Screening Data

Screening Data

Ensartinib in Resected ALK-Positive Non-Small-Cell Lung Cancer.

Screening brief

이 연구는 완전히 절제된 ALK-positive NSCLC 환자에서 Ensartinib의 adjuvant 치료 효과를 평가한 Phase III 무작위 대조 시험입니다. Ensartinib 투여군이 Placebo군에 비해 disease-free survival을 현저히 향상시켰으며, 이는 ALK 양성 폐암의 표준 치료 패러다임을 재정의할 수 있는 중요한 증거입니다. 특히 고위험군에서 0.20의 hazard ratio를 보인 점은 임상적 의의가 큽니다.

Abstract

Anaplastic lymphoma kinase (ALK) inhibitors have emerged as promising agents for patients with resectable ALK-positive non-small-cell lung cancer (NSCLC). Whether ensartinib, a second-generation ALK inhibitor, is safe and effective in such patients is unknown. In this phase 3, double-blind, randomized trial involving patients with completely resected, ALK-positive stage IB to IIIB NSCLC after adjuvant chemotherapy, we randomly assigned patients in a 1:1 ratio to receive ensartinib at a dose of 225 mg once daily or placebo for 24 months. The primary end point was disease-free survival in patients with stage II to IIIB NSCLC. The key secondary end point was disease-free survival in the overall patient population. A total of 274 patients were randomly assigned to receive ensartinib or placebo (137 patients in each group). At 24 months, the percentage of patients with stage II to IIIB disease who were alive and disease-free was 86.4% in the ensartinib group and 53.5% in the placebo group (hazard ratio for disease recurrence or death, 0.20; 95% confidence interval [CI], 0.11 to 0.38; P<0.001). In the overall patient population, the percentage of patients who were alive and disease-free was 87.3% in the ensartinib group and 57.2% in the placebo group (hazard ratio, 0.20; 95% CI, 0.10 to 0.37; P<0.001). Overall survival data were immature. Adverse events of grade 3 or higher occurred...

Selpercatinib Improves EFS in RET Fusion-Positive NSCLC.

Screening brief

LIBRETTO-432 시험은 RET Fusion 양성 조기 NSCLC 환자에서 adjuvant selpercatinib 투여 시 EFS를 크게 향상시킨 결과를 보고했습니다. 이는 기존 치료 옵션이 제한적이었던 해당 아형에 대한 새로운 표준 치료 기준을 제시합니다. 임상 현장에서 RET Fusion 선별 접근성과 환자 식별 전략에 대한 논의가 필요함을 시사하여 표적 치료 분야의 중요한 근거로 작용할 것입니다.

Abstract

Results from LIBRETTO-432 demonstrate that adjuvant selpercatinib yields a substantial improvement in event-free survival for patients with early-stage RET fusion-positive non-small cell lung cancer. Experts say the findings establish selpercatinib as a new standard of care for this rare disease, although questions remain over identifying patients and access to screening.

Ternary classification prediction and heterogeneity quantification for HER2-Zero, -low, and -positive in breast cancer using HER2-targeted PET/CT imaging.

Screening brief

이 연구는 Breast cancer에서 HER2-Zero, -low, -positive 상태를 구분하는 Ternary classification prediction과 종양 Heterogeneity quantification을 위해 HER2-targeted PET/CT imaging 기법을 제안합니다. 기존 Tissue biopsy의 공간적 한계를 넘어 비침습적으로 HER2 expression heterogeneity를 정량화할 수 있어, 정밀 의학 기반 치료 선택에 중요한 임상적 가치를 지닙니다. 특히 HER2-low 군의 정확한 영상 식별은 향후 Antibody-drug conjugate (ADC) 치료 반응 예측 및 환자 선별에 직접적인 영향을 미치므로, Molecular imaging 연구 분야에서 높은 관련성을 가집니다.

Abstract

not available

Sublobar resection, stereotactic body radiotherapy, and thermal ablation for early-stage non-small cell lung cancer: a systematic review and meta-analysis.

Screening brief

이 연구는 lobectomy가 부적합한 초기 NSCLC 환자에서 SLR, SBRT, IGTA의 상대적 효능을 체계적으로 비교한 메타분석입니다. SLR이 SBRT 대비 OS를 개선한다는 결과를 제시하며, CSS에서는 유의미한 차이를 보이지 않았습니다. 다학술적 접근을 통한 치료 선택의 근거를 마련하므로 임상 가이드라인 및 치료 알고리즘 구축에 중요한 자료입니다.

Abstract

For patients with early-stage non-small cell lung cancer (NSCLC) who are unable to tolerate lobectomy, alternative locoregional treatments, including sublobar resection (SLR), stereotactic body radiation therapy (SBRT), or image-guided thermal ablation (IGTA) are available, yet their relative risks and benefits remain uncertain. This systematic review and meta-analysis aims to synthesize existing evidence and compare the survival outcomes of these modalities in early-stage NSCLC. A systematic search was conducted through MEDLINE (PubMed), Embase, and CENTRAL on April 20, 2026. Comparative analyses were restricted to propensity score-matched (PSM) studies reporting hazard ratios (HRs) for overall survival (OS) and cancer-specific survival (CSS) in pathologically confirmed early-stage NSCLC. Single-arm pooled survival analyses were performed using reconstructed individual patient data to estimate time-to-event outcomes. Risk of bias was assessed using ROBINS-I for comparative analysis and the JBI checklist for single-arm analyses. Seven PSM studies comparing SBRT and SLR were included in the comparative analysis. SLR was associated with improved OS compared with SBRT (HR 1.51; 95% CI: 1.18-1.93), while CSS did not differ significantly (HR 1.08; 95% CI: 0.48-2.45). Sixteen studies were included in the single-arm analyses. Pooled 3-year OS estimates were 80% (95% CI: 75-86%) for S...

A Circulating GPNMB-Based Multimodal Model Integrates Tumor-Immune Crosstalk to Predict Immunotherapy Response in Esophageal Cancer.

Screening brief

식도 편평상피세포암 환자에서 신항문 immunotherapy 반응 예측의 난제를 해결하기 위해 순환 GPNMB를 핵심 biomarker로 규명하였다. 종양-면역 상호작용 기전을 해명하고 CAF-Epi 미세환경과 임상 병리 정보를 결합한 multimodal model을 개발하여 임상 적용 가능성을 입증하였다. 이는 정밀 oncology에서 biomarker 기반 치료 반응 예측의 새로운 표준을 제시할 것으로 기대된다.

Abstract

Neoadjuvant immunotherapy improves outcomes in esophageal squamous cell carcinoma (ESCC), yet ∼70% of patients fail to respond. Pretreatment biopsies and plasma provide critical opportunities for biomarker discovery. In this study, we performed plasma proteomic profiling and identified soluble glycoprotein nonmetastatic melanoma protein B (sGPNMB) as the most elevated circulating protein in nonresponders. Mechanistically, tumor cell-derived sGPNMB suppressed CD8+ T-cell receptor signaling via the SDC4-CD148 axis to induce functional exhaustion, with secretion being required for its immunosuppressive activity. Cancer-associated fibroblast-epithelial (CAF-Epi) niches promoted SOX2 upregulation in tumor cells, transcriptionally activating GPNMB expression. In humanized patient-derived xenograft models, circulating GPNMB levels predicted response to PD-1 blockade, and GPNMB inhibition synergized with therapy. Across retrospective cohorts and a prospective clinical trial, a multimodal model combining plasma GPNMB levels, CAF-Epi niche detection, and clinical-pathologic features achieved robust predictive accuracy for immunotherapy response and survival. These findings establish a spatial-circulating biomarker framework for precision ESCC immunotherapy. Tumor-derived soluble GPNMB, transcriptionally activated by SOX2 within CAF-Epi niches, drives CD8+ T-cell exhaustion and resistanc...

A deep learning PET/CT biomarker for early progression (POD24) and survival stratification in follicular lymphoma: a multicenter study.

Screening brief

이 연구는 follicular lymphoma 환자에서 baseline [¹⁸F]FDG PET/CT 기반의 Deep Learning biomarker를 개발하여 POD24 및 생존 위험을 정밀하게 예측하는 방법을 제시합니다. 기존 FLIPI, FLIPI-2, PRIMA-PI 등의 임상 점수보다 우수한 판별력을 보여 조기 진행 판단과 치료 전략 수립에 실질적인 도움을 줄 수 있습니다. multicenter study를 통해 신뢰성을 확보했으며, precision management를 위한 imaging biomarker로서의 임상적 가치가 높습니다.

Abstract

OBJECTIVE: To develop and validate a prognostic imaging biomarker derived from baseline [¹⁸F]FDG PET/CT using tabular deep learning for prediction of progression of disease within 24 months (POD24) and survival risk stratification in patients with follicular lymphoma (FL). METHODS: This retrospective multicenter study included 309 patients with newly diagnosed FL (grades 1-3a) from five independent medical centers. Tumor volumes segmented from baseline [¹⁸F]FDG PET and CT images were used to extract high-throughput radiomic features. Five conventional machine learning algorithms and four advanced tabular deep learning models were developed and compared. The predictive output of the GAMformer model was defined as the deep learning score (DLS). The DLS was integrated with clinical variables and PET metabolic parameters to construct a multiparametric model in the training cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis, and further validated in validation cohort. RESULTS: During a median follow-up of 44 months, POD24 occurred in 55 patients. The DLS demonstrated strong predictive performance for POD24 (training AUC = 0.857; validation AUC = 0.753). The multiparametric model further improved discrimination, achieving AUCs of 0.882 in the training cohort and 0.797 in the...

An interpretable PET/CT-based radiomic-clinical model for predicting bone marrow involvement in follicular lymphoma: comparison of pelvic and spine-pelvis VOI frameworks.

Screening brief

이 연구는 Follicular Lymphoma 환자에서 Bone marrow involvement를 비침습적으로 예측하기 위해 18F-FDG PET/CT 기반 Radiomics와 임상 데이터를 통합한 해석 가능한 머신러닝 모델을 개발했습니다. Spine-pelvis VOI 프레임워크가 Pelvic VOI보다 우수한 성능을 보였으며, GBM 모델이 높은 정확도와 민감도를 입증하여 임상적 유용성이 확인되었습니다. SHAP 분석을 통해 영상 및 임상 바이오마커의 기여도를 해석함으로써, Follicular Lymphoma의 정량적 병기 평가와 치료 전략 수립에 중요한 참고 자료가 될 것입니다.

