Morgan E, Bardot A, Langselius O
… +44 more, Rutherford MJ, Elkader HA, Bennett D, Brennan A, Bucher O, Butler J, Cameron DA, Canfell K, Chiam K, Chiarelli A, Creighton N, De P, Evans S, Fitzpatrick D, Guren MG, Hannah J, Huws DW, Jackson CGCA, Kønig SM, Kumar E, Larønningen S, Lawler M, Liu Q, McClure C, Mehmood A, Mitchell H, Morrison DS, Murray D, Norwood T, Phillips KAM, Ransom D, Shack L, Smits S, Saint-Jacques N, Marvelde LT, Tran D, Turner D, Ursin G, Vernon S, Walker MJ, Woods RR, Zhang B, Bray F, Soerjomataram I
Lancet Oncol
· 2026 Jun · PMID 42225103
·
Full text
BACKGROUND: The COVID-19 pandemic had an impact on cancer services globally. There is a crucial need to understand how the incidence and stage of major cancer types were affected internationally. We aimed to assess these...BACKGROUND: The COVID-19 pandemic had an impact on cancer services globally. There is a crucial need to understand how the incidence and stage of major cancer types were affected internationally. We aimed to assess these metrics in seven countries within the International Cancer Benchmarking Partnership. METHODS: This population-based study used data on 2·6 million patients diagnosed with primary cancers of the colon, rectum, lung, prostate, female breast, ovary, and melanoma of the skin, between Jan 1, 2015, and Dec 31, 2020. Data were collected from cancer registries in 18 jurisdictions from seven countries participating in the International Cancer Benchmarking Partnership; Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the UK. The main outcomes of monthly cases and age-standardised incidence rates by site during the pandemic (April 1 to Dec 31, 2020) were compared with predictions for the same year based on pre-pandemic trends (Jan 1, 2015, to Dec 31, 2019). FINDINGS: Between April 1, and Dec 31, 2020, 55 713 (16%) of 347 666 expected cases were predicted to be missing, with the largest deficits seen for prostate cancer (24%), female breast cancer (18%), and melanoma (18%), and the smallest deficits seen for ovarian (4%) and lung cancer (8%). The largest difference between observed and predicted incidence rates for prostate cancer was seen in the UK (164·9 per 100 000 person-years predicted vs 101·4 per 100 000 person-years observed) and the smallest difference seen in Norway (164·1 vs 168·4). Reductions in incidence were greatest from April 1, to July 31, versus from Aug 1, to Dec 31, in 2020. The percentage deficits between observed and predicted cases were 54% (UK) and 36% (Ireland) for prostate cancer, 40% (UK) and 34% (Ireland) for breast cancer, and 40% (UK) and 35% (Canada) for melanoma. INTERPRETATION: The pandemic's greatest impact was during the first few months of societal lockdowns in 2020 when barriers in access to health care were greatest. Further research is needed to understand whether patients with a missed diagnosis were diagnosed at a later date and if they presented at a later stage. FUNDING: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Higher Education Authority North South Research Programme, Health Data Research UK; Te Aho o Te Kahu, Cancer Control Agency New Zealand; New Zealand Cancer Society; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; The Scottish Government; Western Australia Department of Health; and Wales Cancer Network.
