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The addition of encorafenib and cetuximab to mFOLFOX6 chemotherapy improved outcomes in the primary treatment of metastatic BRAF V600E–mutated colorectal cancer.

A 63-year-old woman was evaluated for dyspnea and edema. Soft-tissue thickening was noted in the retroperitoneum and mediastinum and around the heart and vessels. A diagnosis was made.

A 69-year-old man with multiple myeloma presented with an enlarging purple skin mass on his right shoulder at the surgical site of a recent intramedullary nailing of a humerus fracture.

Neoadjuvant PD-1 blockade with dostarlimab led to organ preservation in a high proportion of patients with early-stage mismatch repair–deficient tumors, with no compromise of surgical options.

In papillary kidney cancer, particularly hereditary leiomyomatosis–associated cases, bevacizumab plus erlotinib showed strong antitumor activity. The likelihood of a response was higher in hereditary cases than in sporadic ones.

In adults with myasthenia gravis, treatment with intravenous inebilizumab, a CD19-specific monoclonal antibody, significantly improved function and reduced disease severity at 26 weeks.

Among patients with tumors harboring tyrosine kinase domain mutations who received zongertinib (a selective inhibitor of the HER2 tyrosine kinase), 71% had a response, and median progression-free survival was 12.4 months.

Myasthenia gravis, an immune-mediated neurologic disorder, has for the past century been treated effectively with various immunotherapies, ranging from thymectomy to approved targeted agents.1,2 The neuromuscular transmission defect of myasthenia gravis is driven by autoreactive immunoglobulins directed postsynaptically. Hence, it is no large leap to posit that therapies...

In the treatment of patients with mismatch repair–deficient (dMMR), metastatic solid tumors, checkpoint blockade has ushered in a revolutionary change, marked by profound and, more importantly, durable responses.1-3 As neoadjuvant therapy, programmed cell death 1 (PD-1) blockade alone or in combination with cytotoxic T-lymphocyte–associated antigen 4 blockade has...

In a phase 3 trial, the addition of neoadjuvant and adjuvant pembrolizumab to standard care improved event-free survival among participants with locally advanced head and neck cancer without affecting surgical outcomes.

Head and neck squamous-cell carcinoma (HNSCC) can arise in response to environmental carcinogens (tobacco and alcohol) or malignant transformation from viral infection (Epstein–Barr virus in the nasopharynx and human papillomavirus [HPV] in the oropharynx). It manifests most frequently as locoregionally advanced HNSCC and is treated with curative-intent surgery and postoperative...

Despite the potential for drug-price negotiation to help rein in spending, several provisions in the Inflation Reduction Act may limit Medicare’s new negotiating authority for biologics.

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.

Among patients undergoing stem-cell transplantation from matched related donors, cyclophosphamide plus cyclosporin led to significantly longer GVHD-free, relapse-free survival than standard prophylaxis.

Liver-targeting adeno-associated virus–mediated gene therapy led to stable long-term factor IX expression and a decrease in bleeding episodes for up to 13 years in 10 men with hemophilia B.

In this trial involving adult patients undergoing elective cardiac surgery, acute normovolemic hemodilution did not reduce the number of patients receiving allogeneic red-cell transfusion.

Two patients had autoimmune hemolytic anemia that relapsed after CD19 CAR T-cell therapy but responded rapidly to BCMA-targeted T-cell–engager therapy with remission, minimal side effects, and hematologic improvement.

In women with node-positive breast cancer whose nodes became free of disease after neoadjuvant therapy, regional nodal irradiation did not reduce breast cancer recurrence or improve survival.

In this randomized trial, biopsy of indeterminate pulmonary lesions with navigational bronchoscopy was noninferior to that with transthoracic needle biopsy and led to fewer complications.

The switch from fetal γ-globin to adult β-globin is controlled by BCL11A. Genetic manipulation of BCL11A improves disease outcomes by turning γ-globin expression back on to compensate for mutant β-globin.

Considered a disease of middle-aged and older adults until the late 20th century, type 2 diabetes has risen markedly worldwide in people under 40 years, with prevalence now exceeding 15% in some countries. The growing burden of early-onset type 2 diabetes forms the focus of a new Series published in The Lancet, which argues that existing approaches are failing to meet the needs of younger people. The disease poses unique challenges. Prolonged duration of type 2 diabetes is associated with rapid progression to complications and multiple long-term conditions.

Type 2 diabetes is characterised by insulin resistance and progressive β-cell decline. Around a third of the people with type 2 diabetes require insulin by 8 years after diagnosis.1 Despite the availability of non-insulin glucose-lowering drugs, there has been no decline, and even a mild increase, in the prevalence of insulin use in real-world studies.2,3 Fear of hypoglycaemia and the frequency of insulin injections negatively affect patient acceptance and adherence to optimal insulin use, especially in older adults.

Sub-Saharan Africa has the highest maternal mortality rate in the world, estimated in 2020 to be 545 maternal deaths per 100 000 livebirths, more than 136 times higher than that of the lowest region.1 In Sierra Leone, adolescent girls (aged 10–19 years) account for up to 40% of all maternal deaths, nearly all of which are preventable.2,3 Efforts to prevent adolescent pregnancies have had limited success, and comprehensive approaches to optimising child and adolescent health are badly needed.4

Treatment-resistant schizophrenia is a disabling illness, affecting approximately 8 million people worldwide with profound effects on patients, families, and society.1,2 Clozapine is the gold standard medication for treatment-resistant schizophrenia and remains the only licensed treatment for this indication. It is clinically effective in 40% of patients with treatment-resistant schizophrenia,3 and improves patients’ quality of life, reduces premature mortality, and is cost-effective.4,5 Furthermore, once commenced on clozapine, the majority of patients prefer clozapine to their previous antipsychotic medications.

