bims-ovdlit 2026-06-07 papers

Issue of 2026–06–07
six papers selected by
Lara Paracchini, Humanitas Research

JAMA. 2026 May 30.

Cancer Diagnostic Delay Rates Associated With a Population-Based Screening Trial Evaluating a Cell-Free DNA Multicancer Early Detection Test.

Sean Mann, Pedro Nascimento de Lima, Joshua Eagan, Agne Ulyte, Beth Ann Griffin.

Importance: Clinical trials evaluating population-based screening tests or other interventions likely to affect care delivery in real-world settings often do not consider spillover effects, such as whether the intervention rollout affects access to limited health care services.
Objective: To examine whether regional participation in a population-based screening trial (NHS-Galleri) of a cell-free DNA-based multicancer early detection (MCED) test was associated with changes in cancer diagnostic delay rates.
Design, Setting, and Participants: Cross-sectional study of all 21 cancer alliance regions in England, 8 of which participated in the population-based MCED screening trial. An event study using difference-in-differences design evaluated changes from 6 months before (April 2021) to 3 years after trial start (September 2024).
Exposures: Regional participation in the population-based MCED screening trial.
Main Outcomes and Measures: The primary outcome was diagnostic delay rates (percentage of patients referred for suspected cancer evaluation taking longer than 28 days to reach diagnostic resolution), a surrogate measure for system-level spillover effects; the secondary outcome was patient referral rates. Analysis focused on a primary group of 3 cancer types (head and neck, lung, and upper gastrointestinal) that were identified in the trial protocol and were not subject to routine screening.
Results: Overall, 1 875 236 patient referrals for suspected head and neck, lung, or upper gastrointestinal cancers were recorded across all 21 regions. In the first 6 months of the population-based screening trial, diagnostic delay rates increased in participating regions (28.6% before trial start and 29.6% after) and decreased in nonparticipating regions (28.9% to 26.3%), an adjusted difference-in-differences estimate of 3.4 percentage points (95% CI, 1.9-5.0; P < .001). This increase persisted during the second 6-month period (adjusted difference-in-differences estimate of 4.8 percentage points [95% CI, 1.9-7.7; P = .003]) and was no longer statistically significant thereafter. Patient referral rates for suspected head and neck, lung, and upper gastrointestinal cancers were also higher in participating regions in the first 6 months (adjusted difference-in-differences estimate of 23.8 per 100 000 population [95% CI, 0.9-46.8; P = .04]).
Conclusions and Relevance: Regional participation in a population-based MCED screening trial was associated with a modest increase in diagnostic delay rates for patients referred for suspected head and neck, lung, and upper gastrointestinal cancers. This increase is unlikely to have materially affected interpretation of the MCED screening trial primary findings. Future trials of population-based screening interventions likely to affect demand for limited health care resources should consider monitoring for system-level spillover effects.

DOI: https://doi.org/10.1001/jama.2026.6803

Cell. 2026 Jun 04. pii: S0092-8674(26)00522-2. [Epub ahead of print]

Plasma signals of lung tumor promotion for molecular cancer prevention.

Tej Pandya, Maria Zagorulya, Michelle M Leung, Marcellus Augustine, Lydia Y Liu, Aino-Maija Leppä, Ulysse Baruchel, Sin Wi Ng, Tamara Klockner, Miriam Mugabo, Anthony J Griffen, Oleg Blyuss, Chrysante S Iliakis, Amalie Grenov, Kerstin Haase, David C Muller, Ka Hung Chan, Jincheng Wu, Vernon A Burk, Neil Wright, Alix Le Marois, Ekaterina Pazukhina, Sophia Ward, Hubert Slawinski, Marc Pelletier, Cian Murphy, Matthew D Park, Thomas Snoeks, Alejandro Suarez-Bonnet, Simon L Priestnall, Alexandros Hardas, Charlotte Grieco, Ami Archer, Alpkaan Celik, Alejandro Jimenez-Sanchez, Rachel Scott, Hana Zahed, Léa Montégut, Rafael Meza, Clinton H Durney, Stephen Lam, Takahiro Karasaki, Roel C H Vermeulen, Huilei Xu, Pablo Serrano-Fernandez, Tatjana Crnogorac-Jurcevic, Usha Menon, Sophia Apostolidou, Alexey Zaikin, Richard Gunu, Harry J Whitwell, Zhe Huang, Zonglun Li, Xin Hu, Bo Zhu, Liming Li, María-Dolores Chirlaque, Marcela Guevara, P Martijn Kolijn, Aghiles Guenoun, Neeloffer Mookherjee, Mattias Johansson, Ziqiao Wang, Nilanjan Chatterjee, Chao-Hua Chiu, Zhengming Chen, Dana Pe'er, Erik Sahai, Saskia Freytag, Andreas Wack, Marc J Gunter, Miriam Merad, Jianjun Zhang, Christopher Carlsten, Pan-Chyr Yang, Hsuan-Yu Chen, Elizabeth A Platz, Lindsay M LaFave, Karl Smith-Byrne, Mariam Jamal-Hanjani, Kevin Litchfield, Nuno R Nene, Nicholas McGranahan, Eva Grönroos, William Hill, Clare E Weeden, Charles Swanton.