Baudin E, Durand A, Beron A
… +28 more, Smith D, Déandreis D, Taieb D, Ansquer C, Dierickx L, Deshayes E, Hentic O, Moalla S, Menu Y, Lebtahi R, Assenat E, Touchefeu Y, Guimbaud R, Dahan L, Lamartina L, Cheurfa N, Quak E, Bouhier-Leporrier K, Haissaguerre M, Hindie E, Cao CD, Lombard-Bohas C, Jannin A, Walter T, Ducreux M, Chaib S, Hadoux J, Foulon S
BACKGROUND: To our knowledge, no randomised trial with peptide receptor radionuclide therapy has been done in patients with metastatic pancreatic neuroendocrine tumours. We aimed to evaluate the antitumour activity and s...BACKGROUND: To our knowledge, no randomised trial with peptide receptor radionuclide therapy has been done in patients with metastatic pancreatic neuroendocrine tumours. We aimed to evaluate the antitumour activity and safety of [Lu]Lu-dota-tate in this setting. METHODS: OCLURANDOM is a randomised, open-label, non-comparative, phase 2 trial conducted in ten academic centres in France. Patients aged 18 years and older with pretreated, progressive, somatostatin receptor-positive, metastatic pancreatic neuroendocrine tumours and an Eastern Cooperative Oncology Group performance status of 0-2 were randomly assigned (1:1) using web-based software to receive intravenous [Lu]Lu-dota-tate (7·4 GBq every 8 weeks up to four cycles) with concomitant amino acid infusion or oral sunitinib (37·5 mg once daily). Amino acid infusion was for at least 4 h starting 30 min before [Lu]Lu-dota-tate infusion and included 16·8 g of arginine and 22 g of lysine in 2 L until May, 2018, and, from that date, a solution of 25 g of arginine and 25 g of lysine in 2 L. Randomisation was stratified according to Ki-67, liver involvement, and previous therapies. The primary endpoint was progression-free survival at 12 months assessed by real-time central review using Response Evaluation Criteria in Solid Tumours version 1.1 in the intention-to-treat population. Cross-over was allowed. Adverse events in the as-treated population were assessed continuously during the active phase of treatment and then every 3 months. Patients and the public were not involved in the design, conduct, reporting, or dissemination plans of this research. This trial was registered with ClinicalTrials.gov, NCT02230176, and is closed to enrolment. FINDINGS: Between Feb 13, 2015, and July 16, 2020, 84 patients were enrolled and randomly assigned to the [Lu]Lu-dota-tate group (n=41) or the sunitinib group (n=43). 44 (52%) patients were women and 40 (48%) were men. Median follow-up was 72·5 months (IQR 61·4-88·4). Progression-free survival rate at 12 months was 33 (80·5% [90% CI 67·5-89·9]) of 41 patients in the [Lu]Lu-dota-tate group versus 18 (41·9% [29·1-55·5]) of 43 patients in the sunitinib group. Grade 3-4 adverse events occurred in 18 (44%) of 41 patients in the [Lu]Lu-dota-tate group and 31 (72%) of 43 patients in the sunitinib group. The most common grade 3-4 adverse events for all treatment groups were neutropenia (two [5%] of 41 in the [Lu]Lu-dota-tate group vs 13 [30%] of 43 in the sunitinib group) and hypertension (four [10%] in the [Lu]Lu-dota-tate group vs eight [19%] in the sunitinib group). Drug-related serious adverse events occurred in six (15%) patients in the [Lu]Lu-dota-tate group (transaminase increase, neutropenia, thrombosis, and fever) and ten (23%) in the sunitinib group (gastrointestinal, general disorders, and sepsis). There was a 10·3-point (95% CI 2·4-18·2) difference in the Global Health Status score between the two groups in favour of [Lu]Lu-dota-tate. Late adverse events (grade 2 or worse) were reported in 24 (60%) patients in the [Lu]Lu-dota-tate group and in three (43%) of seven patients in the sunitinib group. One treatment-related death (acute leukaemia) occurred in the [Lu]Lu-dota-tate group. INTERPRETATION: Using sunitinib as an internal control, our results show clinically significant antitumour efficacy of [Lu]Lu-dota-tate in pretreated, progressive, somatostatin receptor-positive, metastatic pancreatic neuroendocrine tumours, and a better quality of life during the treatment phase. Late adverse events were reported in the [Lu]Lu-dota-tate group that might affect the tolerance of subsequent lines of treatment. FUNDING: French Ministry of Health, through the National Institute for Cancer.
