Short-term predictors of stereotactic radiosurgery outcome for untreated single non-small cell lung cancer brain metastases: a restrospective cohort study.

Stereotactic radiosurgery (SRS) is an option for brain metastases (BM) not eligible for surgical resection, however, predictors of SRS outcomes are poorly known. The aim of this study is to investigate predictors of SRS outcome in patients with BM secondary to non-small cell lung cancer (NSCLC). The secondary objective is to analyze the value of volumetric criteria in identifying BM progression. This retrospective cohort study included patients >18 years of age with a single untreated BM secondary to NSCLC. Demographic, clinical, and radiological data were assessed. The primary outcome was treatment failure, defined as a BM volumetric increase 12 months after SRS. The unidimensional measurement of the BM at follow-up was also assessed. One hundred thirty-five patients were included, with a median BM volume at baseline of 1.1 cm3 (IQR 0.4-2.3). Fifty-two (38.5%) patients had SRS failure at follow-up. Only right BM laterality was associated with SRS failure (p=0.039). Using the volumetric definition of SRS failure, the unidimensional criteria demonstrated a sensibility of 60.78% (46.11%-74.16%), specificity of 89.02% (80.18%-94.86%), positive LR of 5.54 (2.88-10.66) and negative LR of 0.44 (0.31-0.63). SRS demonstrated a 61.5% local control rate 12 months after treatment. Among the potential predictors of treatment outcome analyzed, only the right BM laterality had a significant association with SRS failure. The volumetric criteria were able to identify more subtle signs of BM increase than the unidimensional criteria, which may allow earlier diagnosis of disease progression and use of appropriate therapies.

Head-to-head comparison of 18F-FDG PET/CT and 18F-FDG PET/MRI for lymph node metastasis staging in non-small cell lung cancer: a meta-analysis.

PURPOSE: The current meta-analysis aimed to compare the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) with 18F-FDG PET/magnetic resonance imaging (MRI) in non-small cell lung cancer (NSCLC) lymph node metastasis staging. METHODS: We searched the PubMed, Web of Science, and Embase databases for relevant articles between November 1992 and September 2022. Studies evaluating the head-to-head comparison of 18F-FDG PET/CT and 18F-FDG PET/MRI for lymph node metastasis in patients with NSCLC were included. The quality of each study was assessed using the Quality Assessment of Diagnostic Performance Studies-2 tool. RESULTS: The analysis includes six studies with a total of 434 patients. The pooled sensitivity of 18F-FDG PET/CT and 18F-FDG PET/MRI was 0.78 [95% confidence interval (CI): 0.59-0.90] and 0.84 (95% CI: 0.68-0.93), and the pooled specificity was 0.87 (95% CI: 0.72-0.94) and 0.87 (95% CI: 0.80-0.92), respectively. The accuracy of 18F-FDG PET/CT and 18F-FDG PET/MRI was 0.81 (95% CI: 0.71-0.90) and 0.84 (95% CI: 0.75-0.92), respectively. When the pre-test probability was set at 50%, the post-test probability for 18F-FDG PET/CT could increase to 85%, and the post-test probability for 18F-FDG PET/MRI could increase to 87%. CONCLUSION: 18F-FDG PET/CT and 18F-FDG PET/MRI have similar diagnostic performance in detecting lymph node metastasis in NSCLC. However, the results of this study were from a small sample study, and further studies with larger sample sizes are needed.

Reduced Mortality and Radiation Necrosis After Surgery With Postoperative Stereotactic Radiation in Patients With Multiple Brain Metastases.

