Spontaneous regression (SR) of pulmonary adenocarcinoma is an exceedingly rare event, characterized by the unexplained disappearance or reduction of a tumor without adequate medical intervention. We report a case of a 60-year-old male with a history of heavy smoking and previous gastric adenocarcinoma. A surveillance CT scan identified a suspicious nodule in the right upper lung. PET/CT and biopsy confirmed adenocarcinoma. The patient underwent right upper lobectomy, and histology showed no residual cancer, consistent with SR. Lymph node metastasis was detected, leading to a staging of pTxN2R1M0. The patient is currently with no signs of recurrence. SR in pulmonary adenocarcinoma is extremely rare, and its mechanisms are not well understood. Ongoing research and careful follow-up are essential for better understanding and management.

Metastasis accounts for 90% of cancer-related deaths. Extravasation is a necessary step for cancer metastasis. Currently, there are no drugs that specially target extravasation. Most cancer therapies target either proliferation or angiogenesis. We previously identified "angiopellosis" as the dominant mechanism by which vascular endothelial cells undergo conformational changes and actively "push" circulating cancer cells out of blood vessels. In this study, we developed an image-based high-throughput drug screening assay by coculturing cancer membrane-coated spheres with endothelial monolayers. Through this platform, we identified Bay 61-3606 as a lead angiopellosis inhibitor. Bay 61-3606 substantially reduced cancer cluster extravasation, an activity solely supported by angiopellosis and associated with higher metastatic potential, in both zebrafish and mouse models. Furthermore, Bay 61-3606 decreased distant metastases in murine models of lung carcinoma and triple-negative breast cancer. Mechanistically, Bay 61-3606 targeted the c-Jun amino-terminal kinase signaling pathway, down-regulating COL8A1 expression in endothelial cells and impairing the angiopellosis process.

For metastatic colonization to occur, disseminated tumor cells must survive, adapt to, and remodel distant microenvironments in an organ-specific manner. We established a human multitissue model of cancer spread, with engineered bone and lung linked by vascular flow containing circulating cancer cells. Parental MDA-MB-231 cells extravasated toward both tissues, remodeled their niches, and acquired transcriptional programs reflecting adaptation to the local microenvironment, particularly upon homing to bone. Tissue-specific colonization by the bone- and lung-tropic MDA-MB-231 derivatives was quantified in independently perfused bone or lung platforms. Consistent with in vivo behavior, bone-tropic cells showed stronger bone colonization than lung-tropic cells and induced more pronounced osteolysis. In contrast, lung-tropic cells caused greater epithelial disruption in lung tissue and only modest colonization of bone. Distinct patterns of tissue colonization and secreted factors demonstrate that this device recapitulates key features of organ-specific metastasis observed in vivo for this family of cell lines.

Meningiomas are predominantly benign intracranial neoplasms, with extracranial distant metastasis occurring in fewer than 1% of all patients; pulmonary metastasis represents an exceedingly rare complication of meningioma progression and recurrence. We describe a 44-year-old male patient with sequentially recurrent intracranial meningioma exhibiting dynamic histopathological grade evolution combined with synchronous bilateral pulmonary metastatic lesions, followed for an unprecedented 18 clinical years. Across follow-up, the patient received four open craniotomies, two sessions of stereotactic Gamma Knife radiosurgery, a CT-guided percutaneous lung biopsy, and minimally invasive pulmonary radiofrequency ablation. Post-intervention serial neurological and radiological monitoring documented favorable functional recovery: final Glasgow Coma Scale (GCS) = 15 and Modified Rankin Scale (mRS) = 1 at latest follow-up, with complete resolution of initial left lower limb weakness and stable control of both intracranial residual sinus-associated tumor and all pulmonary metastatic nodules without newly emerging systemic metastasis. This long-duration real-world clinical cohort highlights the critical necessity of full-body systemic imaging screening and lifelong standardized periodic surveillance for meningiomas with superior sagittal sinus invasion and progressive pathological upgrading, to facilitate early identification of occult distant pulmonary metastasis and formulate individualized combined surgical-radiation-ablation treatment regimens for high-risk recurrent meningioma.

Lymphangitis carcinomatosis is a condition characterised by inflammation and malignant infiltration of lymphatic vessels due to metastatic malignancy from a primary location. It usually denotes an end-stage malignancy with poor prognosis. The symptoms are primarily related to the respiratory system but other primary sites have been reported. This case report illustrates a male in his early 50s with no previous history of cancer, presenting with symptoms of unilateral leg ischaemia and respiratory symptoms, for whom his admission led to the discovery of metastasis. Unfortunately, he deteriorated significantly over time due to respiratory failure and passed away. The exact mechanism of lymphangitis carcinomatosis is unclear, but it is presumed that tumour cells are spread within the lymphatic system. Pulmonary lymphangitis carcinomatosis could be one of the first manifestations of an occult primary tumour. This case report aims to highlight the importance of recognising atypical clinical presentations of lymphangitis carcinomatosis to ensure management efforts are made towards the underlying malignancy.

ROS1-targeted therapies have improved outcomes in ROS1-positive non-small cell lung cancer (NSCLC), but acquired resistance, CNS progression, and off-target toxicities remain important limitations. Zidesamtinib (Jideytro[®], NVL-520) is a next-generation, brain-penetrant, tropomyosin receptor kinase (TRK)-sparing ROS1 inhibitor designed to retain activity against resistance mutations, including G2032R. In preclinical models, it demonstrated potent, selective ROS1 inhibition, broad resistance coverage, and durable intracranial activity. Administered orally at 100 mg once daily, zidesamtinib exhibits a favorable pharmacokinetic profile. Data from the ARROS-1 phase 1/2 trial demonstrated durable clinical efficacy and manageable safety in previously treated ROS1-positive NSCLC, including patients with CNS metastases and G2032R resistance. These results led to its accelerated FDA approval on July 22, 2026, for patients previously treated with a ROS1-targeted tyrosine kinase inhibitor.