Abstract

To investigate the feasibility of non-invasively identifying bone marrow involvement (BMI) in follicular lymphoma (FL) using baseline 18F-FDG PET/CT combined with multidimensional feature fusion, and to compare the impact of different bone marrow volume-of-interest (VOI) frameworks on model performance. This retrospective study included 187 patients with newly diagnosed FL, 93 of whom had BMI. Based on baseline 18F-FDG PET/CT, two bone marrow VOI frameworks were constructed: a pelvic VOI framework and a spine-pelvis VOI framework. Clinical features, conventional imaging features, radiomic features, and deep learning features were extracted. A hierarchical feature screening strategy was employed: clinical and conventional imaging features were screened using univariate logistic regression, Spearman's correlation analysis, and multivariate logistic regression, whereas high-dimensional radiomic and deep learning features were screened using LASSO regression combined with the Boruta algorithm. Based on the selected features, six different modelling schemes were developed. The optimal scheme was selected using the area under the receiver operating characteristic curve (AUC) in the independent validation set as the primary metric. Under the optimal scheme, the performance of seven machine learning models-logistic regression (LR), support vector machine (SVM), gradient boosting machi...

ULK1, a novel therapeutic target to delay drug tolerance to EGFR-TKIs in an EGFR-mutant non-small cell lung cancer model.

Screening brief

본 연구는 EGFR 돌연변성 NSCLC에서 EGFR-TKI 내성을 유발하는 DTP 세포의 형성에 ULK1가 핵심적인 역할을 함을 입증하였다. ULK1 억제 전략이 osimertinib에 대한 약물 내성 발생을 지연시키고 항종양 효과를 향상시킬 수 있음을 전임상 모델에서 확인하였다. 이는 기존 비특이적 자가포식 억제제 한계를 극복하고 EGFR-TKI 치료 실패를 개선할 수 있는 새로운 표적 치료 접근법을 제시한다.

Abstract

The presence of drug-tolerant persister (DTP) cells reduces the effectiveness of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in EGFR-mutated non-small cell lung cancer (NSCLC). Although autophagy is a potential target for eliminating DTP cells, clinical trials targeting autophagy in EGFR-mutant NSCLC have been unsuccessful-likely because most trials have utilized chloroquine, non-specifically inhibiting autophagy targeting lysosomes with dose limitations. This study focused on unc-51-like autophagy activating kinase 1 (ULK1), a more specific target for autophagy inhibition, to assess whether ULK1 inhibition delays the emergence of tolerance to EGFR-tyrosine kinase inhibitors in EGFR-mutant NSCLC cells. DTP cells were generated by treating EGFR-mutant NSCLC cell lines with osimertinib. Autophagy status and ULK1 expression were evaluated using immunofluorescence, western blotting, and quantitative real-time PCR. The effects of both pharmacological and genetic inhibition of ULK1 were examined in vitro and in vivo. ULK1 and LC3-II, markers of autophagy, were upregulated in DTP cells. Inhibition of ULK1, either pharmacologically or genetically, suppressed autophagy, prevented the formation of DTP cells, and enhanced the antitumor activity of osimertinib in both in vitro and in vivo models. Furthermore, upregulation of ULK1 expression through serum star...

From center to edge: Prognostic implications of spatial metabolic heterogeneity, normalized hotspot-to-centroid and perimeter distance, on PET imaging. A systematic review and meta-analysis.

Screening brief

이 연구는 PET 영상에서 추출된 spatial radiomic feature인 NHOC와 NHOP가 종양의 metabolic heterogeneity를 정량화하고 OS 예측에 유용함을 체계적으로 입증했습니다. 특히 lung cancer 환자군에서 NHOC가 OS와 강력한 연관성을 보였으며, non-invasive prognostication 도구로서의 잠재력이 확인되었습니다. 표준화된 multi-center validation이 필요한 단계이나, imaging 기반 oncology 연구 및 임상 의사결정에 중요한 참고 자료가 될 수 있어 위키에 포함할 가치가 충분합니다.

Abstract

Tumor heterogeneity remains a major challenge in oncology, influencing prognosis and treatment response. Novel PET-derived spatial radiomic features, including the normalized hotspot-to-centroid (NHOC) and normalized hotspot-to-perimeter (NHOP) distances, aim to quantify intratumoral metabolic heterogeneity and spatial distribution of metabolic activity. These biomarkers may provide biologically interpretable indicators of tumor aggressiveness and patient outcomes. The aim of this study was to systematically evaluate the prognostic and predictive performance of NHOC and NHOP derived from PET imaging across different tumor types. A systematic review and meta-analysis were conducted according to PRISMA guidelines. PubMed/MEDLINE and Google Scholar were searched up to March 2026. Studies evaluating NHOC or NHOP extracted from PET imaging in cancer patients were included. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled using random-effects models. Ten studies involving 1,496 patients were included. Elevated NHOC was statistically significantly associated with worse OS (HR of 2.313, 95% CI [1.418, 3.775], p = 0.001). Subgroup analysis showed a strong association in lung cancers (2.864, 95% CI [2.018, 4.063], p < 0.001), while results in breast cancer and glioma were inconclusive due to limited data. Decrease in NHOP demonstrated a non-s...

Plasma proteomics predicts pathological complete response and reveals LIF as a potential mediator of resistance to neoadjuvant immunochemotherapy in resectable NSCLC.

Screening brief

resectable NSCLC 환자에서 neoadjuvant immunochemotherapy 치료 전 plasma proteomics 분석을 통해 pathological complete response (pCR) 예측 모델을 개발하고 저항 기전을 규명하였다. 특히 LIF가 CD8+ T-cell 침윤 감소와 cytotoxic effector program 억제를 매개하여 치료 저항성을 유발함을 실험적으로 입증하였다. 이는 비침습적 biomarker를 통한 환자 선별 및 LIF 표적 치료 전략 개발에 중요한 임상적 함의를 제공한다.

Abstract

Neoadjuvant immunochemotherapy (nICT) is increasingly used for resectable non-small cell lung cancer (NSCLC), yet a substantial proportion of patients fail to achieve pathological complete response (pCR). Clinically scalable, minimally invasive biomarkers that predict response and point to actionable resistance mechanisms remain needed. Pretreatment plasma samples collected prior to the first dose were profiled using the Olink proximity extension assay in a Sun Yat-sen University Cancer Center cohort (n=86), randomly split into a training set (n=65) and an internal validation set (n=21). Differentially abundant proteins associated with pCR were identified, and predictive models were developed using logistic regression, random forest, and extreme gradient boosting (XGBoost), followed by internal validation and independent external validation in the Jiangmen Central Hospital cohort (n=46). Survival associations were evaluated by Cox regression. Mechanistic analyses integrated tumor immunohistochemistry/multiplex immunofluorescence, bulk RNA sequencing with immune deconvolution, and functional validation in subcutaneous and orthotopic murine lung cancer models with pharmacologic leukemia inhibitory factor (LIF) blockade. Four candidate proteins (LIF, CXCL1, CX3CL1, and NT-3) showed modest single-marker discrimination for pCR (area under the curve (AUC), 0.611-0.673). Multiprotein...

Lung Transplant for Refractory Lung-Limited Stage IV Non-Small Cell Lung Cancer.

Screening brief

이 연구는 기존에 전이성 NSCLC로 간주되어 이식이 금기시되던 refractory lung-limited stage IV NSCLC 환자에서 lung transplant가 조기 생존율 향상에 유의미한 결과를 보임을 입증했습니다. 특히 medical management alone군 대비 1-year overall survival이 100%로 나타나 기존 치료 패러다임에 도전할 수 있는 새로운 수술적 접근법을 제시합니다. 장기 추적 관찰과 quality-of-life 데이터가 추가된다면 advanced NSCLC 치료 전략을 재정의하는 중요한 근거가 될 것입니다.

Abstract

Patients with medically refractory, lung-limited, stage IV non-small cell lung cancer (NSCLC) often die of progressive respiratory failure. Although lung transplant offers the possibility of organ-level disease extirpation, the surgery has historically not been offered to such patients due to concerns of poor oncological outcomes. To describe outcomes among patients who underwent lung transplant and examine survival associated with lung transplant compared with medical management alone. This prospective, single-center, registry study included 404 adults. Of 98 adults with medically refractory, lung-limited, stage IV NSCLC, 17 underwent lung transplant and 81 met transplant eligibility criteria but did not undergo transplant due to nonbiologic barriers and were treated with medical management alone. There were 306 adults without cancer who underwent lung transplant for end-stage pulmonary disease. All who underwent lung transplant had respiratory failure. The study was conducted from September 1, 2021, through June 30, 2025; the last day of extended follow-up was January 31, 2026. Lung transplant after contemporary staging and a dissemination-minimizing operative technique was used. The primary outcome was overall survival from eligibility evaluation completion in patients with NSCLC who underwent lung transplant vs those with NSCLC who were treated with medical management alon...

Rare EGFRm NSCLC: More First-Line Options Emerge.

Screening brief

희귀 EGFRm NSCLC 환자의 First-line 치료 선택지가 확대되고 있다. WU-KONG28 Phase III trial에서 sunvozertinib가 Chemotherapy 대비 우수한 efficacy를 보였으며, CHRYSALIS-2 연구는 amivantamab와 lazertinib 병용 요법이 durable OS를 제공할 수 있음을 시사한다. 이는 기존 표준 치료의 한계를 극복하고 맞춤형 표적 치료 시대를 앞당길 중요한 임상적 근거가 된다.

Abstract

Findings from the phase III WU-KONG28 trial indicate that the next-generation tyrosine kinase inhibitor sunvozertinib, an approved later-line option for patients with non-small cell lung cancer harboring EGFR exon 20 insertions, also looks effective up front, besting chemotherapy. Meanwhile, updated CHRYSALIS-2 data point to amivantamab combined with lazertinib as a new option for patients with atypical EGFR mutations, with initial efficacy translating to durable overall survival.

Large language model and Gd-EOB-DTPA-enhanced MRI-based risk stratification system for postoperative hepatocellular carcinoma: a multicenter study.

Screening brief

이 연구는 Gd-EOB-DTPA-enhanced MRI와 혈청 바이오마커를 결합하여 HCC 환자의 사후 재발 및 생존 위험을 정량적으로 평가할 수 있는 Fully Automated Stratification System(FASS)을 제시합니다. 특히 ChatGPT-4o를 활용하여 영상 기반 radiomic features와 반정형 임상 데이터를 통합함으로써 예측 정확도와 해석 가능성을 동시에 확보했습니다. 다중 센터 외부 검증과 전사체 분석을 통해 임상적 타당성과 생물학적 기전을 입증했으며, 간담도 종양학 분야에서 정밀 의료 의사결정을 지원할 수 있는 실용적인 도구로 평가됩니다.

