Peripheral Lung Cancer Research Articles

Construction and validation of a clinical differentiation model between peripheral lung cancer and solitary pulmonary tuberculosis

ObjectiveTo establish and validate a clinical model for differentiating peripheral lung cancer (PLC) from solitary pulmonary tuberculosis (SP-TB) based on clinical and imaging features. Materials and methodsRetrospectively, 183 patients (100 PLC, 83 SP-TB) in our hospital were randomly divided into a training group and an internal validation group (ratio 7:3), and 100 patients (50 PLC, 50 SP-TB) in Sichuan Provincial People’s Hospital were identified as an external validation group. The collected qualitative and quantitative variables were used to determine the independent feature variables for distinguishing between PLC and SP-TB through univariate logistic regression, multivariate logistic regression. Then, traditional logistic regression models and machine learning algorithm models (decision tree, random forest, xgboost, support vector machine, k-nearest neighbors, light gradient boosting machine) were established using the independent feature variables. The model with the highest AUC value in the internal validation group was used for subsequent analysis. The receiver operating characteristic curve (ROC), calibration curve, and decision curves analysis (DCA) were used to assess the model’s discrimination, calibration, and clinical usefulness. ResultAge, smoking history, maximum diameter of lesion, lobulation, spiculation, calcification, and vascular convergence sign were independent characteristic variables to differentiate PLC from SP-TB. The logistic regression model had the highest AUC value of 0.878 for the internal validation group, based on which a quantitative visualization nomogram was constructed to discriminate the two diseases. The area under the ROC curve (AUC) of the model in the training, internal validation, and external validation groups were 0.915 (95 % CI: 0.866–0.965), 0.878 (95 % CI: 0.784–0.971), and 0.912 (95 % CI: 0.855–0.969), respectively, and the calibration curves fitted well. Decision curves analysis (DCA) confirmed the good clinical benefit of the model. ConclusionThe model constructed based on clinical and imaging features can accurately differentiate between PLC and SP-TB, providing potential value for developing reasonable clinical plans.

The Increased Burden of Morbidity Over the Life-Course Among Patients with COPD: A Register-Based Cohort Study in Sweden.

Patients with a diagnosis of chronic obstructive pulmonary disease (COPD) often have other chronic disorders. This study aims to describe the life-course pattern of morbidity in patients with COPD. Among all residents aged 50-90 years in Sweden in 1997, people with a hospital COPD diagnosis were identified using Swedish national registers (1997-2018). Each patient with COPD was matched by sex, birthyear and county of residency with up to five COPD-free controls. Other chronic disease diagnoses were identified during 1987-2018. Conditional logistic regression calculated risk of diseases diagnosed prior to first COPD diagnosis, producing odds ratios (OR) and 95% confidence intervals (95% CI). Cox regression estimated risk of diagnoses after first COPD diagnosis, producing hazard ratios (HR) and 95% CI. Among 2,706,814 individuals, 225,159 (8.3%) had COPD. The nested case-control sample included 223,945 COPD-cases with 1,062,731 controls. Prior to first COPD diagnosis, future COPD patients had higher risks than controls for most examined conditions. Highest risks were seen for chronic heart failure (OR = 3.25, 3.20-3.30), peripheral arterial disease (OR = 3.12, 3.06-3.18) and lung cancer (OR = 12.73, 12.12-13.37). Following the COPD diagnosis, individuals with COPD had higher risks of most conditions than individuals without COPD. Chronic heart failure (HR = 3.50, 3.46-3.53), osteoporosis (HR = 3.35, 3.30-3.42), depression (HR = 2.58, 2.53-2.64) and lung cancer (HR = 6.04, 5.90-6.18) predominated. The risk of vascular dementia was increased after COPD diagnosis (HR = 1.53, 1.48-1.58) but not Alzheimer's disease. Accumulation of chronic morbidity may precede COPD. Following the diagnosis, an increased burden of cardiovascular disease and cancer is to be expected, but subsequent depression, osteoporosis, and vascular dementia should also be noted. Management strategies for patients with COPD should consider the higher-than-average risk of multimorbidity.