BACKGROUND: About 30% of men with localised prostate cancer undergoing radiotherapy with curative intent have disease recurrence associated with progression-related symptoms and substantial toxicity of salvage therapies....BACKGROUND: About 30% of men with localised prostate cancer undergoing radiotherapy with curative intent have disease recurrence associated with progression-related symptoms and substantial toxicity of salvage therapies. Previous studies with aglatimagene besadenovec (CAN-2409, hereafter referred to as aglatimagene) showed synergy with radiation and immune-mediated cytotoxicity in patients with prostate cancer. We aimed to assess whether addition of aglatimagene plus prodrug (valacyclovir) to standard-of-care external beam radiation therapy (EBRT) could improve disease-free survival in this population. METHODS: We conducted a phase 3, randomised, double-blind, placebo-controlled trial at 51 medical centres (26 community and 25 institutional or military) across the USA and Puerto Rico in patients with intermediate or high-risk prostate cancer. Patients aged at least 18 years who were planning to undergo EBRT and with an Eastern Cooperative Oncology Group score of 0-2 were eligible. Patients were randomly assigned (2:1) via central block-randomisation to receive either three courses of intraprostatic aglatimagene (5 × 10 viral particles) plus valacyclovir or placebo plus valacyclovir, with randomisation stratified by risk category and androgen deprivation therapy (ADT) use. Patients received standard-of-care EBRT (78 Gy in 2 Gy fractions) or hypofractionated EBRT (60 Gy in 3 Gy fractions or 70 Gy in 2·5 Gy fractions) with optional ADT. The primary endpoint was disease-free survival, defined as time-from-randomisation to prostate cancer recurrence or death in the intent-to-treat population (all randomly assigned patients). Safety was assessed in all individuals who received at least one injection. The trial is registered at ClinicalTrials.gov, NCT01436968, and long-term follow-up is ongoing. FINDINGS: Between Feb 21, 2012, and Sept 9, 2021, 745 men (591 [79%] White, 121 [16%] Black) were randomly assigned to receive aglatimagene plus valacyclovir (n=496) or placebo plus valacyclovir (n=249). After a median follow-up of 50·3 months (IQR 35·2-63·3), median disease-free survival was not reached (95% CI 121·78 to not reached) in the aglatimagene plus valacyclovir group versus 86·1 (IQR 29·7-143·0) months in the placebo plus valacyclovir group (hazard ratio 0·70, 95% CI 0·52-0·94; p=0·016). Treatment-emergent adverse events (TEAEs) of grade 3 or worse occurred in 40 (8%) of 479 patients in the aglatimagene group and 17 (7%)of 232 patients in the placebo group. The most common TEAE of grade 3 or worse was acute kidney injury in both the aglatimagene group (nine [2%] of 479 patients) and the placebo group (four [2%] of 232 patients). Serious adverse events occurred in 28 (6%) of 479 patients in the aglatimagene group and 17 (7%) of 232 in the placebo group. Treatment-related serious adverse events occurred in eight (2%) patients in the aglatimagene group (four acute kidney injury, two pyrexia, and one each influenza-like symptoms and urinary retention) and five (2%) in the placebo group (four acute kidney injury, and one each increased creatinine levels and skin rash; one patient reported two serious adverse events). No treatment-related deaths were reported. INTERPRETATION: Aglatimagene plus valacyclovir was associated with longer disease-free survival than placebo plus valacyclovir when added to standard of radiotherapy for the treatment of localised prostate cancer, offering a meaningful benefit without increasing clinically significant toxicity. FUNDING: Candel Therapeutics and US National Institutes of Health.