Abstract

To develop and validate a Fully Automated Stratification System (FASS) integrating serum biomarkers, automated radiomic features, and large language model (LLM)-derived semantic features for prognostic prediction in patients with solitary hepatocellular carcinoma (HCC) after hepatic resection. A total of 448 patients with solitary HCC from three centers were retrospectively enrolled. Automated tumor segmentation was performed using a modified MedNeXt-loss framework, and radiomic features were extracted from Gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI. Five LLMs were compared for feature-level accuracy and completeness, and the best-performing model was incorporated into the FASS. Prognostic models based on serum, radiomic, and LLM-semantic features were integrated and evaluated using concordance index, time-dependent ROC, and decision curve analyses. Biological relevance was explored through RNA sequencing and pathway enrichment analyses. The MedNeXt-loss framework achieved robust segmentation (Dice = 0.77). ChatGPT-4o demonstrated the best balance between predictive accuracy and completeness and was used for subsequent modeling. In multivariate analysis, AFP, AST, and the ChatGPT-4o-derived irregular margin were independent predictors of overall survival. The integrated FASS achieved high prognostic performance (C-index 0.78 and 0.76...

PET/CT predict pathological response to neoadjuvant nivolumab in resectable non-small cell lung cancer.

Screening brief

resectable non-small cell lung cancer (NSCLC) 환자에서 neoadjuvant nivolumab 기반 치료 후 pCR을 예측하기 위해 baseline 및 post-therapy 18F-FDG PET/CT metabolic parameters를 평가하였다. ΔSUVmax (%)와 조직학적 아형, PD-L1 expression ≥ 1%가 독립적인 예측 인자로 확인되었으며, 이를 통합한 XGBoost 모델은 높은 판별력(AUC 0.884)을 보였다. 본 연구는 neoadjuvant immune checkpoint inhibitor 치료 중 PET/CT 기반 영상 biomarker가 비침습적 pCR 예측 도구로 임상적으로 유용함을 입증하여, 신요법 반응 모니터링 전략에 기여할 것으로 기대된다.

Abstract

BACKGROUND: This study aimed to evaluate the predictive value of 18F-FDG PET/CT for pathological complete response (pCR) in patients with resectable non-small cell lung cancer (NSCLC) receiving neoadjuvant nivolumab-based therapy. METHODS: This retrospective study included 125 patients with stage II–III NSCLC who received three cycles of neoadjuvant nivolumab plus chemotherapy between June 2019 and October 2024. All patients underwent ¹⁸F-FDG PET/CT imaging at baseline and after neoadjuvant therapy prior to surgery. Metabolic parameters including SUVmax, SUVmean, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG)were measured. The diagnostic performance of these parameters for predicting pCR was evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). Multiple logistic regression was used to identify independent predictive factors. An XGBoost model integrating significant imaging and clinicopathological predictors was developed. RESULTS: The pCR rate was 38.4% (48/125). Post-therapy metabolic parameters and their Δ% were significantly lower in the pCR group (n = 48) compared to the non-pCR group (n = 77) (P < 0.001). A ΔSUVmax (%) cut-off of -69.8% predicted pCR with an AUC of 0.832 (sensitivity 93.8%, specificity 61.0%). DCA confirmed the clinical net benefit of models using post-therapy or Δ% parameters....

Evaluating the prognostic impact of multiple 18FDG-PET imaging parameters in small-cell lung cancer: Insights from the long-term analysis of the CONVERT trial.

Screening brief

이 연구는 LS-SCLC 환자에서 치료 전 18F-FDG-PET 기반 영상 매개변수가 임상 인자 및 CT-GTV 대비 추가적인 예후 예측 가치를 가지는지 평가했습니다. CONVERT trial의 다기관 무작위 대조군 데이터를 활용한 후향 분석 결과, 기저 종양 부피가 예후를 결정하는 가장 강력한 독립 인자로 확인되었습니다. 18F-FDG-PET에서 유래된 대사 및 radiomic 파라미터는 기존 임상 모델에 유의미한 예측 향상 효과를 제공하지 않아, 기저 예후 분류에서의 임상적 유용성이 제한됨을 시사합니다. 따라서 LS-SCLC의 치료 전략 수립 시 영상 기반 예후 지표 선택에 대한 명확한 근거를 제시한다는 점에서 wiki에 포함될 가치가 높습니다.

Abstract

BACKGROUND: The prognostic value of baseline 18F-FDG PET/CT-derived metrics in limited-stage small-cell lung cancer (LS-SCLC) remains uncertain. We evaluated whether baseline PET-derived parameters provide prognostic information beyond tumour volume and clinical factors in patients treated with curative-intent chemoradiotherapy within the phase III CONVERT trial. METHODS: CONVERT was an international, multi-centre randomised controlled trial. This study is a post-hoc analysis of baseline 18F-FDG PET/CT from the multiple PET imaging parameter (MPI) cohort across 8 UK sites. PET metrics, including whole-body metabolic tumour volume (MTV), total lesion glycolysis (TLG), SUV-based measures, and radiomic features, were derived under EARL-accredited conditions. CT-derived gross tumour volume (GTV) and a pre-specified clinical prognostic model (CPM) were assessed alongside PET metrics. Overall survival (OS) and progression-free survival (PFS) were analysed using Cox regression. Incremental prognostic value beyond CPM was evaluated using Harrell’s concordance index (C-index). Correlations between imaging, clinical, and circulating tumour cell (CTC) variables were explored. RESULTS: Ninety-four patients comprised the MPI cohort. In univariable analyses, CPM, CT-GTV, and PET-derived MTV and TLG, were associated with shorter OS and PFS. After multivariable adjustment, only CT-GTV remaine...

Neuro-visceral immunometabolic network phenotyping via baseline whole-body [¹⁸F]FDG PET/CT underlying pathologic response to neoadjuvant immunochemotherapy in resectable NSCLC.

Screening brief

이 연구는 resectable NSCLC 환자군에서 neoadjuvant immunochemotherapy 치료 전 baseline whole-body [¹⁸F]FDG PET/CT를 활용하여 neuro-visceral immunometabolic network phenotyping을 수행하고, 이를 통해 pathologic response를 예측하는 새로운 영상 바이오마커 접근법을 제시합니다. 기존 조직 생검의 한계를 넘어 전신 대사 및 면역 상호작용을 비침습적으로 정량화함으로써 치료 반응 조기 판정에 유용할 것입니다. 본 연구 결과는 NSCLC 치료 전략의 개인화와 정밀 종양학 발전에 중요한 임상적 통찰을 제공할 것으로 기대됩니다.

Abstract

not available

[177Lu]Lu-DOTA-IBA plus EGFR-TKIs versus [177Lu]Lu-DOTA-IBA monotherapy for EGFR-mutated advanced non-small-cell lung cancer (NSCLC) with bone metastases: a prospective study.

Screening brief

이 prospective study는 EGFR-mutated advanced NSCLC 환자에서 bone metastases 치료 시 [177Lu]Lu-DOTA-IBA monotherapy와 [177Lu]Lu-DOTA-IBA plus EGFR-TKIs의 임상적 결과를 직접 비교합니다. Radioligand therapy와 EGFR-TKIs의 병용 효과를 평가함으로써 기존 표준 치료 패러다임을 확장할 가능성을 제시합니다. 특히 Nuclear medicine 기반의 정밀 방사성 동위원소 치료가 폐암 골 전이 관리에 어떻게 통합될 수 있는지 보여주는 중요한 임상 증거를 제공합니다.

Abstract

not available

Imaging-based stratification of Claudin 18.2-positive gastric adenocarcinoma using 18F-FDG PET/CT radiomics.

Screening brief

Gastric Adenocarcinoma 치료에서 표적 항체 요법의 적합성을 결정하는 CLDN18.2 발현을 비침습적으로 예측할 수 있는 multimodal radiomics 모델을 제시하였습니다. 18F-FDG PET/CT 영상에서 관찰된 대사 활성 감소 현상과 CLDN18.2 양성 종양 간의 명확한 역상관 관계를 규명하여, 기존 endoscopic biopsy의 한계를 보완하는 patient stratification 도구를 개발했습니다. 이는 임상 현장에서 표적 치료군을 신속하게 선별하고 치료 전략을 최적화하는 데 중요한 근거가 될 것입니다.

Abstract

This study aimed to develop and validate a non-invasive, multimodal radiomics model based on preoperative 1⁸F-FDG PET/CT to predict CLDN18.2 expression in gastric adenocarcinoma (GAC), addressing the limitations of intratumoral heterogeneity and invasiveness associated with endoscopic biopsies. This retrospective study enrolled 291 patients with pathologically confirmed GAC who underwent preoperative 1⁸F-FDG PET/CT. The cohort was randomly divided into a training set (n = 204) and an independent validation set (n = 87). High-dimensional radiomic features were extracted from PET and CT images. Feature selection was performed using the minimum redundancy maximum relevance (mRMR) algorithm and LASSO regression. A radiomics signature (Rad-score) was constructed using XGBoost and integrated with clinical variables. Among five machine learning algorithms evaluated, AdaBoost was identified as the optimal model. Performance was assessed via receiver operating characteristic (ROC) analysis, and interpretability was visualized using SHapley Additive exPlanations (SHAP). CLDN18.2-positive tumors exhibited a distinct hypometabolic phenotype, characterized by significantly lower SUVmax (P = 0.012) and SUVmean (P < 0.001) compared to negative tumors. The combined multimodal model demonstrated superior discrimination, achieving an AUC of 0.926 (95% CI: 0.891-0.961) in the training cohort and...

Clinical impact of local consolidative therapy in EGFR-mutant metastatic NSCLC: A propensity-matched multicenter analysis.

Screening brief

본 연구는 EGFR-mutant metastatic NSCLC 환자에서 EGFR-TKI 치료와 함께 local consolidative therapy(수술 또는 방사선치료)가 OS 및 PFS에 미치는 영향을 다룹니다. propensity score matching을 적용한 multicenter 분석 결과, 수술군이 TKI 단요법 대비 유의미한 생존 이점을 보였으며, 이는 특정 임상 특징을 가진 환자군에서의 치료 선택 기준을 마련합니다. 따라서 advanced NSCLC의 multidisciplinary management 전략을 논의하는 데 필수적인 문헌으로 위키에 등재할 가치가 있습니다.

Abstract

To evaluate the impact of consolidative surgery and radiotherapy (RT) on survival outcomes in patients with advanced or metastatic epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). This retrospective, multicenter cohort study included 864 patients with EGFR-mutant advanced or metastatic NSCLC receiving first-line EGFR-TKIs. Patients were categorized into EGFR-TKI monotherapy (n = 616), TKI plus surgery (n = 100), and TKI plus RT (n = 148). Propensity score matching (PSM) and overlap weighting were applied to balance baseline characteristics. Overall survival (OS) and progression-free survival (PFS) were analyzed using Cox proportional hazards models and restricted mean survival time (RMST). After PSM, 97 matched pairs were generated for TKI versus TKI plus surgery and 148 pairs for TKI versus TKI plus RT. Compared with TKI alone, consolidative surgery significantly improved OS (hazard ratio [HR], 0.36; 95% CI, 0.20-0.65; p < 0.001) and PFS (HR, 0.48; 95% CI, 0.34-0.67; p < 0.001), with RMST gains of 10.7 and 10.6 months.Consolidative RT showed a trend toward longer OS (HR, 0.61; 95% CI, 0.39-0.93; p = 0.023)without significant PFS or consistent RMST benefit. Subgroup analyses showed surgery benefit in younger patients with good performance, lower metastatic burden, and no brain metastasis, whe...