Preoperative evaluation of visceral pleural invasion in peripheral lung cancer utilizing deep learning technology.

This study aimed to assess the efficiency of artificial intelligence (AI) in the detection of visceral pleural invasion (VPI) of lung cancer using high-resolution computed tomography (HRCT) images, which is challenging for experts because of its significance in T-classification and lymph node metastasis prediction. This retrospective analysis was conducted on preoperative HRCT images of 472 patients with stage I non-small cell lung cancer (NSCLC), focusing on lesions adjacent to the pleura to predict VPI. YOLOv4.0 was utilized for tumor localization, and EfficientNetv2 was applied for VPI prediction with HRCT images meticulously annotated for AI model training and validation. Of the 472 lung cancer cases (500 CT images) studied, the AI algorithm successfully identified tumors, with YOLOv4.0 accurately localizing tumors in 98% of the test images. In the EfficientNet v2-M analysis, the receiver operating characteristic curve exhibited an area under the curve of 0.78. It demonstrated powerful diagnostic performance with a sensitivity, specificity, and precision of 76.4% in VPI prediction. AI is a promising tool for improving the diagnostic accuracy of VPI for NSCLC. Furthermore, incorporating AI into the diagnostic workflow is advocated because of its potential to improve the accuracy of preoperative diagnosis and patient outcomes in NSCLC.

Efficacy and safety of stereotactic radiotherapy on elderly patients with stage I-II central non-small cell lung cancer.

Many studies demonstrated the safety and efficacy of SBRT in the treatment of elderly patients with early-stage non-small cell lung cancer (NSCLC). However, those studies focused on patients with peripheral lung cancer. This study aimed to evaluate the clinical efficacy and toxicity of SBRT in elderly patients with stage I-II central NSCLC in single institution. From April 2009 to January 2020, a retrospective study was conducted on patients ≥ 65 years old with stage I-II NSCLC that was centrally localized and treated with SBRT at a single institution. Absolute C-reactive protein (CRP)/albumin ratio (CAR) and body mass index (BMI) recorded at pretreatment were analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), cancer-specific death, noncancer-specific death, local progression (LP) and distant progression (DP). Stereotactic body radiation treatment (SBRT) was administered to a total of 44 patients. The most common dose fractionation schedule was 60 Gy given in 5 fractions. The median PFS of the cohort was 31 months (95% CI, 19.47-42.53 months). The median OS of all patients was 69 months (95% CI, 33.8-104.2 months). The median time to noncancer-specific death was 54.5 months. The median time to cancer-specific death was 36 months. The cumulative incidences of cancer-specific death at 1 year, 5 years, and 10 years were 11.63% (95%CI, 4.2-23.23%), 42.99% (95%CI, 27.56-57.53%), and 65.94% (95%CI, 45.76-80.1%), respectively. pre-SBRT BMI of ≤ 22.77 (HR 4.60, 95% CI 1.84-11.51, P=0.001) and pre-SBRT CAR of ≤0.91 (HR 5.19, 95% CI 2.15-12.52, P<0.000) were significant predictors of higher OS on multivariable analysis. The median times to LP and DP were 10 months and 11 months, respectively. In terms of acute toxicity, grade 1 including cough (38.64%), radiation pneumonitis (29.55%), anemia (25%), and fatigue (20.45%) was often observed. There was no evidence of grade 4 or 5 acute toxicity. In terms of late toxicity, 2 patients developed grade 1 pulmonary fibrosis during follow-up. This study showed that SBRT can effectively control local tumor progression, and have acceptable toxicity for elderly patients with centrally located stage I-II NSCLC. Lower pre-SBRT BMI and lower pre-SBRT CAR were associated with a decreased risk of cancer-specific death.

