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Journal of Clinical Oncology, Ahead of Print.

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New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Ahead of Print.

This randomized trial involving patients with clinically node-negative, T1 breast cancer showed that the omission of axillary surgery was noninferior to sentinel-lymph-node biopsy.

In a trial involving patients with subarachnoid hemorrhage and anemia, liberal transfusion of red cells did not result in a lower risk of an unfavorable neurologic outcome than a more restrictive strategy.

A 72-year-old woman with type 2 diabetes had somnolence after a urologic procedure for bladder cancer. She had respiratory acidosis and anion-gap metabolic acidosis. A diagnosis was made.

The role of axillary surgery in the management of breast cancer has changed. Sentinel-lymph-node biopsy is used to identify nodal metastases, but recognition of the lack of therapeutic benefit of this approach, coupled with the emphasis on tumor biology for decisions about systemic therapy, has led to trials examining the...

A woman was seen for evaluation of gastric polyposis, a condition her uncle also had. On upper endoscopy, innumerable polyps in the gastric corpus and an area of pale mucosa along the greater curvature were identified.

Having lost trust in physicians when he lost his daughter, a man with newly diagnosed cancer declines care, leaving the oncologist to consider past failures of communication, connection, and trust.

A woman with a history of metastatic small-cell lung cancer and Cushing’s syndrome was found to have reduced skin thickness, a possible result of antianabolic effects of excess cortisol. Methods of measuring skin thickness are shown in videos.

Patients with a prothrombotic clinical course often associated with thrombocytopenia may have a monoclonal paraprotein, even at low levels, that activates platelets by binding to platelet factor 4.

The addition of blinatumomab after induction chemotherapy in children with standard-risk disease of average or higher risk of relapse significantly improved disease-free survival.

Watching a patient’s family respond adversely to the stock communication tools an intern deploys, a palliative care consultant draws on her training in psychiatry to add nuance to those tools.

A 46-year-old woman with multiple myeloma presented with a 2-month history of hoarseness and painful swallowing. Laryngoscopy showed an exophytic mass involving the laryngeal surface on the right side.

A 65-year-old woman was evaluated for back pain and pancytopenia. A peripheral-blood smear was notable for nucleated red cells, large platelets, and immature granulocytes. A diagnosis was made.

In January, the FDA proposed substantially limiting the level of nicotine permitted in cigarettes. The proposal is expected to face strong industry opposition during a time of political uncertainty.

Among previously untreated patients with chronic lymphocytic leukemia, 3-year progression-free survival was 76.5% with acalabrutinib–venetoclax, 83.1% with acalabrutinib–venetoclax–obinutuzumab, and 66.5% with chemoimmunotherapy.

Bolstering psychological resilience among patients and their family members is important. But conventional resilience recommendations may be incompatible with the experience of serious illness.

The FDA often exercises flexibility in deciding whether to approve highly promising drugs for patients in desperate need of treatment options. But it doesn’t consider a drug’s likely financial toxicity.

An analysis of published studies suggests that a longer duration of immune checkpoint inhibitor therapy is associated with a higher incidence of complete response among patients with mismatch repair–deficient cancers.

Cabozantinib, as compared with placebo, doubled median progression-free survival in patients with extrapancreatic neuroendocrine tumors and tripled it in those with pancreatic neuroendocrine tumors.

Two patients with refractory myeloma who had excellent antitumor responses to cilta-cel CAR T-cell therapy later had T-cell lymphomas that contained the lentivirus construct used to generate the CAR T-cell product.

An 84-year-old man with a history of metastatic melanoma of the scalp who was undergoing immunotherapy presented with new, multiple blue-gray macules on the scalp.

As Justin Trudeau steps down after a decade as leader of Canada's ruling Liberal Party, Canadians face a pivotal moment. Although attention is focused on trade tariffs and souring relations with the USA, there are important health dimensions to Canada's political transition. Trudeau leaves behind a legacy of initiatives, including the Canada Child Benefit, climate change initiatives through the Pan-Canadian Framework, a National Housing Strategy, legalisation of cannabis, the Early Learning and Child Care plan, and the Canadian Dental Care Plan—which has already benefited 1·5 million Canadians—and passed a universal pharmacare plan to institute publicly funded coverage for medications.

