Kaplan-Meier recurrence curves based on patient clustering. External validation of high-expression genes was performed with Kaplan-Meier plotter. RESULTS: There were no significant clinicopathologic differences between patients who did (n = 14) and did not (n = 20) have recurrence. Median time to recurrence was 806 days; median follow-up with no recurrence was 2897 days. K-means clustering of pancytokeratin positive genes resulted in a model with a Kaplan-Meier curve with concordance index of 0.75. K-means clustering for pancytokeratin negative genes was less successful at differentiating recurrence (concordance index 0.6). Genes upregulated or downregulated for recurrence were externally validated using available public databases. Proteomic data did not reach statistical significance but did internally validate the genomic data described. CONCLUSIONS: Genomic difference in lung adenocarcinoma may be able to predict risk of recurrence. After further validation, stratifying patients by this risk may help guide who will benefit from adjuvant therapy.

Stereotactic body radiation therapy in the treatment of early-stage non-small cell lung cancer.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is now a standard treatment option for patients with early-stage non-small cell lung cancer (ES-NSCLC) who are unfit for surgery or refuse to undergo an operation. SBRT is a method of external beam radiotherapy that accurately delivers a high dose of irradiation in one or few treatment fractions. Intensive regimens of biologically effective dose ≥ 100 Gy are associated with good local control and overall survival, higher than in conventionally fractionated radiotherapy. There are still controversial areas in the SBRT indication where data are limited - indications for elderly and comorbid patients, indications for treatment without histological verification, treatment of central/ultracentral lesions, indications for tumors larger than 5 cm, indications for operable patients. The optimal follow-up practice of these patients also remains unclear, including the frequency of imaging, the use of PET-CT, and requirements for biopsy. CT changes after SBRT differ from those following conventional radiotherapy and it is difficult to distinguish them from tumor recurrence. Due to the high local control achieved with lung SBRT, data on the treatment of local failure are insufficient. PURPOSE: The aim of the publication is to demonstrate the current information and the importance of SBRT for patients with ES-NSCLC.