Bronchoscopic treatment of early-stage peripheral lung cancer.

This review article focuses on bronchoscopic treatment of early-stage peripheral lung cancer. Bronchoscopic treatment modalities have garnered considerable attention for early-stage lung cancer. Studies using photodynamic therapy, thermal vapor ablation, laser ablation, cryoablation, and intra-tumoral injection have recently been published. However, the evidence supporting these approaches largely derives from single-arm studies with small sample sizes. Based on the IDEAL-D framework, no technology has progressed passed the idea phase (1). The main weakness of these technologies to date is lack of evidence suggesting they can achieve local control. Presently, no bronchoscopic intervention for lung cancer has sufficient data to warrant its use as part of the standard of care. Despite notable progress, current technologies remain suboptimal, and there is insufficient evidence to support their use outside of a research setting.

Comparison of early patient-reported outcomes between uniportal thoracoscopic segmentectomy and wedge resection for peripheral small-sized non-small-cell lung cancer

BackgroundAnalysis of patient-reported outcomes (PROs) offers valuable insights into distinguishing the effects of closely related medical procedures from the patient’s perspective. In this study we compared symptom burden in patients undergoing uniportal thoracoscopic segmentectomy and wedge resection for peripheral small-sized non-small cell lung cancer (NSCLC).MethodsThis study included patients with peripheral NSCLC from an ongoing longitudinal prospective cohort study (CN-PRO-Lung 3) who underwent segmentectomy or wedge resection with tumor diameter ≤ 2 cm and consolidation tumor ratio (CTR) ≤ 0.5. PROs data were collected using the Perioperative Symptom Assessment for Lung Surgery questionnaire pre-operatively, daily post-surgery up to the fourth hospitalization day, and weekly post-discharge up to the fourth week. Propensity score matching and a generalized estimation equation model were employed to compare symptom severity. In addition, short-term clinical outcomes were compared.ResultsIn total, data of 286 patients (82.4%) undergoing segmentectomy and 61 patients (17.6%) undergoing wedge resection were extracted from the cohort. No statistically significant differences were found in the proportion of moderate-to-severe symptoms and mean scores for pain, cough, shortness of breath, disturbed sleep, fatigue, drowsiness, and distress during the 4-day postoperative hospitalization or the 4-week post-discharge period before or after matching (all p > 0.05). Compared with segmentectomy, wedge resection showed better short-term clinical outcomes, including shorter operative time (p = 0.001), less intraoperative bleeding (p = 0.046), and lower total hospital costs (p = 0.002).ConclusionsThe study findings indicate that uniportal thoracoscopic segmentectomy and wedge resection exert similar early postoperative symptom burden in patients with peripheral NSCLC (tumor diameter ≤ 2 cm and CTR ≤ 0.5).Clinical trial registrationNot applicable.

Abstract LB266: AMG510-mediated inactivation of BCL-xL protein promotes Gasdermin-E-dependent pyroptosis in KRAS-G12C mutant non-small cell lung cancer

