New survey highlights the role of clinical practice guidelines to improve care for patients with rare cancers

 Results from a recent ESMO (European Society for Medical Oncology) and EURACAN (European Reference Network to Cancers) had led to a "call for policy action to standardize care pathways for rare cancers after analysis links guidance adherence to patient survival").  According to the survey, conducted between September - October 2025, patients with rare malignancies equate to 650,000 new cases per year, representing 24% if all cancer diagnoses across Europe.  

ESMO and EURACAN thus propose the following actions: 

• Centralize rare cancer surgeries in accredited centres  
• Enforce mandatory multidisciplinary decision-making and time-critical standards throughout patient diagnosis, treatment, and follow-up
• Track adherence to established Clinical Practice Guidelines via national dashboards

Click here to learn more

Overall survival not substantially improved with CDK4/6 inhibitors used in first- compared with second-line treatment in Patients with HR-positive, HER2-negative advanced breast cancer

 Findings from SONIA, a phase III Dutch study comparing "the sequence of an aromatase inhibitor plus CDK4/6 inhibitor as first-line treatment followed by fulvestrant as second-line treatment (CDK4/6 inhibitor first-line group") did not improve overall survival compared with second-line treatment. Rather, this treatment regimen increased treatment-related and financial toxic effects in patients with HR-positive HER-2 negative advanced breast cancer.  Following an analysis of 1050 patients enrolled in SONIA, median overall survival was 47.9 months with first-line CDK4/6 inhibitor and 48.1 months with second-line CDK4/6 inhibitor  

To learn more about the SONIA study, click here. 

Sources mentioned: 

• Wortelboer N, van Ommen-Nijhof A, Konings IR, et al. Overall Survival With First-Line vs Second-Line CDK4/6 Inhibitor Use in Advanced Breast Cancer A Randomized Clinical Trial  JAMA Oncology; Published online 19 February 2026. doi: 10.1001/jamaoncol.2025.6585
• 
  
• Valenza C, Burstein HJ. Lessons From the SONIA Trial on Timing of CDK4/6 Inhibitors in Advanced Breast Cancer—The Sooner, the Better? JAMA Oncology; Published online 19 February 2026. doi: 10.1001/jamaoncol.2025.6345

Research unlocks insights into lung cancer evolution from electronic medical records

 A recently completed study at the University Hospital of Toulouse, France emphasized the benefits of a "domain-specific natural language processing (NLP) pipeline...in extracting clinically meaningful information from diverse clinical documents of patients with non-small cell lung cancer."  Following an analysis of 1,028 discharge summaries and external consultation letters from 120 non-small cell lung cancer patients undergoing oral targeted therapy, "the domain-adapted NLP solution achieved an F1 score of 79.7% for tumor evolution concept extraction and 62.0% for temporality alignment." 

To read more about this study, click here. 

Source mentioned: 

Vinot, C., et al. "Automated extraction of temporalized tumor evolution from oncology EMRs using natural language processing." ESMO Real World Data and Digital Oncology 11 (2026): 100660.

Worse survival among patients diagnosed with cancer during first 2 years of the COVID-19 pandemic

A recently published U.S. population-based cohort study found "significant reductions in 1-year cause-specific survival rates among patients diagnosed with both early-stage and late-stage cancer in 2020 and 2021."   Compared to cancer patients diagnosed between 2015-2019, patients with a diagnosis of esophageal cancer (early-stage, 3.67%-3.89%), colorectal cancer (0.78%-1.08%) and prostate cancer (late-stage, 0.64%-0.77%)), were noted to have the largest site-specific survival reductions during the first 2 years of the COVID-19 pandemic.  The authors of this cohort study thus propose that "swift action should be taken to increase cancer screening, rebuild healthcare capacity, and improve patient communication." 

Source mentioned:

Burus T, Damgacioglu H, Huang B, et al. Survival of Patients Diagnosed With Cancer During the COVID-19 Pandemic . JAMA Oncology; Published online 5 February 2026. doi:10.1001/jamaoncol.2025.6332

Trustworthy and explainable AI – a key to equitable oncology

Trustworthiness of artificial intelligence (AI) applications and validating data analysis in cancer care was recently discussed at the ESMO Women for Oncology Forum.  