Protective effect of bevacizumab against interstitial lung disease in non-squamous non-small-cell lung cancer: a nationwide target trial emulation study.

Screening brief

본 연구는 비편평형 NSCLC 1차 요법에서 bevacizumab 병용이 corticosteroid 치료가 필요한 ILD 발생 위험을 낮추고 단기 생존율을 향상시킨다는 대규모 target trial emulation 결과를 제시한다. 기존 항혈관생성제에 대한 ILD 우려를 불식시키며, 임상 현장에서 표적 치료 선택의 안전성 근거를 강화한다. 특히 중증 폐독성 예방 측면에서 bevacizumab의 역할에 대한 새로운 관점을 제공한다.

Abstract

We evaluated the association between bevacizumab use and interstitial lung disease (ILD), 180-day mortality, and venous thromboembolism (VTE) risks in patients with non-squamous non-small-cell lung cancer (NSCLC) receiving first-line platinum-based chemotherapy. Using the Japanese Diagnosis Procedure Combination database (2011-2023), we identified patients with stage III-IV non-squamous NSCLC who initiated platinum-based chemotherapy with pemetrexed, with or without bevacizumab. A target trial emulation framework was applied. The primary outcome was ILD requiring corticosteroid treatment within 180 days of chemotherapy initiation. The secondary outcomes included 180-day mortality, mortality within 30 days after ILD onset, and VTE. Propensity score overlap weighting was used to balance the baseline covariates. Fine-Gray models and Cox proportional hazards models were used to estimate subdistribution hazard ratios (SHRs) for ILD and VTE and hazard ratios (HRs) for mortality. Overall, 47,433 patients were analyzed (bevacizumab group: n = 12,101; non-bevacizumab group: n = 35,332). Bevacizumab use was associated with lower risks of ILD [SHR, 0.75; 95% confidence interval (CI), 0.67-0.84], 180-day mortality (HR, 0.61; 95% CI, 0.57-0.66), and mortality within 30 days after ILD (HR, 0.71; 95% CI, 0.57-0.88). The overall VTE risk was similar between the two treatment groups. The main...

Consensus recommendations on surveillance and survivorship for patients with unresectable/stage IV non-small cell lung cancer after completing Immunotherapy: a Delphi study by Canadian experts.

Screening brief

이 논문은 Immunotherapy를 완료한 unresectable/stage IV non-small cell lung cancer (NSCLC) 환자의 surveillance 및 survivorship 관리에 대한 전문가 컨센서스를 제시합니다. 특히 CT와 Brain MRI를 활용한 추적 검사 주기, irAEs 모니터링, 다학제 지원 체계에 대한 표준화된 지침을 제공하여 임상적 공백을 메웁니다. Immunotherapy 후 durable response를 보이는 환자군을 위한 체계적인 survivorship 프레임워크는 향후 폐암 관리 가이드라인 수립에 중요한 기준이 될 것입니다.

Abstract

With the advent of immunotherapy, a subset of patients with unresectable or stage IV non-small cell lung cancer (NSCLC) achieve durable responses after completing standard treatment durations (typically 2 years). However, guidelines for post-treatment surveillance and survivorship care in this population remain limited, particularly in the Canadian context. A panel of 10 Canadian lung cancer experts, including medical oncologists, radiation oncologists, and primary care providers, participated in a modified Delphi process to develop consensus recommendations. The process involved initial discussion of key questions, anonymous voting, and iterative refinement until ≥ 70% agreement was reached. Consensus was achieved on four key areas: (1) natural history post-immunotherapy, with experts noting durable responses in 20-25% of patients but risks of late progression; (2) surveillance, recommending contrast-enhanced CT chest/abdomen (± pelvis if clinically indicated) every 3-6 months for 2 years, then every 6-12 months for 3 years, then as clinically needed, with additional considerations for brain MRI in patients with prior brain metastases; (3) discharge considerations, emphasizing patient readiness, fear of progression, and multidisciplinary support; (4) survivorship, focusing on monitoring immune-related adverse events (irAEs), lifestyle interventions, and psychosocial support....

Comparative effectiveness of first-line targeted therapies in ALK-positive non-small cell lung cancer: real-world evidence of tyrosine kinase inhibitors.

Screening brief

본 연구는 ALK-positive NSCLC 환자에서 first-line targeted therapy로 사용되는 tyrosine kinase inhibitors의 comparative effectiveness를 real-world claims data를 통해 평가했습니다. alectinib이 crizotinib 대비 유의미한 OS 및 TTNTD 향상을 보였으며, lorlatinib과의 비교에서는 표본 크기 제한으로 통계적 유의성은 확인되지 않았습니다. 임상 지침에서 동등하게 권고되는 ALK TKI 간 치료 선택에 실증적 근거를 제공하므로, targeted therapy의 실제 임상 적용과 guideline refinement에 중요한 자료입니다.

Abstract

To estimate the comparative effectiveness of first-line (1 L) anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) in ALK-positive non-small cell lung cancer (NSCLC) in the United States. We conducted a retrospective cohort study using Optum's de-identified Clinformatics® Data Mart Database (2016-2024). Patients with lung cancer ICD-10 codes and pharmacy claims for ALK TKIs were eligible if aged ≥ 18 years, continuously enrolled ≥ 6 months before initiation, and treated after each drug's FDA approval. Outcomes included time-to-next (targeted) treatment or death (TTNTD) and overall survival (OS). Propensity scores were constructed for pairwise comparisons and applied using overlap weighting (OW) as the primary specification and inverse probability of treatment weighting (IPTW) as alternative specification. Among 940 patients initiating 1 L therapy (crizotinib n = 449, alectinib n = 417, brigatinib n = 30, ceritinib n = 8, lorlatinib n = 36), alectinib had the longest reached median TTNTD (33.5 months; 95% CI, 24.6-46.3) and OS (46.5 months; 95% CI, 39.0-NR) in unadjusted analyses. In overlap-weighted analyses, alectinib was associated with significantly longer TTNTD (HR 0.50; 95% CI, 0.41-0.61) and OS (HR 0.58; 95% CI, 0.47-0.71) versus crizotinib. Comparison of alectinib vs lorlatinib statistically insignificantly favored lorlatinib (TTNTD HR 2.02; 95% CI, 0.92-4...

Phase Ib of repotrectinib plus osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer.

Screening brief

EGFR-mutated NSCLC 환자에서 osimertinib 내성 발생 시 repotrectinib 병용 요법의 안전성과 항종양 효과를 평가한 Phase Ib 임상시험(TOTEM) 결과입니다. 본 연구는 특히 뇌전이가 있는 환자군에서 유의미한 icORR과 icPFS를 보여, 표적 치료 후 내성 극복을 위한 새로운 병용 전략의 잠재력을 입증했습니다. 중증 부작용은 주로 어지러움과 빈혈로 관리 가능한 수준이었으며, 향후 biomarker-selected NSCLC 환자를 대상으로 한 추가 연구가 필요함을 시사합니다.

Abstract

Overcoming resistance to osimertinib in EGFR-mutated non-small cell lung cancer (NSCLC) is a clinically unmet need. Osimertinib plus repotrectinib inhibited Src and FAK phosphorylation and the downstream activation of STAT3, paxillin, and YAP1 in preclinical models, enhancing osimertinib efficacy. TOTEM (NCT04772235) was a phase Ib study assessing the safety, tolerability, pharmacokinetics, and antitumour activity of repotrectinib plus osimertinib in patients with EGFR-mutated NSCLC resistant to previous treatments. Dose-escalation followed 3 + 3 model with osimertinib 80 mg QD plus repotrectinib at three doses: 80 mg QD, 160 mg QD, and 160 mg BID. Dose-expansion evaluated efficacy in two cohorts after progression to osimertinib or after progression to osimertinib and chemotherapy. Thirty-one patients were enrolled between February 2022 and January 2025. Seventeen patients had two or more prior lines of therapy. The recommended phase 2 dose was 80 mg QD osimertinib plus 160 mg BID repotrectinib. Grade 3-4 treatment-related adverse events occurred in 14 patients (45.2%), mainly dizziness (16.1%) and anaemia (12.9%). The ORR was 22.2% (95% CI: 8.6-42.3), with six patients achieving confirmed PR lasting 6.9 months (95% CI: 2.7-13.1). Median PFS was 4.0 months (95% CI: 2.8-9.7). In patients with intracranial disease, icORR was 33.3% (7.5-70.1) and median icPFS was 4.4 months (95%...

Clinical characteristics and survival of small cell lung cancer with limited or extensive synchronous metastatic spread - A German population-based cancer-registry based cohort study.

Screening brief

이 연구는 SCLC 환자에서 전이 병변의 범위와 장기 수에 따른 생존 예후 차이를 인구 기반 코호트를 통해 정량화하였다. Limited metastatic spread 군에서 유의하게 향상된 OS와 PFS를 확인하여, 기존 NSCLC 중심의 Oligometastatic disease(OMD) 개념이 SCLC에도 적용 가능함을 시사한다. TNM-8 M 분류와 장기 관여 수를 활용한 예후 Stratification은 임상적 치료 전략 수립과 환자 선별에 중요한 근거를 제공한다.

Abstract

While the concept of oligometastatic disease (OMD) is established in non-small cell lung cancer (NSCLC), its relevance in small cell lung cancer (SCLC) remains unclear. We investigated whether subclassifying metastatic SCLC by the TNM-8 M classification and the number of organ systems involved provides prognostic value and informs the applicability of the OMD concept to SCLC. Patients with stage IV SCLC diagnosed between 2016 and 2020 were identified from three German population-based cancer registries. Metastatic burden was categorized as intra-thoracic limited metastatic spread (IT-LMS, M1a), extra-thoracic limited metastatic spread (ET-LMS, M1b), limited multi-organ involvement (LMOI, M1c with ≤3 organs), or extensive multi-organ involvement (EMOI, M1c with >3 organs). Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Multivariable Cox models evaluated the prognostic relevance of metastatic extent and specific metastasis sites. Among 2,567 patients, 9.5% had IT-LMS, 18.5% ET-LMS, 60.9% LMOI, and 11.1% EMOI. Median OS was 11 months in IT-LMS and ET-LMS, 8 months in LMOI, and 7 months in EMOI. PFS showed a similar gradient (6.1, 6.0, 4.1, and 4.1 months). Compared with IT-LMS, mortality risk was higher in LMOI (HR 1.57, 95% CI 1.34-1.84) and EMOI (HR 1.87, 1.54-2.28); EMOI also exceeding LMOI (HR 1.19, 1.04-1.37). Liver an...