Abstract Introduction: Studies have shown that molecular targeted therapy can mediate Gasdermin-E (GSDME) dependent pyroptosis. However, GSDME expression is suppressed in many mutated patients, including those with KRAS-G12C-mutated non-small-cell lung cancer (NSCLC). The efficacy of AMG510 against KRAS-G12C inhibition (KRAS-G12Ci) is constrained by tumor recurrence. Pyroptosis is widely involved in the occurrence and development of tumors. However, the role and molecular mechanism of AMG510 in pyroptosis have not been well identified. Here, we demonstrate that inactivation of anti-apoptotic Bcl-2 family members during KRAS-G12Ci treatment enhances pyroptosis, which then promotes the sensitivity of AMG510 in NSCLC. Methods: We assessed pyroptosis using live cells imaging, LDH release assays, ELISA, Western blotting, and flow cytometry. In vitro assays were used to investigate the function of GSDME. Co-culture between peripheral blood mononuclear cells (PBMCs) and KRAS-G12C mutant lung cancer cell lines explored the anti-tumor immunity of cytotoxic T lymphocytes affected by knockdown of GSDME. The molecular mechanism was determined using bulk RNA sequencing, molecular cloning technology, and Western blotting. Results: We demonstrated that KRAS G12Ci treatment promotes cleavage of GSDME, release of high mobility group protein B1 (HMGB1), and LDH, markers of pyroptotic cell death. Additionally, GSDME was significantly downregulated in KRAS-mutated NSCLC compared with patients of KRAS wild type in TCGA cohort, while significantly upregulated after AMG510 treatment and downregulated after AMG510 resistance in vitro assay. We identified that KRAS-G12Ci resulted in the inactivation of BCL-xL, leading to caspase-3-dependent cleavage of gasdermin E. Conversely, amplification of BCL-xL downregulated the expression of GSDME, therefore suppressing the process of pyroptosis. GSDME knockdown in KRAS-G12C mutant lung cancer cell lines showed defective HMGB1 release, reduced caspase-3 viability, and decreased granzyme B and IFN-γ secretion by CD8+ T cells in response to KRAS-G12Ci, and more frequent tumor cell growth. Conclusion: Our findings indicate that GSDME-dependent pyroptosis is a critical determinant of KRAS-G12C-targeted inhibitor AMG510, and through the modulation exerted by the Bcl-2 family protein BCL-xL upon GSDME. These findings suggest that activation of GSDME may provide an effective strategy to sensitize cancer cells to KRAS-G12Ci treatment. Citation Format: Linfeng Luo, Anlin Li, Wei Du, Maojian Chen, JIng Li, Yixin Zhou, Li Zhang, Shaodong Hong. AMG510-mediated inactivation of BCL-xL protein promotes Gasdermin-E-dependent pyroptosis in KRAS-G12C mutant non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB266.

Abstract 2800: Shotgun metagenomics of COPD-associated lung cancer tissue microbiome

Abstract The gut microbiome plays a crucial role in the development of multiple chronic diseases. Several solid tumors including lung cancer are also implicated in the gut microbiome in cancer initiation and progression, possibly affecting signaling pathways in the tumor microenvironment. However, the microbiome in the peripheral lung tissue is unexplored and their relationship to the lung tumor microenvironment is still unknown. Thus, to explore the relationship between the microbiome and the tumor microenvironment of lung cancer, we performed shotgun metagenomic sequencing of the lung cancer tissue, especially in lung cancer patients accompanied by chronic obstructive pulmonary disease (COPD). We confirmed the presence of a diverse microbiome in peripheral lung cancer tissue. Next, we focused on individual species. We observed significant differences in the relative abundance of several species between COPD and non-COPD patients, and cancer and non-cancer tissue. Then, we focused on the metagenomic diversity between samples. The number of species in COPD patients and cancer tissue were decreased. And the bacterial total abundance in each sample were observed similar trend. On the other hand, alpha diversity in each sample were showed different trend to them. In the analysis of beta diversity using Principal Coordinate Analysis (PCoA), clusters were formed in each group. These findings suggest that microbiome imbalance known as dysbiosis in the peripheral lung tissue may affect the tumor microenvironment resulting in cancer progression. Citation Format: Atsushi Matsuoka, Kazuhiko Shien, Shuta Tomida, Daisuke Mizuno, Masayoshi Ohki, Ryo Yoshichika, Tomohiro Higashihara, Naohiro Hayashi, Fumiaki Mukohara, Mao Yoshikawa, Ken Suzawa, Hiromasa Yamamoto, Shinichi Toyooka. Shotgun metagenomics of COPD-associated lung cancer tissue microbiome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2800.

Factors associated with cavity formation after stereotactic body radiation therapy for peripheral early-stage lung cancer.