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 on oral conditions represents a landmark moment for the community.1 For the first time, a comprehensive analysis of the global, regional, and national burden of oral diseases has been published in The Lancet. Previously confined to dental research journals, this broader platform underscores the increasing significance of oral diseases in global health.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a common and particularly severe subset of sinonasal inflammatory disease that is characterised by benign outgrowths of the inflamed mucosa. The management framework of CRSwNP substantially shifted with the introduction of biological agents.1–3 These therapies, targeting the Th2 cell cytokine pathways, drove reductions in both systemic steroid use and surgical interventions. Biological drugs were able to provide significant and sustained control of symptoms without the need for revision sinus surgery.

Oral anticoagulation is the most effective intervention for the prevention of ischaemic stroke in people with atrial fibrillation.1 However, the prescription and uptake of oral anticoagulation for this indication has been suboptimal, often because of concerns about bleeding in ageing populations, who bear a growing burden of multimorbidity and frailty.2 Such so-called haemophobia, which contributes to physicians' greater fear of acts of commission than acts of omission, is a human factor frequently seen in our clinical practice.

Elevated blood pressure is the most important risk factor for cardiovascular disease. Numerous clinical practice guidelines for blood pressure coexist, emanating from European,1,2 North American,3 Asian, and global medical societies. These blood pressure guidelines are scrutinised for their differences, with the focus typically on how they deviate.4 Little attention is given to why they differ. The 2024 European Society of Cardiology (ESC) guidelines1 create an opportunity to take a fresh look at the current landscape of major hypertension guidelines, emphasising the potential reasons these guidelines differ and whether these reasons matter to clinicians and patients.

In December, 2024, after more than 50 years in power in Syria, the regime of the Assad family was swept away. This dramatic political shift illuminated the state of health in Syria, exposing widespread fractures in a health system that has been politicised and fragmented, including widespread erosion of public trust in medical care.1 Health has been decimated during Syria's almost 14-year conflict by attacks on infrastructure, the forced exodus of health-care workers, and severe under-resourcing.

President Subianto's ambitious plan of health checks for all is one of Indonesia's biggest ever health initiatives, but not everyone is convinced it will have the desired effect. Chris McCall reports.

Many Indians are exposed to silica dust, but experts and patients lament the lack of information and health services related to silicosis. Sophie Cousins reports from West Bengal.

Shirin Heidari, the Executive Director of GENDRO and Senior Researcher at the Gender Centre, Geneva Graduate Institute in Switzerland, was born in Tehran 6 years before the 1979 Iranian revolution. Coming from a family with “many strong women as role models, and always a sense of activism”, the revolution, which “resulted in a regime oppressing women, men, as well as any dissidents, followed by political oppression and war”, left her with “a very strong distaste for injustice”, and a profound awareness, “very early on”, of the devastating impacts of “a lack of rights, and the lack of a justice system”.

As a clinician, educator, and emotion researcher, I have long believed that our efforts to optimise the wellbeing of health-care professionals are doomed if we cannot talk openly about the emotional and psychological experience of practising medicine. Hidden behind the more observable forms of distress we can measure, such as burnout, are unpleasant, complex, and entirely human experiences, such as feeling insecure or unlikeable, needing validation, experiencing shame or self-doubt, and wanting to feel loved and accepted.

The Sainsbury Centre is an art museum situated on the University of East Anglia campus near Norwich, UK. Its Living Area—a calm, expansive exhibition space in a hanger-like, purpose-built, Norman Foster designed building—hosts a diverse permanent art collection, including works by modern artists such as Francis Bacon and Henry Moore, alongside historical objects from across the globe. This impressive core collection was donated by British businessman, philanthropist, and supermarket heir Sir Robert Sainsbury and his wife Lady Lisa Sainsbury.

Science editor, journalist, author, and mentor. Born on Oct 9, 1940, in Rawene, New Zealand, he died in Eastbourne, UK, on Feb 10, 2025, aged 84 years.

Africa accounts for only 3% of all medicine production globally, and more than 90% of drugs and 99% of vaccines consumed are imported.1 The continent has not been well positioned to address these gaps due to capacity challenges related to limited research and development (R&D) infrastructure and skilled researchers, the absence of a well defined continental health research governance framework, and scarcity of sustainable financing for R&D.2 Moreover, there is inadequate local funding, and most research conducted on the continent is donor-driven and often not informed by national or regional priorities, underscoring the urgent need for research prioritisation, coordination, and governance.