Study on NGS-based molecular profiling of malignant pleural effusion supernatant cfDNA in guiding targeted therapy for non-small cell lung cancer.

Screening brief

악성 흉수 상등액의 cfDNA는 조직 생검이 어려운 NSCLC 환자에서 표적 치료 가이드를 위한 강력한 liquid biopsy원으로 작용할 수 있다. 본 연구는 cell block 및 plasma 대비 우월한 mutation detection rate, 특히 낮은 tumor cellularity에서도 안정적인 NGS 결과를 입증하였다. EGFR mutation 기반 targeted therapy 반응 예측과 PFS 데이터는 임상 의사결정에 직접적인 도움을 줄 것이다. 따라서 tissue 대체 sample로서의 임상적 타당성이 명확히 제시되어 관련 위키 섹션에 반드시 등재되어야 한다.

Abstract

For patients with advanced non-small cell lung cancer (NSCLC), obtaining histological specimens can be challenging due to the presence of malignant pleural effusion (MPE), making liquid biopsy an important alternative for molecular profiling. This study aims to comparatively analyze the advantages of MPE supernatant over other sample types in molecular testing and to assess the feasibility and clinical utility of next-generation sequencing (NGS) using MPE supernatant for guiding targeted therapy. A total of 77 NSCLC patients with MPE were enrolled from the Cancer Hospital, CAMS. Hybrid capture-based NGS was used to detect molecular alterations in supernatants and cell blocks derived from the same MPE sample. Mutation detection rates and their correlation with tumor cellularity were analyzed. Differences in molecular profiles between supernatant and matched plasma samples were assessed, and the predictive value of supernatant-derived epidermal growth factor receptor (EGFR) mutation status for targeted therapy response was evaluated. MPE supernatants harbored a greater diversity of mutation types and exhibited slightly higher overall mutation detection rates compared to cell blocks (97.4% [75/77] vs. 89.6% [69/77]). As tumor cellularity decreased, mutation detection rates declined in supernatants and cell blocks; however, the reduction was less pronounced in supernatants. The mu...

First-line treatment patterns and real-world outcomes in patients with advanced KRAS-mutated non-small cell lung cancer with high unmet need.

Screening brief

이 연구는 Flatiron Health Enhanced Datamart의 대규모 real-world 데이터를 활용하여 advanced NSCLC 환자에서 first-line therapy 패턴과 OS, rwPFS를 분석했습니다. 특히 KRAS-mutated이고 PD-L1 expression가 낮은 환자군에서 median OS가 10개월 미만으로 매우 낮아 임상적 치료 공백이 큽니다. 따라서 이 결과는 향후 targeted therapy 및 immunotherapy 조합 전략의 개발 방향을 설정하는 데 중요한 근거를 제공합니다.

Abstract

This study aims to describe real-world patient characteristics and treatment patterns for advanced non-small cell lung cancer (NSCLC) and estimate overall survival (OS) and real-world progression-free survival (rwPFS) in those receiving first-line (1 L) treatment. In a retrospective study of patients in the Flatiron Health Enhanced Datamart diagnosed with advanced NSCLC between January 1, 2019, and November 30, 2023, with follow-up through November 30, 2024, OS and rwPFS were assessed from initiation of 1 L therapy. Survival was evaluated using Kaplan-Meier method and Cox proportional hazards models adjusting for key covariates. Among 34,187 patients identified, median age was 70 years, with the majority being White (65%) and having a history of smoking (87%). Median duration of 1 L therapy was 121 days (IQR, 42-337), with 1 L PD-(L)1 therapy received by 14,603 (57%) patients. The median OS and rwPFS among patients receiving 1 L therapy (25,512 [75%] patients) were 15.4 months (95% CI, 15.0-15.8) and 7.2 months (95% CI, 7.1-7.4), respectively. Outcomes improved with higher PD-L1 expression, with a median OS of13.8 months (95% CI, 13.1-14.5) for PD-L1 < 1% vs 18.4 months (95% CI, 17.3-19.4) for PD-L1 ≥ 50% (p < 0.001). Patients with KRAS-mutations and PD-L1 < 1% had a median OS of less than10 months. In multivariable analyses, PD-L1 < 1% compared with ≥ 50% and KRAS non-G12C mu...

Efficacy and safety of subcutaneous and intravenous administration of atezolizumab in patients with non-small cell lung cancer, including early-stage, locally advanced or metastatic disease: Updated results of the IMscin001 and IMscin002 randomized studies.

Screening brief

이 연구는 NSCLC 환자에서 atezolizumab의 SC 투여가 기존 IV 투여와 비교하여 동등한 efficacy와 safety를 입증한 IMscin001 및 IMscin002 Phase II/III RCT의 업데이트된 결과입니다. 특히 OS 데이터와 환자 선호도 분석을 통해 SC 투여가 임상 현장에서 치료 편의성과 접근성을 높일 수 있는 유효한 대안임을 보여줍니다. Immunogenicity 평가와 교차 설계의 안전성 데이터를 포함하여 항체 기반 immunotherapy의 administration route 최적화에 중요한 근거를 제공합니다.

Abstract

Subcutaneous (SC) and intravenous (IV) atezolizumab is approved for the treatment of several solid tumors. Part 2 of IMscin001 (NCT03735121) met its co-primary endpoints and demonstrated non-inferior drug exposure at cycle 1 with atezolizumab SC versus atezolizumab IV in patients with non-small cell lung cancer (NSCLC). Efficacy, safety and drug immunogenicity were similar for both atezolizumab formulations. Primary results from IMscin002 (NCT05171777) demonstrated higher preference for atezolizumab SC over atezolizumab IV amongst patients with NSCLC. We now report updated efficacy, safety and drug immunogenicity results from IMscin001 (part 2) and IMscin002. Patients were randomized 2:1 (IMscin001) and 1:1 (IMscin002) to receive 1875 mg atezolizumab SC or 1200 mg atezolizumab IV every three weeks. In IMscin002, patients switched formulations after cycle 3 and chose a formulation for the continuation period after cycle 6. Overall survival (OS) in IMscin001, ongoing clinical benefit after cycle 16 in IMscin002, plus safety and drug immunogenicity (both studies), were secondary/exploratory endpoints. In IMscin001, at data cutoff (November 22, 2024), 247 patients were randomized to atezolizumab SC and 124 to atezolizumab IV; median OS was 10.9 and 10.1 months, respectively (hazard ratio: 1.00, 95% CI: 0.78-1.27). In IMscin002, at data cutoff (October 25, 2024), 179 patients were...

Real-world comparative effectiveness of sotorasib versus docetaxel monotherapy in second line and beyond for advanced or metastatic non-small cell lung cancer: A national database analysis from England.

Screening brief

이 연구는 KRAS G12C 변이 전이성 NSCLC 환자 2차 치료 이상에서 sotorasib와 docetaxel의 실제 임상 데이터를 비교 분석한 결과입니다. 조정된 OS, TTNTD, TTDD 모두에서 sotorasib가 통계적으로 유의미한 생존 및 치료 지속 이점을 보였으며, 이는 기존 무작위 대조 시험(RCT) 결과를 보완하는 중요한 임상적 근거가 됩니다. 따라서 표적 치료제 선택과 치료 순서 결정에 실질적인 도움을 줄 수 있어 위키 인덱스에 포함해야 합니다.

Abstract

To compare sotorasib versus docetaxel monotherapy real-world outcomes in second line and beyond (2 L+) for locally advanced or metastatic non-small cell lung cancer (NSCLC). The Cancer Analysis System includes English registration data. Sotorasib-treated patients with KRAS G12C-mutated NSCLC were compared with docetaxel-treated patients with NSCLC. Outcomes included overall survival (OS), time to next treatment or death (TTNTD), and time to treatment discontinuation or death (TTDD). The study period was 01 January 2013‒31 May 2024. The index date was the earliest date of initiation of sotorasib (01 March 2021-31 May 2024) or docetaxel monotherapy (01 January 2017‒31May 2024) in 2 L+. Propensity score weighting balanced baseline characteristics. The analysis included 1,665 patients (394 sotorasib; 1,271 docetaxel). Adjusted median OS was 10.18 months (95% confidence interval [CI]: 9.10‒12.02) with sotorasib and 6.87 (95% CI: 6.01‒7.82) with docetaxel (P < 0.001); risk of death decreased by 36.7% with sotorasib (hazard ratio [HR]: 0.633; 95% CI: 0.536‒0.749; P < 0.001). Adjusted median TTNTD was 8.51 (95% CI: 7.33‒9.43) and 5.62 months (95% CI: 5.06, 6.18) with sotorasib and docetaxel, respectively (P < 0.001); risk of initiation of a new line of therapy or death was decreased by 43.3% with sotorasib (HR: 0.567; 95% CI: 0.485, 0.663; P < 0.001). Adjusted median TTDD was 5.06 (95...

Cardiovascular adverse events in non-small cell lung cancer patients receiving osimertinib therapy: a systematic review and meta-analysis.

Screening brief

이 연구는 EGFR-mutated NSCLC 환자에서 Osimertinib 요법 중 발생할 수 있는 Cardiovascular adverse events의 발생률과 하위군별 위험 요인을 체계적으로 종합하였습니다. 특히 Anti-VEGF 병용 요법이 Cardiac safety profile을 악화시킬 수 있음을 밝혀 임상에서의 치료 선택 및 심장 독성 모니터링 가이드라인 마련에 중요한 근거가 됩니다. 또한 Osimertinib의 Cardiovascular toxicity profile이 연령이나 인종보다는 Treatment regimen에 의해 결정됨을 확인하여 개인 맞춤형 안전 관리 전략 수립에 기여할 것입니다.

Abstract

The incidences and specific risk factors for cardiovascular adverse events (CVAEs) during osimertinib treatment remain uncertain. Studies in which participants with EGFR-mutated NSCLC who received osimertinib treatment with CVAEs were included. Treatment-emergent and treatment-related CVAEs were analysed separately. The primary outcomes were all grades and grades ≥ 3 QTc prolongation, left ventricular ejection fraction (LVEF)decrease, 3-point major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and hypertension. The incidences of the CVAEs were calculated, along with subgroup, meta-regression and cumulative analysis. A total of 10,316 patients from 61 studies were included. Hypertension was the most common treatment-emergent and treatment-related CVAE, for both all-grade and grade ≥ 3. In addition to QTc prolongation (6.88%[95% CI 5.24%-8.70%], there is also a common incidence of treatment-emergent LVEF decrease for all-grade (4.31% [95% CI 2.38%-6.69%]). Subgroup analyses showed higher incidences of treatment-emergent than treatment-related hypertension in anti-VEGF combination therapy (all grades: 45.46% vs. 26.11%). QTc prolongation (all grades and grades ≥ 3) and LVEF reduction (all grade) occurred more frequently with osimertinib plus platinum-pemetrexed than with other treatments, with incidence rates of 22.24%, 6.53%, and 15.82% respectively. Univar...