This retrospective study aimed to identify the factors associated with cavity formation after SBRT in peripheral early-stage lung cancer patients. We analyzed the occurrence of cavity changes after SBRT. We examined 99 cases with T1-T2aN0 peripheral non-small cell lung cancer treated with SBRT from 2004 to 2021. Patients underwent respiratory function tests, including diffusing capacity for carbon monoxide (DLco), before treatment. The median observation period was 35months (IQR 18-47.5months). Treatment involved fixed multi-portal irradiation in 67% of cases and VMAT in 33%. The total radiation doses ranged from 42 to 55Gy, delivered over 4 to 5 fractions. Cavity formation occurred in 14 cases (14.1%), appearing a median of 8months after SBRT. The cavity disappeared in a median of 4months after formation. High DLco and total radiation dose were identified as factors significantly associated with cavity formation. There have been no confirmed recurrences to date, but one patient developed a lung abscess. Although cavity formation after SBRT for peripheral early-stage lung cancer is infrequent, it can occur. This study showed high DLco and total radiation dose to be factors significantly associated with cavity formation. These findings can be applied to optimizing radiation therapy (RT) and improving patient outcomes. Further research is needed to determine the optimal radiation dose for patients with near-normal DLco for whom surgery is an option. This study provides valuable insights into image changes after RT.

Single isocenter versus dual isocenter treatment using flattening filter-free and jaw-tracking volumetrically modulated arc therapy for boot-shaped lung cancer: Evaluation of dosimetric and feasibility.

To determine whether a dual-isocenter volumetrically modulated arc therapy (VMAT) technique results in lower normal pulmonary dosage compared to a traditional single isocenter technique for boot-shaped lung cancer. A cohort of 15 patients with advanced peripheral or central lung cancer who had metastases in the mediastinum and supraclavicular lymph nodes was randomly selected for this retrospective study. VMAT plans were generated for each patient using two different beam alignment techniques with the 6-MV flattening filter-free (FFF) photon beam: single-isocenter jaw-tracking VMAT based on the Varian TrueBeam linear accelerator (S-TV), and dual-isocenter VMAT based on both TrueBeam (D-TV) and Halcyon linear accelerator (D-HV). For all 45 treatment plans, planning target volume (PTV) dose coverage, conformity/homogeneity index (CI/HI), mean heart dose (MHD), mean lung dose (MLD) and the total lung tissue receiving 5, 20, 30Gy (V5, V20, V30) were evaluated. The monitor units (MUs), delivery time, and plan quality assurance (QA) results were recorded. The quality of the objectives of the three plans was comparable to each other. In comparison with S-TV, D-TV and D-HV improved the CI and HI of the PTV (p<0.05). The MLD was 13.84±1.44Gy (mean±SD) for D-TV, 14.22±1.30Gy and 14.16±1.42Gy for S-TV and D-HV, respectively. Lungs-V5Gy was 50.78±6.24%, 52.00±7.32% and 53.36±8.48%, Lungs-V20Gy was 23.72±2.27%, 26.18±2.86% and 24.96±3.09%, Lungs-V30Gy was 15.69±1.76%, 17.20±1.72% and 16.52±2.07%. Compared to S-TV, D-TV provided statistically significant better protection for the total lung, with the exception of the lungs-V5. All plans passed QA according the gamma criteria of 3%/3mm. Taking into account the dosimetric results and published clinical data on radiation-induced pulmonary injury, dual-isocenter jaw-tracking VMAT may be the optimal choice for treating boot-shaped lung cancer.