Predicting lung cancer risk would enhance prevention trials. Although the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial demonstrated reduced lung cancer incidence with interleukin (IL)-1β inhibition, the high number needed to treat (NNT) to prevent lung cancer limits its use in unselected populations. Using machine learning, we identified a 14-protein plasma signature predicting lung cancer more than 5 years before diagnosis. The signature, validated across eight cohorts, was elevated in current smokers and individuals exposed to particulate matter (PM) and linked to lung myeloid and alveolar cells. In epidermal growth factor receptor (EGFR)-driven lung adenocarcinoma, diverse epithelial lineages converged on a keratin8+/claudin4+ alveolar transitional state (KAC), whose transcriptional programs correlated with signature emergence. Components of the signature were induced by PM, oncogenic EGFR, or IL-1β, whereas IL-1β inhibition restrained PM-driven KAC expansion and early tumorigenesis. In CANTOS, the signature identified individuals who seemed to benefit more from anti-IL-1β therapy, lowering the NNT threshold and nominating circulating signals of tumor promotion for prevention.

Keywords: cancer cell of origin; cancer prevention; lung adenocarcinoma; lung cancer initiation; lung cancer prevention; lung cancer risk; plasma proteomics; secretory alveolar niche; tumor promotion

DOI: https://doi.org/10.1016/j.cell.2026.05.005

Ann Surg Oncol. 2026 Jun 02.

Predictive Features Specific to FIGO IIIA1 Ovarian Cancer: What Drives Prognosis.

Matteo Bruno, Davide Arrigo, Marco Paratore, Giustina Lopopolo, Valerio Gallotta, Andrea Rosati, Marco D'Indinosante, Anna Fagotti.

BACKGROUND: FIGO stage IIIA1 ovarian cancer, defined by lymph node-only metastasis, represents a biologically distinct pattern of spread within epithelial ovarian cancer. Patients with IIIA1 disease experience more favorable outcomes than those with peritoneal dissemination; however, the prognostic determinants within this subgroup remain incompletely defined and underexplored.
METHODS: A narrative review was conducted by using concept‑based searches. Eligible reports included those specifically addressing stage IIIA1 or providing extractable node‑positive subsets within stage III cohorts. Given heterogeneity in surgical eras, lymphadenectomy practices, and histologic composition, no quantitative pooling was performed.
RESULTS: Nodal size and the IIIA1(i)/(ii) subdivision did not consistently correlate with survival. In contrast, nodal topography showed signals of prognostic relevance in selected cohorts. The lymph node ratio (LNR) emerged as the most robust determinant of outcome. Systematic pelvic and para‑aortic lymphadenectomy, typically involving retrieval of ≥10-20 nodes, was linked to improved staging accuracy and long‑term survival. Tumor microenvironment features provided additional prognostic stratification, while IIIA1‑specific molecular data remained limited.
CONCLUSIONS: In FIGO IIIA1 ovarian cancer, nodal topography and burden represent the most reliable prognostic indicators. Systematic lymphadenectomy appears beneficial in appropriately selected patients, and tumor microenvironment features offer complementary risk stratification. Future studies should focus on genomically characterized IIIA1 cohorts to refine risk‑adapted surgical and maintenance strategies.

Keywords: Host inflammatory markers; Epithelial ovarian cancer; Lymph node ratio; Lymphadenectomy; Nodal metastasis; Para‑aortic lymph nodes; Prognostic factors

DOI: https://doi.org/10.1245/s10434-026-19895-5

Lancet Oncol. 2026 Jun 04. pii: S1470-2045(26)00284-6. [Epub ahead of print]

Cancer screening expands as implementation gaps remain.

Paul Adepoju.

DOI: https://doi.org/10.1016/S1470-2045(26)00284-6

Nat Commun. 2026 Jun 04.

The cumulative impact of passenger mutations on cancer development.

Akshatha Nayak, Candace S Y Chan, Ioannis Mouratidis, Ilias Georgakopoulos-Soares.

The traditional binary classification of somatic mutations in cancer as either drivers or passengers overlooks the potential cumulative impact of smaller-effect mutations. Here, we analyze more than 11,000 whole-genome-sequenced primary tumors across 3 cancer cohorts to assess the functional contribution of passenger mutations in cancer development. We find that in the absence of canonical driver mutations, passenger mutations in cancer genes are significantly enriched, exhibit higher predicted pathogenicity, and are associated with aberrant expression, splicing disruption, altered transcription factor binding, and clinical outcomes that resemble those in the presence of driver mutations. The accumulation of passenger mutations in tumor suppressor genes correlates with significantly reduced expression and poorer prognosis, suggesting that progressive mutational burden may contribute to gradual impairment of tumor suppressor function, mirroring the functional outcomes of driver mutations. Together, these results support a continuum model of mutational impact, where the collective influence of passenger mutations contributes to oncogenesis and clinical outcomes. This work advocates for integrative cancer models that incorporate all somatic mutations to more accurately reflect the complexity of tumor evolution.

DOI: https://doi.org/10.1038/s41467-026-73930-3