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A retrospective cohort study involving children born between 1996 and 2016 suggests a significant but small associated increased risk of hematologic cancer among those exposed to radiation from medical imaging.

MGUS is a common, asymptomatic plasma-cell disorder in older adults that can progress to cancer or systemic illness. Diagnosis warrants follow-up, but treatment is not required unless progression is confirmed.

Improvements in medical-imaging technology and approaches have substantively advanced diagnosis, screening, and treatment for a wide range of health conditions. Many medical-imaging applications confer clearly established benefits, yet some lack strong evidence or provide little gain (e.g., repeating initial diagnostic examinations). Long-standing concerns about overuse are illustrated by persistent variation...

In patients with provoked venous thromboembolism and ongoing risk factors, extended treatment with low-dose apixaban for 12 months resulted in a lower risk of recurrent VTE than placebo, with a low risk of major bleeding.

Among patients with chronic lymphocytic leukemia, undetectable MRD and progression-free survival were more common with ibrutinib–venetoclax than with ibrutinib alone or chemoimmunotherapy, with benefits sustained at 5 years.

For decades, the guidance was simple: treat a provoked venous thromboembolism (VTE) — one caused by a transient factor such as surgery, trauma, or immobility — for 3 to 6 months, stop, and move on.1 Safer anticoagulants and emerging evidence now challenge this long-held approach.2 Recurrence...

A 65-year-old man presented with a 4-month history of a rash and a 2-month history of diarrhea and weight loss. Examination showed a maculopapular eruption. CT revealed osteosclerosis of thoracic vertebral bodies.

Even with the most reticent patients, Dr. Kolhouse somehow uncovered the things that mattered most to them, discovering each one’s unique definition of a good day — and offering them more of those.

In patients with localized colorectal cancer and PIK3CA hotspot mutations in exon 9 or 20, daily low-dose aspirin resulted in a significantly lower recurrence rate than placebo.

Tumor lysis syndrome has evolved and become less predictable with the introduction of new cancer therapies. This review explores risk factors and causes of the syndrome, as well as strategies for treatment and prevention.

The painkilling, antipyretic, and antiinflammatory properties of aspirin have been known for centuries. The understanding that aspirin targets cyclooxygenase-1 (COX-1) (also known as prostaglandin-endoperoxide synthase 2 [PTGS1]) and COX-2 (also known as PTGS2), which are key enzymes required for prostaglandin synthesis, provided a rationale for using aspirin to treat thrombosis....

A 30-year-old woman presented with a 10-week history of painful skin nodules and a 6-week history of fevers and night sweats. A physical examination was notable for palpable subcutaneous nodules with overlying erythema.

The editors announce a new Perspective series that will critically evaluate strategies for reducing global tobacco consumption, with a focus on specific challenges and opportunities in low- and middle-income countries.

There is an urgent need for low- and middle-income countries to ensure equitable, affordable, and sustained access to tobacco-cessation medications at scale.

Many race-adjusted clinical tools have recently been scrutinized and replaced with race-neutral versions — efforts that have faced obstacles and generated contentious debate about the use of race in medicine.

A 93-year-old woman was evaluated by her primary care physician because of dyspnea. She had a history of aortic stenosis and atrial fibrillation and flutter. A diagnosis was made.

Despite high cancer-related mortality, health systems serving American Indian and Alaska Native populations offer only primary care. The University of Oklahoma is bridging the gap with oncology services.

In advanced non–small-cell lung cancer with EGFR mutations, amivantamab–lazertinib led to longer overall survival than osimertinib but was associated with an increased risk of adverse events of grade 3 or higher.

In patients with heparin-induced thrombocytopenia, pathogenic antibodies were found to be monoclonal, which challenges previous views of HIT as a polyclonal disorder and suggests new avenues for diagnosis and treatment.

China has recently emerged as an important player in new drug development — a field traditionally dominated by the United States and Europe. This shift has implications for global access to new medicines.

Dementia is a major public health challenge. 55 million people live with dementia worldwide. Alzheimer's disease accounts for 50–70% of cases, and around 69 million people with mild cognitive impairment due to Alzheimer's disease will develop dementia within a few years. With ageing populations and current trends in risk factors, these numbers are set to triple by 2050. Furthermore, the impact of Alzheimer's disease on caregivers—mostly women—is often neglected. Caregivers might experience emotional distress and negative effects on their health, relationships, and lives.

Foundational pharmacotherapy has transformed outcomes in heart failure with reduced left ventricular ejection fraction (HFrEF), and two large trials1,2 now aid in delineating where vericiguat, a soluble guanylate cyclase stimulator, could fit into the management of this condition. In the VICTORIA trial, which enrolled patients with recent worsening heart failure (defined as either a hospitalisation for heart failure within the previous 6 months or outpatient use of intravenous diuretics within the previous 3 months), vericiguat reduced the primary composite endpoint of cardiovascular death or first hospitalisation for heart failure—largely via fewer hospitalisations, without a clear effect on cardiovascular death.

The management of moderate-to-severe psoriasis has been revolutionised by biological therapies targeting cytokines such as tumour necrosis factor, interleukin (IL)-17, and IL-23. These agents offer high efficacy and durable disease control but come with notable limitations: parenteral administration, high production costs, and the need for cold-chain logistics. Icotrokinra (JNJ-77242113), an orally administered peptide targeting the IL-23 receptor, represents a substantial therapeutic advance, combining the immunological specificity and high efficacy of biologics with the convenience of oral dosing.

Type 1 diabetes remains a persistent health-care burden despite substantial advances in care. Its preclinical disease course proceeds through well characterised stages,1,2 but, despite this knowledge, clinical disease management remains centred on insulin replacement, rather than underlying disease modification. Partly prompted by US regulatory approval in 2022 of an immunotherapy to delay clinical disease onset,3 there has been renewed energy worldwide in testing disease-modifying immunotherapies in type 1 diabetes.

Discussions about how a government's policies affect health often focus on health ministries or agencies responsible for medical or public health services. This is certainly true in the USA, where concerns about health policy under the administration of US President Donald Trump are largely focused on the Department of Health and Human Services (HHS).

Does science face a research integrity crisis? Charles Piller, science journalist and author of Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer's (2025), certainly believes so. His book is an angry j’accuse against the Alzheimer's disease science community. He charges scientists with “exaggeration, hype, and sheer fakery and fraud”. He claims to have discovered “a scientific underworld of deceit and lies”. And he extrapolates his findings and arguments far beyond this one disease.

Experts warn that a decline in commitments to gender equity policies at many global health organisations risks progress in health. Sophie Cousins reports.

The Advisory Committee on Vaccine Practices’ recommendations for COVID-19 vaccination prompt questions and concern. Washington Correspondent Susan Jaffe reports.

Methanol poisoning of western tourists makes international headlines, but those most commonly affected are from countries where diagnosis and treatment options are limited. Sophie Cousins reports.

A quarter of the way into the 21st century, emerging from the most consequential pandemic in 100 years, public health finds itself in a tricky moment. Although there has been enormous progress in health and wellbeing worldwide, many countries remain dogged by far worse health indicators than they should have. In the USA life expectancy has taken about a 10-year setback, and the health of people continues to be characterised by inequities and inequalities, including major divides between socioeconomic and racial and ethnic groups.

Being a doctor is a treacherous business. I will never forget the medical school Dean, in his welcome address to my cohort of eager, new students, moving swiftly from cordial congratulations to a set of truly hair-raising statistics about our choice of career. With higher rates of divorce, depression, alcoholism, and even suicide, we should be under no illusions, he told us, that patients would not be our only clinical priority. As physicians, we would also have to take care of ourselves.

Innovative neuroscientist who advanced knowledge of spatial awareness and memory. Born in Dublin, Ireland, on March 27, 1970, she died of pneumonia in London, UK, on Jan 4, 2025, after contracting cancer of the spine, aged 54 years.

As the horizon for the Sustainable Development Goals (SDGs) approaches, progress towards target 3.4 —reducing premature mortality from non-communicable diseases (NCDs) by one-third—remains largely uneven and insufficient.1 Cardiovascular disease (CVD), cancers, diabetes, chronic respiratory diseases, and mental health conditions together account for more than 43 million deaths annually, with more than 40% occurring before the age of 70 years.2 Low-income and middle-income countries bear a disproportionate burden, with premature NCD mortality exceeding 50% in some parts of sub-Saharan Africa.

The Presidential Proclamation of June 4, 2025, barring entry to the USA to individuals from 12 nations has created an immediate and preventable crisis for the US health-care system.1 Although intended as a national security measure, its consequence is that, as of July 1, hundreds of accomplished international medical graduates (IMGs) who were already certified by the Educational Commission for Foreign Medical Graduates (ECFMG) and matched into US residency positions have been blocked from starting training.

Oesophageal cancer, a leading global cancer with more than 500 000 annual cases, poses a major clinical and public health challenge.1 Locally advanced oesophageal cancer exemplifies the tension between personalised and standardised care. Although neoadjuvant therapy followed by surgery remains the first-line approach, heterogeneous patient responses introduce clinical dilemmas: non-responders risk delayed access to effective treatment, whereas specific pathological complete responders might undergo unnecessary surgical intervention.

The Lancet recently published two important contributions on legal accountability.1,2 Both were triggered by the 2025 landmark advisory opinion from the International Court of Justice on climate change. These publications focused on judicial processes rather than non-judicial accountability, such as parliamentary oversight committees, UN human rights mechanisms, national human rights commissions, independent media, civil society organisations, citizen forums, and peoples’ tribunals.

The publication of the HARMONi-2 trial by Anwen Xiong and colleagues represents a substantial advancement in the treatment of PD-L1-positive non-small-cell lung cancer (NSCLC).1 However, we would like to draw attention to several methodological and interpretational concerns that warrant further discussion.