In May, 2025, the World Health Assembly (WHA) will vote on re-establishing a mandate for WHO to address the health consequences of nuclear weapons and war.1 Health professionals and their associations should urge their governments to support such a mandate and support the new UN comprehensive study on the effects of nuclear war.

WHO's policy framework for healthy ageing from the World Report on Ageing and Health recognises frailty as the foremost geriatric syndrome in older adults and a key determinant of functional ability.1 Frailty poses a major public health challenge, with a substantial impact on the people living with it, their families, health-care systems, and social support services.1,2 However, frailty is a poorly understood condition globally. Without an adequate understanding of frailty and its causal pathways, policy makers cannot develop effective preventive strategies to reduce frailty prevalence and its associated burden.

Conservative justices agreed with the state and Trump administration that banning minors’ treatment for gender dysphoria is not discriminatory. Susan Jaffe reports.

Gilead's lenacapavir approval by the US Food and Drug Administration (FDA) marks a milestone in HIV prevention, but experts warn over its expense. Sophie Cousins reports.

The House of Commons has approved the Terminally Ill Adults Bill amid narrowing support and ongoing debate. Jacqui Thornton reports.

In March, 2024, Safiyyah Abbas and Lucy Mitchell1 highlighted the atrocities unfolding in Gaza and the failure of Australian medical institutions to mount a meaningful protest. Since then, the Israeli Government's sustained and widespread assaults on civilians—combined with deliberate obstruction of food, water, fuel, and medical supplies—have prompted the International Criminal Court to issue arrest warrants for Israeli leaders, Benjamin Netanyahu and Yoav Gallant, for the war crime of starvation as a method of warfare, and the crimes against humanity of murder, persecution, and other inhuman acts.

The abrupt cessation of global health funding has placed millions of lives at risk.1 This sudden funding freeze violates basic bioethical principles and values, including human rights, universality, and equity as part of WHO's constitution and guidance for ethical research, and does not have adequate transition plans to care and clinical services.2 Working with member states, WHO has led the eradication of smallpox and contributed to drastic reductions in other major public health threats. WHO staff have been on the front lines of conflicts and natural disasters, ensuring life-saving help reaches those in need.

Yellow fever was once mainly sylvatic in remote Colombian regions throughout the 20th century. However, the 21st century has seen the re-emergence of yellow fever in endemic zones and it has spread to populated areas, raising the risk of urban outbreaks due to ecoepidemiological shifts.

The current mpox outbreak in Sierra Leone is the largest ever recorded in the country and the first major epidemic caused by the clade IIb monkeypox virus in Africa. Since a public health emergency was declared on Jan 13, 2025,1 3682 confirmed cases have been reported in Sierra Leone (as of June 4, 2025), with 2225 (60·4%) cases in Freetown (western urban), 748 (20·3%) cases in nearby suburban towns (western rural), and 709 (19·3%) cases distributed across the 14 other districts. Case numbers remained low throughout mid-April, but surged in late April (week 17) and throughout May, exceeding 600 confirmed cases weekly and indicating sustained transmission despite early signs of stabilisation (unpublished data).

We write to highlight an urgent, yet preventable public health tragedy unfolding in the Ecuadorian Amazon. In May, 2025, eight Indigenous Achuar children from Taisha—an Amazonic village from the Morona Santiago province—died from leptospirosis,1 a zoonotic disease transmitted through contact with contaminated water or soil. The outbreak involved at least 46 symptomatic individuals,2 some with confirmed co-infections of dengue virus and Salmonella spp.3

Huseyin Naci and colleagues1 suggest lowering the quality-adjusted life-year (QALY) threshold for new drugs, thereby reducing the potential negative effect on population health by opportunity costs.

Huseyin Naci and colleagues1 estimated a net loss of approximately £1·25 million quality-adjusted life-years (QALYs) in the National Health Service (NHS) due to the adoption of new drugs, with costs per QALY exceeding £15 000.1 In an accompanying Comment,2 Victoria Charlton stated the Article1 contributes to existing evidence that decisions by National Institute for Health and Care Excellence (NICE) might not be ethically justified, implying that the cost-effectiveness thresholds used by NICE might be too high.

Analysis by Huseyin Naci and colleagues1 overlooks the broader policy context influencing the National Health Service expenditure on branded medicines. The Department of Health, through the Voluntary Scheme for Branded Medicines Pricing and Access scheme and the commercially equivalent statutory scheme,2 ensures the branded medicines budget growth rate (2%)2 remains below the overall health-care budget growth rate (5·9%).3 If the National Institute for Health and Care Excellence (NICE)'s decisions lead to expenditure surpassing the agreed amount, the pharmaceutical industry covers the excess via rebates—estimated to be 22·9% of branded medicine sales revenue in 2025.

The conclusion from Huseyin Naci and colleagues1 that more quality-adjusted life-years (QALYs) would have been gained if funding for new drugs was allocated elsewhere crucially relies on an opportunity cost estimate of £15 000 per QALY.1 A key question, however, is how should the funding have been allocated? Medicines make up less than 12% of National Health Service spending2 and most expenditure—more than £70 billion—is on salaries.

We appreciate the responses to our Article,1 which suggest that the health cost of paying for new pharmaceuticals in the National Health Service (NHS), estimated at £1·25 million quality-adjusted life-years (QALYs) lost between 2000 and 2020, might be justified by the benefits of incentivising future innovation, attracting industry funding, or prioritising certain populations—we disagree.