BACKGROUND: We quantified trends and heterogeneity in lung cancer burden attributable to high fasting plasma glucose (HFPG) among women aged ≥50 years (used as a population-level proxy for postmenopausal status) globally...BACKGROUND: We quantified trends and heterogeneity in lung cancer burden attributable to high fasting plasma glucose (HFPG) among women aged ≥50 years (used as a population-level proxy for postmenopausal status) globally and across BRICS countries from 1990 to 2021. METHODS: HFPG-attributable lung cancer deaths and DALYs for women ≥50 years were obtained from GBD 1990-2021. Burden was summarized as numbers and age-standardized rates (ASR) per 100,000, stratified by age, SDI quintile, and country. Trends were assessed using EAPC from log-linear regression. RESULTS: Global HFPG-attributable deaths and DALYs increased markedly from 1990 to 2021, with rising ASR (global EAPC 1.21; 95% CI, 1.11-1.31). A strong age gradient was observed; EAPC increased from 0.53% (50-54 years) to 3.65% (≥95 years). In 2021 the DALYs ASR peaked in the 75-79-year group (59.38 per 100,000). High-SDI settings consistently had the highest ASR and increasing burden. In BRICS, DALY ASR increased in all five countries with substantial heterogeneity: India showed the fastest increase (EAPC 3.05; 95% CI, 2.91-3.19), followed by South Africa (2.82; 2.64-3.00) and Brazil (2.36; 2.31-2.42), while China showed the smallest increase (0.87; 0.70-1.03). CONCLUSIONS: HFPG-attributable lung cancer burden in women aged ≥50 years rose substantially from 1990 to 2021, with disproportionate growth in older ages and clear SDI/BRICS differences, supporting integrated metabolic prevention within cancer control and healthy aging strategies.
Liu KJ, Huang LX, Jiang GM
… +7 more, Guo NN, Tan QL, Cai YM, Chen SY, Du W, Fang NX, Jia J
Clin Med Insights Oncol
· 2026 · PMID 42222664
·
Full text
BACKGROUND: Dacomitinib has demonstrated superior efficacy compared with first-generation tyrosine kinase inhibitors (TKIs) in patients with epidermal growth factor receptor (EGFR) exon 21-mutated non-small-cell lung can...BACKGROUND: Dacomitinib has demonstrated superior efficacy compared with first-generation tyrosine kinase inhibitors (TKIs) in patients with epidermal growth factor receptor (EGFR) exon 21-mutated non-small-cell lung cancer (NSCLC). However, the standard 45 mg dose often leads to a high incidence of grade 3 and 4 toxicities, limiting its clinical application. This study aimed to evaluate the preliminary efficacy and safety of a proactive low-dose dacomitinib strategy as first-line treatment. METHODS: This retrospective cohort study analyzed data from 31 patients with EGFR exon 21-mutated advanced NSCLC consecutively enrolled between August 2019 and April 2023, who initiated dacomitinib at 15 or 30 mg/d. A comparative cohort of 35 patients receiving first-generation EGFR-TKIs was also included. Initial dose selection was based on clinical judgment regarding patient age, comorbidities, and performance status. The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline. RESULTS: The objective response rate (ORR) in the low-dose dacomitinib group was 67.7%, higher than that observed in the first-generation EGFR-TKI group ( = .009). Subgroup analysis showed ORRs of 75% and 60% in the 15 mg and 30 mg cohorts, respectively ( = .389). The median progression-free survival (PFS) in the low-dose dacomitinib group was 14.2 months (95% confidence interval [CI] = 12.4-15.9 months). Compared with first-generation EGFR-TKIs, low-dose dacomitinib was associated with significantly prolonged PFS (HR = 0.43, 95% CI = 0.25-0.72; = .001). No significant difference in PFS was observed between the 15 mg and 30 mg groups (HR = 0.81, 95% CI = 0.37-1.76; = .594). While grade 1 and 2 toxicities were common, the 15 mg group exhibited a significantly lower incidence of grade 3 and 4 rash compared with the 30 mg group (0% vs 33.3%). CONCLUSIONS: Initial low-dose dacomitinib demonstrated promising efficacy with an improved safety profile in patients with EGFR exon 21-mutated NSCLC. These findings support the feasibility of a dose-optimization strategy, although further prospective studies are warranted.