BACKGROUND AND OBJECTIVES: Although stereotactic radiation has frequently supplanted whole-brain radiation therapy (WBRT) in treating patients with multiple brain metastases, the role of surgery for these patients remains unresolved. No randomized trials have compared surgical resection with postoperative stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) to SRS/SRT alone. Previous studies addressing surgery for patients with multiple brain metastases are often limited by small sample sizes, a lack of appropriate comparison groups, or a focus on patients treated before recent advances in targeted therapy and immunotherapy. We compared outcomes in patients with multiple brain metastases treated with surgical resection and postoperative SRS/SRT to those treated with SRS/SRT alone. METHODS: We studied 734 patients with multiple newly diagnosed brain metastases (surgery with SRS/SRT, n = 228; SRS/SRT alone, n = 506) from 2011 to 2022 in a retrospective, single-institution cohort. Patients who received upfront whole-brain radiotherapy were excluded. Cox proportional hazards models were constructed for overall survival and additional intracranial outcomes. RESULTS: After adjustment for potential confounders, surgery with postoperative SRS/SRT was associated with decreased all-cause mortality compared with SRS/SRT alone (hazard ratio [HR]: 0.67, 95% CI [0.50-0.89], P = 5.56 × 10 -3 ). The association between surgical resection and overall survival was replicated in a subset of the cohort after cardinality matching (HR: 0.64, 95% CI [0.46-0.88], P = 6.68 × 10 -3 ). Patients with melanoma benefited significantly less from surgical resection compared with patients with other tumor types, most notably non-small-cell lung cancer. Compared with definitive SRS/SRT, cavity SRS/SRT was associated with a significantly reduced risk of both symptomatic radiation necrosis (HR: 0.22, 95% CI [0.08-0.59], P = 2.70 × 10 -3 ) and radiographic radiation necrosis (HR: 0.23, 95% CI [0.09-0.57], P = 1.43 × 10 -3 ) in multivariable models. CONCLUSION: In patients with multiple brain metastases, surgical resection before SRS/SRT is associated with reduced mortality and radiation necrosis. Prospective studies may further delineate patient populations that benefit from aggressive local, brain-directed treatment even with significant intracranial disease burden.

Case report: Successful sequential therapy of crizotinb and entrectinib in ROS1-positive non-small-cell lung cancer with brain metastasis in later-settings.

RATIONALE: Crizotinib has been approved in many countries for the treatment of patients with advanced ROS1-rearranged non-small cell lung cancers (NSCLC). Entrectinib is a ROS1 inhibitor that has been designed to effectively penetrate and remain in the central nervous system (CNS) and has been recommended as first-line therapy. Few reports have precisely described sequential crizotinb followed by entrectinib in patients with ROS1 fusion in later settings. PATIENT CONCERNS: A 56-year-old man with a history of occasional smoking visited our hospital with cough, sputum, and shortness of breath. DIAGNOSIS: He was diagnosed with right lung adenocarcinoma (T4N2M1a, stage IV) after image and histological examination, without EGFR or ALK fusion mutation. INTERVENTIONS: He received three prior lines of therapies, including chemotherapy, nivolumab monotherapy, and paclitaxel plus anlotinib, with progression-free survival (PFS) of 5, 2, and 11.5 months, respectively. Then the patient began to have headaches and dizziness, and brain magnetic resonance imaging showed multiple brain metastases. Next-generation sequencing (NGS) of the biopsy from neck lymph node identified EZR-ROS1 (1.25% abundance). After 2 months of crizotinib (250 mg daily) plus bevacizumab, all pulmonary and brain lesions decreased, but a small liver lesion was discovered. As treatment went on for another 4 months, the liver lesion continued to grow while other lesions kept decreased or stable state. NGS analysis on the peripheral blood found the disappearance of EZR-ROS1 fusion and a new NTRK2 mutation (c.5C>T, p.Ser2Leu, 0.34% abundance) without other targetable molecular alteration. He received entrectinib (600 mg daily) plus bevacizumab and achieved a partial response. After 7 months of therapy, examination revealed progression of brain lesions. OUTCOMES: The patient had a total PFS of 13 months from sequential crizotinib and entrectinib therapy. LESSONS: A ROS1-rearranged NSCLC with CNS metastases responded to sequential tyrosine kinase inhibitors treatment of crizotinb followed by entrectinib. This report has potential implications in guiding decisions for the treatment after crizotinib resistance.