Kloppenburg M, Namane M, Cicuttini F. Osteoarthritis. Lancet 2025; 405: 71–85—In this Seminar, the Risk factors section has been updated to: “Particularly in women, sarcopenic obesity seems to play a role,8 which aligns with a recent systematic…”. The Genetics section has been amended to: “Genetic correlations have also been seen with pain phenotypes.16,17 These genes could be…”, and “…other phenotypes of osteoarthritis,16 and is involved in…”. The Pathogenesis section has been updated to: “…microtrauma that might interplay with genetic susceptibility…”.

Efsitora is a well tolerated and efficacious once-weekly alternative to daily basal insulin, with a reduced injection frequency, for the treatment of adults with type 2 diabetes.

Efsitora showed non-inferior HbA1c reductions and similar rates of combined clinically significant or severe hypoglycaemia versus glargine U100 in participants with type 2 diabetes treated with basal and prandial insulin. These findings show that efsitora is a well tolerated and efficacious once-weekly alternative to daily basal insulin, with a reduced injection frequency, for the treatment of adults with type 2 diabetes.

2YoungLives, a community-based mentoring intervention for adolescent girls from pregnancy up to 1 year after birth, was feasible to implement in urban and rural communities in Sierra Leone and significantly reduced a composite of maternal deaths, stillbirths and neonatal deaths.

The incidence of early-onset type 2 diabetes is increasing, with a growing number of cases now occurring in children, adolescents, and young adults. This transition is primarily driven by the rising prevalence of obesity in younger populations, especially in high-income countries. However, the relationship between obesity and early-onset type 2 diabetes varies across ethnic groups, with some populations exhibiting a higher risk at lower BMI thresholds, possibly due to differences in insulin resistance and β-cell function.

Early-onset type 2 diabetes (defined as type 2 diabetes diagnosed in people aged <40 years) is increasingly prevalent with substantial health and socioeconomic implications. Unlike late-onset type 2 diabetes, early-onset type 2 diabetes is a high-risk and aggressive phenotype, with accelerated pancreatic β-cell decline and greater insulin resistance due to the rising rate of obesity. People with early-onset type 2 diabetes have higher rates of macrovascular and microvascular complications with increased health-care use and premature mortality (due to cardiovascular and non-cardiovascular complications) than do people with late-onset type 2 diabetes.

Early-onset type 2 diabetes (defined as type 2 diabetes diagnosed in people aged <40 years) is an increasingly prevalent condition with a more aggressive disease trajectory than late-onset type 2 diabetes. It is associated with accelerated microvascular and macrovascular complications, reduced life expectancy, and adverse pregnancy outcomes. Despite its rising incidence, global management strategies have mostly been extrapolated from studies in older adults with limited evidence specific to younger populations.

April 30, 2025, marked the first 100 days of President Donald Trump's second term in office—and the most tumultuous period in modern American politics. Among the maelstrom of ill-conceived and devastating executive orders there has been an “all-out assault” on the environment that could take “a generation or more to repair”, according to the environmental nonprofit organisation, Natural Resources Defense Council.

Cancer is a progressive disease that can lead to high symptom burden, functional decline, and substantial morbidity. Treatment for cancer can also result in substantive symptomatic adverse reactions. Because of the effects of both disease and treatment on patient functioning and wellbeing, symptom and functional assessments have played an important role in the clinical development of cancer therapies. The assessment of symptoms, function, and their impact on health-related quality of life (HRQoL) assessed by patient-reported outcomes (PROs) emerged in the 1980s and has since gained recognition as important information for measuring the efficacy and safety assessment of cancer drugs.

With the increasing use of prostate-specific membrane antigen (PSMA) PET imaging for early biochemical recurrence after definitive treatment for prostate cancer, small and limited nodal recurrences within the pelvis are detected more frequently than with conventional imaging.1 However, there is an ongoing debate regarding the best treatment for such lesions, as current evidence mainly relies on conventional imaging. The STOMP and ORIOLE trials have shown a cancer control benefit of metastasis-directed therapy (MDT) in patients with oligorecurrent prostate cancer.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of unresectable hepatocellular carcinoma (HCC), replacing multi-tyrosine kinase inhibitors (TKIs) as first-line therapies for most patients. Following positive phase 3 trials, atezolizumab–bevacizumab and durvalumab–tremelimumab are now guideline-recommended in multiple countries, and nivolumab–ipilimumab has recently received approval from the European Medicines Agency.1,2 Although ICIs with anti-angiogenics or dual immune checkpoint blockade have an established role in HCC management, attempts to add ICIs to TKIs have yielded inconsistent results.

Gastric cancer is the fifth most common malignancy, with 968 000 new cases and 659 000 deaths reported worldwide in 2022.1 Early-onset gastric cancer, as is the case for other gastrointestinal malignancies, is steadily increasing. Most patients with gastric cancer have locally advanced or metastatic disease at diagnosis; systemic therapy is used for all but the earliest stages. Cytotoxic chemotherapy remains an important part of multimodal therapy for operable gastric cancer and is the primary treatment for incurable disease.

Two studies in The Lancet Oncology address the role of risk-reducing salpingo-oophorectomy and mastectomy to reduce the risk of ovarian and breast cancers in BRCA pathogenic variant carriers. Risk-reducing surgery is not a new concept. In a 1958 editorial, Culiner1 addressed the controversial practice of oophorectomy at the time of hysterectomy to reduce ovarian cancer risk, concluding that “the most favorable results will probably be achieved by pondering the individual merits of the procedure,” and predicting personalised medicine's role today, nearly 70 years ago.