We appreciate the Correspondence from Mingyang Xue and Wenyi Jin, which raises valuable questions about the HARMONi-2 study.1

We congratulate Larissa I van der Windt and colleagues1 for their well-designed randomised controlled trial comparing atosiban to placebo in threatened preterm labour from 30+0 to 33+6 weeks of gestation. Their findings, however, raise two important questions.

In a recent issue of The Lancet, Larissa I van der Windt and colleagues reported the results from APOSTEL 8, a randomised clinical trial comparing atosiban to placebo in 752 participants with threatened preterm birth between 30+0 and 33+6 weeks of gestation.1 Although atosiban prolonged pregnancy beyond 48 h (78% vs 69%; relative risk [RR] 1·13 [95% CI 1·03–1·23]) and led to more completed courses of antenatal corticosteroids (76% vs 68%; RR 1·11 [95% CI 1·02–1·22]), atosiban did not improve neonatal outcomes.

We thank Lola Loussert and colleagues and Ruben Ramirez Zegarra and colleagues for their thoughtful responses to our study.1 Both Correspondences raise important questions regarding the standard regimen of antenatal corticosteroids, which is often comprised of two doses administered 24 h apart within 48 h.

Early Breast Cancer Trialists' Collaborative Group. Extending the duration of endocrine treatment for early breast cancer: patient-level meta-analysis of 12 randomised trials of aromatase inhibitors in 22 031 postmenopausal women already treated with at least 5 years of endocrine therapy. Lancet 2025; 406: 603–14— In figure 4 of this Article, the subheadings were incorrectly removed. In figure 6, the first column heading should have read “Events/woman-years” and the last column heading should have read “Ratio of annual event rates (95% CI)”.

Frisoni GB, Aho E, Brayne C, et al. Alzheimer's disease outlook: controversies and future directions. Lancet 2025; 406: 1424–42—In the Declaration of interests section of this Series paper, statements should have been included for Christopher C Rowe. These corrections have been made to the online version as of Sept 25, 2025, and the printed version is correct.

Among patients with HFrEF and no recent worsening, vericiguat did not reduce the risk of a composite endpoint of time to cardiovascular death or heart failure hospitalisation. Fewer cardiovascular deaths were observed in the vericiguat group than in the placebo group.

Vericiguat reduced the risk of hospitalisation for heart failure and cardiovascular death in patients with HFrEF across a broad range of clinical severity, including those receiving contemporary guideline-directed medical therapy. Vericiguat might be suitable as an additional treatment option for selected patients with HFrEF.

Icotrokinra showed superior clinical response rates versus placebo and deucravacitinib in phase 3 moderate-to-severe plaque psoriasis trials, with similar adverse event rates to placebo. These findings suggest the potential of once-daily oral icotrokinra to provide robust efficacy and a favourable safety profile.

In young people with recent-onset, clinical type 1 diabetes, 2·5 mg/kg and 0·5 mg/kg ATG reduced loss of β-cell function, showing the potential of an affordable, repurposed agent, ATG, in a low and safe dose, as a disease-modifying agent in this population.

Alzheimer's disease involves a drastic departure from the cognitive, functional, and behavioural trajectory of normal ageing, and is both a dreaded and highly prevalent cause of disability to individuals, and a leading source of health and social care expenditure for society. Before the advent of biomarkers, post-mortem examination was the only method available to establish a definitive diagnosis. In this first paper of the Series, we review state-of-the-art diagnostic practices and the typical patient journey in specialist settings, where clinicians engage in a differential diagnosis to establish whether Alzheimer's pathology (cerebral deposition of β-amyloid and hyperphosphorylated tau) is a contributor to cognitive impairment.

Over the last three decades, the evidence on how to best treat the cognitive and non-cognitive symptoms of patients with Alzheimer's disease has increased. Although these pharmacological and non-pharmacological strategies have significantly improved health outcomes for patients with Alzheimer's disease, many lack stringent evidence of efficacy. In this second paper of the Series, we provide practical and realistic advice on how to prioritise pharmacological and non-pharmacological strategies to ameliorate cognitive impairment and behavioural and psychological symptoms of dementia.

For the first time, reductions in cerebral β-amyloid pathology load and rate of cognitive and functional decline have been achieved in Alzheimer's disease, through pharmacological intervention in randomised controlled trials. However, the results from phase 3 randomised controlled trials of anti-β amyloid monoclonal antibodies are interpreted in different ways, with some experts supporting a clinically meaningful disease-modifying effect, and others judging insufficient benefit-to-risk ratio and opposing market authorisation.

Roughly 5 years since the emergence of SARS-CoV-2, the post-pandemic world feels increasingly fractured, with rising inequality, distrust in governmental bodies, and disinformation. In many countries, the response to long-term recovery has been one of austerity—by September, 2022, 143 countries had reduced capacity for public services and health care. Despite global cost-cutting, mRNA technology—a decades-old concept that came to prominence as a success story of the COVID-19 pandemic—has witnessed increased public and private investments.

The advent of metastasis-directed therapy has reshaped treatment strategies across various solid tumours, including renal-cell carcinoma.1,2 Once deemed to be radioresistant, renal-cell carcinoma can now be effectively treated in select patients using stereotactic ablative radiotherapy.3,4 In this context, the phase 2 trial by Chad Tang and colleagues, published in The Lancet Oncology,5 adds to the growing evidence for sequential metastasis-directed therapy in patients with systemic therapy-naive oligometastatic clear-cell renal-cell carcinoma—a strategy first reported in 2019 and explored prospectively since 2016.

A growing list of contemporary phase 3 trials have shown that more drugs (quadruplet therapies) are superior to less drugs (triplet therapies) in patients with newly diagnosed multiple myeloma who are transplant eligible and in those who are transplant ineligible.1–4 However, the reality is that not all patients need or are able to tolerate the toxicities of 4, or even 3, agents.5 Unfortunately, the populations meeting these criteria are historically under-represented in clinical trials of transplant-ineligible patients.

Surgical resection remains the cornerstone of curative-intent treatment for biliary tract cancers, yet most patients present with locally advanced, unresectable disease at diagnosis. The concept of conversion therapy—shrinking tumours to enable resection—has gained traction, particularly with the integration of chemoimmunotherapy.1

Pancreatic cancer is a growing global health concern, with rising incidence rates, particularly in Europe and North America. At diagnosis, only 10–20% of patients present with localised disease amenable to surgery, which remains essential for any curative approach.1 However, due to the high rate of occult micrometastases—present in more than 90% of apparently localised cases—systemic therapy is also required.1

The utility of genotyping tumours to enhance prognostication and guide treatment decision making for patients with differentiated thyroid cancer has been a topic of significant investigation over the past two decades.1 Preoperatively, work has focused on improving diagnostic accuracy and informing the extent of surgery. Postoperatively, the literature concentrates on the risk of structural disease recurrence and mortality prognostication through tumour phenotype. This process has evolved from testing for select individual mutations such as BRAFV600E to complex, commercialised panels that use DNA and RNA sequencing and microRNA signatures.

WHO projects a global health workforce shortfall of 11 million professionals by 2030.1 A contributing factor is rising levels of workforce burnout, which leads to clinicians working fewer hours and, in some cases, leaving clinical practice altogether.2 Global health-care systems also face an unbalanced distribution of workforce between metropolitan and rural areas and between high-income and low-income and middle-income countries due to factors such as resource inequities, workforce migration, career and training opportunities, and political environments.

Active surveillance is the preferred standard of care for men with low-risk prostate cancer. Active surveillance uses a combination of serial prostate-specific antigen (PSA) measurements, MRI, and prostate biopsies to monitor the disease, and reserves curative-intent therapy for when progression is detected. The strong recommendation to defer immediate treatment is based on multiple randomised trials in men with predominately low-risk cancer that used less intensive monitoring strategies than active surveillance, including watchful waiting and active monitoring (effectively PSA monitoring).

The PACE-C trial reported by Alison C Tree and colleagues1 provides pivotal evidence comparing stereotactic body radiotherapy (SBRT) with moderately hypofractionated radiotherapy (MHRT) in patients with intermediate-risk or high-risk prostate cancer. Although the study's robust design and comprehensive endpoints are commendable, a critical flaw in the toxicity assessment timing undermines the comparability of acute toxicity outcomes between the two study groups.

We thank Lanwei Guo for their interest in the acute toxicity comparison from the PACE-C trial.1 We agree, as acknowledged in the paper, that the differential treatment length between the moderately hypofractionated radiotherapy (MHRT) and five-fraction (SBRT) groups of the trial caused difficulties in comparing cumulative toxicity rates, as most toxicity occurs towards the end of a 4-week course of MHRT, but peaks after the completion of SBRT. We reported a significantly higher rate of early Common Terminology Criteria for Adverse Events (CTCAE) gastrointestinal toxicity in the SBRT group (17% vs 10%; p=0·0011).

The CONTACT-02 trial by Neeraj Agarwal and colleagues evaluated cabozantinib plus atezolizumab versus an androgen receptor pathway inhibitor (ARPI) switch in patients with metastatic castration-resistant prostate cancer (mCRPC) following progression on a previous ARPI.1 Eligibility was restricted to patients with extrapelvic soft-tissue progression (ie, lymph node or visceral metastases). Although the trial met its primary endpoint of progression-free survival with a statistically significant improvement in the cabozantinib plus atezolizumab group versus the ARPI switch group (6·3 vs 4·2 months), no difference was found in overall survival.

We acknowledge the Correspondence from Dries Develtere on the CONTACT-02 trial, which raises concerns that the progression-free survival benefit of cabozantinib plus atezolizumab found in our trial was modest with no overall survival advantage, that the regimen is toxic, and that the control group was not appropriate.