Immune checkpoint inhibition and single fraction stereotactic radiosurgery in brain metastases from non-small cell lung cancer: an international multicenter study of 395 patients.

PURPOSE: Approximately 80% of brain metastases originate from non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) are frequently utilized in this setting. However, concerns remain regarding the risk of radiation necrosis (RN) when SRS and ICI are administered concurrently. METHODS: A retrospective study was conducted through the International Radiosurgery Research Foundation. Logistic regression models and competing risks analyses were utilized to identify predictors of any grade RN and symptomatic RN (SRN). RESULTS: The study included 395 patients with 2,540 brain metastases treated with single fraction SRS and ICI across 11 institutions in four countries with a median follow-up of 14.2 months. The median age was 67 years. The median margin SRS dose was 19 Gy; 36.5% of patients had a V12 Gy ≥ 10 cm3. On multivariable analysis, V12 Gy ≥ 10 cm3 was a significant predictor of developing any grade RN (OR: 2.18) and SRN (OR: 3.95). At 1-year, the cumulative incidence of any grade and SRN for all patients was 4.8% and 3.8%, respectively. For concurrent and non-concurrent groups, the cumulative incidence of any grade RN was 3.8% versus 5.3%, respectively (p = 0.35); and for SRN was 3.8% vs. 3.6%, respectively (p = 0.95). CONCLUSION: The risk of any grade RN and symptomatic RN following single fraction SRS and ICI for NSCLC brain metastases increases as V12 Gy exceeds 10 cm3. Concurrent ICI and SRS do not appear to increase this risk. Radiosurgical planning techniques should aim to minimize V12 Gy.

Comparison of preoperative versus postoperative treatment dosimetry plans of single-fraction stereotactic radiosurgery for surgically resected brain metastases.

OBJECTIVE: Stereotactic radiosurgery (SRS) for operative brain metastasis (BrM) is usually administered 1 to 6 weeks after resection. Preoperative versus postoperative timing of SRS delivery related to surgery remains a critical question, as a pattern of failure is the development of leptomeningeal disease (LMD) in as many as 35% of patients who undergo postoperative SRS or the occurrence of radiation necrosis. As they await level I clinical data from ongoing trials, the authors aimed to bridge the gap by comparing postoperative with simulated preoperative single-fraction SRS dosimetry plans for patients with surgically resected BrM. METHODS: The authors queried their institutional database to retrospectively identify patients who underwent postoperative Gamma Knife SRS (GKSRS) after resection of BrM between January 2014 and January 2021. Exclusion criteria were prior radiation delivered to the lesion, age < 18 years, and prior diagnosis of LMD. Once identified, a simulated preoperative SRS plan was designed to treat the unresected BrM and compared with the standard postoperative treatment delivered to the resection cavity per Radiation Therapy Oncology Group (RTOG) 90-05 guidelines. Numerous comparisons between preoperative and postoperative GKSRS treatment parameters were then made using paired statistical analyses. RESULTS: The authors' cohort included 45 patients with a median age of 59 years who were treated with GKSRS after resection of a BrM. Primary cancer origins included colorectal cancer (27%), non-small cell lung cancer (22%), breast cancer (11%), melanoma (11%), and others (29%). The mean tumor and cavity volumes were 15.06 cm3 and 12.61 cm3, respectively. In a paired comparison, there was no significant difference in the planned treatment volumes between the two groups. When the authors compared the volume of surrounding brain that received 12 Gy or more (V12Gy), an important predictor of radiation necrosis, 64% of patient plans in the postoperative SRS group (29/45, p = 0.008) recorded greater V12 volumes. Preoperative plans were more conformal (p < 0.001) and exhibited sharper dose drop-off at the lesion margins (p = 0.0018) when compared with postoperative plans. CONCLUSIONS: Comparison of simulated preoperative and delivered postoperative SRS plans administered to the BrM or resection cavity suggested that preoperative SRS allows for more highly conformal lesional coverage and sharper dose drop-off compared with postoperative plans. Furthermore, V12Gy was lower in the presurgical GKSRS plans, which may account for the decreased incidence of radiation necrosis seen in prior retrospective studies.

