An inflammatory myofibroblastic tumor (IMT) is a neoplasm composed of myofibroblastic and fibroblastic spindle cells accompanied by inflammatory cells, including lymphocytes and eosinophils. It is an ultra-rare tumor, the optimal management of which remains to be defined. Surgery is the treatment of choice for localized tumors. The treatment of advanced disease is not precisely defined. Chemotherapy regimens result in an overall response rate of approximately 50% based on retrospective data. The latest pathophysiological data highlight the role played by tyrosine kinase fusion genes in IMT proliferation. Anaplast lymphoma kinase (ALK) oncogenic activation mechanisms have been characterized in approximately 80% of IMTs. In this context, data regarding targeted therapies are most important. The aims of this article are to review the latest published data on the use of systematic therapy, particularly the use of molecular targeted therapy, and to publish an additional case of an IMT with Ran-binding protein 2 (RANPB2)-ALK fusion showing a long response to a tyrosine kinase inhibitor.

This study aimed to identify the worst "bad actors" in mixtures of pollutants contributing to liver damage and shorter telomeres in the U.S. population, using weighted quantile sum (WQS) modeling with stratification by race/ethnicity. We conducted a comprehensive cross-sectional analysis of mixtures of pollutants in National Health and Nutrition Examination Survey datasets: (1) 33,979 adults with blood levels of cadmium (Cd), lead (Pb), and mercury, including subsets with measurements of per-/polyfluoroalkyl substances (PFAS), and polychlorinated biphenyls (PCBs)/polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs); and (2) 7360 adults with measurements of telomeres, Cd, and Pb. Multivariable-adjusted WQS regression examined associations between WQS mixture indices and liver injury (alanine aminotransferase (ALT)-elevation), advanced liver-fibrosis (LF), and telomere length. WQS_metal indices were associated with advanced-LF in all racial/ethnic groups. The top contributor was Cd in the total population and in non-Hispanic Whites (NHW), while Pb was the top contributor in non-Hispanic Blacks (NHB). The WQS_{metal-PCB-PCDD/F} index was associated with ALT-elevation, with PCB126, Cd and Pb as main contributors; the odds ratio (OR) per decile was 1.50 (95 % CI, 1.26-1.78), while the OR per decile of the WQS_metal-PFAS index was 1.03 (95 % CI, 0.98-1.05), not significant. WQS_metal indices were associated with shorter telomeres. Cd was main contributor associated with advanced-LF in NHW, while Pb was the major bad actor in NHB, suggesting that NHB may be especially susceptible to Pb toxicity. Metals were associated with shorter telomeres. Metal and PCB/PCDD/F mixtures were associated with ALT-elevation. Heavy metals and organic chemicals may contribute to liver-related morbidity and healthcare disparities.

Background & Aims: Angiogenesis is critical in intrahepatic cholangiocarcinoma (ICC), a highly lethal cancer with limited treatment options. Sunitinib, a multi‐receptor tyrosine kinase inhibitor, has strong antiangiogenic and antitumor effects. We aimed to evaluate the efficacy and tolerability of sunitinib as a second‐line treatment in chemotherapy‐pretreated patients with advanced ICC. Methods: This open‐label, single‐arm, phase II trial was conducted across five French centres. Eligible patients were aged ≥ 18, had advanced ICC not suitable for curative surgery and had been pre‐treated with gemcitabine and/or platinum. Patients received oral sunitinib at 37.5 mg daily. The primary endpoint was overall survival (OS), with secondary endpoints including progression‐free survival (PFS), objective response rate (ORR), disease control rate (DCR) and safety. Tumour response was evaluated using RECIST v1.1, with exploratory analysis using Choi criteria. VEGF‐A, VEGF‐C and plasma sunitinib levels were measured. Results: Fifty‐three patients were included. Median OS was 9.6 months (95% CI, 6.1–13.1), median PFS was 3.7 months (95% CI, 3.1–6.4), the ORR was 14% and the DCR was 84%. Grade 3–4 cytopenias occurred in 25% of patients, hypertension in 21% and fatigue in 19%. Higher baseline levels of VEGF‐A and VEGF‐C correlated with longer OS. Patients with dose reductions maintained adequate drug exposure. Choi criteria, applied to 24 patients, predicted response duration better than RECIST v1.1. Baseline tumour density, assessed in 14 patients, showed a potential association with treatment responses. Conclusions: Sunitinib demonstrated efficacy and manageable toxicity as a second‐line treatment in patients with advanced ICC previously treated with chemotherapy, suggesting it may represent a viable therapeutic option for this population. Trial Registration: ClinicalTrials.gov NCT01718327

Rationale: Lung cancer screening has made early-stage non–small cell lung cancer (NSCLC) more common and highly curable. However, evidence on post-treatment surveillance, new radiological findings, and distinguishing recurrence from new primary cancers remains limited. Objectives: Our study evaluated outcomes in patients with pathologic stage 0/1A first primary NSCLC after surgery, including overall survival and the classification of new findings as either recurrence or second primary tumors. We also explored potential improvements to current classification criteria. Methods: We analyzed 653 patients with pathologic stage 0/1A NSCLC from the IELCART cohort (2016–2023). Radiological findings were reviewed to classify lung cancer diagnoses as second primaries or recurrences using a five-step approach based on histopathology, genetics, timing, and multidisciplinary discussions. Survival was analyzed with Kaplan-Meier curves and log-rank tests. Results: Among 653 patients (61.1% women, median age 69 yr), 74 (11.3%) later had radiological findings confirmed as lung cancer, which was more frequent in men (15.7% vs. 8.5%), those with higher pack-years, and chronic obstructive pulmonary disease. New malignant events were most common in current smokers (19.1%), followed by former smokers (15.2%) and never smokers (1.6%). Of these, 30 (5%) were second primaries, and 44 (7%) were recurrences. Nonsolid cancers showed no recurrences. Recurrences peaked at 12–18 months, whereas second primaries occurred steadily at 0.6% annually. Overall survival differed significantly between patient groups (P < 0.0001), with overall survival of 58.2% with recurrences, 77.9% with new primaries, and 94.3% with no new cancer after a median follow-up of 3.5 years. Conclusion: Among 653 patients, 7% had recurrences, whereas new primaries (5%) became more frequent after 3 years, occurring steadily at 0.6% per year, with distinct survival outcomes. New malignant events were more common in men, smokers, and those with chronic obstructive pulmonary disease. Notably, all malignancies in nonsolid cancers were new primaries. These findings emphasize the need for tailored surveillance strategies.

Mesothelioma is a malignancy of serosal membranes. Parietal pleura is the most common site, with peritoneum being the second most frequent location. Malignant peritoneal mesothelioma (MPM) is a rare and aggressive disease. The prognosis is often very poor with median overall survival ranging from 6 to 18 months in patients who are not candidates for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) due to non-resectable disease or comorbid conditions. For patients with resectable disease, CRS and HIPEC have become the standard of care. However, for patients with unresectable malignant mesothelioma there is unfortunately no effective systemic treatment beyond the first line. Based on the results of a recent phase II trial, lurbinectedin has clinical activity and acceptable toxicity in the second- and third-line treatment of malignant pleural mesothelioma. However, until present, no data have been available for patients with MPM and for patients who become refractory after multiple treatment lines. We report on two patients with metastatic MPM who achieved durable disease control of 10+ and 8 months with lurbinectedin in the fourth and fifth treatment line, respectively.