Primary chest wall tumors are rare malignant neoplasms, most commonly sarcomas, for which complete surgical resection is the main curative therapy. Surgical resection conferred substantial survival benefit compared with nonoperative management. Histology-specific differences were notable, with chondrosarcoma demonstrating favorable long-term survival and high-grade soft tissue sarcomas having poorer prognosis. Adjuvant radiotherapy improved local control in high-risk soft tissue sarcomas, while systemic therapy was essential for chemosensitive histologies. In conclusion, multi-institutional data underscore the central role of complete surgical resection in achieving optimal oncologic outcomes for primary chest wall tumors, with adjunctive therapy reserved for selected high-risk patients.

We describe a case of febrile neutropenia in a patient with metastatic non-small cell lung cancer, occurring after 36 cycles of nivolumab therapy. A bone marrow aspirate was performed which showed myeloid maturation arrest without a clear alternative cause, supporting an immune-mediated mechanism. The patient responded well to broad-spectrum antibiotics and granulocyte colony-stimulating factor (G-CSF), with successful rechallenge until other immune-related toxicities led to discontinuation. While uncommon, haematological immune-related adverse events are potentially life-threatening, with neutropenia reported in <1% of patients treated with immune checkpoint inhibitors. This case demonstrates three important points: (1) neutropenia may occur even late in the course of treatment with immunotherapy, highlighting the persistent need for vigilance; (2) bone marrow biopsy and the careful review of medications are essential to differentiate immune-mediated from chemotherapy or other drug-related cytopenias; and (3) management requires urgent recognition, antimicrobial cover, and G-CSF, and caution in the consideration of rechallenge.

Malignant Brenner tumours (MBT) are extremely rare surface epithelial tumours of the ovary. We present a case of ovarian MBT, causing ureteric obstruction. A middle-aged female in her 40s, postabdominal hysterectomy, with a left percutaneous nephrostomy tube in situ, presented to the gynaecology department with lower abdominal pain for 6 months, radiating from the left flank to the groin. On evaluation, she was found to have a neoplastic left adnexal mass involving the distal left ureter. She underwent complete surgical staging with left distal ureter resection and ureteric reimplantation with a psoas hitch. Histopathological findings were suggestive of MBT stage IIIA1(i). She received six cycles of platinum-based adjuvant chemotherapy. Currently, she is in remission at a 1-year follow-up.

Ewing sarcoma (ES) and its variants are rare and aggressive malignancies, occurring in paediatric and younger adult populations. Adamantinoma-like ES (ALES) is one of its variants, characterised by EWSR1::FLI1 fusions, and is exceptionally rare, especially in older adults. There are a few similar cases reported in the literature. We report a rare case of an older adult with a complicated medical history and reported a left neck mass on a follow-up visit; the mass developed over nine months. After evaluation, he was found to have a rare diagnosis of ALES in this age group, specifically with this Ewing Sarcoma RNA binding protein 1 and nuclear factor of activated T cells cytoplasmic 2 (EWSR1::NFATC2) gene fusion. This case highlights the challenges of diagnosing and the multidisciplinary management of rare variants of ES with uncommon gene fusions and raises awareness for the future potential of molecular diagnostics and treatment-specific applications for improved access to care and better outcomes for this population.

Neoadjuvant immunochemotherapy holds tremendous potential for patients with esophageal squamous cell carcinoma (ESCC); however, effective biomarkers for predicting its efficacy are lacking. This study explored the correlation between tertiary lymphoid structures (TLSs) with pathological response and disease-free survival (DFS) to predict the efficacy of neoadjuvant immunochemotherapy in ESCC.

Osteosarcoma (OS) is a malignant tumor originating from osteoblasts. Methyltransferase-like 14 (METTL14) is an N6-methyladenosine (m6A) methyltransferase that has been reported to promote OS progression; however, its underlying mechanism remains unclear.

The role of traditional Chinese medicine in cancer treatment is becoming increasingly pivotal. Tupistra chinensis Baker (STCB), a member of the Lily family, is an herbal plant with antipyretic and detoxifying properties. It has also been used to alleviate abdominal distension. Previous studies have shown that saponin extracted from STCB inhibits proliferation of hepatic carcinoma (HCC) cells. The present study aimed to explore the mechanisms implicated in the regulation of HCC progression by STCB.

Complete macroscopic resection is the key objective of cytoreductive surgery for peritoneal malignancy. However, heterogeneity in terminology and operative technique persists across centres and between surgical and gynaecological disciplines. This study sought to establish international consensus on the nomenclature of cytoreductive surgery procedures, key technical principles of peritonectomy procedures and visceral resections, and management of regional lymph nodes in the context of peritoneal malignancy. A modified Delphi process was undertaken involving 148 surgical and gynaecological oncologists across six continents. Cytoreductive surgery was endorsed as the preferred term for potentially curative surgery for peritoneal malignancy. Agreement was reached on core principles guiding peritonectomy, including the extent of peritoneal resection around tumour deposits. For visceral resections, the panel favoured a conservative, tumour biology-informed strategy that considers disease distribution and patient-specific factors. The group recommended selective removal of clinically enlarged nodes only. This global consensus defines foundational principles for cytoreductive surgery in patients with peritoneal malignancy and provides standardised terminology and operative guidance that can be integrated into routine surgical practice across various surgical oncology disciplines. Adoption of these recommendations has the potential to reduce variability in cytoreductive surgery techniques, facilitate comparison between studies by increasing standardisation, and facilitate the design and conduct of high-quality surgical trials in peritoneal malignancy.