Sub-lobar resections for peripheral non-small cell lung cancer measuring ≤ 2 cm: Insights from recent clinical trials

The findings of two well conducted trials that randomised 1803 patients with a peripheral non-small cell lung cancer measuring ≤ 2 cm to a lobar to sub-lobar resection have established the latter as a new standard of care. It is important for non-surgical oncologists to appreciate the details of study design and outcomes of both studies, given the possible impact they have for considerations of stereotactic ablative radiotherapy (SABR) for operable patients with early-stage NSCLC. Differences in overall survival between the study populations highlight the impact of confounding factors like smoking history and comorbidities on reported outcomes. For example, despite low post-operative mortality rates in both trials, the 5-year disease-free survival rate in the CALGB 140503 trial was only approximately 60 % with either surgical procedure. Both phase III trials required guideline recommended nodal staging, which does not reflect real world surgical practice, and which may limit the generalisability of the reported findings to local institutional outcomes. Furthermore, the emergence of other malignancies was recorded in 15–18 % of study patients during follow-up, and patients who underwent sub-lobar resections had a better long-term survival associated with a higher likelihood of undergoing additional curative treatments. These findings from the JCOG0802 and the CALGB 140503 will encourage more interest in enrolling patients into ongoing trials comparing surgical resection with SABR.

Ten-year follow-up of a patient after an anatomical upper-zonal lung resection for peripheral non-small cell lung cancer

Ten-year follow-up of a patient after an anatomical upper-zonal lung resection for peripheral non-small cell lung cancer

Advanced navigation technology enables endobronchial brachytherapy for peripheral lung cancer: An old technique plays a new role

Background: To investigate the feasibility of super-selectively endobronchial brachytherapy in the treatment of peripheral lung cancer guided by advanced navigation technology. Patients and Methods: Six patients with peripheral lung tumors successfully underwent treatment with super-selectively endobronchial brachytherapy guided by advanced navigation technology following pathway planning, and were subsequently followed up to assess survival and treatment-related toxicities. Results: The endobronchial applicators were successfully placed inside the tumors of all patients using advanced navigation techniques according to the pre-treatment plan, and brachytherapy was delivered at curative doses after evaluation using radiotherapy planning software. None of the patients showed local progression of the treated lesions during the follow-up for a duration ranging from 11 months to 35 months, with a median follow-up time of 23 months. The patient with the longest follow-up, nearly 3 years, exhibited a stable condition. After undergoing endobronchial brachytherapy, patients predominantly experienced localized fibrosis as indicated. No significant alterations in cardiopulmonary function were detected during the follow-up, and no other adverse effects were found. Conclusion: The use of endobronchial brachytherapy for the curative treatment of peripheral lung cancers is feasible. Furthermore, the development of novel bronchial navigation techniques has the potential to broaden the application of endobronchial brachytherapy.

Clinicopathological and computed tomography features associated with recurrence-free survival of patients with small-sized peripheral invasive lung adenocarcinoma after sublobectomy.

Sublobar resection is gradually becoming a standard treatment for small-sized (≤2 cm) peripheral non-small cell lung cancer (NSCLC), with lung adenocarcinoma (LADC) being the most frequent histologic subtype. However, the prognostic predictors for preoperatively determining whether sublobectomy is feasible for patients with early LADC have not yet been well identified. Therefore, this study aimed to investigate the clinicopathological and computed tomography (CT) features associated with the recurrence-free survival (RFS) of patients with small-sized invasive LADC (SILADC) after sublobar resection. This retrospective cohort study analyzed 107 patients with SILADC who underwent preoperative chest CT scan and sublobar resection from December 2012 to March 2019. The Kaplan-Meier survival was used to analyze the relationship between clinicopathological characteristics, preoperative chest CT findings, and RFS. The Cox proportional hazards regression was used to identify independent prognostic factors of poor RFS. For clinicopathological characteristics, RFS was shorter in patients aged ≥70 years, smokers, and those with micropapillary/solid-predominant adenocarcinomas (all P values <0.05). For preoperative CT features, RFS was shorter in patients with tumor size ≥1.4 cm, solid component size ≥1.1 cm, proportion of solid component ≥72%, solid density, spiculation, vascular convergence sign, peripheral fibrosis, and type II pleural tag (all P values <0.05). Multivariate analysis showed proportion of solid component ≥72% [hazard ratio (HR): 5.920; P=0.006; 95% confidence interval (CI): 1.686-20.794], spiculation (HR: 5.026; P=0.001; 95% CI: 2.008-12.581), and type II pleural tag (HR: 4.638; P=0.002; 95% CI: 1.773-12.136) were independent risk factors for poor prognosis in patients with SILADC after sub-lobectomy. Clinicopathological and CT characteristics are helpful for predicting the RFS of patients with SILADC after sublobar resection and can be used as an auxiliary tool for thoracic surgeons to choose the best surgical mode.