We read with interest the Article by Mitsue Saito and colleagues.1 The study showed that adding 5 mg olanzapine after chemotherapy to standard anti-emetics improved control of chemotherapy-induced nausea and vomiting (CINV) while minimising infusion-related sedation, supporting a practical outpatient strategy. As supportive oncology evolves, optimising anti-emetic strategies is increasingly vital. We aim to highlight methodological limitations of the trial and offer perspectives on optimising endpoint selection, toxicity evaluation, and individualised supportive care.

We appreciate any readers’ interest and comments on our Article1 and we would like to provide a comprehensive response to the Correspondence by Man Sun and colleagues.

The pooled cohort analysis published in the July issue of The Lancet Oncology by Katie O’Brien and colleagues provides important new insight into the relationship between hormone therapy and breast cancer risk in younger women (aged 16–54 years). The finding that oestrogen plus progestin therapy is disproportionately associated with oestrogen receptor-negative (HR 1·44 [95% CI 1·11–1·88]) and triple-negative breast cancer subtypes (1·50 [1·02–2·20]) warrants urgent attention.1

We commend Allen S Ho and colleagues for their rigorous effort in advancing prognostic tools for human papillomavirus (HPV)-positive oropharyngeal carcinoma.1 The study's use of large-scale data to refine carcinoma staging is a valuable contribution. However, we wish to highlight three potential issues that might affect the broader applicability of the findings, and suggest avenues for improvement to enhance their clinical relevance.

We thank Shaokun Liu and colleagues for their thoughtful correspondence on the American Joint Committee on Cancer and Union for International Cancer Control Version 9 (AJCC9V) staging system for HPV-positive oropharyngeal carcinoma.1

We read with great interest the secondary analysis of the HD21 trial by Justin Ferdinandus and colleagues,1 which sheds light on fertility outcomes in patients with advanced-stage Hodgkin lymphoma treated with chemotherapy. Although a regimen of BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone) showed reduced gonadotoxicity compared with eBEACOPP (escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), results regarding the safety of BrECADD in terms of ovarian function require cautious interpretation.

We thank Virginie Barraud-Lange and colleagues for their thoughtful comments on our analysis of fertility in the HD21 trial.1 Their letter highlights important nuances in interpreting endocrine recovery, ovarian reserve, and real-world family building after therapy.

Kuemmel S, Graeser M, Schmid P, et al. Chemotherapy-free neoadjuvant pembrolizumab combined with trastuzumab and pertuzumab in HER2-enriched early breast cancer (WSG-KEYRICHED-1): a single-arm, phase 2 trial. Lancet Oncol 2025; 26: 629–40—In this Article, the first sentence of the fifth paragraph of the Discussion section should have read “Our translational research suggests that higher baseline expression of ERBB2, PD-1, and PD-L1, and ctDNA negativity are associated with pathological complete response after neoadjuvant pembrolizumab plus dual HER2 blockade.” This correction has been made to the online version as of Sept 29, 2025.

Hungria V, Robak P, Hus M, et al. Belantamab mafodotin plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): updated overall survival analysis from a global, randomised, open-label, phase 3 trial. Lancet Oncol 2025; 26: 1067–80—In this Article, the affiliation for Prof Marek Hus and Michał Mielink should have been “Medical University of Lublin”. This correction has been made to the online version as of Sept 29, 2025.

Concin N, Matias-Guiu X, Cibula D, et al. ESGO–ESTRO–ESP guidelines for the management of patients with endometrial carcinoma: update 2025. Lancet Oncol 2025; 26: e423–35. In this Policy Review, several typographical, formatting, language, and editing errors have been identified. These corrections have been made to the online version as of Sept 29, 2025.

Oncologists and experts are warning the Trump administration's termination of almost US$500 million in contracts to develop mRNA vaccines together with cuts to health insurance will have a negative impact on cancer patients and research.

On Aug 12, 2025, the federal government of Australia, working with Cancer Australia (NSW, Australia), declared an investment of AU$24·6 million (AUD) in new cancer research grants for the country's First Nations communities which includes the Aboriginal Australians and the Torres Strait Islanders.

The cost of UK visas is proving an obstacle to the recruitment of global scientific talent to the country, which is in turn substantially impeding cancer research, according to a new report from Cancer Research UK (CRUK).

A new briefing has called for radical reform to the Multidisciplinary Team (MDT) model in England. The briefing was published on Aug 28, 2025, and was endorsed by several professional bodies, including The Royal College of Radiologists and the Association of Cancer Physicians. The briefing proposal argued that the established practice of scheduling MDT meetings for each patient with cancer is massively time-consuming, delays access to care, and neglects service improvement.

A parliamentary committee has asked the Indian Government to impose price caps on certain cancer medicines, citing concerns over affordability and access for patients. Currently, India enforces a 30% trade margin cap covering 42 essential anti-cancer drugs. The new recommendation seeks to expand this list to include cancer vaccines, immunotherapy, and oral chemotherapy. The committee also advised monitoring the quality of generic medicines, noting hesitancy among clinicians to prescribe them.

Speaking on behalf of a large international group of researchers, Alexander Drilon (Memorial Sloan Kettering Cancer Center, New York, NY, USA) showed that zidesamtinib, a next-generation ROS1 tyrosine kinase inhibitor (TKI), has clinically meaningful activity in patients with CNS disease, with ROS1 G2032R mutations, or in those who have exhausted all other available treatment options. In a large phase 1/2 trial, 432 patients were recruited. 50% of patients had received previous ROS1 TKIs including lorlatinib, repotrectinib, and taletrectinib.

On Sept 5, 2025, WHO released new editions of its Model Lists of Essential Medicines (EML) and Essential Medicines for Children (EMLc). Several glucose-lowering therapies, which also prompt weight loss, were added to the EML for individuals with type 2 diabetes and specified co-morbidities, including obesity, a risk factor for 13 cancers. The PD-1 inhibitor pembrolizumab was also added to the EML for the treatment of three different cancers. The bispecific T-cell engager molecule blinatumomab was added to both lists for the treatment of CD-19-positive B-lineage acute lymphoblastic leukaemia.

Ghana will begin providing free essential cancer medicines to children from low-income families in early 2026, health officials announced in Accra on Sept 5, 2025, during the launch of the National Childhood Cancer Awareness Month. The programme will run through nine treatment centres nationwide, including Korle-Bu Teaching Hospital (Accra, Ghana), Komfo Anokye Teaching Hospital (Kumasi, Ghana) and Greater Accra Regional Hospital (Accra, Ghana). Six additional facilities will support wider coverage and improve access for families outside the major cities.

Experts have warned against any delay to England's National Cancer Plan, which is expected to by the Department of Social Care (DHSC) this autumn—although no date is yet confirmed.

On Sept 9, 2025, the Council of Ministers in Spain gave their approval to a draft tobacco law that includes new measures to combat smoking and regulate tobacco products.

On Sept 14, 2025, New Zealand First introduced the Health (Prostate Cancer Screening Services) Amendment Bill to Parliament. The bill seeks approval for a 4-year, free, risk-stratified pilot prostate cancer screening programme in two New Zealand regions—one in the North Island and one in the South Island. The programme would combine prostate-specific antigen (PSA) testing with multiparametric MRI (mpMRI) and targeted biopsies for men at elevated risk of developing prostate cancer. Modelling by the New Zealand Institute of Economic Research (NZIER) estimates that, if the pilot were followed by a national rollout, the programme could save the health system more than NZ$100 million over 20 years.

Performers have many different reasons for sharing their stories at the Edinburgh Festival Fringe, the world's largest arts festival, which was held on Aug 1–25, 2025, in Edinburgh, UK. For Keith Alessi, the motivation to perform Tomatoes Tried To Kill Me But Banjos Saved My Life, his 1-hour musical monologue, was to convince members of his audiences that their stories of overcoming adversity matter too and that they should also share their experiences with others. Alessi trained as an accountant and found financial success by turning around struggling companies, but 13 days after giving up his job as a chief executive in order to pursue his dream of learning to play the banjo on stage, he was diagnosed with stage 3b oesophageal cancer, which required radiotherapy, chemotherapy, and then 7·5 hours of surgery.

It was a quiet summer, and I was determined to switch off—no clinics, no case logs, just rest. One afternoon, while unpacking a forgotten tote bag, I came across the black diary I had carried through my oncology postings. I opened it casually, not expecting much. But the pages pulled me back to bed 32, where Meena once lay. To questions I still could not answer and to moments I had never spoken about. I did not find case summaries. I found pieces of myself I had left behind.

Select patients with oligometastatic disease can be managed with serial metastasis-directed therapy with prolonged time off systemic therapy, favourable progression-free survival, and limited adverse events.

Tarlatamab plus a PD-L1 inhibitor as maintenance after first-line chemo-immunotherapy showed a manageable safety profile with promising anticancer activity, supporting the ongoing phase 3 trial (NCT06211036).

Neoadjuvant TAR-200 plus cetrelimab showed a high pathological complete response rate with a manageable safety profile. These results support continued investigation of TAR-200 in patients with muscle-invasive bladder cancer planned for radical cystectomy.

In the IFM2017-03 trial, use of lenalidomide plus daratumumab, with dexamethasone limited to the first 2 treatment cycles, reduced the risk of progression or death compared with lenalidomide plus dexamethasone, with no additional safety concerns. Lenalidomide plus daratumumab could therefore be considered as a treatment option for older patients with frailty and newly diagnosed multiple myeloma.

With promising efficacy and manageable safety, GOLP represents a potentially feasible and high-efficiency conversion regimen for unresectable locally advanced biliary tract cancer.

This randomised trial did not show a difference in overall survival between neoadjuvant FOLFIRINOX and neoadjuvant gemcitabine-based chemoradiotherapy in patients with resectable or borderline resectable PDAC. Both neoadjuvant treatment regimens may be considered in these patients.

First-line ICIs with or without chemotherapy were associated with improved overall survival compared with BRAF and MEK inhibitors in participants with metastatic BRAFV600E-mutated NSCLC, particularly among specific subpopulations. These findings, although suggesting potential clinical relevance, remain exploratory and require confirmation from prospective studies.