Click here to read about an interview with Alessandra Pedrocchi, founder of the laboratory for oncology at the National Cancer Institute in Milan.  

RAS inhibition in pancreatic cancer

 The Experimental Oncology Group at the National Research Centre (CNIO) in Madrid has recently unveiled findings from genetically engineered mice afflicted with pancreatic ductal adenocarcinoma.  The mice "underwent rapid apoptotic cell death that resulted in complete tumour regressions and remained tumour-free for over 200 days post-treatment."  While results of these animal studies are promising towards determining therapeutic vulnerabilities of pancreatic cancer, Dr. Ben Westphalen, chair of the European Society of Medical Oncology (ESMO) Precision Oncology Task Force cautions that these results cannot yet be applied to patient care. More work is needed to determine side effects of the triple combination therapy in humans. 

Click here to learn more about this news story. 

Structured exercise enters ESMO guidelines for colon cancer as recommended treatment

 The European Society of Medical Oncology (ESMO) has released an update to their colon cancer guidelines, whereby "physical activity, when personalized and delivered as a structured program" is now recommended...for patients with resected stage III or high-risk stage II colon cancer." Over a period of 3 years, 889 stage III or stage II high-risk colon cancer patients enrolled in the CHALLENGE study saw significant improvements in disease-free survival over 5 years (80.3%) compared to 73.9% of patients who received health education materials and standard surveillance with no structured exercise program. 

Click here to learn more about the CHALLENGE study. 

European parliament adopts its position on the Critical Medicines Act, strengthening security of cancer care in Europe

 The European Parliament recently adopted first-reading of the Critical Medicines Act, expanding "collaborative procurement and solidarity mechanisms, explicitly acknowledging their relevance to specialized treatments, including in oncology."  Now entering interinstitutional negotiations, the Critical Medicines Act ensures that continuity of care for cancer patients will remain a key focus area for European Union health policy. 

To read more about the Critical Medicines Act, click here. 

Biological mechanism enabling breast cancer to spread to the brain uncovered

Researchers from the Gray Faculty of Medical and Health Sciences in Tel Aviv, in partnership with researchers in 14 laboratories in Israel, USA, Italy, Germany, Poland, and Austria, have uncovered "a mechanism that allows breast cancer to send metastases to the brain - a highly lethal occurrence for which there is currently no effective treatment."   Following injection of cancer cells with or without functional gene P53, results indicated that "cells with disrupted P53 activity thrived much more." These findings are crucial towards developing new drugs and personalized monitoring for early detection and treatment of brain metastases. 

Click here to learn more. 

Source: 

Laue K, Pozzi S, Zerbib J, et al. p53 inactivation drives breast cancer metastasis to the brain through SCD1 upregulation and increased fatty acid metabolism. Nat Genet. Published online December 29, 2025. doi:10.1038/s41588-025-02446-1

Grey Horizon postings will resume week of January 5, 2026.

 To all Grey Horizon readers, 

Thank you for your continued support of this blog.  Postings will resume the week of January 5, 2026. 

Season's Greetings and all the best for the new year.  

Neoadjuvant immunotherapy and understanding anticancer immunity

 Study results currently being presented at the ESMO Immuno-Oncology Congress (held in London, England, December 10-12, 2025) showcase the rise of neoadjuvant immunotherapy studies "from small investigator-led window-of-opportunity...to standard of care paradigms across various tumour types."  Using triple-negative breast cancer and early-stage non-small cell lung cancer as examples, treating patients before surgery provides "access to living tumour ecosystems responding - or not- to immunotherapy." 

Click here to read more and note the Immuno-Oncology Congress program details below: 

Mulder K, et al. Residual tumour immune microenvironment shapes relapse risk in early TNBC following immunotherapy. ESMO Immuno-Oncology Congress 2025 - Abstract 328MO

Nijman H, et al. Neoadjuvant immune checkpoint inhibition skews the B cell response in mismatch repair deficient endometrial cancer. ESMO Immuno-Oncology Congress 2025 - Abstract 329MO

Pircher A, et al. Neoadjuvant induction with pembrolizumab (Pembro) plus lenvatinib (Len) in resectable early-stage NSCLC impacts the tumor microenvironment (TME): Clinical results including multi-omic deconvolution of the TME from the INNWOP01 study. ESMO Immuno-Oncology Congress 2025 - LBA1

Going beyond protocol is key for young people with cancer

 Recently, at the ESMO Asia Congress 2025, emphasis was placed on the diagnosis of cancer in adolescents and young adults (AYA), which "varies considerably by age, sex, and socioeconomic status." While Western countries are increasingly dedicating research pursuits to AYA cancer care, "countries with low and low-middle sociodemographic indices" carry high AYA cancer burden. 