Lymph node dissection in small peripheral lung cancer: Supplemental analysis of JCOG0802/WJOG4607L

ObjectiveThe optimal region of lymph node dissection (LND) during segmentectomy in patients with small peripheral non–small cell lung cancer requires clarification. Through a supplemental analysis of the Japan Clinical Oncology Group (JCOG) 0802/West Japan Oncology Group (WJOG) 4607L, we investigated the associated factors, distribution, and recurrence pattern of lymph node metastases (LNMs) and proposed the optimal LND region. MethodsOf the 1106 patients included in the JCOG0802/WJOG4607L, 1056 patients with LNDs were included in this supplemental analysis. We investigated the distribution and recurrence pattern of LNMs along with the radiologic findings (with ground-glass opacity, part-solid tumor; without ground-grass opacity component, pure-solid tumor). ResultsThe radiologic findings were the only significant factor for LNMs. Of 533 patients with part-solid tumors, 8 (1.5%) had LNMs. Further, only 3 (0.5%) patients had pN2 disease, and no patients had interlobar LNMs from nonadjacent segments. Of the 523 patients with pure-solid tumors, 55 (10.5%) had LNMs, and 28 (5.4%) had pN2 disease. Five patients had metastases to nonadjacent interlobar lymph nodes (LNs). Two (2.0%) patients with S6 tumors had upper mediastinal LNMs. In addition, the incidence of mediastinal LN recurrence in patients with S6 lung cancer was greater in those who underwent selective LND than those who underwent systematic LND (P = .0455). ConclusionsNonadjacent interlobar and mediastinal LND have little impact on pathologic nodal staging in patients with part-solid tumors. In contrast, selective LND is recommended at least for patients with pure-solid tumors.

Biomedical advances and future prospects of high-precision three-dimensional radiotherapy and four-dimensional radiotherapy.

Biomedical advances of external-beam radiotherapy (EBRT) with improvements in physical accuracy are reviewed. High-precision (±1 mm) three-dimensional radiotherapy (3DRT) can utilize respective therapeutic open doors in the tumor control probability curve and in the normal tissue complication probability curve instead of the one single therapeutic window in two-dimensional EBRT. High-precision 3DRT achieved higher tumor control and probable survival rates for patients with small peripheral lung and liver cancers. Four-dimensional radiotherapy (4DRT), which can reduce uncertainties in 3DRT due to organ motion by real-time (every 0.1-1 s) tumor-tracking and immediate (0.1-1 s) irradiation, have achieved reduced adverse effects for prostate and pancreatic tumors near the digestive tract and with similar or better tumor control. Particle beam therapy improved tumor control and probable survival for patients with large liver tumors. The clinical outcomes of locally advanced or multiple tumors located near serial-type organs can theoretically be improved further by integrating the 4DRT concept with particle beams.

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.

Segmentectomy for patients with early-stage pure-solid non-small cell lung cancer.