10-year overall survival and recurrence-free survival were improved for patients with high-risk endometrial cancer treated with adjuvant chemoradiotherapy versus radiotherapy alone, with most clinically relevant benefit suggested for p53 abnormal cancers.

Integrating the genetic statuses of BRAF and TERTp into the AJCC system changes the original risk stages of the AJCC system and significantly improves the accuracy of its mortality risk classification for papillary thyroid cancer.

Childhood and adolescent cancer survivors (age at diagnosis: 0–21 years) face increased risk for long-term health complications and less favourable outcomes in terms of functioning and social participation. Moreover, they often experience inadequate health-care transitions to appropriate services after leaving paediatric or adolescent services, while the prevalence and severity of late effects increase as they become adults. To address transition challenges, we developed evidence-based recommendations as part of the European Network of Youth Cancer Survivors project with the goal to improve health-care transitions to both long-term survivorship and adult care, ensuring continuity and addressing survivors’ unique needs.

Pathological response is a surrogate marker of efficacy of neoadjuvant therapy in various tumour types, but there is no consensus on reporting pathological response for renal cell carcinoma. We aimed to assess the status of pathological response reporting in renal cell carcinoma and develop a recommendation on tissue preparation and response reporting for neoadjuvant treatment. We conducted a systematic review of publications on the PubMed and Web of Science databases to identify manuscripts reporting response to pre-surgical therapy in renal cell carcinoma.

Countries across Africa are experiencing the dual challenge of rising cancer burden and severe health-care workforce shortages, which threaten to overwhelm its already strained health systems. Simultaneously, advancements in digital health technologies, including electronic health records, telemedicine, mobile health, and artificial intelligence (AI), offer promising solutions to address these challenges. This Policy Review explores the potential of digital health innovations to transform cancer care in Africa by improving access, efficiency, and equity.

Since the reform of China's drug review and approval in 2015, it has successfully stimulated the enthusiasm of domestic pharmaceutical companies to carry out innovative drug research and development, especially in oncology. Chinese pharmaceutical companies that developed cancer drugs have begun shifting from an in China, for China model to an in China, for global model given the constrained market share. However, many challenges are confronting Chinese pharmaceutical companies when entering overseas markets.

A 57-year-old woman visited Hunan Provincial People's Hospital and The First Affiliated Hospital of Hunan Normal University (Changsha, Hunan, China) in December, 2024, because of a 1-year history of chest and back pain. She had a previous medical history of hypertension and had undergone a hysterectomy for uterine leiomyoma 10 years ago. Clinical manifestations, physical examination, and laboratory tests were unremarkable. PET–CT scan revealed a space-occupying lesion in the basal segment of the right lower lung and multiple hypermetabolic nodules in the right pleura (figure, A).

Global health targets must balance ambition with achievability to create meaningful change for those individuals affected. In 2015, the UN adopted the Sustainable Development Goals (SDGs) to promote peace and prosperity worldwide. One goal, SDG 2, aims to end all forms of malnutrition by 2030, with the prevalence of anaemia in women as a key indicator (SDG 2.2). Anaemia affects approximately 1·9 billion people globally, making it the third leading cause of disability worldwide. It is particularly prevalent in low-income and middle-income countries and disproportionately affects children, adolescent girls, and women of reproductive age, including pregnant women.

Anaemia is a persistent global health problem and has been a subject of the World Health Assembly (WHA) since 1959.1 It affects children, adolescents, and adults, causing symptoms such as fatigue and shortness of breath, which reduces the capacity for learning and physical work. Anaemia substantially increases the risk of maternal and newborn morbidity and mortality, with mothers more likely to experience placental abruption and postpartum haemorrhage, and newborns more likely to have low birthweight, be small for gestational age, or be stillborn.

The Lancet Haematology Commission on anaemia1 serves as a reminder not only of the widespread and harmful impact of this public health issue, but also of the scientific and programmatic advances in managing the disease and the knowledge gaps that need to be addressed. Since its founding in 1961, the United States Agency for International Development (USAID) has actively worked to address anaemia and many other global challenges. In this Comment, we highlight some of USAID's past and recent contributions to the management of anaemia and micronutrient deficiencies, as a tribute to an institution that supported vital public goods worldwide until its operations were halted by the incoming US administration in January, 2025.

The world is facing a climate crisis that is jeopardising gains made in health and nutrition security.1 Certain conditions such as anaemia are particularly at risk of reversing course due to its multifactorial cause. Indirect causes of anaemia include the absence of or inadequate access to health-care and nutrition services, inadequate access to water, sanitation, and hygiene, as well as inadequate vector control, while direct causes include nutritional deficiencies, pregnancy, gynecological conditions, as well as communicable (eg, malaria and soil-transmitted helminths) and non-communicable diseases (eg, cancer, obesity, and autoimmune conditions).

Stratton P. Enhancing sexual function after haematopoietic transplantation. Lancet Haematol 2025; 12: e562–63. In this Comment, a statement has been added to the Acknowledgments to reflect recent updated policies for National Institutes of Health employees. This correction has been made to the online version as of Aug 13, 2025.

Anaemia is a major global public health problem with more than 1·9 billion people affected worldwide. India has one of the highest burdens of anaemia across all age groups compared with other countries of the world. In 2019–21, 52% of pregnant women, 57% of women of reproductive age, 59% of adolescent girls, and 67% of children had anaemia. Not only is the burden of anaemia very high in the country, progress to reduce prevalence has also been stagnant over past few decades, highlighting the recalcitrant nature of the problem.

When Fatuma's child was admitted to the hospital for the third time, her face was swollen, and she had a fever, headache, and dizziness. “So, I had to bring her to the hospital, when they checked, they said she had no blood”, Fatuma recalled. Her story is not unique. In the paediatric ward at Kilifi County Referral Hospital in coastal Kenya, two mothers, identified here by the pseudonyms Fatuma and Halima, shared their lived experiences caring for children admitted to hospital with severe anaemia and its underlying conditions.

Our findings suggest that a value-based global target for anaemia reduction will be substantially lower than the existing international commitment. Value-based targets using evidence from available interventions and cost-effectiveness for what is achievable given countries' differing contexts can provide better incentives for progress and offer more realistic forecasts of human development.

Our standardised methodology and dataset estimate country-level unit costs and describe cost drivers for WHO-recommended anaemia interventions. These findings can facilitate cost-effectiveness analyses of anaemia interventions for women of reproductive age and strengthen priority-setting processes.

In regular donors with low ferritin, iron supplementation—60 mg taken daily, in particular—effectively mitigates iron deficiency, low ferritin, and low haemoglobin. Iron supplementation is an effective alternative or supplement to extended donation intervals for whole-blood donors with low ferritin levels.

ASTX727 could be a potential treatment option after HSCT in patients with acute myeloid leukaemia or myelodysplastic syndrome at very high risk of relapse. Further investigation is warranted to establish the efficacy and safety of this therapeutic approach.

Anaemia, a condition affecting more than 1·9 billion people worldwide, disproportionately affects children, adolescent girls, and women. Despite longstanding interventions and guidelines, most countries are not on track to meet global anaemia reduction targets, and cuts in global health funding in 2025 further threaten progress. This Lancet Haematology Commission aims to reinvigorate efforts to prevent and control anaemia by addressing key gaps in data, evidence, implementation, governance, and target-setting approaches.

A 71-year-old man presented to the Department of Dermatology at The First Hospital of China Medical University in November, 2023, with a 2-year history of recurrent reddish-purple skin papules distributed aoss his neck, chest, and back after receiving the inactivated COVID-19 vaccine (figure A). He was initially diagnosed with urticaria, dependent on glucocorticoids, but developed femoral head necrosis leading to discontinuation of the medication. On further questioning, he also reported recurrent fever, weight loss, fatigue, and joint pain.

MML policies may have affected the type of opioid prescribed and increased adverse hospital events among patients with cancer and resection surgery. Additional investigation of medical marijuana’s impact on cancer pain management is warranted.

A substantial proportion of patients in phase 3 cancer trials withdraw without a specified rationale. Inconsistent withdrawal documentation practices, limited use of a retention strategy, and unclear postwithdrawal data policies highlight the need for standardized approaches to improve trial quality.

The large differences in stage‐specific 5‐year cancer survival between rural and urban areas and between Black and White persons likely reflect disparities in the receipt of guideline‐concordant care.

In premenopausal women with hormone‐responsive early BC, depression at baseline is a risk factor for poorer DFS and OFS. Further investigation of the underlying interactive processes is needed.

In the context of widespread policy changes, this study showed a modest decline in new and additional opioid prescribing for patients with cancer. In metastatic cancer, prescribing remained stable for patients reporting pain and declined steeply for those reporting no pain.

Poor sleep and low sexual satisfaction commonly co‐occur among distressed breast cancer survivors and are cross‐sectionally related. However, changes in these domains occurred independently over time, highlighting the importance of evaluating both concerns and providing domain‐specific survivorship care.

In an analysis reported in the Journal of Clinical Oncology, Germani et al identified the impact of HER2 status in patients with metastatic colorectal cancer (mCRC) receiving chemotherapy plus either bevacizumab or anti-EGFR agents.

Stereotactic radiation therapy (SABR) was found to be noninferior to surgical resection in terms of overall survival for patients with early-stage non–small cell lung cancer (NSCLC), according to 10-year results from the STARS trial presented at the American Society for Radiation Oncology (ASTRO)...

Health-related quality-of-life measurements demonstrated that both proton and photon radiation therapy led to excellent and similar impacts on quality of life for patients with breast cancer undergoing comprehensive nodal irradiation, according to findings from the phase III RadComp trial that was...