Click here to learn more: 

ESMO Publishes First-Ever Guidance on Validation Requirements for AI-Based Biomarkers in Oncology

 The European Society for Medical Oncology (ESMO) has released the Basic Requirements for AI-Based Biomarkers in Oncology (EBAI) framework, "the first comprehensive guidance for the safe, trustworthy and effective integration of AI-derived biomarkers in cancer care."  The framework provides guidance for developers, clinicians, regulators and healthcare institutions on means of integrating digital technologies in cancer care.  

To view the complete framework, click here. 

Source mentioned: 

ESMO Basic Requirements for AI-based Biomarkers In Oncology (EBAI)
DOI: 10.1016/j.annonc.2025.11.009

 

ESMO launches first congress on artificial intelligence and digital oncology: a milestone in shaping the future of cancer care

The European Society for Medical Oncology (ESMO) recently launched the inaugural Congress on Artificial Intelligence and Digital Oncology, taking place in Berlin this week, November 12-14, 2025.  With over 1100 participants scheduled to attend, the conference program will include discussions of: 

• Multimodal AI for clinical decision support, showcasing applications in molecular tumour boards and real-world data integration.
• AI-based biomarkers for precision oncology, featuring discussions on validation frameworks and predictive modelling, including the announcement of the imminent publication of the ESMO Basic Requirements for AI-based Biomarkers in Oncology (EBAI) framework
• Generative AI and large language models, with keynote lectures featuring speakers from Google DeepMind and Harvard Medical School.
• Digital health in practice, exploring wearable technologies, remote monitoring, decentralised trials.
• Ethics, regulation, and patient perspectives, addressing trust, explainability and the societal implications of AI in oncology.

To learn more about this conference, click here. 

Rucaparib monotherapy provides long-term benefit as first-line maintenance for patients with advanced ovarian cancer with and without HRD

 Results of ATHENA-MONO/GOG-3020/ENGOT-ov45, a phase III trial investigating rucaparib as a monotherapy in first-line maintenance treatment for advanced ovarian cancer patients, who presented in poster format at the recent ESMO (European Society of Medical Oncology) conference in Berlin, Germany. The study concluded that "sustained long-term improvement with rucaparib was observed in all subgroups examined regardless of HRD or risk status, with 29% of patients in the rucaparib group remaining progressing free at 5 years." 

To read more about this study, click here. 

Sources mentioned: 

• Kristeleit RS, Ghamande S, Lisyanskaya AS, et al. Rucaparib maintenance for newly diagnosed advanced ovarian cancer: interim overall survival, progression-free survival, and safety at 5 years of follow-up from the phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 study . Annals of Oncology; Published online 18 October 2025. DOI: 10.1016/j.annonc.2025.10.007  
• 
  
• Abstract 1073P – Kristeleit RS, Ghamande S, Lisyanskaya AS, et al. 5-year progression-free survival (PFS) with rucaparib (RUCA) maintenance in patients with newly diagnosed advanced ovarian cancer in ATHENA-MONO (GOG-3020/ENGOT-ov45) . Annals of Oncology 2025;36(Suppl 2):S721-722.  

Antitumour activity of patritumab deruxtecan in heavily pretreated patients with active brain metastases of breast cancer and NSCLC

 Results from TUXEDO-3, a prospective multicentre open-label single-arm multicohort phase II study were recently published on The Lancet Oncology.  TUXEDO-3 evaluated patritumab deruxtecan in 3 patient cohorts: 1. patients with metastatic breast cancer with untreated or progressing brain metastases after local treatment"; 2. "patients with advanced non-small cell lung cancer with untreated or progressing brain metastases after local treatment" 3. "patients with treatment-naive leptomeningeal disease (LMD) or LMD progressing after radiotherapy from any advanced solid tumour."   