Current uses and applications of stereotactic body radiation therapy.

Stereotactic body radiation therapy (SBRT) is a modality that delivers high doses of radiation to a well-defined tumor target in a single or a few fractions and with high precision, which significantly reduces the dose received by surrounding normal tissues. SBRT is indicated for inoperable, early stage (T1 and T2) primary non-small cell lung cancer, lung metastases with a controlled primary tumor, prostate tumors and oligometastatic disease. Despite the lack of long-term or phase III studies, efficacy results in local control are higher than 90%, with similar toxicity to that reported with conventional fractionated radiotherapy. This article describes SBRT technology and technique, along with clinical applications, indications and limitations of this therapeutic modality.

La radioterapia corporal estereotáctica es una modalidad que con alta precisión administra dosis alta de radiación a un objetivo tumoral bien definido, en una o en pocas fracciones, y reduce significativamente la dosis que reciben los tejidos sanos circundantes. Está indicada en cáncer primario de pulmón de células no pequeñas en estadios tempranos (T1 y T2) no operable, metástasis pulmonares con un tumor primario controlado, tumores prostáticos y enfermedad oligometastásica. A pesar de la falta de estudios a largo plazo o fase III, los resultados de su eficacia en el control local es superior a 90 %, con toxicidad similar a la reportada con fraccionamientos convencionales de radioterapia. Este artículo describe la tecnología y la técnica de radioterapia corporal estereotáctica, con las aplicaciones clínicas, indicaciones y limitaciones de esta modalidad terapéutica.

Accuracy of nodal staging by 18F-FDG-PET/CT in limited disease small-cell lung cancer.

BACKGROUND: Small-cell lung cancer (SCLC) is highly aggressive with a nearly incurable disease in most cases. The most important prognostic factor is the status of the mediastinal lymph nodes. Only a small proportion of patients can be diagnosed at early stages and directed to curative multimodal treatment. Therefore, accuracy of nodal staging by (18F)-Fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) computed tomography (18F-FDG-PET/CT) in (very) limited disease SCLC, although not well investigated, is highly important. METHODS: Treatment naive, non-bulky patients treated or diagnosed with SCLC between June 2012 and April 2020 with complete data including FDG-PET/CT and invasive mediastinal staging were retrospectively analyzed (n = 19). Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy of mediastinal lymph node staging of 18F-FDG-PET/CT was calculated. RESULTS: The FDG-PET/CT showed a sensitivity of 91%, and the specificity was calculated as 87.5%. In this cohort, the disease prevalence in lymph nodes was 58% (n = 11). Positive predictive value was 91%, NPV 88% and accuracy calculated at 89%. One patient was upstaged from single-level N2 to multilevel N2. In one patient, upstaging in invasive staging was performed from N2 to N3, and one patient was downstaged from N1 to N0. CONCLUSIONS: FDG-PET/CT is a valuable tool for the detection of distant metastases, but in mediastinal staging of SCLC some limitations might remain. Invasive methods remain the gold standard. Therefore, the mediastinal lymph nodal status of patients with SCLC screened for multimodal treatment should be further evaluated by additional invasive techniques to verify the exact N-staging and to optimize treatment stratification.

The efficacy and outcomes of stereotactic body radiotherapy in adrenal gland metastases.