For patients with intermediate-risk, localized prostate cancer, radiation therapy delivered in five sessions reduced patient-reported side effects compared to longer courses of radiation, according to results of a large, randomized phase III trial. Patients treated with stereotactic body radiation...

A new phase III clinical trial has found that intensity-modulated radiation therapy (IMRT) and proton-beam therapy resulted in similar quality-of-life outcomes and low rates of side effects for people with locally advanced oropharyngeal cancer. The TORPEdO trial, a randomized study conducted across ...

The National Cancer Institute (NCI) is requesting over $11.5 billion in federal funding for fiscal year (FY) 2027, an increase of more than $4 billion from FY25.

Adjuvant radiation therapy following radical cystectomy and chemotherapy was found to be safe and efficacious for patients with locally advanced muscle-invasive bladder cancer, according to findings from the phase III randomized BART trial presented at the American Society for Radiation Oncology...

The U.S. Food and Drug Administration (FDA) has approved ropeginterferon alfa-2b-njft (Besremi) for the treatment of adults with polycythemia vera. The new agent is a monopegylated, long-acting interferon, which exhibits its cellular effects in polycythemia vera in the bone marrow.

In a phase III trial (MPD-RC 112) reported in the journal Blood, John Mascarenhas, MD, and colleagues found no difference in 12-month complete response rates between treatment with pegylated interferon-alfa vs hydroxyurea in previously untreated patients with high-risk polycythemia vera or...

In a UK phase II trial (MAJIC-PV) reported in the Journal of Clinical Oncology, Harrison et al found that ruxolitinib produced a higher complete response rate vs best available therapy in patients with polycythemia vera intolerant of or resistant to hydroxycarbamide.

On September 15, the U.S. Food and Drug Administration (FDA) approved momelotinib (Ojjaara) for the treatment of intermediate- or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post–polycythemia vera and post–essential thrombocythemia), in adults with anemia. 

In the phase II REVIVE trial reported in The New England Journal of Medicine, Marina Kremyanskaya, MD, PhD, and colleagues found that the hepcidin mimetic rusfertide reduced the number of phlebotomies (during a dose-finding phase) and improved response rate vs placebo (during a randomized phase) in ...

In a German single-center study reported in The New England Journal of Medicine, Gagelmann et al determined that clearance of driver mutations after allogeneic hematopoietic stem-cell transplantation was associated with better outcomes in patients with myelofibrosis.

Ropeginterferon alfa-2b demonstrated superior efficacy and safety compared with anagrelide as second-line therapy for patients with essential thrombocythemia (ET) who were intolerant or resistant to hydroxyurea, according to data from the phase III SURPASS-ET trial presented at the European...

A new clinical trial found that people with a limited number of metastases from recurrent prostate cancer lived significantly longer without disease progression when they received a radiopharmaceutical drug before targeted radiation compared with radiation alone.

Assessment with a genomic test could help predict which patients with recurrent prostate cancer are most likely to benefit from the addition of hormonal therapy to radiation following prostatectomy, according to findings from the phase II BALANCE trial (NRG GU006) presented in a press briefing...

In a study (BMT CTN 1702) reported in the Journal of Clinical Oncology, Lee et al found little difference in 2-year survival outcomes between patients considered “very likely” vs “very unlikely” to find an HLA-matched unrelated donor (MUD) for allogeneic hematopoietic cell transplantation as...

In an analysis reported in The Lancet Oncology by Gui et al in the International Consortium on Meningiomas, TERT expression in meningiomas was found to be associated with poorer progression-free survival.  

Anthony Letai, MD, PhD, was sworn in on September 29 as Director of the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), by Health and Human Services Secretary Robert F. Kennedy, Jr.

In a phase II trial (PASS-01) reported in the Journal of Clinical Oncology, Knox et al found similar progression-free survival with modified leucovorin, fluorouracil, irinotecan, oxaliplatin (mFOLFIRINOX) vs gemcitabine/nab-paclitaxel in patients with previously untreated metastatic pancreatic...

On September 25, the U.S. Food and Drug Administration (FDA) removed the Risk Evaluation and Mitigation Strategies (REMS) program for vandetanib, according to an announcement from the agency.

There has been a rapid increase in the global number of cancer cases and deaths between 1990 and 2023, despite advances in cancer treatment and efforts to tackle cancer risk factors over that same period. Without urgent action and targeted funding, 30.5 million people are forecast to receive a new...

The University of California, Los Angeles (UCLA) and UC Davis will co-lead a newly funded, multi-institutional clinical trial to evaluate whether artificial intelligence (AI) can help support radiologists in interpreting mammograms more accurately, with the goal of improving breast cancer screening ...

Zidesamtinib, an investigational oral, highly selective ROS1 tyrosine kinase inhibitor designed to overcome common resistance mechanisms and improve brain penetration, has demonstrated activity in both pretreated and tyrosine kinase inhibitor–naive patients with ROS1-positive non–small cell lung...

The U.S. Food and Drug Administration (FDA) has approved imlunestrant, an estrogen receptor antagonist, for adults with estrogen receptor (ER)-positive, HER2-negative, estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer with disease progression after at least one line of...

Right ventricle (RV) dysfunction is associated with poorer outcomes in heart failure with preserved ejection fraction (HFpEF). Females are more likely to have HFpEF but males have worse prognosis and resting RV function. The contribution of dynamic RV-pulmonary artery (RV-PA) coupling between sex and its impact on peak exercise capacity (VO2) in HFpEF is not known.

A Phase I, single-center investigation demonstrated that 8 weeks of antimycobacterial therapy improved sarcoidosis forced vital capacity (FVC). Safety and efficacy assessments have not been performed in a multicenter cohort.

All aspects of medical education were affected by the Novel Coronavirus Infectious Disease-19 (COVID-19) pandemic. Several challenges were experienced by trainees and programs alike due to the economic repercussions of the pandemic, how social distancing affected the delivery of medical education, testing and interviewing, how the surge of patients affected redeployment of personnel, potential compromise in core training and the overall impact on the wellness and mental health of trainees and educators.

In this meta-analysis of observational studies, RV dysfunction was associated with higher short-term and long-term mortality in sepsis and septic shock.

Legionella is an uncommon cause of CAP, occurring primarily from late spring through early autumn. Testing is uncommon, even among patients with risk factors, and many positive patients failed to receive empiric coverage for LP.

The nS classification could be used to provide a more accurate prognosis in patients with resected NSCLC. The nS is worth taking into consideration when defining nodal category in the forthcoming ninth edition of the staging system.

NLP successfully identified a large cohort with CC. Most patients were identified through NLP alone, rather than diagnoses or medications. NLP improved detection of patients nearly seven-fold, addressing the gap in ability to identify and characterize CC disease burden. Nearly all cases appeared to be managed in primary care. Identifying these patients is important for characterizing treatment and unmet needs.

Pulmonary arterial hypertension (PAH) is a rare disease and much of our understanding stems from single-center studies, which are limited by sample size and generalizability. Administrative data offer an appealing opportunity to inform clinical, research, and quality improvement efforts for PAH. Yet, there is currently no standardized, validated method to distinguish PAH from other subgroups of pulmonary hypertension (PH) within this data source.

A transparent DL algorithm improves on traditional clinical criteria to predict the need for MV in hospitalized patients, including in those with COVID-19. Such an algorithm may help clinicians optimize timing of tracheal intubation, better allocate resources and staff, and improve patient care.

To assess airway and lung parenchymal damage non-invasively in cystic fibrosis (CF), chest MRI has been historically out of the scope of routine clinical imaging due to technical difficulties such as the low proton density and respiratory and cardiac motion. However, technological breakthroughs have recently emerged to dramatically improve lung MRI quality (including signal-to-noise ratio, resolution, speed, contrast). At the same time, novel treatments have changed the landscape of CF clinical care.

Bronchoscopic lung volume reduction with one-way endobronchial valves is a guideline treatment option for patients with advanced emphysema, supported by extensive scientific data. Patients limited by severe hyperinflation, with a suitable emphysema treatment target lobe and with absence of collateral ventilation are the responders to this treatment. Detailed patient selection, a professional treatment performance, and dedicated follow-up of the valve treatment, including management of complications, are key ingredients to success.

Chronic Obstructive Pulmonary Disease (COPD) may cause profound dyspnea, functional impairment, and reduced quality of life. Available pharmacologic therapy provides suboptimal symptom improvement in many patients. Bronchoscopic lung volume reduction (BLVR), achieved with endobronchial valve (EBV) placement, can effectively improve dyspnea and functional status in appropriately selected patients. Operationalizing a safe and effective BLVR program requires appropriate oversight which can be achieved by a BLVR Nurse Coordinator (NC).

Empathy-based, stigma-reducing communication may lead to improved assessments of tobacco use and smoking cessation for patients with smoking-related cancers. These findings support the dissemination and further testing of a new ECS model for training OCPs in best practices for assessment of smoking history and engagement of patients who currently smoke in tobacco treatment delivery.

In clinical practice, reslizumab may have been initiated in response to heavy symptom burden and CAEs. Reslizumab was associated with improved clinical and patient-reported outcomes and significant reductions in asthma-related HRU.

Quantitative emphysema measured on LDCT of the chest can be leveraged to improve lung cancer risk prediction and help diagnose COPD in individuals who currently or formerly smoked undergoing lung cancer screening.

ALASCCA: an aspirin a day keeps colorectal cancer away

MARIPOSA demonstrates overall survival benefit from amivantamab–lazertinib

Maintenance tarlatamab extends overall survival

Final results from the phase I AMPLIFY-201 trial show that ELI-002 2P, a therapeutic cancer vaccine targeting mutant KRAS, elicits polyfunctional T cell responses in patients with minimal residual disease-positive pancreatic or colorectal cancer. Importantly, the magnitude of this response correlated with improved clinical outcomes. Herein, we discuss how these results could set the stage for ongoing randomized trials.