To read more about the TUXEDO-3 study, click here. 

Sources mentioned: 

• Bartsch R, Marhold M, Garde-Noguera J, et al. Patritumab deruxtecan (HER3-DXd) in patients with active brain metastases of breast cancer (TUXEDO-3): a multicentre, single-arm, phase 2 trial . The Lancet Oncology 2025;26(11):1467-1478.  
• 
  
• Fuereder T, Garde-Noguera J, García-Mosquera JJ, et al. Patritumab deruxtecan (HER3-DXd) in patients with active brain metastases of non-small cell lung cancer (TUXEDO-3): a multicentre, single-arm, phase 2 trial . The Lancet Oncology 2025;26(11):1454-1466.   
• 
  
• Jerzak KJ, Leighl NB, Sahgal A. Systemic therapy for brain metastases: a changing landscape . The Lancet Oncology 2025;26(11):P1398-1400. 

Rethinking the limits of tissue-agnostic cancer therapy

A recent editorial published in the ESMO Daily Reporter raises questions about the impact of precision medicine in personalized cancer care, considering that "patients are still largely treated according to the primary organ where their cancer originates."  Tumour-agnostic agents, drugs approved if cancer cells cause gene or protein changes, no matter where in the body the cancer originated, calls for physicians and patients to engage in precision medicine, "a first step toward a common understanding...in which tissue-agnostic development should be preferred to conventional trials."  

Click here to learn more. 

Thymic health linked to cancer patients’ response to immunotherapy

A recent international study focused on immune checkpoint inhibitor treatment has shown that higher thymic health was associated with a 35% lower risk of cancer progression in a group of 1200 non-small cell lung cancer patients.    While further validation of this finding is required, thymic health "could serve as a non-invasive biomarker of adaptive immune competence in a range of different cancers." 

To learn more about this study, click here. 

Source mentioned: 

Abstract 108O - ‘Thymic health is associated with immunotherapy outcomes in patients with cancer ‘, presented by Dr Simon Bernatz during Proffered Paper session 1: Basic science & Translational research on Saturday, 18 October, from 10:15 to 11:45 (CEST) in Hall 5.2 (Nuremberg Auditorium)  

Increased risk of haematologic malignancies among children and adolescents exposed to radiation from medical imaging

 Findings from Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) a cohort study of 3 700 000 children from Canada and the U.S. found a "significant dose-response relation between cumulative radiation dose to bone marrow and haematologic malignancies risk." The RIC study further found that susceptibility of children to radiation-induced cancer is high due to longer life expectancy compared to adults.  In addition, a European EPI-CT study indicates a "50% higher risk among children undergoing two or three CT scans than among those undergoing one scan." 

To read more about this study, click here. 

Source mentioned: 

• Smith-Bindman R, Alber SA, Kwan ML, et al. Medical Imaging and Pediatric and Adolescent Hematologic Cancer Risk . NEJM; Published online 17 September 2025. DOI: 10.1056/NEJMoa2502098
• 
  
• Morton LM. Studying Cancer Risks Associated with Diagnostic Procedures — Interpret Wisely . NEJM; Published online 17 September 2025. DOI: 10.1056/NEJMe2511613

Study presents an AI-guided approach to target cancer antigens

 A recent study published in Science provides proof-of-concept that "generative artificial intelligence can offer a valid alternative approach to design precise, functional, and adaptable peptide binders capable of redirecting T cell responses against cancer antigens".  While the authors are optimistic regarding AI-guided methods, they do caution that further investigation is required to determine long-term impact on immune cell function. 

To learn more about this study, click here. 

Source mentioned: 

Johansen KH, Wolff DS, Scapolo B, Fernández-Quintero ML, Risager Christensen C, Loeffler JR, Rivera-de-Torre E, Overath MD, Kjærgaard Munk K, Morell O, Viuff MC, Lacunza I, Damm Englund AT, Due M, Gharpure A, Forli S, Rodriguez Pardo C, Tamhane T, Qingjie Andersen E, Haldrup Björnsson K, Fernandes JS, Voss LF, Thumtecho S, Ward AB, Ormhøj M, Reker Hadrup S, Jenkins TP. De novo-designed pMHC binders facilitate T cell-mediated cytotoxicity toward cancer cells. Science. 2025 Jul 24;389(6758):380-385. doi: 10.1126/science.adv0422. Epub 2025 Jul 24. PMID: 40705893.