As cancer treatments improve, survival increases—alongside the potential for subsequent neoplasms (SNs). Survivors of childhood cancer (diagnosed aged 0–14 years) are particularly vulnerable to subsequent neoplasms; a 2024 Swiss report found they had a six times higher SN risk than age-peers without a primary cancer.1 Survivors of adolescent and young adult (AYA) cancers (diagnosed aged 15–39 years) had a two times higher risk, and those first diagnosed after age 40 years had a 1·2 times higher risk of SNs.

After complete surgical resection of a localised tumour there is an inherent risk for local or systemic recurrence. Neoadjuvant, adjuvant, or neoadjuvant and adjuvant (so called perioperative) treatments are administered with the aim to reduce this risk of recurrence and, ultimately, to increase cure rate. As for any anti-cancer treatment, although overall there is a regulatory expectation of benefit at population level, benefits and harms are not uniformly distributed. In perioperative settings, this contrast is particularly pronounced; some patients not cured by surgery alone might derive a clear benefit, yet others cured by surgery alone might suffer unacceptable or long-term toxicity.

The cancer workforce in Europe is facing an unprecedented crisis that is affecting the quality of care for people with cancer. Cancer is one of the leading causes of morbidity and mortality in Europe, and its incidence is rising, with the International Agency for Research on Cancer predicting 5·4 million cancer cases across Europe by 2045. Therapeutic advances are making cancer treatment more complex. Additionally, the cancer care workforce is not growing fast enough to keep pace; WHO estimates that the shortfall in health-care providers will reach 18 million by 2030.

Sustainable and affordable access to oncology drugs is an increasing issue worldwide, including in Europe.1 Due to the increasing incidence of cancer, more registered treatment options, and rising treatment costs,2 there is a growing need to ensure reliable and equal access to these life-saving medications. Additionally, the environmental sustainability of oncology drugs is an urgent challenge because prescription medications are among the largest contributors to health-care's carbon emissions3 and pose an additional environmental burden relating to pharmaceutical pollution.

The extended analysis of the Young-PEARL trial, reported by Hee Kyung Ahn and colleagues in The Lancet Oncology, has shown sustained improvement in progression-free survival with palbociclib plus exemestane and ovarian function suppression over capecitabine in premenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who recurred or progressed during or after previous tamoxifen treatment.1 Considering the progression-free survival benefit, albeit with no improvement in overall survival, the authors showed that the upfront use of palbociclib plus endocrine therapy is the preferred treatment option for premenopausal women.

We appreciate the interest shown by Wenjin Yin and colleagues in our Article and their thoughtful observation regarding the overall survival analysis, which might raise questions about the proportional hazards assumption and the appropriate statistical method.

We read with interest Hervé Bonnefoi and colleagues’ Article on the UCBG 3-06 START non-comparative, randomised, phase 2 trial.1 Although we congratulate the authors on completing the trial, we are concerned that the design of UCBG 3-06 START as a non-comparative randomised trial might have undercut its value and interpretation.

Lou E, Choudhry MS, Starr TK, et al. Targeting the intracellular immune checkpoint CISH with CRISPR-Cas9-edited T cells in patients with metastatic colorectal cancer: a first-in-human, single-centre, phase 1 trial. Lancet Oncol 2025; 26: 559–70—In this Article, several appendix citations referred to the incorrect page and have been updated, and a corrected appendix file has been uploaded. Additionally, minor typographical errors have been amended. These changes have been made to the online version of the Article, as of May 28, 2025.

The USA appeared to move closer to imposing tariffs on pharmaceuticals after filing a federal notice on April 14, 2025, announcing an investigation into whether medicine and active ingredient imports threaten national security.

Te Aho o Te Kahu, the New Zealand Government's Cancer Control Agency, is creating a new national chemotherapy database that will enable monitoring of treatment outcomes for ovarian cancer on a country-wide scale.

The UK Government should negotiate better regulations for clinical trials, drug imports, and employing European scientists to lessen the blow to science caused by Britain's exit from the EU in 2020, says a March, 2025 report entitled Nothing should stand in the way by the charity Cancer Research UK.

UK scientists, including cancer researchers, are reaping the rewards of the return to the EU's Horizon research programme, with EU data showing more than £500 million (US$670 million) in funding awarded to UK research teams since the country was granted Associate Membership on the programme in December 2023, under the former government of then UK Prime Minister Rishi Sunak.

According to Gert De Meerleer (University Hospitals Leuven, Belgium) and colleagues, adding elective para-aortic radiotherapy to whole pelvic radiotherapy along with androgen deprivation therapy yields excellent oncological outcomes. With a median follow-up of 50 months, an interim analysis of 96 patients with pN1 prostate cancer enrolled into a phase 2 trial showed 5-year clinical recurrence-free survival (cRFS) of 81% (95% CI 71–90), with significantly better cRFS in patients receiving adjuvant radiotherapy versus those given salvage radiotherapy (92% vs 76%; p=0·029).

The health insurance system in Japan faces political manoeuvring ahead of the House of Councillors elections in July, 2025.

The benefit-risk assessment of cancer treatments usually focuses on traditional clinical and disease outcomes, such as overall survival, progression-free survival, and tumour response, balanced against clinician-reported adverse events. Patient-reported outcomes (PROs) measuring symptoms, functioning, and other health-related quality of life (HRQOL) impacts can be used to ensure that a drug's effect on symptoms and functioning are quantified and evaluated as part of cancer clinical research and drug development.

In 2023, we reported on two patients with metastatic head and neck squamous cell carcinoma (HNSCC) with different responses to immune checkpoint inhibitor (ICI)-based treatment.