Several persistent challenges limit the efficacy and applicability of adoptive T cell therapies for cancer, including suboptimal function and/or persistence in vivo, a narrow range of targetable antigens and complex manufacturing processes. This Review discusses the potential of ‘CRISPR 2.0’ precision gene-editing platforms, such as base editing and prime editing to address all of these challenges, and describes the progress made towards clinical translation of these technologies.

Targeted radionuclide therapy (TRT) is a therapeutic modality that combines the strengths of radiotherapy and systemic molecularly targeted therapy. Over the past few years, new TRT agents have been developed against an expanding array of molecular targets, particularly in cancers with limited treatment options. The authors of this Review discuss these advances, focusing on what constitutes an optimal target and discussing lessons learned from past experience in order to broaden the scope of TRT.

Some of the most consequential conflicts in oncology and medicine overall are not financial; these remain poorly defined and weakly regulated. Here we offer a policy-relevant definition and examine how reputation, ambition, ideology and institutional loyalty can shape research, guidelines, policy and hiring decisions. We argue for structural safeguards to preserve trust in medicine.

The Radiomics Quality Score (RQS) was developed to assess the rigour of studies using radiomics, a tool for medical imaging analysis. The RQS has been widely used in the field and now needs an update (RQS 2.0) to address contemporary needs. The authors of this Review introduce RQS 2.0, which integrates radiomics readiness levels to provide a structured framework towards clinical implementation.

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No abstract available

No abstract available

Resistance to cytarabine is a key problem in the treatment of acute myeloid leukemia (AML). To understand the molecular biology of resistance to cytarabine, a viability-based chemosensitizer screen was utilized. We screened synthetic lethal targets using 437 different small interfering RNAs (siRNAs) directed against factors involved in DNA repair mechanisms and cytarabine as the chemical compound. Three hits were identified: CUL4A, TP73, and RFC2. We show here that the ubiquitin ligase CULLIN 4A (CUL4A) and the tumor-suppressive transcription factor p73 contribute to drug resistance by modulating DNA damage response. P73 confers resistance to cytarabine therapy by transactivation of REV3L, encoding the catalytic subunit of translesion DNA polymerase ζ, and CUL4A probably by influencing proliferating cell nuclear antigen (PCNA) and the polymerase switch towards error-prone translesion DNA polymerases. Abrogation of the polymerase ζ by siRNA causes identical effects as siRNAs against CUL4A or TP73 and resensitizes cells towards cytarabine therapy in vitro. As CUL4A needs to be activated by neddylation to facilitate the degradation of several proteins including PCNA, we propose a novel explanation for the synergism between cytarabine and the neddylation inhibitor pevonedistat by inhibition of translesion synthesis. In keeping with this, in AML patients treated with cytarabine, we found high expression of CUL4A and TP73 to be associated with poor prognosis.

Data on outcome of patients with mantle cell lymphoma (MCL) and COVID-19 infection are limited. The European MCL (EMCL) registry is a centralized registry of the EMCL network, collecting real-world information about treatments and disease courses. During the COVID-19 pandemic, additional data on MCL patients with COVID-19 infection were collected, aiming to identify risk factors for mortality from COVID-19. In our retrospective, multicenter, international study, we collected data from 63 MCL patients with a median age of 64 years (range, 44–84) in 9 countries with evidence of a COVID-19 infection between February 2020 and October 2021. The overall mortality rate was high (44.4%), especially in hospitalized patients (61%) and in patients with need for intensive care unit care (94%). Patients receiving rituximab had significantly poorer survival than patients not receiving rituximab (P = 0.04). Our data highlight the importance of prevention strategies and underline the need for effective vaccination in this vulnerable cohort.

Immune dysregulation has been highlighted as a key player in the pathogenesis of myelodysplastic syndromes (MDS), but little is known about cytokine profiles in patients with unexplained cytopenia with or without mutations in MDS-associated genes (clonal cytopenias of undetermined significance [CCUS] and idiopathic cytopenias of undetermined significance [ICUS], respectively), which often precede MDS. Here, we study the cytokine profiles in 111 patients with ICUS (N = 41), CCUS (N = 30), lower-risk MDS (LR-MDS; N = 22) and higher-risk MDS (HR-MDS; N = 18), and in healthy elderly controls (N = 21). Twenty cytokines were examined in blood plasma at time of diagnosis using Luminex assays and enzyme linked immunosorbent assays. The cytokine levels were compared between patient groups, and in patients versus controls. Associations between cytokines and MDS-associated mutations were evaluated. An aberrant cytokine profile was observed in all patient groups relative to healthy elderly controls. Patients had significantly higher levels of IL-6 (P< 0 .001), tumor necrosis factor α (P < 0.001), IL-10 (P < 0.001), and C-X-C motif chemokine 10 (P < 0.001) and lower levels of transforming growth factor beta 1 (P < 0.001), CCL5/regulated on activation normal T-cell expressed and secreted (P < 0.001), and S100A4 (P < 0.001) compared with healthy controls. Survival was significantly shorter in CCUS and MDS patients with a high systemic inflammatory cytokine load (median overall survival [OS] 21 months) compared with those with low-moderate systemic inflammatory cytokine load (median OS 64 months; P < 0.0001). These data suggest that patients with ICUS and CCUS have cytokine levels as abnormal as in LR-MDS. Indeed, high cytokine levels are present before MDS is diagnosed and cytokine levels are elevated irrespective of the presence or size of the myeloid clones. Cytokines may have a prognostic impact at a very early premalignant stage of myeloid disorders.

No abstract available

No abstract available

Musculoskeletal symptoms in chronic graft-versus-host disease (cGVHD) are rare manifestations contributing to disease burden. This study assesses the frequency of muscle cramps, joint and muscle aches, and muscle weakness in a cohort of patients severely affected by cGVHD. Three hundred thirty-four patients participated in the NCI natural history study of cGVHD (NCT00092235) from October 2004 to March 2017. Five-point Lee cGVHD Symptom Scale was dichotomized (less symptom bother—0, 1, 2; severe symptom bother—3, 4) and tested for associations with: Short Form 36 (SF36), 2-minute walk test, grip strength, joint range of motion, and human activity profile, clinical and laboratory data. Seventy-five point four percent of patients reported joint and muscle aches (36.8% severe, Lee Symptom Scale score 3–4), 74.3% muscle cramps (33.5% severe), and 82.34% muscle weakness (45.51% severe), which were associated with reduced functional capacity (SF36 Physical Component Scale, P < 0.0001). Muscle cramps were associated with limited joint movement (P < 0.0001) and skin manifestations (skin thickening, P = 0.0008; itchy skin, P = 0.0003). Muscle cramps did not show association with potential causative agents, such as concomitant calcineurin inhibitors therapy, statins, or use of antidiabetic drugs. Joint and muscle aches showed associations with multiple variables (including strong associations with mood symptoms and fatigue, P < 0.0001). Muscle weakness was not associated with steroid dose, but was significantly associated with depression (P < 0.0001) and anxiety (P = 0.0009). This study documents a high frequency of musculoskeletal symptoms in a cohort of adult patients with cGVHD. The multivariable logistic regression models showed that a joint set of factors were moderately well associated with musculoskeletal symptoms in this study.

No abstract available

No abstract available

Drug resistance and treatment failure in pediatric acute lymphoblastic leukemia (ALL) are in part driven by tumor heterogeneity and clonal evolution. Although bulk tumor genomic analyses have provided some insight into these processes, single-cell sequencing has emerged as a powerful technique to profile individual cells in unprecedented detail. Since the introduction of single-cell RNA sequencing, we now have the capability to capture not only transcriptomic, but also genomic, epigenetic, and proteomic variation between single cells separately and in combination. This rapidly evolving field has the potential to transform our understanding of the fundamental biology of pediatric ALL and guide the management of ALL patients to improve their clinical outcome. Here, we discuss the impact single-cell sequencing has had on our understanding of tumor heterogeneity and clonal evolution in ALL and provide examples of how single-cell technology can be integrated into the clinic to inform treatment decisions for children with high-risk disease.

Real-world data on the efficacy and tolerability of isatuximab with pomalidomide and dexamethasone (IsaPomDex) in relapsed/refractory myeloma patients have not been reported. In this UK-wide retrospective study, IsaPomDex outcomes were evaluated across 24 routine care cancer centers. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), duration of response (DOR) for patients who achieved an objective response (≥partial response [PR]), and adverse events (AEs). In a total cohort 107 patients, median follow up (interquartile range [IQR]) was 12.1 months (10.1–18.6 mo), median age (IQR) was 69 years (61–77). Median (IQR) Charlson Comorbidity Index (CCI) score was 3 (2–4); 43% had eGFR <60 mL/min. Median (IQR) number of prior therapies was 3 (3–3). Median (IQR) number of IsaPomDex cycles administered was 7 (3–13). ORR was 66.4%, with responses categorized as ≥ very good partial response: 31.8%, PR: 34.6%, stable disease: 15.9%, progressive disease: 15%, and unknown 2.8%. Median PFS was 10.9 months. Median DOR was 10.3 months. There was no statistical difference in median PFS by age (<65: 10.2 versus 65–74 13.2 versus ≥75: 8.5 mo, log-rank P = 0.4157), by CCI score (<4: 10.2 mo versus ≥4: 13.2, log-rank P = 0.6531), but inferior PFS was observed with renal impairment (≥60: 13.2 versus <60: 7.9 mo, log-rank P = 0.0408). Median OS was 18.8 months. After a median of 4 cycles, any grade AEs were experienced by 87.9% of patients. The most common ≥G3 AEs were neutropenia (45.8%), infections (18.7%), and thrombocytopenia (14%). Our UK-wide IsaPomDex study demonstrated encouraging efficacy outcomes in the real world, comparable to ICARIA-MM trial.