Aim: This retrospective study presents our single-institutional experience with stereotactic body radiotherapy for adrenal gland metastases. Materials and Methods: We evaluated patients with adrenal metastases treated by stereotactic body radiotherapy (SBRT) from 2014 to 2020. We performed an analysis of 35 patients. The median age of the patients was 62.2. Dosimetric parameters and treatment outcomes were evaluated. Results: The primary diagnosis of the majority of patients was non-small cell lung cancer (94.3%). Treatment was performed in a median of 3 fractions, and the median prescribed dose was 24 Gy (range 22,5-27). The median follow-up was 17 months. Treatment response according to Response Evaluation Criteria in Solid Tumours was categorized as complete response in 11 patients, partial response in nine patients, stable disease in 7, and progressive disease in eight patients. Twenty seven patients had oligometastatic disease and treatment response. Patients with oligometastatic disease had a significantly higher rate of complete response and partial response to treatment than patients with common disease (P = 0,011). The 6-month and 1-year local control rates were 68.4% and 43%, respectively. In general, SBRT was well tolerated and no acute toxicities were observed. Conclusion: Our retrospective study shows that SBRT can be applied safely in adrenal metastases with good results especially in patients with oligometastatic disease.

Efficacy of neoadjuvant stereotactic radiotherapy in brain metastases from solid cancer: a systematic review of literature and meta-analysis.

Neoadjuvant stereotactic radiotherapy (NaSRT) is a novel strategy for brain metastasis (BM) treatment, promising to achieve good local control, improved survival, and low toxicity. This is a systematic review of available literature and meta-analysis of 8 articles eligible for inclusion after searching MEDLINE via PubMed, Web-of-science, Cochrane Wiley, and Embase databases up to March 2023. A total of 484 patients undergoing NaSRT to treat 507 lesions were included. The median age was 60.9 (IQR 57-63) years, with a median tumor volume of 12.1 (IQR 9-14) cm3. The most frequent histology was non-small-cell lung cancer (41.3%), followed by breast (18.8%), and melanoma (14.3%). Lesions had a preferred supratentorial location (77.4%). Most of the studies used a single fraction schedule (91% of patients, n = 440). Treatment parameters were homogeneous and showed a median dose of 18 (IQR 15.5-20.5) Gy at a median of 80% isodose. Surgery was performed after a median of 1.5 (IQR 1-2.4) days and achieved gross-total extent in 94% of cases. Median follow-up was 12.9 (IQR 10-15.7) months. NaSRT showed an overall mortality rate of 58% (95% CI 43-73) at the last follow-up. Actuarial outcomes rates were 60% (95% CI 55-64) for 1-year overall survival (1y-OS), 38% (95% CI 33-43) for 2y-OS, 29% (95% CI 24-34) for 3y-OS; overall 15% (95% CI 11-19) for local failure, 46% (95% CI 37-55) for distant brain failure, 6% (95% CI 3-8) for radionecrosis, and 5% (95% CI 3-8) for leptomeningeal dissemination. The median local progression-free survival time was 10.4 (IQR 9.5-11.4) months, while the median survival without distant failure was 7.4 (IQR 6.9-8) months. The median OS time for the entire cohort was 17 (IQR 14.9-17.9) months. Existing data suggest that NaSRT is effective and safe in the treatment of BMs, achieving good local control on BMs with and low incidence of radionecrosis and leptomeningeal dissemination. Distant control appears limited compared to other radiation regimens.

Single-Session Gamma Knife Radiosurgery for Patients With 20 or More Brain Metastases.