The online BREAKING-ICE App, where ICE stands for informative censoring exploration, is designed to visually demonstrate the impact of informative censoring on trial outcomes. The app aims to transform informative censoring, at times perceived as a dry statistical notion disconnected from clinical practice, into a clear and intuitive concept.

Not Much Rhymes with Cancer: A Book of Healing Poems (Valley Press, 2024) is a collection of poems by Emily Thomas, described by the author as “mostly a tale of hope, positivity and gratitude”. Compiled after Thomas’ diagnosis of stage IV breast cancer at the age of 38 years and published posthumously by her friends and family, Not Much Rhymes with Cancer contains a variety of powerful and emotional poems that explore life with cancer and reveal the honesty and vulnerability with which Thomas treated her writing—many of them first being publicised on her Instagram page.

To our knowledge, this is the first randomised trial for metachronous PET-detected nodal recurrences comparing two local treatment approaches (MDT and ENRT) in combination with 6 months of androgen deprivation therapy. By showing an improved metastasis-free survival with ENRT, this trial establishes ENRT as a potential standard treatment approach, awaiting a phase 3 trial confirming these results.

Good 6-month complete clinical responses rates were seen in both groups. Early results suggest rd-IMRT is well tolerated with oncological outcomes maintained. 3-year locoregional failure rates are awaited.

Anlotinib plus penpulimab significantly improved progression-free survival and overall survival versus sorafenib in unresectable HCC and might be a new first-line option. These findings require verification in other regions of the world.

The modified FLOT/TFOX regimen significantly improved progression-free survival, overall survival, and objective response rate compared with FOLFOX in previously untreated patients with advanced HER2-negative gastric and gastro-oesophageal junction adenocarcinoma. The modified FLOT/TFOX regimen might represent a new first-line treatment option for patients eligible for this docetaxel triplet chemotherapy.

Zanidatamab plus palbociclib and fulvestrant was generally safe and showed promising antitumour activity, supporting further evaluation of this chemotherapy-free triplet regimen.

In this global cohort of BRCA carriers with previous breast cancer diagnosis at a young age, RRM and RRSO were both associated with a significant improvement in overall survival. These findings provide evidence for a tailored counselling of a unique and high-risk patient population on cancer risk management strategies.

The evidence supports offering BSO to BRCA1 and BRCA2 pathogenic variant carrriers with a personal history of breast cancer, as they appear to benefit from having the procedure, without evidence of an increased risk of adverse long-term health outcomes.

The targeted-therapy induction regimen did not improve progression-free survival compared with first-line treatment with immune checkpoint inhibitors in unselected patients with advanced melanoma with BRAFV600E or BRAFV600K mutations.

Enfortumab vedotin plus pembrolizumab significantly improved survival outcomes versus platinum-based chemotherapy without detriment to GHS/QOL, pain, or functioning. Patients with moderate to severe baseline pain had clinically meaningful improvements in worst pain and GHS/QOL with enfortumab vedotin plus pembrolizumab. These data provide further evidence to support the use of enfortumab vedotin plus pembrolizumab as a preferred treatment option for patients with previously untreated locally advanced or metastatic urothelial cancer.

Cancer treatments and genetic predisposition are primary contributors to the risk of SNs in childhood cancer survivors, and lifestyle factors seem to have a minimal effect. These results highlight the crucial need to consider both treatment history and genetic factors in developing effective risk assessment and surveillance strategies for this vulnerable population.

Survivors of head and neck cancer have complex nutritional and supportive care needs. These needs result from the tumour's proximity to organs essential for normal eating function and the intensive treatment targeting those organs. Despite the crucial role of nutrition and supportive care in head and neck cancer, research and funding are lacking compared with other cancer types. This Review was compiled and written by a team of multidisciplinary medical professionals. Topics include poor access to medical nutrition therapy (MNT), MNT reimbursement policies, long-term survivorship care needs, percutaneous endoscopic gastrostomy tube placement, nutrition literacy, psychological services, speech–language pathology care, and concomitant physical activity.

Cancer is a global health challenge, with considerable disparities in care and outcomes across regions. Up to half of health outcome disparities are driven by social determinants of health. Addressing these disparities has become a priority. The Commonwealth of Nations—an international association of 56 countries tied together by common language and historical heritage—has a focus on universal health coverage, yet cancer incidence rates are rising, especially in the low-income and middle-income country (LMIC) member nations, where cancers caused by communicable diseases, such as cervical cancer, are prevalent.

In this Policy Review, we examine cancer incidence and mortality rates across Latin America and the Caribbean, focusing on national cancer control plans (NCCPs) as frameworks for reducing the cancer burden in the region. By 2022, only 16 countries had active NCCPs, with eight being cancer specific and eight being integrated into public health plans. Our analysis found that dedicated NCCPs were linked to reduced cancer incidence but not reduced mortality. Broader socioeconomic indicators, such as universal health coverage and a higher Human Development Index, were more strongly associated with improved cancer outcomes, including reduced mortality-to-incidence ratios.

A 67-year-old woman presented to Qingdao Chengyang People's Hospital (Shandong, China) with a 5-day history of a left breast mass in December, 2024. Physical examination showed a palpable mass measuring 3·5 cm × 4·0 cm in the outer upper quadrant of the left breast, with no palpable axillary lymph nodes. The mass was firm, with ill-defined margins, restricted mobility, and mild tenderness. There were no other systemic abnormalities, such as gingival hypertrophy or hepatosplenomegaly. The patient denied any history of infection or surgical trauma.