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The hierarchical framework of the adult blood system as we know it from current medical and hematology textbooks, displays a linear branching network of dividing and differentiated cells essential for the growth and maintenance of the healthy organism. This view of the hierarchy has evolved over the last 75 years. An amazing increase in cellular complexity has been realized; however, innovative single-cell technologies continue to uncover essential cell types and functions in animal models and the human blood system. The most potent cell of the hematopoietic hierarchy is the hematopoietic stem cell. Stem cells for adult tissues are the long-lived self-renewing cellular component, which ensure that differentiated tissue-specific cells are maintained and replaced through the entire adult lifespan. Although much blood research is focused on hematopoietic tissue homeostasis, replacement and regeneration during adult life, embryological studies have widened and enriched our understanding of additional developmental hierarchies and interacting cells of this life-sustaining tissue. Here, we review the current state of knowledge of the hierarchical organization and the vast heterogeneity of the hematopoietic system from embryonic to adult stages.

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It has been unclear what role metabolism is playing in the pathophysiology of chronic lymphocytic leukemia (CLL). One reason is that the study of CLL metabolism is challenging due to the resting nature of circulating CLL cells. Also, it is not clear if any of the genomic aberrations observed in this disease have any impact on metabolism. Here, we demonstrate that CLL cells in proliferation centers exhibit upregulation of several molecules involved in glycolysis and mitochondrial metabolism. Comparison of CXCR4/CD5 intraclonal cell subpopulations showed that these changes are paralleled by increases in the metabolic activity of the CXCR4lowCD5high fraction that have recently egressed from the lymph nodes. Notably, anti-IgM stimulation of CLL cells recapitulates many of these metabolic alterations, including increased glucose uptake, increased lactate production, induction of glycolytic enzymes, and increased respiratory reserve. Treatment of CLL cells with inhibitors of B-cell receptor (BCR) signaling blocked these anti-IgM-induced changes in vitro, which was mirrored by decreases in hexokinase 2 expression in CLL cells from ibrutinib-treated patients in vivo. Interestingly, several samples from patients with 17p-deletion manifested increased spontaneous aerobic glycolysis in the unstimulated state suggestive of a BCR-independent metabolic phenotype. We conclude that the proliferative fraction of CLL cells found in lymphoid tissues or the peripheral blood of CLL patients exhibit increased metabolic activity when compared with the bulk CLL-cell population. Although this is due to microenvironmental stimulatory signals such as BCR-engagement in most cases, increases in resting metabolic activity can be observed in cases with 17p-deletion.

The rapid evolution of genomic technologies over the last years has led to the development of different methods for the detection, measurement and analysis of cell-free DNA fragments (cfDNA) which are shed into the bloodstream by apoptotic cells and circulate at a low concentration in plasma. In cancer patients, the proportion of tumor-derived cfDNA is defined as circulating tumor DNA. This analysis, commonly known as liquid biopsy, allows to access tumor DNA through a simple blood sampling and therefore without the need of an invasive tissue biopsy. For this reason, this tool may have several clinical applications in terms of diagnosis, prognosis, and monitoring of minimal residual disease. However, there are still several critical issues that need to be resolved. In this review, we will discuss some of the controversies around this method and its potential clinical applications.

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Genotyping is not routinely performed at diagnosis of von Willebrand disease (VWD). Therefore, the association between genetic variants and pathogenic mechanism or the clinical and laboratory phenotype is unknown in most patients, especially in type 1 VWD. To investigate whether genotyping adds to a better understanding of the pathogenic mechanisms and variability in phenotype, we analyzed the VWF gene in 390 well-defined VWD patients, included in the WiN study. A VWF gene variant was found in 155 patients (61.5%) with type 1, 122 patients (98.4%) with type 2, and 14 patients (100%) with type 3 VWD. Forty-eight variants were novel. For each VWF gene variant, the pathogenic mechanisms associated with reduced VWF levels was investigated using the FVIII:C/VWF:Ag and VWFpp/VWF:Ag ratios. In type 1 VWD, reduced synthesis or secretion of VWF was most frequently found in patients with nonsense variants, frameshift variants, and deletions, whereas rapid clearance of VWF was mainly found in patients with missense variants. Furthermore, type 1 VWD patients with and without a VWF gene variant were clearly distinct in their clinical features such as age of diagnosis, laboratory phenotype, and bleeding phenotype. In type 2 VWD, 81% of variants were associated with an increased clearance of VWF. To conclude, we identified the pathogenic mechanisms associated with various VWF gene variants in type 1, 2, and 3 VWD patients. Additionally, major differences in the phenotype of type 1 VWD patients with and without a variant were observed, which may be of importance for clinical management.

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Measurable residual disease (MRD) quantified by multiparameter flow cytometry (MFC) is a strong and independent prognostic factor in acute myeloid leukemia (AML). However, several technical factors may affect the final read-out of the assay. Experts from the MRD Working Party of the European LeukemiaNet evaluated which aspects are crucial for accurate MFC-MRD measurement. Here, we report on the agreement, obtained via a combination of a cross-sectional questionnaire, live discussions, and a Delphi poll. The recommendations consist of several key issues from bone marrow sampling to final laboratory reporting to ensure quality and reproducibility of results. Furthermore, the experiences were tested by comparing two 8-color MRD panels in multiple laboratories. The results presented here underscore the feasibility and the utility of a harmonized theoretical and practical MFC-MRD assessment and are a next step toward further harmonization.

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Mastocytosis is a hematologic neoplasm characterized by expansion and focal accumulation of neoplastic mast cells (MC) in diverse organs, including the skin, bone marrow (BM), spleen, liver, and gastrointestinal tract. The World Health Organization classification divides the disease into prognostically distinct variants of cutaneous mastocytosis (CM) and systemic mastocytosis (SM). Although this classification remains valid, recent developments in the field and the advent of new diagnostic and prognostic parameters created a need to update and refine definitions and diagnostic criteria in MC neoplasms. In addition, MC activation syndromes (MCAS) and genetic features predisposing to SM and MCAS have been identified. To discuss these developments and refinements in the classification, we organized a Working Conference comprised of experts from Europe and the United States in August 2020. This article reports on outcomes from this conference. Of particular note, we propose adjustments in the classification of CM and SM, refinements in diagnostic criteria of SM variants, including smoldering SM and BM mastocytosis (BMM), and updated criteria for MCAS and other conditions involving MC. CD30 expression in MC now qualifies as a minor SM criterion, and BMM is now defined by SM criteria, absence of skin lesions and absence of B- and C-findings. A basal serum tryptase level exceeding 20 ng/mL remains a minor SM criterion, with recognition that hereditary alpha-tryptasemia and various myeloid neoplasms may also cause elevations in tryptase. Our updated proposal will support diagnostic evaluations and prognostication in daily practice and the conduct of clinical trials in MC disorders.

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This expert opinion originally developed by a panel of the Italian Society of Thalassemias and Hemoglobinopathies (SITE), reviewed and adopted by the European Hematology Association (EHA) through the EHA Scientific Working Group on Red Cells and Iron, has been developed as priority decision-making algorithm on evidence and consensus with the aim to identify which patients with transfusion-dependent beta-thalassemia (TDT) could benefit from a gene therapy (GT) approach. Even if the wide utilized and high successful allogeneic hematopoietic stem-cell transplantation provides the possibility to cure several patients a new scenario has been opened by GT. Therefore, it is important to establish the patients setting for whom it is priority indicated, particularly in the early phase of the diffuse use outside experimental trials conducted in high selected centers. Moreover, actual price, limited availability, and resources disposal constitute a further indication to a rational and progressive approach to this innovative treatment. To elaborate this algorithm, the experience with allogeneic transplantation has been used has a predictive model. In this large worldwide experience, it has been clearly demonstrated that key for the optimal transplant outcome is optimal transfusion and chelation therapy in the years before the procedure and consequently optimal patient’s clinical condition. In the document, different clinical scenarios have been considered and analyzed for the possible impact on treatment outcome. According to the European Medicine Agency (EMA) for the GT product, this expert opinion must be considered as a dynamic, updatable, priority-based indications for physicians taking care of TDT patients.

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As a result of significant recent developments, the management of patients with chronic lymphocytic leukemia (CLL) is changing, and new therapeutic options will continue to emerge in the near future. The recommendations of the French Innovative Leukemia Organization (FILO-CLL) group presented here are intended to provide practical recommendations for physicians taking care of CLL patients, taking into account the availability of both biological tests and therapies in daily practice in France at the time of publication. This text details the documented information and guidelines on diagnosis, indications for treatment, infectious complications and therapeutic strategies in frontline and relapsed CLL as well as in particular conditions such as autoimmune cytopenia or Richter syndrome.

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Infections are a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). These can be exacerbated by anti-leukemic treatments. In addition, the typical patients with CLL already have fragilities and background risk factors that apply to the general population for severe COVID-19. On these bases, patients with CLL may experience COVID-19 morbidity and mortality. Recurrent seasonal epidemics of SARS-CoV-2 are expected, and doctors taking care of patients with CLL must be prepared for the possibility of substantial resurgences of infection and adapt their approach to CLL management accordingly. In this Guideline Article, we aim at providing clinicians with a literature-informed expert opinion on the management of patients with CLL during SARS-CoV-2 epidemic.

In the light of the COVID-19 pandemic, the International Workshop on Waldenström Macroglobulinemia (IWWM) Treatment Recommendations Panel felt the need to provide a consensus statement for the management of Waldenström Macroglobulinemia (WM) patients during this challenging time. We followed the current recommendations by the American Society of Hematology, which have been modified accordingly to fit the specific realities associated with the management of WM. In this Consensus Statement, the Panel addresses questions related to treatment initiation, preferred therapies, minimizing visit to clinics and infusions centers, supportive care and guidance for WM patients in clinical trials. Finally, we also provide information on timing and appropriateness of testing and management of COVID-19 infected patients, as well as ways to get physicians and patients involved in registry studies that could help others.