Liver metastases (LM) in small cell lung cancer (SCLC) are associated with a limited response to immune checkpoint inhibitors (ICIs). In this trial, we evaluated the efficacy of first-line envafolimab plus chemotherapy in SCLC patients with LM and explored potential predictive biomarkers. Patients received envafolimab in combination with chemotherapy for four cycles, followed by envafolimab monotherapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included safety, objective response, overall survival, and identification of predictive biomarkers. Whole-exome sequencing (WES), transcriptome sequencing, DNA methylation sequencing, circulating tumor DNA (ctDNA) analysis, and cell-free DNA (cfDNA) methylation sequencing were performed on tumor tissues and peripheral blood samples. The objective response rate (ORR) was 75.9%, the disease control rate (DCR) was 100%, and the median PFS was 4.3 months. Granulocyte turnover and TNFRSF9 expression emerged as key indicators across transcriptomic and epigenomic analyses, and were associated with prognosis and liver dysfunction. cfDNA-based assessment of granulocyte turnover reflected both liver damage and tumor dynamics, suggesting its potential for real-time monitoring. These findings suggest that granulocyte activity may contribute to an immunosuppressive tumor microenvironment and serve as a predictive marker for treatment stratification in SCLC with LM.

Brain metastasis (BM) is a common complication of advanced non-small cell lung cancer (NSCLC). Although immune checkpoint inhibitors (ICIs) have demonstrated efficacy in treating NSCLC-BM, their clinical benefits are often limited. The combination of radiotherapy (RT) and ICIs has emerged as a promising strategy for overcoming these challenges. This review summarizes the current knowledge regarding the immune landscape of NSCLC-BM as well as the clinical evidence supporting and challenging the RT-ICI combination, and it provides an expanded mechanistic framework detailing how RT reshapes the tumor immune microenvironment. RT can enhance the antitumor immune response by disrupting the blood-brain barrier, reprogramming the tumor microenvironment, and improving immune cell infiltration. Clinical studies have supported the synergistic potential of RT and ICIs against NSCLC-BM, showing improved survival and progression-free survival rates. However, challenges such as resistance and toxicity remain, and further investigation is required to refine treatment strategies. We further discuss optimal RT fractionation and sequencing strategies, toxicity mitigation, including practical approaches for managing radiation necrosis, and emerging biomarkers that may guide personalized treatment. A clearer understanding of these biological and clinical interactions is essential to refine treatment algorithms and maximize the therapeutic potential of radioimmunotherapy in NSCLC-BM.

Therapy-related chronic myeloid leukaemia (t-CML) is an extremely rare myeloid neoplasm. Here, we report a first case of CML developing during long-term treatment with alectinib, a highly selective tyrosine kinase inhibitor (TKI) targeting anaplastic lymphoma kinase (ALK). A 53-year-old never-smoking woman with ALK-positive non-small cell lung cancer (NSCLC) developed mediastinal lymph node and brain metastases after curative surgery. Alectinib therapy achieved sustained systemic and intracranial disease control for nearly 3 years without serious adverse events. However, 3 years and 1 month after initiating alectinib, progressive leukocytosis with marked basophilia and circulating immature myeloid cells was observed. Bone marrow analysis confirmed the diagnosis of CML with BCR-ABL1 fusion. Nilotinib was initiated while alectinib was continued, resulting in a rapid hematologic response without serious adverse events. Further accumulation of cases is needed to clarify the potential leukemogenic risk of ALK-TKIs and to establish the safety and clinical utility of combined ALK-TKI and BCR-ABL-TKI therapy.

Metastatic pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, and survival beyond a decade is exceptional. We report a 59-year-old man with stage IV PDAC presenting with oligometastatic disease involving a pancreatic head/uncinate primary tumor, clustered right posterior hepatic metastases, and left supraclavicular nodal metastasis. Endoscopic ultrasound-guided biopsy of the pancreatic primary lesion confirmed poorly differentiated adenocarcinoma; metastatic involvement was diagnosed radiographically. Baseline disease was limited to three locally treatable sites, and CA19-9 remained within the normal range throughout follow-up. The patient received four courses of high-dose hypofractionated, high-BED lesion-directed radiotherapy with limited systemic therapy. RT1 treated the three baseline disease sites with concurrent oral S-1. Post-RT1 MRI showed partial response of the pancreatic primary tumor and right posterior hepatic metastases according to RECIST 1.1, and PET/CT showed resolution of abnormal pancreatic hypermetabolism in the pancreatic lesion, with a post-treatment SUVmax of 1.1. Metachronous oligoprogression subsequently occurred in the liver and lung: RT2 and RT3 each treated one new hepatic lesion with concurrent S-1, and RT4 treated three clinically progressive pulmonary metastatic targets without concurrent systemic therapy. No grade ≥3 treatment-related toxicity was documented. After RT4, no further systemic antitumor therapy was administered. Radiographic non-progression was documented for approximately 5 years and 5 months after the final thoracic radiotherapy, until February 2023. At telephone follow-up on May 27, 2026, the patient remained alive, independent in daily living, and had an ECOG performance status of 0-1. Overall survival exceeded 11 years and 8 months from diagnosis. This case highlights exceptional long-term survival in oligometastatic and oligoprogressive metastatic PDAC after repeated high-BED lesion-directed radiotherapy. This observation is hypothesis-generating and should not be interpreted as evidence that radiotherapy can replace systemic therapy.