The past decades have seen a vast increase in the number of available therapeutics for patients with haemato­logical malignancies. Treatment decisions are becoming increasingly complex, and some cancers are now treated as chronic diseases which can have unique side-effects from continuous treatment. Although some treat­ments provide large benefits, many new approved treat­ments do not necessarily help patients live longer or better. With this wider range of choice, taking into consideration the associated adverse events of these treatments becomes increasingly important to consider alongside survival outcomes.

Blood donor management has traditionally relied on haemoglobin-based deferral policies, despite ferritin's superior sensitivity for detecting iron deficiency. Although haemoglobin remains a central criterion for donation eligibility, iron depletion can occur even in donors with normal haemoglobin concentrations. In The Lancet Haematology, Wanjin Li and colleagues introduce machine learning models predicting next-donation haemoglobin concentrations and ferritin recovery, aiming to mitigate iron depletion in frequent blood donors.

The start of the 21st century has brought remarkable growth in the number of novel therapeutics approved for the treatment of different cancer types, particularly in haematological malignancies. Between 2000 and 2020, for example, the United States Food and Drug Administration approved 206 novel cancer therapies for 573 indications across solid tumours and malignant haematological diseases: annual approvals increased from 7·4 per year for 2000–2004 to 56 per year for 2017–2022. Targeted drugs and biologics for leukaemia, lymphoma, and myeloma were disease areas with a surge in products approved after 2015 (figure).

Haematological malignancies encompass a heterogeneous group of life-threatening disorders, including leukaemias, lymphomas, and myelomas, which need intricate and frequently intensive therapeutic interventions. Advances in chemotherapy, targeted therapies, and immunotherapies have transformed outcomes; however, these treatments are associated with substantial toxic effects, leading to severe and sometimes fatal adverse events. Effective management of these events is crucial to optimising survival, maintaining quality of life, and ensuring treatment adherence.

Health-care professionals are faced with the challenge of communicating diagnostic, treatment, and prognostic information to patients. Communication about a venous thromboembolism diagnosis often occurs in a chaotic acute care setting. These settings might be crowded, noisy, and anxiety-provoking, making effective communication and shared decision-making challenging. As a result, patients may lack trust in their health-care professional and perceive their care to be inferior, which could exacerbate anxiety.

“The first patient during my haematology–oncology fellowship had well controlled chronic lymphocytic leukaemia. From the moment she walked through the door, I knew I was going to utilise the skills I refined during 4 years practicing as a general internist prior to fellowship. The patient had been dizzy for the previous week, unable to walk without feeling that she would fall, actively avoiding ambulation and driving. She had presented to urgent care and was prescribed meclizine without improvement.

Long-term data indicate durable haemolysis control with iptacopan in paroxysmal nocturnal haemoglobinuria, maintained normal or near-normal haemoglobin, and no new safety concerns. We believe that these data support iptacopan as a potential therapy option, suggesting that we are in a new treatment era for paroxysmal nocturnal haemoglobinuria.

Machine-learning models predicting haemoglobin and ferritin at return donations generalised well across diverse settings and could enable individualised approaches to manage iron deficiency while maintaining a sufficient blood supply.

The regimen of 12 Gy in four fractions is safe and shows promising activity as a local treatment for patients with indolent non-Hodgkin lymphoma. Given the retrospective registration of the trial, further studies evaluating the efficacy of this strategy are warranted.

As the therapeutic landscape in haematological malignancies has evolved from traditional chemotherapies to novel biological, targeted, and cellular therapies, adverse event profiles have accordingly shifted with emerging and newly described chronic, cumulative, and delayed symptomatic adverse events. The current standard of toxicity reporting in clinical trials, centred on maximum-grade adverse events, is wholly inadequate for characterising the tolerability of therapies in the modern era. As such, the science of adverse event measurement, analysis, and reporting in clinical trials needs to evolve with our ever-growing repertoire of therapeutics to facilitate more comprehensive and accurate toxicity assessment for treatment decision making.

Incorporating patient-generated data into drug development is crucial for assessing the tolerability of treatments, particularly in patients with haematological malignancies, some of whom receive high-intensity, short-duration treatments and others who endure chronic therapies for months to years at a time. With increasing use of novel therapies such as oral targeted agents and immunotherapy, including chimeric antigen receptor T-cell therapy and bispecific antibodies across different haematological malignancies, new types of toxicity assessment techniques that harness patient-generated data, including patient-reported outcomes (PROs) are required to fully evaluate short-term and long-term side-effects.

The increasing use of immunotherapeutic approaches, cellular therapies, and targeted agents is rapidly and profoundly changing the treatment paradigms of haematological malignancies. These novel therapies are increasingly incorporated into earlier lines of treatment. Some are administered for a fixed duration, often with curative intent, whereas others are administered chronically for disease control. The associated acute, mid-term, and long-term toxic effects can differ markedly from conventional cytotoxic chemotherapy and radiotherapy.

A woman in her fifties attended our institution for evaluation of epistaxis. She had a history of limited cutaneous systemic sclerosis that was diagnosed in her thirties after the onset of intermittent digital claudication and ulceration, oedematous thickening of the skin of her hands, gastrointestinal reflux disease, and positive anti-centromere antibodies. Physical examination was notable for small, flat, red lesions of varying round or elongated morphologies present diffusely across the palmar surface of both hands, consistent with telangiectasias (figure A).

In this population‐based study of 777 patients with T1 glottic squamous cell carcinomas, no significant difference in overall survival was observed at 5 years based on treatment modality (MLS or RT). Overall survival was worse for patients with T1b carcinomas, and these patients were at an elevated risk of requiring laryngectomy. An increased risk of recurrence within 3 years was observed after surgical treatment for both T1a and T1b tumors.