The objective of this guideline is to aid clinicians in making individual salvage treatment plans for pediatric and adolescent patients with first relapse or refractory (R/R) classical Hodgkin lymphoma (cHL). While salvage with standard dose chemotherapy followed by high dose chemotherapy and autologous stem cell transplant is often considered the standard of care in adult practice, pediatric practice adopts a more individualized risk stratified and response adapted approach to salvage treatment with greater use of non-transplant salvage. Here, we present on behalf of the EuroNet Pediatric Hodgkin Lymphoma group, evidence and consensus-based guidelines for standardized diagnostic, prognostic and response procedures to allocate children and adolescents with R/R cHL to stratified salvage treatments.

Myeloid neoplasms (MNs) with germline predisposition have recently been recognized as novel entities in the latest World Health Organization (WHO) classification for MNs. Individuals with MNs due to germline predisposition exhibit increased risk for the development of MNs, mainly acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Setting the diagnosis of MN with germline predisposition is of crucial clinical significance since it may tailor therapy, dictate the selection of donor for allogeneic hematopoietic stem cell transplantation (allo-HSCT), determine the conditioning regimen, enable relevant prophylactic measures and early intervention or contribute to avoid unnecessary or even harmful medication. Finally, it allows for genetic counseling and follow-up of at-risk family members. Identification of these patients in the clinical setting is challenging, as there is no consensus due to lack of evidence regarding the criteria defining the patients who should be tested for these conditions. In addition, even in cases with a strong suspicion of a MN with germline predisposition, no standard diagnostic algorithm is available. We present the first version of the Nordic recommendations for diagnostics, surveillance and management including considerations for allo-HSCT for patients and carriers of a germline mutation predisposing to the development of MNs.

Healthy subjects frequently report minor bleedings that are frequently ‘background noise’ of normality rather than a true disorder. Nevertheless, unexpected or unusual bleeding may be alarming. Thus, the distinction between normal and pathologic bleeding is critical. Understanding the underlying pathologic mechanism in patients with an excessive bleeding is essential for their counseling and treatment. Most of these patients with significant bleeding will result affected by non-severe inherited bleeding disorders (BD), collectively denominated mild or moderate BD for their relatively benign course. Unfortunately, practical recommendations for the management of these disorders are still lacking due to the current state of fragmented knowledge of pathophysiology and lack of a systematic diagnostic approach. To address this gap, an International Working Group (IWG) was established by the European Hematology Association (EHA) to develop consensus-based guidelines on these disorders. The IWG agreed that grouping these disorders by their clinical phenotype under the single category of mild-to-moderate bleeding disorders (MBD) reflects current clinical practice and will facilitate a systematic diagnostic approach. Based on standardized and harmonized definitions a conceptual unified framework is proposed to distinguish normal subjects from affected patients. The IWG proposes a provisional comprehensive patient-centered initial diagnostic approach that will result in classification of MBD into distinct clinical-pathological entities under the overarching principle of clinical utility for the individual patient. While we will present here a general overview of the global management of patients with MBD, this conceptual framework will be adopted and validated in the evidence-based, disease-specific guidelines under development by the IWG.

Chronic myelomonocytic leukemia (CMML) is a disease of the elderly, and by far the most frequent overlap myelodysplastic/myeloproliferative neoplasm in adults. Aside from the chronic monocytosis that remains the cornerstone of its diagnosis, the clinical presentation of CMML includes dysplastic features, cytopenias, excess of blasts, or myeloproliferative features including high white blood cell count or splenomegaly. Prognosis is variable, with several prognostic scoring systems reported in recent years, and treatment is poorly defined, with options ranging from watchful waiting to allogeneic stem cell transplantation, which remains the only curative therapy for CMML. Here, we present on behalf of the European Hematology Association and the European LeukemiaNet, evidence- and consensus-based guidelines, established by an international group of experts, from Europe and the United States, for standardized diagnostic and prognostic procedures and for an appropriate choice of therapeutic interventions in adult patients with CMML.

On September 25, 2025, the Food and Drug Administration approved imlunestrant (Inluriyo, Eli Lilly and Company), an estrogen receptor antagonist, for adults with estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-negative, estrogen receptor-1 (ESR1)-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

On September 19, 2025, the Food and Drug Administration approved pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex, Merck) for subcutaneous injection for adult and pediatric (12 years and older) solid tumor indications approved for the intravenous formulation of pembrolizumab (Keytruda, Merck). See the prescribing information for the specific indications.

On September 10, 2025, the Food and Drug Administration approved selumetinib (KOSELUGO, AstraZeneca Pharmaceuticals LP) granules and capsules for pediatric patients 1 year of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). FDA previously approved selumetinib capsules for pediatric patients 2 years of age and older with NF1 who have symptomatic, inoperable PN.

On September 9, 2025, the Food and Drug Administration approved gemcitabine intravesical system (Inlexzo, Janssen Biotech, Inc.) for adults with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. Gemcitabine intravesical system is co-packaged with a urinary catheter and stylet used for insertion through the urinary catheter into the bladder.

On August 8, 2025, the Food and Drug Administration granted accelerated approval to zongertinib (Hernexeos, Boehringer Ingelheim Pharmaceuticals, Inc.), a kinase inhibitor, for adults with unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy.

On August 6, 2025, the Food and Drug Administration granted accelerated approval to dordaviprone (Modeyso, Jazz Pharmaceuticals, Inc.), a protease activator, for adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.

On July 2, 2025, the Food and Drug Administration granted accelerated approval to sunvozertinib (Zegfrovy, Dizal (Jiangsu) Pharmaceutical Co., Ltd.) for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

On July 2, 2025, the Food and Drug Administration granted accelerated approval to linvoseltamab-gcpt (Lynozyfic, Regeneron Pharmaceuticals, Inc.), a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, for adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody.

On June 23, 2025, the Food and Drug Administration granted accelerated approval to datopotamab deruxtecan-dlnk (Datroway, Daiichi Sankyo, Inc.) for adults with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy.

On June 18, 2025, the Food and Drug Administration approved tafasitamab-cxix (Monjuvi, Incyte Corporation) with lenalidomide and rituximab for adults with relapsed or refractory follicular lymphoma (FL).  

On June 12, 2025, the Food and Drug Administration approved pembrolizumab (Keytruda, Merck) for adults with resectable locally advanced head and neck squamous cell carcinoma (HNSCC) whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test, as a single agent as neoadjuvant treatment, continued as adjuvant treatment in combination with radiotherapy (RT) with or without cisplatin after surgery, and then as a single agent.

On June 12, 2025, the Food and Drug Administration approved mitomycin intravesical solution (Zusduri, UroGen Pharma) for adult patients with recurrent low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC).

On June 11, 2025, the Food and Drug Administration approved taletrectinib (Ibtrozi, Nuvation Bio Inc.), a kinase inhibitor, for adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).

On June 3, 2025, the Food and Drug Administration (FDA) approved darolutamide (Nubeqa, Bayer Healthcare Pharmaceuticals Inc.) for metastatic castration-sensitive prostate cancer (mCSPC). The FDA previously approved darolutamide in combination with docetaxel for mCSPC.

On May 15, 2025, the Food and Drug Administration approved retifanlimab-dlwr (Zynyz, Incyte Corporation) with carboplatin and paclitaxel for the first-line treatment of adults with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). The FDA also approved retifanlimab-dlwr, as a single agent, for adults with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy.

On May 14, 2025, the Food and Drug Administration granted accelerated approval to telisotuzumab vedotin-tllv (Emrelis, AbbVie Inc.), a c-Met-directed antibody and microtubule inhibitor conjugate, for adults with locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression [≥50% of tumor cells with strong (3+) staining], as determined by an FDA-approved test, who have received a prior systemic therapy.

On May 14, 2025, the Food and Drug Administration approved belzutifan (Welireg, Merck & Co., Inc.) for adult and pediatric patients 12 years and older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma (PPGL). This represents the first FDA approval of an oral therapy for PPGL.

On May 8, 2025, the Food and Drug Administration granted accelerated approval to the combination of avutometinib and defactinib (Avmapki Fakzynja Co-pack, Verastem, Inc.) for adult patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy.

On April 23, 2025, the Food and Drug Administration approved penpulimab-kcqx (Akeso Biopharma Co., Ltd.) with cisplatin or carboplatin and gemcitabine for the first-line treatment of adults with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC).

On April 11, 2025, the Food and Drug Administration approved nivolumab (Opdivo, Bristol Myers Squibb Company) with ipilimumab (Yervoy, Bristol Myers Squibb Company) for the first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC).

On April 8, 2025, the Food and Drug Administration approved nivolumab (Opdivo, Bristol Myers Squibb Company) with ipilimumab (Yervoy, Bristol Myers Squibb Company) for adult and pediatric patients 12 years of age and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC). The FDA also converted the accelerated approval to regular approval for single agent nivolumab for adult and pediatric patients 12 years of age and older with MSI-H or dMMR metastatic CRC, that has progressed following fluoropyrimidine, oxaliplatin, and irinotecan.

On March 28, 2025, the Food and Drug Administration approved durvalumab (Imfinzi, AstraZeneca) with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent durvalumab as adjuvant treatment following radical cystectomy, for adults with muscle invasive bladder cancer (MIBC).

On March 28, 2025, the Food and Drug Administration expanded the indication for lutetium Lu 177 vipivotide tetraxetan (Pluvicto, Novartis Pharmaceuticals Corporation) to include adults with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibitor (ARPI) therapy and are considered appropriate to delay taxane-based chemotherapy.

On March 26, 2025, the Food and Drug Administration approved cabozantinib (Cabometyx, Exelixis, Inc.) for adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET) and well-differentiated extra-pancreatic neuroendocrine tumors (epNET). 

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