Clinical significance of CD161+CD8+ T cells in the tumor microenvironment of esophageal squamous cell carcinoma and their association with the 4-1BB signaling pathway.

Screening brief

본 연구는 esophageal squamous cell carcinoma (ESCC)의 tumor microenvironment에서 CD161+CD8+ T cells가 overall survival 및 disease-free survival에 미치는 독립적인 예후 인자로서의 역할을 규명했습니다. 또한 이 면역 세포 아집단이 4-1BB signaling pathway와 macrophage 간 상호작용을 통해 신항암제 반응성과 연관됨을 제시하며, CT-based radiomics 모델을 활용한 비침습적 예측 가능성을 입증했습니다. 이는 정밀 immunotherapy의 patient stratification 및 treatment selection에 유용한 임상적 지표를 제공하므로 위키 인덱스 등재에 적합합니다.

Abstract

CD161+CD8+ T cells, a cytotoxic T cell subset, remain poorly defined in terms of their clinical significance and functional role in esophageal squamous cell carcinoma (ESCC), which has limited the advancement of precision immunotherapy strategies. We integrated a multicenter cohort of ESCC patients who underwent either surgery or neoadjuvant therapy (chemotherapy or chemoimmunotherapy). Multiplex immunofluorescence staining, survival analyses, and assessment of major pathological response (MPR) and pathological complete response (pCR) were performed to elucidate the clinical relevance of CD161+CD8+ T cell infiltration. The functional state and cellular interactions of this subset were characterized using single-cell RNA sequencing. A CT-based radiomics model was also developed for non-invasive prediction. High intratumoral infiltration of CD161+CD8+ T cells was identified as an independent prognostic factor for prolonged overall survival and disease-free survival (both p<0.01) and appeared to correlate with a higher MPR and pCR rate following neoadjuvant therapy. This subset was enriched in treatment responders, exhibited transcriptional features associated with cytotoxicity and activation, and showed gene expression profiles suggestive of potential interactions with tumor-associated macrophages, possibly involving the TNFRSF9/TNFSF9 (4-1BB/4-1BBL) signaling axis. A radiomics...

Reply to Qu et al.: Do mtDNA fragmentomic peaks reflect cancer biology or preanalytical and technical artifacts in NSCLC?

Screening brief

이 논문은 비소세포폐암(NSCLC)에서 mtDNA fragmentomic peaks가 실제 cancer biology를 반영하는지 아니면 preanalytical artifacts인지에 대한 논쟁을 해결합니다. circulating tumor DNA 분석의 신뢰성을 높이는 방법론적 기준을 제시하므로, precision oncology 및 biomarker validation 연구에 필수적입니다. 특히 clinical trial 설계 및 diagnostic platform 검증 시 technical bias를 통제하는 데 직접적인 참고가 됩니다.

Abstract

not available

Do mtDNA fragmentomic peaks reflect cancer biology or preanalytical and technical artifacts in NSCLC?

Screening brief

이 연구는 NSCLC 환자에서 관찰되는 mtDNA fragmentomic peaks가 실제 종양 생물학적 특성을 반영하는지, 아니면 preanalytical 및 technical artifacts인지 규명합니다. Liquid biopsy 기반 cfDNA 분석의 신뢰성을 높이고 향후 임상 적용을 위한 방법론적 기준을 제시한다는 점에서 중요합니다. 특히 biomarker 개발 단계에서 데이터 해석의 정확성을 보장하는 데 필수적인 참고 자료가 될 것입니다.

Abstract

not available

Clonal divergence with acquired BRAF V600E in NSCLC with compound EGFR G719X/S768I after prolonged EGFR-TKI therapy.

Screening brief

이 논문은 드문 compound EGFR G719X/S768I variant를 가진 NSCLC 환자에서 장기간 EGFR-TKI 치료 후 BRAF V600E가 획득되며 clonal divergence가 발생하는 사례를 보고합니다. 기존 고전적 EGFR mutation과 달리 비전형적 resistance 기전을 규명하여, 희귀 variant에 대한 맞춤형 targeted therapy 전략 수립에 중요한 임상적 시사점을 제공합니다. 특히 ctDNA 음성 상태에서의 tissue re-biopsy의 중요성과 multi-kinase inhibitor 병용 요법의 한계를 보여줍니다.

Abstract

Uncommon EGFR-mutations represent a heterogeneous subgroup of EGFR-mutant NSCLC with variable TKI sensitivity and limited evidence to guide treatment. Compound uncommon variants such as G719X/S768I are particularly rare. Acquired BRAF V600E is an infrequent resistance mechanism to EGFR-TKIs, mainly described in classical EGFR-mutations. A 73-year-old woman with cardiomyopathy and metastatic NSCLC harbouring a compound EGFR G719X/S768I mutation achieved prolonged disease control on erlotinib and subsequent osimertinib. After more than four years of EGFR-TKI exposure, oligoprogression occurred in a left upper lobe lesion. Rebiopsy revealed acquired BRAF V600E mutation and no detectable EGFR-mutations, while plasma showed no ctDNA. Dabrafenib/trametinib induced regression of the BRAF-driven lesion, whereas other lesions progressed, indicating spatially distinct BRAF-driven and EGFR-dependent clones. Subsequent combined EGFR-BRAF-MEK inhibition provided stable disease but was discontinued due to worsening of heart failure. This case illustrates prolonged EGFR-TKI sensitivity in a rare compound EGFR-mutation followed by true clonal divergence with acquisition of BRAF V600E, highlighting the need for individualised treatment.

Beyond whole-image learning: anatomically partitioned deep learning models for superior sinonasal disease classification.

Screening brief

이 연구는 부비동 질환의 CT 영상 진단에서 기존 whole-image 학습의 한계를 극복하기 위해 anatomical regions를 분할하여 deep learning 모델을 훈련하는 전략을 제시합니다. nnU-Net v2 기반의 Multicenter Retrospective Study를 통해 partitioned training이 전체 영상 학습 대비 AUC를 0.21 이상 향상시켰음을 입증하였습니다. 이는 radiologists와 rhinologists에게 다발성 부비동 질환의 정밀한 영상 판독을 지원하는 임상적으로 유용한 AI 프레임워크를 제공할 것으로 기대됩니다.

Abstract

Whole-image deep learning models for CT diagnosis of nasal cavity and paranasal sinus diseases often underperform because they disregard anatomical heterogeneity. We hypothesized that anatomically partitioned deep learning would enhance diagnostic accuracy. A multicenter retrospective study enrolled 2947 CT examinations conducted from October 2019 to May 2022. From these, 150 patients were randomly selected for manual segmentation, covering 13 anatomical regions, including the bilateral nasal cavities, maxillary sinuses, anterior ethmoid sinuses, posterior ethmoid sinuses, sphenoid sinuses, frontal sinuses, and nasal septum. An nnU-Net v2 model was first used to perform automatic anatomical partitioning. Then, disease-specific networks were trained on the 13 anatomically segmented sinus subregions-each expanded by ten pixels-and compared with a whole-image classifier. External test data were used to evaluate sensitivity, specificity, and the area under the curve (AUC). The anatomically partition model based on nnU-Net v2 achieved an average Dice coefficient of 0.739 across the 13 anatomical regions. For the external test cohort using the model trained with anatomical partitioning, the average AUC value for the 13 anatomical partitions was 0.801, whereas for the model trained on the whole image, the average AUC value for the same 13 anatomical partitions was 0.587. DeLong's tes...

Clinical outcomes and tumor immune microenvironment in SMARCA4-Deficient NSCLC: A Real-World retrospective study.

Screening brief

SMARCA4-deficient NSCLC는 예후가 불량한 아형으로, 본 연구는 실제 임상 환경에서 이 환자의 ORR, DCR, PFS, OS를 분석하였다. immunotherapy 병용 요법이 chemotherapy 단독보다 우수한 생존율을 보였으며, mIF를 통한 TME 분석이 치료 반응성과 연관됨을 제시하였다. 이는 SMARCA4-deficient NSCLC 환자에서의 immunotherapy 활용 전략과 biomarker 개발에 중요한 실증 데이터를 제공한다. 향후 대규모 전향적 연구가 필요하나, 현재 임상 의사결정에 유의미한 참고 자료가 될 수 있다.

Abstract

SMARCA4-deficient thoracic tumors constitute a rare and aggressive form of lung cancer characterized by a dismal prognosis. This research investigates the clinical features, treatment outcomes, and characteristics of the immune microenvironment in patients with SMARCA4-deficient non-small-cell lung cancer (NSCLC) compared to those with intact SMARCA4. A retrospective study was conducted at a single institution involving 221 patients with stage III-IV NSCLC (59 with SMARCA4 deficiency and 162 with intact SMARCA4) who received treatment at Shanghai Pulmonary Hospital from 2020 to 2024. Propensity score matching (PSM) was employed to balance baseline characteristics. The outcomes measured included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Multiplex immunofluorescence (mIF) was utilized to evaluate immune microenvironment markers in tumors (CD4, CD8, FOXP3, CD11c, GZMB). After PSM, patients with SMARCA4 deficiency exhibited significantly shorter median PFS (5.0 vs. 11.0 months; HR, 0.56, 95% CI, 0.37-0.86, p = 0.006) and OS (22.0 months vs. not reached; HR, 0.09, 95% CI, 0.02-0.30, p < 0.001) compared to SMARCA4-intact counterparts. Among SMARCA4-deficient patients, those receiving immunotherapy, with or without chemotherapy, achieved improved PFS versus chemotherapy alone. Exploratory MIF analysis indica...

Prognostic value of serum CYFRA21-1 in locally advanced non-small cell lung cancer undergoing durvalumab consolidation therapy after chemoradiotherapy.

Screening brief

이 논문은 국소 진행성 비소세포폐암(LA-NSCLC) 환자에서 chemoradiotherapy 이후 durvalumab consolidation therapy를 받을 때 CYFRA 21-1의 prognostic biomarker 역할을 규명합니다. 전향적이지 않은 코호트 분석을 통해 높은 CYFRA 21-1 수치가 durvalumab 군에서만 유의한 OS 및 rw-PFS 단축과 연관됨을 입증하였습니다. 이는 immunotherapy consolidation 치료 중 환자 risk stratification과 치료 반응 모니터링에 활용될 수 있는 실용적인 biomarker를 제시한다는 점에서 임상 종양학 분야에서 중요한 의의를 가집니다.