Cancer predisposition due to constitutional (germline) genetic variants in high-risk or moderate-risk cancer predisposition genes presents clinical opportunities for risk mitigation. Focusing genetic testing only on patients who are most likely to be positive for germline variants might enhance the clinical utility of positive results, but this approach could fail to assess the rate and pattern of such variants in patients with cancer overall. We aimed to assess the frequency and nature of constitutional variants in cancer predisposition genes in patients with cancer in the UK health-care system.

Ifinatamab deruxtecan is a novel B7-H3-directed antibody-drug conjugate that leverages the clinically validated deruxtecan technology. We report dose-escalation results from a trial of ifinatamab deruxtecan in patients with solid tumours.

Lutetium-177 [177Lu]-prostate-specific membrane antigen (PSMA)-617 improves overall survival and progression-free survival in metastatic castration resistant prostate cancer (mCRPC), whereas immune checkpoint inhibitors (ICIs) have limited activity. Preclinical evidence suggests radioligand therapy might induce immunogenic cell death that can be enhanced with ICIs. This study evaluates the activity and adverse event profile associated with multiple doses of [177Lu]Lu-PSMA-617 with pembrolizumab.

[177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 (177Lu-PSMA-617) is a novel treatment for metastatic castration-resistant prostate cancer. Here, we aimed to evaluate 177Lu-PSMA-617 in patients with PSMA-expressing oligometastatic hormone-sensitive prostate cancer (HSPC).

Fulzerasib, a KRASG12C inhibitor, has shown clinical activity in previously treated non-small-cell lung cancer (NSCLC). Clinical studies indicate that combining a KRASG12C inhibitor with an anti-EGFR antibody is effective in colorectal cancer; however, its benefit in NSCLC remains to be explored.

Survival discrepancy between male and female patients in lung cancer is a well-known, but still poorly understood phenomenon. Previous studies have used different patient cohorts and clinical covariates and have not included obesity, which is associated with longer lung cancer survival. We evaluated the relationship between survival, obesity, sex and other covariates using comprehensive, harmonized patient cohorts and a federated analysis approach.

Cell reprogramming can be used to short-circuit the cancer-immunity cycle.

Extrachromosomal circular DNA (eccDNA) are molecules that originate from chromosomal DNA but exist independently. While large eccDNA (ecDNA) contributes to tumorigenesis, the role of smaller eccDNA (<100,000 base pairs) in cancer remains unclear. Our analysis of 25 colorectal cancer (CRC) tumors and normal adjacent tissues revealed that eccDNA is significantly more abundant in tumor tissues, correlating strongly with chromosomal amplifications. The presence of whole intact genes on 1.29% of eccDNA was nonrandom. We identified 84 genes that recurred across tumors of multiple patients when present on eccDNA, with 19% of genes being cancer-associated. eccDNA-borne genes were often accompanied by increased expression, and their contribution to expression was much larger than that from linear amplifications and the larger ecDNA. The cytokine gene CXCL5 exemplified this phenomenon, showing substantial copy-number increase and upregulation when present on eccDNA. Functional validation in cell lines showed that CXCL5 eccDNA enhanced transcriptional output and immune cell recruitment function. The recurrence and overexpression of CRC-related genes on eccDNA indicate their selection in tumors, suggest that eccDNA can serve as an additional mechanism for dynamically influencing gene expression and is capable of conferring cancer phenotypes on cells. Analysis of chromatin landscapes revealed that eccDNA preferentially forms at sites of open chromatin and active transcription, with architectural boundaries marked by CTCF protein. Clinically, higher eccDNA levels correlated with poorer relapse-free survival in a small patient cohort. These findings suggest that circular DNA elements across the entire size spectrum participate in cancer evolution and warrant further investigation in larger cohorts.