BACKGROUND: Stereotactic radiosurgery (SRS) is a widely accepted treatment modality for brain metastases. The role of SRS in patients with higher numbers of metastases remains controversial. OBJECTIVES: To define outcomes in patients with ≥20 brain metastases managed using single-session SRS. METHODS: This single-institution retrospective cohort study studied 75 patients (26 non-small-cell lung cancer, 21 small-cell lung cancer, 14 breast cancer, and 14 melanoma) undergoing single-session SRS. The median number of tumors per patient was 24, and the median cumulative tumor volume was 3.70 cc. The median margin dose prescribed to each individual tumor was 16 Gy. The median integral cranial dose was 5492 mJ. The median beam on time was 160 minutes. Univariate and multivariate analyses were performed with significance set at P < .05. RESULTS: The median overall survival after SRS was 8.8 months (patients with non-small-cell lung cancer), 4.6 months (patients with small-cell lung cancer), 11.3 months (patients with breast cancer), and 4.1 months (patients with melanoma). Primary cancer type, number of brain metastases, and concurrent immunotherapy were significant factors in predicting survival. Local tumor control rate per patient was 97.3% and 94.6% at 6 and 12 months after SRS, respectively. Thirty-six patients underwent additional SRS for new tumor development with a median time after SRS of 5 months. Three patients experienced adverse radiation events. CONCLUSION: Single-session SRS is a well-tolerated palliative treatment option even in patients with ≥20 brain metastases, achieving local control rate >90% with low risks of neurotoxicity while continuing concurrent systemic oncological care.

Analysis of Serious Weight Gain in Patients Using Alectinib for ALK-Positive Lung Cancer.

INTRODUCTION: Alectinib is a standard-of-care treatment for metastatic ALK+ NSCLC. Weight gain is an unexplored side effect reported in approximately 10%. To prevent or intervene alectinib-induced weight gain, more insight in its extent and etiology is needed. METHODS: Change in body composition was analyzed in a prospective series of 46 patients with ALK+ NSCLC, treated with alectinib. Waist circumference, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle were quantified using sliceOmatic software on computed tomography images at baseline, 3 months (3M), and 1 year (1Y). To investigate an exposure-toxicity relationship, alectinib plasma concentrations were quantified. Four patients with more than 10 kg weight gain were referred to Erasmus MC Obesity Center CGG for in-depth analysis (e.g., assessments of appetite, dietary habits, other lifestyle, medical and psychosocial factors, and extensive metabolic and endocrine assessments, including resting energy expenditure). RESULTS: Mean increase in waist circumference was 9 cm (9.7%, p < 0.001) in 1Y with a 40% increase in abdominal obesity (p = 0.014). VAT increased to 10.8 cm2 (15.0%, p = 0.003) in 3M and 35.7 cm2 (39.0%, p < 0.001) in 1Y. SAT increased to 18.8 cm2 (12.4%, p < 0.001) in 3M and 45.4 cm2 (33.3%, p < 0.001) in 1Y. The incidence of sarcopenic obesity increased from 23.7% to 47.4% during 1Y of treatment. Baseline waist circumference was a positive predictor of increase in VAT (p = 0.037). No exposure-toxicity relationship was found. In-depth analysis (n = 4) revealed increased appetite in two patients and metabolic syndrome in all four patients. CONCLUSIONS: Alectinib may cause relevant increased sarcopenic abdominal obesity, with increases of both VAT and SAT, quickly after initiation. This may lead to many serious metabolic, physical, and mental disturbances in long-surviving patients.

FAM3C in circulating tumor-derived extracellular vesicles promotes non-small cell lung cancer growth in secondary sites.