Canada has joined the world's largest research and innovation programme (Horizon Europe), with its strong life science and technology focus and the launch of a policy dialogue to advance health priorities. Canada and the EU have taken steps towards transnational collaboration, which is paramount to successfully take on global challenges, such as cancer, antimicrobial resistance, health security, rare diseases, and non-communicable diseases.1,2 However, the proposed dialogue does not directly reference the crucial importance of health data access and exchange.

In an Offline piece,1 Richard Horton commented on several issues regarding human rights and remembrance in Argentina.

We enjoyed the Viewpoint by Jeremy W Jacobs and colleagues and agree with their major observations.1 Defining the true need for blood is an essential challenge. The authors rightly noted that the annual blood donation to population ratio threshold cannot define true blood need. This definition should be specific to geographical scale and depend on disease burden, geographical heterogeneity and the isolation of communities in resource and disease distributions, and access to blood and blood products within the context of health-care access, among other factors.

In their open-label, multicentre, randomised, non-inferiority trial of home-based ovulation monitoring in the management of frozen-thawed embryo transfers (FETs), Tjitske Zaat and colleagues showed their ability to organise national collaborative research efforts involving multiple fertility centres.1 In the accompanying Comment,2 Shari Mackens and Christophe Blockeel state that there is little in Zaat and colleagues’ study that warrants the consideration of home-based ovulation monitoring as a new gold standard.

In Tjitske Zaat and colleagues’ study,1 fewer than 3% of patients in natural menstrual cycles were administered exogenous progesterone for luteal phase support. In their Comment,2 Shari Mackens and Christophe Blockeel suggest that, with more evidence, progesterone supplementation could become part of the prescribed natural cycle frozen-thawed embryo transfer (FET) protocol. This change could simplify monitoring and reduce the number of hospital visits.

In the CASTING study,1 the TRiP(cast) score was utilised to identify patients at low risk of venous thromboembolism. The cumulative incidence of venous thromboembolism was estimated to be 2·0%, indicating that most patients, approximately 98%, were at low risk and did not require anticoagulation. Therefore, it was inappropriate to identify low-risk subgroups from a population already consisting mostly of individuals at low risk of developing the condition. In contrast, there was no significant difference in the incidence of venous thromboembolism (1·1% vs 1·0%) between the intervention phase, guided by the TRiP(cast), and the control phase, during which 16% of patients would be classified as high risk but did not receive anticoagulation.

We would like to congratulate Douillet and colleagues1 on their CASTING study, which showed a relevant reduction in prophylactic anticoagulation by using the TRIP(cast) score without an increase in the risk of venous thromboembolism. However, we were surprised by the inclusion of male sex as a risk factor in the TRIP(cast) score. The TRIP(cast) score was developed on the basis of two prior scores. One score was based on expert consensus (TIP score) that did not include male sex as a risk factor.

I read with great interest the CASTING study by Douillet and colleagues.1 I appreciate the authors’ contribution; however, there are several issues I would like to discuss.

We thank Liang V Tang and colleagues, Perrine Truong and Francois-Xavier Ageron, and Wei Xiong for their interest in our CASTING study and their comments.

Al-Walah MA, Donnelly M, Alhusaini AA, Heron N. Evaluating the acceptability of “I'm an Active Hero”: a mixed methods process evaluation of a preschool-based physical activity intervention feasibility trial. Lancet 2024; 404 (suppl): S67 (abstr)—In this Abstract, Neil Heron should have been listed as an author and his affiliations listed as both Queen's University Belfast and Keele University. This correction has been made as of March 4, 2025.

Veltkamp R, Korompoki E, Harvey KH, et al. Direct oral anticoagulants versus no anticoagulation for the prevention of stroke in survivors of intracerebral haemorrhage with atrial fibrillation (PRESTIGE-AF): a multicentre, open-label, randomised, phase 3 trial. Lancet 2025; 405: 927–36—In this Article, the final sentence of the Findings in the Summary was incorrect and has been deleted. This correction has been made to the online version as of March 13, 2025, and the printed version is correct.