These consensus recommendations provide guidance regarding the management of appendiceal tumors with peritoneal involvement, including a review of current evidence in the management of recurrent and unresectable disease.

The consensus‐driven clinical pathway for gastric cancer with synchronous peritoneal metastases offers vital clinical guidance for practitioners. There is a growing body of high‐quality evidence to support management strategies, and future clinical trials are eagerly awaited.

With growing but still primarily observational evidence currently dictating care, these consensus recommendations provide expert guidance in the treatment of appendiceal tumors without peritoneal involvement.

This study reveals mitochondrial pathways as critical drivers of melanoma progression and resistance, providing a rationale for targeting mitochondrial translation and OXPHOS in advanced melanoma. Combining mitochondrial inhibitors with existing therapies could overcome treatment resistance and improve patient outcomes.

This study revealed significant TRD in TP53 P/LPV inheritance among Israeli LFS families. A potential mechanism involves the role of TP53 in the cell cycle, in which reduced TP53 function may enhance embryonic cell proliferation, offering a survival or implantation advantage. TRD in LFS has implications for genetic counseling, reproductive decision making, and clinical management. These findings underscore the need for further research to validate TRD across diverse populations and elucidate the underlying mechanisms.

Despite changes in cardiac function while on MTKIs, reductions because of cardiac toxicity were infrequent. Routine monitoring of cardiac function during MTKI use and early intervention may enable patients to continue therapy while safeguarding cardiovascular health.

LC outcomes were driven by histology and age with superior LC among leiomyosarcomas and patients of age <45 years. OS was driven by nonleiomyosarcoma histology and the presence of progressive extracranial disease.

IHC is a useful biomarker for the early detection of TP53‐mutant MDS or AML and for prediction of TP53 allelic state. The results suggest a role for IHC across global markets, especially in geographic areas with inaccessibility to NGS testing.

The addition of losartan to mFOLFIRINOX in the AFPAC study did not provide an early signal of efficacy in improving progression‐free survival in advanced PDAC. The trial will not proceed to full accrual of phase 3 design.

KHK2455 + mogamulizumab was safe and well tolerated with manageable toxicities, and resulted in dose‐dependent suppression of IDO1 activity; signals of antitumor activity were observed.

Restrictive CCT eligibility criteria and social determinants of health may pose structural barriers that disproportionately affect patient diversity. Investigators should leverage real‐world data to design appropriate trial eligibility criteria.

These results demonstrate the independent prognostic value of KRAS mutations across treatment modalities, including both conventional chemotherapy and hematopoietic stem cell transplantation.

In an analysis from a phase III trial (PACE-C) reported in The Lancet Oncology, Tree et al compared early toxicity rates with intensity-modulated moderately hypofractionated radiotherapy (IMRT) vs stereotactic body radiotherapy (SBRT) in patients with intermediate- and high-risk prostate...

In an interim analysis of a phase III trial (KEYNOTE-689) reported in The New England Journal of Medicine, Uppaluri et al examined the survival benefit of adding perioperative pembrolizumab to standard care in patients with locally advanced head and neck squamous cell carcinoma.

Breast cancer survivors may have a slightly lower risk of developing Alzheimer dementia compared with cancer-free individuals, according to the results of a study published by Jeong et al in JAMA Network Open.

A combination of menin inhibition and KAT6A/7 inhibition significantly improved survival for NUP98-rearranged pediatric acute myeloid leukemia (AML) in AML model systems, even in menin inhibitor–resistant cells, according to findings published in Cancer Discovery.

New data reported in The Cancer Atlas, Fourth Edition showed that an estimated 50% of all cancer deaths worldwide are attributed to modifiable risk factors, including tobacco and alcohol use, infections, excess body weight, unhealthy diet, physical inactivity, ultraviolet radiation exposure,...

While artificial intelligence (AI) large language models (LLMs) hold the promise to help consumers find trustworthy health information, a study assessing the safeguards incorporated into these models has found that they are vulnerable to malicious instruction that converts them into health...

A novel immuno–positron-emission tomography (immunoPET) imaging agent targeting GPC3 demonstrated high sensitivity and specificity in detecting GPC3-positive hepatocellular carcinoma (HCC) tumors, including those under 1 cm, according to the results of a pilot clinical study presented at the...

The National Comprehensive Cancer Network^® (NCCN^®) has announced a new, interactive digital delivery format for the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®). The NCCN Guidelines^® are the recognized standard for clinical decision-making and policy in cancer care and are the...

In patients with polycythemia vera requiring frequent phlebotomies, the investigational hepcidin mimetic rusfertide, given as a weekly subcutaneous injection, more than doubled the clinical response rate and significantly improved quality of life in the global phase III VERIFY study.¹ These...

The U.S. Food and Drug Administration (FDA) has approved a label expansion of a kit for the preparation of gallium Ga-68 gozetotide for injection (Illuccix) to include patient selection for radioligand therapy in the pre-taxane setting.

In a phase III Japanese trial reported in The Lancet Oncology, Saito et al examined the efficacy of adding 5 mg of olanzapine to triplet antiemetic therapy in controlling chemotherapy-induced nausea and vomiting in the overall phase when given after receipt of anthracycline-cyclophosphamide...

In an interim analysis of the phase III LEAP-015 trial reported in the Journal of Clinical Oncology, Shitara et al examined the survival benefit of adding lenvatinib-pembrolizumab to chemotherapy in patients with advanced/metastatic gastroesophageal adenocarcinoma.

The most aggressive melanomas may hyperactivate two key processes in mitochondria, according to a novel study, and blocking these pathways with currently available drugs may eliminate melanoma cells, explained investigators. These findings were published by Kim et al in the journal Cancer.