De-escalated radiotherapy after surgery in HPV-associated oropharyngeal squamous cell carcinoma

A recently published phase III trial in Lancet Oncology, lower doses of adjuvant radiotherapy plus docetaxel "were associated with reduced toxicity and need for percutaneous endoscopic gastrostomy", impacting a patient's quality of life.  Following 194 patients with stage III-IV HPV-associated oropharyngeal squamous cell carcinoma indicated grade 3 or higher toxic effect "of at least possible attribution to treatment...3 months after radiotherapy.." at 3% in the de-escalated adjuvant radiotherapy group compared to 11% in the standard of care group. 

To read more about this study, click here. 

ESMO campaigns against the use of ‘Low-Alcohol’ labelling in response to council agreement on EU’s wine package

The European Society for Medical Oncology (ESMO) in partnership with the European Alliance on Alcohol (EHAA) has issued a statement against the use of the phrase 'low alcohol' "for beverages containing more than 1.2% ABC and for transparent information on the health risks of consuming alcohol."   Alcohol consumption increases the risk of developing at least 7 types of cancer, leading the International Agency for Research on Cancer (IARC) classifying alcohol as a group one carcinogen. 

To read the complete position statement, click here. 

ESMO urges EU policymakers to protect the wellbeing of the oncology workforce

 The European Society for Medical Oncology (ESMO) has produced a new health workforce crisis plan, stressing "the urgent need for dedicated legislation, strategies, and resources to safeguard the sustainability of the oncology workforce."  Proposed measures to alleviate burnout, a leading work-related psychosocial risk, includes adequate staffing levels, greater control over workload, flexible hours, reduced overtime, sufficient leave entitlement, enhanced career development, job security, training opportunities, and long-term workforce retention strategies. 

Click here to read the full workforce crisis plan. 

Arsenic trioxide in combination with all-trans retinoic acid for the treatment of newly diagnosed patients with high-risk APL

 Results from APOLLO, a randomized phase III study, indicated that a "near-chemotherapy free treatment of arsenic trioxide in combination with all-trans retinoic acid plus low-dose idarubicin significantly improved outcomes of patients with newly diagnosed, high-risk acute promyelocytic leukaemia."  A median follow-up of 37 months indicated that 2-year event free survival was 88% in patients receiving all-trans retinoic acid and arsenic trioxide vs. 71% in patients receiving all-trans retinoic acid plus anthracycline-based chemotherapy. 

To read more about the APOLLO study, click here. 

Sources mentioned: 

• Platzbecker U, Adès L, Montesinos P, et al. on behalf of the SAL, AMCL-CG, AML-SG, OSHO, PETHEMA, HOVON and GIMEMA study groups. Arsenic Trioxide and All-Trans Retinoic Acid Combination Therapy for the Treatment of High-Risk Acute Promyelocytic Leukemia: Results From the APOLLO Trial . JCO; Published online 18 August. DOI: https://doi.org/10.1200/JCO-25-00535
• 
  
• Iland HJ. APOLLO: Optimizing the Treatment of High-Risk Acute Promyelocytic Leukemia With All-Trans Retinoic Acid and Arsenic Trioxide While Minimizing the Role of Chemotherapy . JCO; Published online 18 August 2025. DOI: https://doi.org/10.1200/JCO-25-01496

Blog postings will resume in September 2025

 Dear Grey Horizon readers, 

Thank you for your continued support of this blog.  Postings will resume in September 2025.  

No survival benefit from adding adjuvant chemotherapy to endocrine therapy in older women with a genomic grade index high-risk ER-positive, HER2-negative breast cancer

Findings from ASTER 70s, a phase III randomized superiority study conducted on women 70 years or older "with a genomic grade index (GGI) high-risk oestrogen receptor (ER)-positive, HER2-negative breast cancer" identified no statistically significant effect of adding adjuvant chemotherapy to the prescribed treatment plan.  While the authors od this study admit that more evidence of genomic profiling is needed to determine "whether chemotherapy is necessary for older patents with ER-positive tumours", ASTER 70s has provided little evidence on the benefit of adjuvant chemotherapy for older breast cancer patients. 