Rationale: Metastasis is a complex process with a molecular underpinning that remains unclear. We hypothesize that cargo proteins conducted by extracellular vesicles (EVs) released from tumors may confer growth and metastasis potential on recipient cells. Here, we report that a cytokine-like secreted protein, FAM3C, contributes to late-stage lung tumor progression. Methods: EV protein profiling was conducted with an unbiased proteomic mass spectrometry analysis on non-small cell lung cancer (NSCLC) and normal lung fibroblast cell lines. Expression of FAM3C was confirmed in a panel of NSCLC cell lines, and correlated to the invasive and metastatic potentials. Functional phenotype of endogenous FAM3C and tumor-derived EVs (TDEs) were further investigated using various biological approaches in RNA and protein levels. Metastasis potential of TDEs secreted by FAM3C-overexpressing carcinoma cells was validated in mouse models. Results: Transcriptomic meta-analysis of pan-cancer datasets confirmed the overexpression of FAM3C - a gene encoding for interleukin-like EMT inducer (ILEI) - in NSCLC tumors, with strong association with poor patient prognosis and cancer metastasis. Aberrant expression of FAM3C in lung carcinoma cells enhances cellular transformation and promotes distant lung tumor colonization. In addition, higher FAM3C concentrations were detected in EVs extracted from plasma samples of NSCLC patients compared to those of healthy subjects. More importantly, we defined a hitherto-unknown mode of microenvironmental crosstalk involving FAM3C in EVs, whereby the delivery and uptake of FAM3C via TDEs enhances oncogenic signaling - in recipient cells that phenocopies the cell-endogenous overexpression of FAM3C. The oncogenicity transduced by FAM3C is executed via a novel interaction with the Ras-related protein RalA, triggering the downstream activation of the Src/Stat3 signaling cascade. Conclusions: Our study describes a novel mechanism for FAM3C-driven carcinogenesis and shed light on EV FAM3C as a driver for metastatic lung tumors that could be exploited for cancer therapeutics.

Deep Learning Based on Enhanced MRI T1 Imaging to Differentiate Small-cell and Non-small-cell Primary Lung Cancers in Patients with Brain Metastases.

OBJECTIVES: To differentiate the primary small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) for patients with brain metastases (BMs) based on a deep learning (DL) model using contrast-enhanced magnetic resonance imaging (MRI) T1 weighted (T1CE) images. METHODS: Out of 711 patients with BMs of lung cancer origin (SCLC 232, NSCLC 479), the MRI datasets of 192 patients (lesions' widths and heights > 30 pixels) with BMs from lung cancer (73 SCLC and 119 NSCLC) confirmed pathologically were enrolled, retrospectively. A typical convolutional neural network ResNet18 was applied for the automatic classification of BMs lesions from lung cancer based on T1CE images, with training and testing groups randomized per patient to eliminate learning bias. A 5-fold cross-validation was performed to evaluate the classification of the model. The receiver operating characteristic (ROC) curve, accuracy, precision, recall and f1 score were calculated. RESULTS: For a 5-fold cross-validation test, the DL model achieved AUCs of 0.8019 and 0.8024 for SCLC and NSCLC patients with BMs, respectively, and a mean overall accuracy of 0.7515±0.04. The DL model performed well in differentiating the primary SCLC and NSCLC with BMs. CONCLUSION: The proposed DL model is feasible and effective in differentiating the pathological subtypes of SCLC and NSCLC causing BMs, which may be used as a new tool for oncologists to diagnose noninvasively BMs and guide therapy based on the imaging structure of tumors.

Correlation of EGFR mutation subtypes and survival in surgically treated brain metastasis from non-small-cell lung cancer.

OBJECTIVE: Epidermal growth factor receptor (EGFR) mutation is a positive prognostic factor for survival in patients with non-small-cell lung cancer (NSCLC). In such patients, brain metastasis signifies negative outcomes. Patients with NSCLC brain metastasis that may benefit from neurosurgery is under investigation. We aim to investigate the impact of different mutation loci in surgically treated NSCLC brain metastasis patients. METHODS: This retrospective cohort study included patients with NSCLC brain metastasis who underwent brain lesionectomy, followed by radiotherapy and chemotherapy or targeted therapy. Demographics and tumor characteristics were compared between the EGFR mutant type and wild type groups. Postoperative survival and risk factors were analyzed using log rank and Cox regression methods. RESULTS: Overall, 101 patients were included, with 57 belonging to the EGFR mutant type group and 44 to the EGFR wild type group. The median postoperative survival was 17 months for the entire cohort, with the duration being 19 and 14 months for EGFR mutant type and wild type patients (p = 0.013), respectively. Multivariate analysis revealed that exon 19 del (p = 0.02) and a high Karnofsky Performance Scale score (p < 0.01) were independent positive prognostic factors to predict survival. The timing of development of the brain metastasis or the location of the intracranial metastasis was not associated with EGFR mutations. CONCLUSION: EGFR mutations are associated with better survival outcomes in patients with NSCLC brain metastasis suitable for surgical treatment. This advantage was attributed to patients having a specific mutation of exon 19 deletion.