Xu G, Liu C, Xue J
… +5 more, Chen J, Zou Z, Mo S, Zhou Z, Zhan X
Clin Med Insights Oncol
· 2026 · PMID 42222663
·
Full text
BACKGROUND: Osteosarcoma (OS) is a malignant tumor originating in the bones, predominantly affecting children and adolescents, characterized by high aggressiveness and poor prognosis. Identifying new prognostic biomarker...BACKGROUND: Osteosarcoma (OS) is a malignant tumor originating in the bones, predominantly affecting children and adolescents, characterized by high aggressiveness and poor prognosis. Identifying new prognostic biomarkers is crucial for improving the diagnosis and treatment of OS. METHODS: In this study, we collected gene expression data from 88 OS samples from the UCSC Xena platform and normal tissue expression data from 396 Genotype-Tissue Expression (GTEx) samples. Prognosis-related genes were first screened by univariate Cox regression and then further selected using the Least Absolute Shrinkage and Selection Operator (LASSO) regression. Based on these candidate genes, non-negative matrix factorization (NMF) was used for molecular subtype identification, and the Kaplan-Meier analysis was applied to compare survival among subtypes. Tumor microenvironment and immune cell infiltration analyses were performed to characterize differences between risk groups. In addition, the expression patterns of key genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR), hematoxylin-eosin staining, immunohistochemistry, and immunofluorescence. RESULTS: Pyrroline-5-carboxylate reductase 1 (PYCR1) was consistently upregulated in OS and was associated with poor prognosis. In contrast, glycogen phosphorylase, muscle-associated (PYGM) showed analysis-level-dependent expression patterns: it was downregulated at the bulk transcriptomic and tumor cell levels compared with normal controls, whereas within the OS cohort, relatively higher PYGM expression was observed in the high-risk group. Tumor microenvironment and immune cell infiltration analyses revealed significant immune differences between high- and low-risk groups. Histological and protein-level assays further confirmed the presence and cellular localization of PYCR1 and PYGM in OS tissues. CONCLUSION: This study systematically identified and validated PYCR1 and PYGM as potential prognostic biomarkers for OS using integrated statistical and machine learning approaches. The PYCR1 showed a consistently tumor-promoting expression pattern, whereas PYGM demonstrated context-dependent expression changes across bulk tissue, risk-stratified tumor samples, and tumor cell lines, highlighting the biological complexity of metabolic biomarkers in OS.
Jiang Q, Yang AY, Mo GL
… +5 more, Mo LG, Deng T, Huang SN, Hou ST, Huang QR
Mol Ther Oncol
· 2026 Jun · PMID 42222348
·
Full text
Lower-grade glioma (LGG) is a highly heterogeneous disease, making accurate prognosis prediction and the development of precise, personalized treatment plans for patients challenging. The multi-omics data from patients w...Lower-grade glioma (LGG) is a highly heterogeneous disease, making accurate prognosis prediction and the development of precise, personalized treatment plans for patients challenging. The multi-omics data from patients with LGG were analyzed using 10 clustering algorithms to identify subgroups at very high resolution. Ten machine learning algorithms were subsequently integrated to develop a robust artificial intelligence model (AIM). We identified two cancer subtypes (CSs) linked to prognosis through multi-omics clustering. After screening 46 hub genes, we integrated 10 machine learning algorithms into 117 combinations to select the AIM with the highest average C-index. The gradient boosting machine (GBM)-based AIM outperformed previous prognostic signatures in nearly all cohorts. Patients in the low-AIM group had a better prognosis and greater sensitivity to immunotherapy, whereas those in the high-AIM group had a poorer prognosis and lower immunotherapy sensitivity. However, MG132 showed promise as a potential therapeutic agent. studies confirmed the oncogenic role of the hub gene in LGG cells; its knockdown reduced the proliferation, invasion, and migration of these cells. In summary, the AIM we developed is highly valuable for predicting the prognosis of patients with LGG and identifying those who are sensitive to immunotherapy.