On June 23, the U.S. Food and Drug Administration (FDA) granted accelerated approval to datopotamab deruxtecan-dlnk (Datroway), an antibody-drug conjugate that targets trophoblast cell surface antigen 2 (TROP2), for adults with locally advanced or metastatic EGFR-mutated non–small cell lung cancer...

In a Canadian study (MATCH) reported in the Journal of Clinical Oncology, Carlson et al investigated the effects of mindfulness and Tai Chi interventions on mood in distressed cancer survivors.

The order of colorectal cancer diagnosis seems to have a significant impact on outcomes in patients with multiple primary malignancies, according to the results of a study of Surveillance, Epidemiology, and End Results (SEER) Program data. Findings from the study were published in the Journal of...

Universal germline testing is essential for identifying hereditary cancer risk, especially for patients with young-onset colorectal cancer who were diagnosed before the age of 50. However, the implementation of universal germline testing has been hampered by increasing demand and limited physician...

In an update from the UK phase III FLAIR trial reported in The New England Journal of Medicine, Munir et al compared the survival benefit of measurable residual disease (MRD)–guided therapy with ibrutinib/venetoclax vs ibrutinib alone in chronic lymphocytic leukemia.

The relationship between genetic variants and the risk of late-onset cardiomyopathy remains poorly understood in survivors of childhood cancer despite being otherwise well established. Scientists from St. Jude Children’s Research Hospital have helped address this gap, assessing whether variant...

The first individualized risk prediction model for adults with early-stage classical Hodgkin lymphoma (cHL) has been developed and validated. According to a report published in NEJM Evidence, the Early-Stage cHL International Prognostic Index (E-HIPI) model estimates 2-year progression-free...

A healthy gut microbiome prior to chemotherapy could help protect against cardiotoxicity as a result of breast cancer therapy, according to new findings presented by Antoniades et al at the European Society of Cardiology (ESC) Cardio-Oncology 2025 annual conference.

In a French-Belgian phase III trial (MIDAS) reported at the 2025 ASCO Annual Meeting and in The New England Journal of Medicine, Perrot et al examined the outcomes of treatments guided by measurable residual disease (MRD) status in patients with newly diagnosed multiple myeloma. 

Whether a patient’s breast cancer was detected through symptoms or routine screening mammography significantly affected their risk for advanced disease or death, according to a study published recently in Radiology: Imaging Cancer.

The American Society of Hematology (ASH) announced that it will recognize 11 hematologists who have made notable contributions to the field with several honorific awards and prestigious lectures at the 2025 ASH Annual Meeting & Exposition in Orlando, Florida, from December 6–9, 2025. The...

In the United States, approximately 55% of patients with resected gallbladder cancer undergo oncologic surgery without additional systemic treatment. However, as gallbladder cancer progresses to T3 (locally or regionally advanced) or T4 (distant metastasis) disease, the tumor frequently infiltrates ...

I’ve been a physician for several decades, seeing patients and functioning as a medical teacher; clinical, translational, and bench researcher; and administrator. Adapting to medical practice in three nations and several U.S. states has been quite challenging at different times, but I really think...

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.

From ASCO 2025

Zanidatamab shows promise as first-line therapy for advanced-stage HER2⁺ GEA

Second-line tarlatamab improves OS in SCLC

Robot-assisted laparoscopic surgery confers improved oncological outcomes

Adding durvalumab to perioperative FLOT improves gastric cancer outcomes

Immune-checkpoint inhibitors (ICIs) have improved lung cancer outcomes, although resistance to these agents presents a substantial challenge. This Review describes the progress made in developing the next generation of immunotherapies for non-small-cell and small cell lung cancers, including novel immune-checkpoint modulators, immune cell engagers, adoptive cell therapies and therapeutic vaccines, as well as the mechanisms by which these agents might overcome resistance to the current generation of ICIs.

Liquid biopsy-based tests have demonstrated potential as a minimally invasive and broadly applicable approach to simultaneously screen individuals for multiple cancer types. In this Review, Wan, Sasieni and Rosenfeld discuss the promises and limitations of such multi-cancer early detection tests as well as future directions for this field.

A new first-line standard-of-care for BRAF^V600E-mutated mCRC

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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.

No abstract available

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 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). 

On March 19, 2025, the Food and Drug Administration granted traditional approval to pembrolizumab (Keytruda, Merck) with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1).

On February 14, 2025, the Food and Drug Administration approved vimseltinib (Romvimza, Deciphera Pharmaceuticals, LLC), a kinase inhibitor, for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity.

On February 11, 2025, the Food and Drug Administration approved brentuximab vedotin (Adcetris, Seagen Inc., a subsidiary of Pfizer) in combination with lenalidomide and a rituximab product for adult patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy who are ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) or CAR T-cell therapy.

On February 11, 2025, the Food and Drug Administration approved mirdametinib (Gomekli, SpringWorks Therapeutics, Inc.), a kinase inhibitor, for adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.

On January 21, 2025, the Food and Drug Administration approved treosulfan (Grafapex, medac GmbH), an alkylating agent, with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult and pediatric patients 1 year of age and older with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

On January 27, 2025, the Food and Drug Administration approved fam-trastuzumab deruxtecan-nxki (Enhertu, Daiichi Sankyo, Inc.) for unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-approved test, that has progressed on one or more endocrine therapies in the metastatic setting.

On January 17, 2025, the Food and Drug Administration approved datopotamab deruxtecan-dlnk (Datroway, Daiichi Sankyo, Inc.), a Trop-2-directed antibody and topoisomerase inhibitor conjugate, for adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.

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