Is extrathoracic metastasis screening necessary for clinical stage IA non-small cell lung cancer?

BACKGROUND: Detecting distant metastases when staging lung cancer is critical to avoid unnecessary surgery and provide appropriate multidisciplinary treatment. However, it is controversial as to whether staging studies should be performed routinely for patients with early-stage lung cancer who have no evidence of distant metastasis. Thus, this study aimed to examine the need for extrathoracic metastasis screening in patients with clinical stage IA non-small cell lung cancer, understand the association between extrathoracic metastasis and other clinical features, and evaluate the diagnostic efficiency of imaging screening for preoperative extrathoracic metastasis in patients with early-stage lung cancer. METHODS: From 2010 to 2019, 510 patients diagnosed with clinical T1N0 lung cancer, excluding contralateral lung metastases, pleural dissemination, malignant pleural effusion, and malignant pericardial effusion, were treated for primary lung cancer. Patients were divided into two groups, and their clinicopathological characteristics were investigated. RESULTS: Five patients (1.0%) had extrathoracic metastases. The histological types were adenocarcinoma in three of the cases, and squamous cell carcinoma and large cell neuroendocrine carcinoma in the other two cases. The T factor was T1b in one case and T1c in four cases. Four patients had solid tumors and one had a solid predominant tumor with an average tumor diameter of 23.0 ± 2.9 mm. The size of solid tumors with extrathoracic metastases was larger than their counterparts. CONCLUSION: When evaluating stage IA non-small cell lung cancer with a solid component diameter < 22 mm, or clinical T1mi-1bN0 in computed tomography evaluation, screening for preoperative extrathoracic metastasis may be omitted.

From Postoperative to Preoperative: A Case Series of Hypofractionated and Single-Fraction Neoadjuvant Stereotactic Radiosurgery for Brain Metastases.

BACKGROUND: Postoperative stereotactic radiosurgery after resection of brain metastases is currently the standard of care. However, rates of leptomeningeal disease (LMD) after postoperative stereotactic radiosurgery have been reported to be >30%. Neoadjuvant stereotactic radiosurgery (NaSRS) has been proposed as an alternative treatment approach to decrease this risk. OBJECTIVE: To report the local control (LC) and LMD rates in patients undergoing NaSRS. METHODS: Our retrospective multicenter case series included consecutive patients planned for SRS followed by resection of intracranial lesions with a confirmed primary malignancy. Concurrent SRS alone to other intracranial lesions was permitted. Exclusion criteria included previous local treatment to that particular lesion and Eastern Cooperative Oncology Group performance status ≥3. Outcomes reported included LC, distant intracranial control (DC), overall survival, LMD, and radionecrosis (RN) rates. RESULTS: Overall, 28 patients with 29 lesions were eligible for analysis. The median follow-up was 12.8 months. The mean age was 62.5 (range 43-80) years, and 55% were Eastern Cooperative Oncology Group performance status 0 to 1. The most common primary malignancies included non-small cell lung cancer (43%) and melanoma (32%). Hypofractionated SRS was used in 62.1%. The 12-month LC and LMD rates were 91.3% and 4.0%, respectively. The 12-month RN, DC, and overall survival rates were 5.0%, 51.5%, and 60.1%, respectively. CONCLUSION: Compared with postoperative SRS, our study suggests that NaSRS leads to comparable local control with a decreased risk of LMD and RN. This is the first NaSRS series with a majority of patients treated with fractionated SRS. NaSRS is a promising approach for appropriate patients where surgical resection is a component of local therapy.