Assessment of hepatic functional reserve is critically important for preventing serious complications after hepatectomy such as liver failure. While the indocyanine green clearance test (ICG) is a liver-specific test that is not affected by other organs and is commonly used to evaluate liver reserve capacity. We lack knowledge regarding what test should be performed for patients with jaundice, portal shunts, or intolerance whose liver function cannot be accurately assessed by ICG. To close this gap, we focused on changes in amino acid metabolism associated with impaired liver function. The branched-chain amino acid-to-tyrosine ratio (BTR) reflects the severity of liver disease. The research objectives are to evaluate whether BTR is useful as an alternative test to ICG. The primary endpoint of this study is to clarify the correlation between BTR and ICG. The secondary endpoints are to provide pathological confirmation of liver fibrosis and clarify the relationship with short- and long-term outcome and to examine whether it is clinically significant as a marker of preoperative liver reserve capacity. This retrospective single-center cohort study included patients who underwent hepatectomy for HCC between January 2011 and December 2016. In this study, 235 patients were enrolled, with a median BTR of 5.58. The BTR and indocyanine green stagnation rates at 15 min (ICG-R15) showed a significant correlation (r = -0.57, p < 0.001), whereas 1/BTR showed an even stronger correlation (r = 0.66, p < 0.0001). Conversion formulas that is a regression equation predicting ICG test results with BTR as an explanatory variable were analyzed. In addition to its correlation with ICG-R15, BTR was significantly associated with liver fibrosis in the background liver pathology of resected specimens, demonstrating higher sensitivity for detecting cirrhosis compared to ICG. The high BTR group exhibited significantly longer survival than the low BTR group (p = 0.020). The results indicate that BTR and ICG are significantly correlated. Comparable to ICG, BTR is a predictor of liver fibrosis and a prognostic factor for postoperative outcomes in patients with HCC. Although 99mTc-GSA scintigraphy has been reported to correlate with IGC, the correlation coefficient and number of cases in this study are equivalent. BTR can be tested through routine blood sampling. The results of this study demonstrate the potential for clinically evaluating preoperative hepatic reserve capacity in a less invasive, more cost-effective without facility limitations.

Glioblastoma (GBM) remains a significant therapeutic challenge. While GBM-derived extracellular vesicles (EVs) are known to remodel the normal blood-brain barrier (BBB) into a blood-tumour barrier (BTB), the underlying mechanism is largely not understood. Here, we reveal that nucleolin (NCL) is transferred via GBM-derived EVs to the surface of brain endothelial cells, where it promotes BTB formation. Furthermore, the NCL-specific aptamer AS1411 exploits this pathway, crossing the BTB through receptor-mediated transcytosis and selectively entering GBM cells in an NCL-dependent manner. Proteolysis-targeting chimeras (PROTACs), heterobifunctional molecules that recruit E3 ligases to degrade target proteins, show therapeutic potential but are hindered by inefficient brain penetration in GBM. Capitalizing on the BTB-penetrating capability of AS1411 and our prior finding that AS1411 can intracellularly recruit the E3 ligase MDM2 via employing NCL as a molecular bridge, we engineered AS1411-based PROTACs against VEGFR2 and EGFR. These PROTACs induced NCL- and MDM2-dependent ubiquitination and degradation of VEGFR2 or EGFR in GBM cells, demonstrating potent anti-tumour activity. Collectively, our findings identify EV-transferred NCL as a key mediator of BTB formation and a functional transcytosis receptor for AS1411, providing a promising strategy for developing BTB-permeable, targeted therapy for GBM.

BTK inhibitors (BTKi) have reshaped the therapeutic algorithm of lymphoproliferative diseases, but class-specific adverse events (AEs) have emerged. Dose adjustment (DA) is often attempted to mitigate AEs, particularly with ibrutinib, the first BTKi approved for relapsed/refractory (R/R) mantle cell lymphoma (MCL) patients. We described ibrutinib DA in 226 consecutive R/R MCL who started ibrutinib between 2016 and 2023. We assessed DA rate and calculated single patient's relative ibrutinib dose as a percentage of the expected full dose during the entire treatment period, grouping patients into 4 dose levels (DL1a 95%-100%, DL1b 75%-94%, DL2a 50%-74%, DL2b < 50%). We evaluated changes in response, progression free survival (PFS), overall survival (OS) and time to next treatment (TTNT) between groups. Thirty-four percent of patients started ibrutinib at reduced dose, mainly due to age/comorbidities. Overall, 44% of patients reduced ibrutinib dose, mostly due to AEs. Thirty-five percent of patients interrupted treatment, predominantly for AEs, and 65% of patients discontinued ibrutinib, most often due to progressive disease (70%). No statistically significant differences in response rates/PFS/OS were observed across DLs. Interestingly, patients on the lowest dose tended to remain on treatment longer. This is the first real-life report evaluating ibrutinib DA in MCL. We showed that DA is common, particularly in older comorbid patients, and doesn't compromise efficacy, making it a feasible strategy for managing ibrutinib-related toxicities.

Fine-needle aspiration biopsy (FNAB) and core-needle biopsy (CNB) are common methods to evaluate the pathology of an abnormal tissue mass. However, both methods have their limitations, e.g., FNAB samples often remain inadequate, and CNB is more invasive. A novel device, ultrasound-enhanced fine-needle aspiration biopsy (USeFNAB), can collect samples with greater cellular content quantitatively without compromising tissue quality. The purpose of this prospective study was to evaluate USeFNAB for the first time in humans in vivo.