For decades, lobectomy has been the recommended surgical procedure for non-small cell lung cancer (NSCLC), including for small-sized lesions. However, two recent pivotal clinical trials conducted by the Japanese Clinical Oncology Group/West Japan Oncology Group (JCOG0802/WJOG4607L) and the Cancer and Leukemia Group B (CALGB140503), which compared the survival outcomes between lobectomy and sublobar resection (the JCOG0802/WJOG4607L included only segmentectomy, not wedge resection), demonstrated the efficacy of sublobar resection in patients with early-stage peripheral lung cancer measuring ≤ 2 cm. The JCOG0802/WJOG4607L demonstrated the superiority of segmentectomy over lobectomy with respect to overall survival, implying the survival benefit conferred by preservation of the lung parenchyma. Subsequently, the JCOG1211 also demonstrated the efficacy of segmentectomy, even for NSCLC, measuring up to 3 cm with the predominant ground-glass opacity phenotype. Segmentectomy has become the standard of care for early-stage NSCLC and its indications are expected to be further expanded to include solid lung cancers > 2 cm. However, local control is still a major concern for segmentectomy for higher-grade malignant tumors. Thus, the indications of segmentectomy, especially for patients with radiologically pure-solid NSCLC, remain controversial due to the aggressive nature of the malignancy. In this study, we reviewed previous studies and discussed the efficacy of segmentectomy for patients with such tumors.

Detection of Tumor DNA in Bronchoscopic Fluids in Peripheral NSCLC: A Proof-of-Concept Study

IntroductionDNA genotyping from plasma is a useful tool for molecular characterization of NSCLC. Nevertheless, the false-negative rate justifies the development of methods with higher sensitivity, especially in difficult-to-reach peripheral lung tumors. MethodsWe aimed at comparing molecular analysis from the supernatant of guide sheath flush fluid collected during radial-EndoBronchial UltraSound (r-EBUS) bronchoscopy with plasma sampling and tumor biopsies in patients with peripheral NSCLC. The DNA was genotyped using high-throughput sequencing or the COBAS mutation test. There were 65 patients with peripheral lung tumors subjected to concomitant sampling of guide sheath flush supernatant, plasma tumor DNA, and tumor biopsy and cytology using r-EBUS. There were 33 patients (including 24 newly diagnosed with having NSCLC) with an identifiable tumor mutation in the primary lesion selected for the comparative analysis. ResultsGuide sheath flush-based genotyping yielded a mutation detection rate of 61.8% (17 of 24 mutated EGFR, one of two ERBB2, one of one KRAS, one of one MAP2K, one of four MET, and zero of one STK11), compared with 33% in plasma-based genotyping (p = 0.0151). Furthermore, in eight of 34 r-EBUS without tumor cells on microscopic examination, we were able to detect the mutation in four paired guide sheath flush supernatant, compared with only two in paired plasma. ConclusionThe detection of tumor DNA in the supernatant of guide sheath flush fluid collected during r-EBUS bronchoscopy represents a sensitive and complementary method for genotyping NSCLC.

THE FIRST EXPERIENCE OF USING NON-INTUBATION VIDEO-ASSISTED THORACOSCOPIC RESECTIONS FOR LUNG CANCER IN THE REPUBLIC OF KAZAKHSTAN

Relevance:Several studies have shown that non-intubation surgical interventions, especially, have proven themselves well in patients with low reserve of the cardiovascular and respiratory systems, as well as in the diagnosis of interstitial lung diseases.&#x0D; The study aimed to describe the experience of introducing into clinical practice surgical interventions without intubation on spontaneous breathing for malignant neoplasms of the lungs and mediastinal organs.&#x0D; Methods: two clinical cases are described of the main points of the anesthesia and technical features of surgical intervention.&#x0D; Results: A surgery in two patients with peripheral lung cancer was performed. In the first case, the operation included NI-VATS on the right and the resection of the upper (S2) and lower lobe (S6, S9); in the second case – NI-VATS on the right, lower lobectomy, and lymph node dissection. Based on the results of histological examination, both patients were diagnosed with NSCLC in the initial stages. Postoperative chemoradiotherapy is not indicated. The patients were registered at the dispensary in clinical group III.&#x0D; Conclusion: As the literature data and our preliminary results of NI-VATS show, surgical interventions in the surgical treatment of lung cancer have places to be and should be widely introduced into clinical practice in oncothoracic departments of the Republic of Kazakhstan.