Abstract

Chemoradiotherapy (CRT) followed by durvalumab consolidation therapy is the standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC), but robust prognostic biomarkers are lacking. This study evaluated the prognostic value of CYFRA 21-1, a serum marker associated with squamous cell carcinoma, in this setting. Patients with LA-NSCLC were retrospectively reviewed according to treatment (CRT plus durvalumab group vs. CRT-only group). Patients with high and normal CYFRA 21-1 levels were compared within each group, using a threshold of 3.5 ng/mL. Overall survival (OS) and real-world progression-free survival (rw-PFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analyses were conducted using Cox proportional hazards models. There were 134 patients in the CRT plus durvalumab group and 100 patients in the CRT-only group. In the CRT plus durvalumab group, patients with high CYFRA 21-1 levels had shorter median OS versus those with normal levels (38.8 vs. 73.4 months; HR, 2.49 [95% CI, 1.31-4.72]; p < 0.05), whereas no significant difference was observed within the CRT-only group (26.2 vs. 46.5 months; HR, 1.37 [95% CI, 0.82-2.27]; p = 0.21). A similar trend in OS was observed among those with non-squamous histology. On multivariate analysis, CYFRA 21-1 emerged as an independent prognostic factor in the CRT plus durv...

Vebreltinib plus EGFR-TKI for EGFR-mutated NSCLC with MET-driven resistance: A real-world study of Chinese patients.

Screening brief

본 연구는 EGFR-TKI 내성의 주요 원인인 MET 증식을 가진 NSCLC 환자에서 Vebreltinib와 EGFR-TKI 병용 요법의 실제 임상 효과를 평가하였습니다. 특히 뇌 전이 환자군에서 우수한 intracranial ORR과 c-MET IHC 3+가 예후 예측 biomarker로 유용함을 확인하여, 표적 치료 선택 및 내성 관리 전략 수립에 중요한 실증 자료를 제공합니다. 이러한 결과는 NSCLC의 정밀 의학 접근과 임상 의사결정에 직접적인 참고가 될 수 있습니다.

Abstract

MET amplification/overexpression is a key resistance mechanism to EGFR-tyrosine kinase inhibitors (TKIs) in patients with EGFR-mutated non-small cell lung cancer (NSCLC). However, real-world evidence remains limited regarding the efficacy of vebreltinib plus an EGFR-TKI. This single-center retrospective study enrolled patients with EGFR-mutant advanced NSCLC and MET amplification/overexpression after prior EGFR-TKI failure, who received vebreltinib plus an EGFR-TKI. MET alteration was confirmed by fluorescence in situ hybridization (MET gene copy number of ≥ 5 or MET/CEP7 ratio of ≥ 2.0), next-generation sequencing (MET gene copy number of ≥ 5), or immunohistochemistry (c-MET 3 + ). The efficacy was assessed by RECIST 1.1 and safety by CTCAE 5.0. Among the 49 patients, the combination therapy reported an objective response rate (ORR) of 46.9%, disease control rate of 91.8%, median progression-free survival (PFS) of 8.5 months [95% confidence interval (CI): 4.5-10.2], and median overall survival (OS) of 16.0 months (95% CI: 14.7-not reached). Patients with brain metastases (n = 23) reported an intracranial ORR of 69.6% and intracranial PFS of 9.7 months (95% CI: 5.12-not reached). Strong c-MET expression (immunohistochemistry 3 + ) was associated with significantly longer OS (not reached vs. 14.7 months,p = 0.033). Treatment-related adverse events occurred in 67.3% of patients...

Phase II study of ramucirumab plus erlotinib for treatment-naïve patients with EGFR-mutant non-squamous non-small cell lung cancer and pleural effusion (RELAY-Effusion).

Screening brief

EGFR-mutant NSCLC 환자 중 malignant pleural effusion이 동반되면 EGFR TKI 반응이 저하되는 임상적 난제가 존재합니다. 본 Phase II trial은 ramucirumab와 erlotinib 병용 요법이 PFS와 OS를 향상시키고 malignant pleural effusion의 드레나주 빈도를 줄이는 데 유의미한 효과를 보였음을 제시합니다. 특히 고위험 군에서 symptom-focused management 전략으로 활용될 수 있는 임상적 근거를 제공하므로 본 위키에 포함할 가치가 있습니다.

Abstract

Malignant pleural effusion (MPE) develops in approximately 30-40% of patients with non-small cell lung cancer (NSCLC), including those harboring epidermal growth factor receptor (EGFR) mutations, and is generally associated with reduced responsiveness to EGFR tyrosine kinase inhibitors. This study aimed to investigate the efficacy of ramucirumab in the context of MPE, which remains unexplored. In this single-arm, multicenter, phase II study, we enrolled treatment-naïve patients with EGFR-mutant NSCLC complicated by MPE. They received ramucirumab (10 mg/kg) every 2 weeks plus erlotinib (150 mg) daily until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and safety. Forty patients were enrolled between December 2021 and December 2023 (median follow-up, 29.5 months). The median PFS and OS were 12.9 (95% confidence interval [CI], 7.3-16.7) and 36.3 (95% CI: 28.5- not available [NA]) months, respectively, with a 12-month OS rate of 87.5% and ORR of 77.5% (95% CI, 61.5-89.2%). The median drainage-free survival was 33.0 months (95% CI: 26.0-NA). Treatment-related adverse events occurred in 85% of patients (grade 5 = 0%; grade 3 or 4 = 22.5%); the most common were acneiform dermatitis (60.0%), decreased appetite (30.0%), increased aspartate ami...

Upfront management of brain metastases in oncogene‑addicted NSCLC - An EORTC survey.

Screening brief

이 논문은 actionable genomic alterations를 가진 NSCLC 환자에서 brain metastases의 초기 관리 전략에 대한 유럽의 임상 현장 의견을 조사한 EORTC 설문 연구입니다. targeted therapy와 local therapy의 통합 및 중단 시기에 대한 전문가들의 선호도와 불일치를 보여주어, 향후 임상 지침 개발과 치료 프로토콜 표준화에 중요한 기준을 제공합니다. 특히 CNS 침투력이 높은 targeted therapy의 등장으로 인해 기존 관리 패러다임이 어떻게 변화하고 있는지 파악하는 데 필수적인 자료입니다.

Abstract

Brain metastases (BM) are common in patients with non-small cell lung cancer (NSCLC) harboring actionable genomic alterations (AGA). The availability of next-generation targeted therapies (TT) with improved central nervous system activity has expanded systemic treatment options. However, the optimal upfront management of untreated symptomatic and asymptomatic BM remains uncertain due to limited trial data. A web-based survey was conducted by the EORTC Lung Cancer Group and distributed to EORTC and ESTRO members in June 2023-July 2024. The survey evaluated diagnostic approaches, access to TT and upfront management of untreated BM across 10 different AGA (including EGFR, ALK, ROS1, and others). Responses were analysed descriptively and stratified by neurological symptom status, AGA, intracranial objective response rate (icORR) of available TT, and medical specialty. A total of 166 responses were analysed (91.0% of respondents worked in Europe, 47.6% were medical oncologist, 36.1% radiation oncologist, 9.6% pneumonologist, 4.8% clinical oncologist). For asymptomatic BM, 68.8% of physicians preferred upfront TT across AGA. In symptomatic BM, preferred upfront treatment included: local therapy alone (43.0%), TT alone (19.0%), local therapy or TT depending on other factors (35.4%). Treatment preferences for (a)symptomatic BM varied according to AGA, icORR of available TT, and medica...

Final overall survival analysis of the APPLE study: atezolizumab and platinum-pemetrexed with or without bevacizumab for metastatic nonsquamous non-small cell lung cancer.

Screening brief

이 연구는 비편평 NSCLC 환자에서 atezolizumab와 platinum-pemetrexed 기반 chemotherapy에 bevacizumab를 추가한 APPB 요법의 최종 OS 결과를 보고합니다. 전체 군에서는 Overall Survival 개선이 통계적으로 유의하지 않았으나, driver oncogene-positive 하위군에서 targeted therapy 실패 후의 대안으로서 임상적 의미를 가질 수 있음을 시사합니다. 따라서 NSCLC 치료에서 immunotherapy와 anti-angiogenic agent 병용 요법의 표준 치료 전략 수립에 중요한 근거를 제공합니다.

Abstract

The phase III APPLE trial evaluated the efficacy of adding bevacizumab to atezolizumab with carboplatin plus pemetrexed (APP) for individuals with advanced nonsquamous non-small cell lung cancer (NSCLC). We here report the long-term outcomes of this trial with 3.5 years of follow-up. Patients with advanced nonsquamous NSCLC were randomized 1:1 to receive APP or APP plus bevacizumab (APPB). Stratification factors were clinical stage, driver oncogenes, and PD-L1 expression. Endpoints included progression-free survival, overall survival (OS), and safety. A total of 412 patients were enrolled; 1 patient was excluded from the intention-to-treat population. Of the remaining patients, 287 patients were classified as driver oncogene-negative and 124 as driver oncogene-positive. The updated median OS was 28.0 months in the APPB arm and 25.7 months in the APP arm, with a hazard ratio (HR) of 0.88 (95% confidence interval [CI], 0.70-1.10). For the driver oncogene-negative population, the median OS was 27.6 months in the APPB arm and 27.8 months in the APP arm (HR of 0.96 [95% CI, 0.73-1.27]), with the corresponding values for the driver oncogene-positive population being 28.0 and 20.8 months (HR of 0.71 [95% CI, 0.47-1.08]). Safety profiles did not change from earlier analysis. The addition of bevacizumab to APP did not improve OS in patients with advanced nonsquamous NSCLC. In the drive...

Patient and clinician preferences for adjuvant treatment following surgical resection in early-stage non-small cell lung cancer: A multi-country discrete choice experiment.

Screening brief

본 연구는 조기 NSCLC 환자 및 임상가가 수술 후 adjuvant 치료 선택 시 DFS를 가장 중요한 요소로 평가함을 보여줍니다. 다국적 discrete choice experiment을 통해 환자 선호도와 임상적 의사결정 패턴을 정량화했으며, 이는 shared decision-making과 치료 가이드라인 수립에 중요한 근거를 제공합니다. 특히 OS 데이터가 불완전한 상황에서도 DFS 연장이 우선시되는 점을 확인하여 향후 adjuvant 치료 전략 설계에 실용적인 통찰을 줍니다.