To read more about this study, click here. 

Sources mentioned: 

• Brain E, Mir O, Bourbouloux E, et al. for the GERICO&UCBG/Unicancer. Adjuvant chemotherapy and hormonotherapy versus adjuvant hormonotherapy alone for women aged 70 years and older with high-risk breast cancer based on the genomic grade index (ASTER 70s): a randomised phase 3 trial . The Lancet 2025;406(10502):p489-500.
• 
  
• Linn SC, Hilbers FS. Balancing quality and quantity of life in older patients with breast cancer . The Lancet 2025;406(10502):P422-424.

ESMO joins the European Health Alliance on Alcohol (EHAA) to reduce preventable cancer cases linked to alcohol use

The European Society for Medical Oncology (ESMO) has joined the European Health Alliance on Alcohol (EHAA).  Classified as a group 1 carcinogen by the International Agency for Research on Cancer (IARC), consumption of alcohol has been linked to liver, breast, mouth, and colorectal cancer.  As a result of joining the alliance, ESMO will collaborate with EHAA "on devising and promoting evidence-based alcohol policies aimed at preventing cancer." 

Click here to read more about the European Health Alliance on Alcohol. 

Savolitinib plus osimertinib show a high response in EGFR-mutated NSCLC progressed on first-line osimertinib due to MET-driven resistance mechanisms

 Results of SAVANNAH, a phase II study comprised of "one of the largest datasets evaluating an oral MET tyrosine kinase inhibitor in EGFR-mutated non-small cell lung cancer" was recently reported in Annals of Oncology.   Considered to be the first study to use a novel biomarker-based patient selection strategy, results from SAVANNAH "demonstrate efficacy benefit with a chemotherapy-free, orally administered, combined EGFR and MET targeted treatment regimen." 

To learn more about the SAVANNAH study, click here. 

Source mentioned: 

de Marinis F, Kim TM, Bonanno L, et al. Savolitinib plus osimertinib in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer with MET overexpression and/or amplification following disease progression on osimertinib: primary results from the phase II SAVANNAH study . Annals of Oncology 2025;36(8):P920-933. DOI: https://doi.org/10.1016/j.annonc.2025.04.003

HER2 immunohistochemistry testing may not be needed in all solid tumours

 Results from a large-scale cohort study conducted on 65 000 patients with solid tumours undergoing pan-tumour HER2 immunohistochemistry (IHC) testing has shown that "upfront HER2 IHC testing may not be required for all tumour types, especially those that are rarely positive." 

The cohort study further revealed highest HER2 IHC 3+ rates in bladder cancer (13.9%), uterine serous carcinoma (13.6%), oesophago-gastric junction cancer (12.1%), breast cancer (7.8%), gastric adenocarcinoma (6.6%), and salivary gland cancer (6.5%); additional remaining cancer types were all found to have a HER2 IHC 3+ rate of 5% or less. 

To read more about this study, click here.  

Source mentioned: 

Bryant D, Feldman R, Abdulla F, et al. A Real-World Experience in Pan-Tumor Testing for HER2 IHC in More Than 65 000 Solid Tumors . JAMA Oncol; Published online 26 June 2025. doi: 10.1001/jamaoncol.2025.1791

Breastfeeding patterns and relation to breast cancer outcomes after early, hormone receptor-positive breast cancer

 Findings from POSITIVE, the largest known study evaluating "breastfeeding frequency, patterns, and relation to breast cancer outcomes in women previously diagnosed with early, hormone receptor-positive breast cancer" were recently unveiled in the Journal of Clinical Oncology.  According to data reported in the POSITIVE study, breastfeeding was not shown to be associated with a higher short-term rate of breast cancer related events, news particularly relevant to women planning pregnancy and breastfeeding after receiving a breast cancer diagnosis. 

To learn more about the POSITIVE study, click here. 

Source mentioned: 

Peccatori FA, Niman SM, Partridge AH, et al. for the International Breast Cancer Study Group and the POSITIVE Trial Collaborators. Breastfeeding After Hormone Receptor–Positive Breast Cancer: Results From the POSITIVE Trial . JCO; Published online 9 July 2025. DOI: https://doi.org/10.1200/JCO-24-02697