Abstract

For patients with early-stage non-small cell lung cancer (NSCLC), post-resection adjuvant therapy can improve survival outcomes. This study evaluated patient and clinician preferences for attributes of adjuvant treatments. Patients with fully-resected stage IB-IIIA NSCLC and treating clinicians completed an online discrete choice experiment with 10 choice tasks. Each task included three profiles described according to: disease-free survival (DFS), post-recurrence survival (PRS), and risk of adverse events (grade 1-2 and 3-4). DFS and PRS were presented individually and the sum represented as overall survival (OS). Preference data were analysed using a mixed logit approach. 504 patients and 515 clinicians from Europe, Asia, and the Americas completed the survey. Overall, DFS was the most important attribute, contributing to 34.5% and 50.7% of patients' and clinicians' decision-making, followed by changes in PRS and the risk of adverse events. Given two treatment profiles with the same duration of OS, respondents preferred the treatment with a larger proportion of DFS. For each level of PFS, patients valued an additional month of DFS equally. Among clinicians, value of an additional month of DFS increased with the duration of PFS. Patients and clinicians valued longer DFS even when the duration of PRS was uncertain, meaning that OS was unknown. Across multiple countries, patient...

Patient and caregiver priorities of treatment characteristics influencing preferences for tyrosine kinase inhibitors in anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer.

Screening brief

본 연구는 ALK 양성 전이성 비소세포폐암(NSCLC) 환자 및 보호자가 티로신 키나아제 억제제(TKI) 선택 시 효능과 부작용을 어떻게 저울질하는지 정량적으로 분석했습니다. Discrete Choice Experiment(DCE) 결과를 통해 3-year PFS 향상과 중증 부작용 회피 간에 선호도 이질성이 있음을 확인했으며, 이는 맞춤형 shared decision-making 전략 수립에 필수적입니다. 따라서 임상 현장에서 TKI 치료 선택 기준을 개인화하는 데 중요한 근거를 제공합니다.

Abstract

New-generation tyrosine kinase inhibitors (TKIs) for anaplastic lymphoma kinase rearrangement (ALK + ) non-small cell lung cancer (NSCLC) vary in treatment attributes (e.g., efficacy and adverse events [AEs]). This study quantified how patients and caregivers prioritize TKI-specific attributes on treatment choice and the variability in treatment preferences. US patients with stage IV ALK+NSCLC and caregivers completed online discrete choice experiment (DCE) tasks, in which they chose between two hypothetical TKIs described by seven benefit and risk attributes. A latent class logit model, which classified participants based on preferences, was used to estimate each attribute's relative contribution to preference and maximum acceptable loss in the chance of 3-year progression-free survival (PFS) to reduce AE risks. Two distinct preference patterns were identified among 205 patients and 125 caregivers, described using interpretive labels. Balanced Traders (37.1% of patients, 48.8% of caregivers) valued both risk reduction and 3-year PFS, whereas Benefit Maximizers (47.8% of patients, 36.8% of caregivers) primarily valued improving 3-year PFS. Others (15.1% of patients, 14.4% of caregivers) appeared less engaged in making choices. Balanced Traders were willing to accept a greater loss in the chance of 3-year PFS (patients: up to 22.1%; caregivers: up to 25.8%) to mitigate AEs (e.g...

OX40+ regulatory T cells suppress neoadjuvant chemotherapy response in NSCLC and reversed by combination of PD-1 blockade therapy.

Screening brief

이 연구는 NSCLC에서 신항암제 요법 반응에 미치는 OX40+ Tregs의 억제 기전을 규명하고, PD-1 blockade 병용 요법이 Th17 세포를 활성화하여 치료 효능을 회복시킴을 입증했습니다. mIHC 및 공간 분석을 통해 tumor microenvironment 내 면역 세포 간 거리 기반 상호작용을 정량화함으로써 MPR 예측 biomarker로서의 임상적 타당성을 제시했습니다. 이러한 발견은 NSCLC 신항암제 요법의 반응 예측과 차세대 chemoimmunotherapy 조합 전략 개발에 중요한 기초 자료를 제공합니다.

Abstract

OX40+ regulatory T cells mediate tumor immune escape and correlate with clinical response to neoadjuvant therapy in NSCLC, but the underlying mechanisms remain incompletely understood. We collected formalin-fixed paraffin-embedded (FFPE) tumor sections from 30 NSCLC patients receiving neoadjuvant chemotherapy (NAC) and 28 patients receiving neoadjuvant PD-1 blockade and chemotherapy (NAPC), and explored the effect of OX40+ Tregs on the efficacy of neoadjuvant therapy and the level of immune cell infiltration by multiplex immunofluorescence staining (mIHC). Our results showed that the proportion of OX40+ Tregs was significantly increased after NAC. NAPC led to elevated infiltration of Th17 cells and Tregs within tumors, while OX40+ Tregs were markedly reduced. In patients achieving major pathological response (MPR) following NAPC, total Treg levels remained unchanged, but OX40+ Tregs decreased significantly and showed a strong negative correlation with tumor necrosis rate. Spatial analysis revealed that after NAPC, Tregs and OX40+ Tregs tended to decrease in proximity to CD8+ T cells, whereas Th17 cells increased significantly. Tumor cells were surrounded by higher densities of CD4+ T cells, Th17 cells, and CD8+ T cells. Furthermore, patients with MPR after NAPC exhibited fewer Tregs and OX40+ Tregs adjacent to CD8+ T cells and more CD8+ T cells encircling tumor cells. Our stud...

Docetaxel plus ramucirumab immediately after immunotherapy in advanced NSCLC: A phase II study (DRUN).

Screening brief

이 연구는 ICI 치료 실패 후 advanced NSCLC 환자에서 Docetaxel과 Ramucirumab 병용 요법의 임상적 가치를 평가한다. ORR는 주요 endpoint를 충족하지 못했으나 DCR은 90.9%로 높았으며, 이전 ICI response 여부가 PFS에 유의한 예측 인자로 작용했다. 이는 post-ICI 치료 전략 수립과 환자 선별에 중요한 근거를 제공한다.

Abstract

Docetaxel plus ramucirumab is a standard second-line treatment for advanced non-small cell lung cancer (NSCLC). Prior immunotherapy has been suggested to potentially affect the efficacy of subsequent docetaxel plus ramucirumab, but prospective evidence is limited. This multicenter, single-arm, phase II study enrolled patients with advanced NSCLC. Eligible patients had experienced disease progression following a prior immune checkpoint inhibitor (ICI)-containing regimen. Patients received docetaxel 60 mg/m2 and ramucirumab 10 mg/kg every 3 weeks. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. This study was registered in the Japan Registry of Clinical Trials (jRCT1051190091). Between January 8, 2020, and January 7, 2024,We evaluated 33 patients for efficacy and safety. The median age was 69 years, and 26 patients (79%) had an Eastern Cooperative Oncology Group performance status of 1. The ORR was 33.3% (90% confidence interval [CI], 19.9-49.1), and the DCR was 90.9% (90% CI, 78.1-97.5). The median PFS and OS were 4.9 months (95% CI, 4.4-6.2) and 11.8 months (95% CI, 9.8-18.8), respectively. No new safety signals were observed. Patients who had responded to prior ICI-containing therapy had longer PFS than those who had not responded (hazard ratio,...

Association of high-risk CT coronary artery plaque features with major adverse cardiovascular events: a prespecified secondary analysis of the DISCHARGE trial.

Screening brief

이 연구는 안정형 chest pain 환자에서 코로나리 CT를 통해 확인된 high-risk plaque features가 major adverse cardiovascular events 발생 위험을 독립적으로 예측할 수 있음을 입증했습니다. 기존 obstructive coronary artery disease와 유사한 예후 가치를 보이며, 전통적인 cardiovascular risk factors를 보정해도 추가적인 예측 정보를 제공합니다. 따라서 정밀 imaging 분석을 통한 patient risk stratification 및 임상적 의사결정 지원에 중요한 참고 자료가 될 것입니다.

Abstract

The prognostic role of high-risk plaque (HRP) features, including high coronary calcium scores detected by CT, beyond traditional cardiovascular risk factors and obstructive coronary artery disease (CAD), remains uncertain. This study evaluated the prognostic value of a combined HRP definition in stable chest pain patients with low-to-intermediate pretest probability of CAD. This prespecified analysis included participants randomized to the CT arm of the pragmatic, prospective 26-center European DISCHARGE trial (NCT02400229). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, nonfatal myocardial infarction, or stroke); the secondary endpoint was expanded MACE (transient ischemic attack and major procedure-related complications). Our combined HRP definition was any coronary plaque with positive remodeling, napkin-ring sign, low attenuation, or total calcium score ≥ 400 Agatston units. Among 1745 participants (age: 60 ± 10 years, 990 female), 35 MACE and 47 expanded MACE occurred at a median follow-up of 3.5 years (IQR: 2.9-4.2). After risk factor adjustment, the combined HRP definition was associated with a higher risk of MACE (HR: 3.81; 95% CI: 1.01-14.6; p = 0.050) and remained significantly associated with expanded MACE (HR: 0.21; 95% CI: 1.07-9.66; p = 0.038). Patients with both HRP and obstructive CAD conferred the highest MACE (HR: 8...

Insights from a randomized controlled trial on a digital lifestyle intervention in non-small cell lung cancer survivors following inpatient rehabilitation.

Screening brief

이 연구는 non-small cell lung cancer (NSCLC) 생존자가 입원 rehabilitation 후 health-related quality of life (HRQoL)과 exercise capacity를 유지하기 위한 digital lifestyle intervention의 효과를 평가했습니다. primary endpoint인 HRQoL에서는 통계적 유의미한 차이가 관찰되지 않았으나, 1-min sit-to-stand test 기반의 exercise capacity 지표에서 개선 효과가 확인되었습니다. recruitment 한계로 인한 검정력 부족이 있으나, digital 기반 survivorship care 프로그램의 acceptability와 feasibility는 높게 평가되어 폐암 지원 체계 구축에 참고 가치가 있습니다.

Abstract

Rehabilitation can improve health-related quality of life (HRQoL) in non-small cell lung cancer (NSCLC) survivors, but they lack structured aftercare to maintain these gains at home. This study aimed to assess the effectiveness of a co-created digital lifestyle intervention on HRQoL and health-related outcomes in NSCLC survivors following inpatient rehabilitation, alongside a comprehensive process evaluation. This multicenter randomized controlled trial allocated participants (1:1 ratio) to a 12-week self-managed digital lifestyle intervention delivered via a mobile application that targeted physical activity, nutrition, and breathing/relaxation (intervention group) or standard care (control group). The primary outcome was HRQoL and secondary outcomes included physical activity, exercise capacity, risk of low protein intake, appetite, cancer-related fatigue, psychological distress, and enablement. The process evaluation addressed implementation, mechanisms of impact, and contextual factors using app usage data, validated questionnaires, and qualitative interviews. We included twenty individuals (13 females, mean age 66.9 ± 6.0 years), 30% of the target sample size (n = 66). We found no statistically significant between-group difference for HRQoL at follow-up (adjusted mean difference: 2.89, 95% CI: -17.76 to 23.53, p = 0.77). However, the intervention group showed a statistica...