The minor changes in the burden of oral conditions over the past 30 years demonstrate that past and current efforts to control oral conditions have not been successful and that different approaches are needed. Many countries now face the double challenge of controlling the occurrence of new cases of oral conditions and addressing the huge unmet need for oral health care.

Depemokimab significantly improved clinically relevant coprimary endpoints versus placebo and was well tolerated, supporting its use as a twice per year treatment option, with the potential to reduce treatment burden for people with CRSwNP.

DOACs effectively prevent ischaemic strokes in survivors of intracerebral haemorrhage with atrial fibrillation but a part of this benefit is offset by a substantially increased risk of recurrent intracerebral haemorrhage. To optimise stroke prevention in these vulnerable patients, further evidence from ongoing trials and a meta-analysis of randomised data is needed, as well as the evaluation of safer medical or mechanical alternatives for selected patients.

Human African trypanosomiasis or sleeping sickness is caused by infection with Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense parasites, which are transmitted by tsetse flies in sub-Saharan Africa. Control of human African trypanosomiasis is based on case detection, treatment, and vector control. In the past decade, simple rapid diagnostic tests were introduced for gambiense human African trypanosomiasis, facilitating screening in primary health-care facilities. A new oral drug, fexinidazole, became the first-line treatment for gambiense human African trypanosomiasis without severe meningo-encephalitic disease, as well as for rhodesiense human African trypanosomiasis.

On Feb 3, 2025, the UK Medicines and Healthcare Products Agency (MHRA) released preliminary guidance on personalised mRNA cancer immunotherapies (also known as cancer vaccines) with an 8-week consultation period, during which they invite stakeholders (eg, developers and patients) to provide feedback. mRNA therapies have shown potential to address gaps in the prevention and treatment of cancer; however, they are markedly different from conventional cancer therapies and careful consideration of the regulatory framework for these potential new therapies is needed.

Since the existence of the oligometastatic disease state was posited three decades ago,1 there has been interest in investigating the role of metastasis-directed therapy—largely in the form of stereotactic body radiotherapy (SBRT)—either as an adjunct to systemic therapy or in place of it. In prostate cancer, the STOMP2 and ORIOLE3 trials evaluated whether metastasis-directed therapy improved androgen deprivation therapy (ADT)-free survival and progression-free survival compared with observation in men with biochemically recurrent disease; a pooled analysis of these trials found that median progression-free survival was prolonged from 5·9 months to 11·9 months (HR 0·44 [95% CI 0·29–0·66]).

For advanced gastric cancer, randomised studies have emphasised the importance of combining chemotherapy or chemoradiotherapy with surgery as a strategy to improve outcomes beyond surgery alone.1 However, approaches have differed globally in the timing of this treatment, with Asian countries preferring adjuvant therapy and Western countries favouring perioperative treatment.

Premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer face substantial unmet clinical needs, largely stemming from their historical under-representation in clinical trials. Consequently, chemotherapy has traditionally been the cornerstone of first-line treatment for these patients, driven by the more aggressive nature of their disease and scarce evidence supporting the use of endocrine therapy in this setting.1 However, the advent of CDK4/6 inhibitors has reshaped the clinical landscape, offering substantial progression-free survival benefits, and overall survival advantages in some cases, while preserving the quality of life (QoL) for premenopausal women.

Triple-negative breast cancer is a subgroup of breast cancer with scarce targeted treatment options, resulting in a poor prognosis and high recurrence rates compared with other breast cancer subtypes.1 As current standard-of-care options for triple-negative breast cancer are focused on chemotherapy and immunotherapy, exploring androgen receptor (AR)-targeted therapy offers new avenues for patients with AR-positive triple-negative breast cancer. The luminal androgen receptor (LAR) subtype of triple-negative breast cancer has historically had a poorer response to chemotherapy regimens than other subtypes,2 prompting several clinical trials with AR as a clinical target, but has shown low clinical efficacy and inconsistent results in this patient population.

In the past 5 years, the emergence of immune checkpoint inhibitors has revolutionised the treatment framework for patients with early-stage triple-negative breast cancer. The KEYNOTE-522 trial1 has shown substantial and clinically meaningful improvements in pathological complete response, event-free survival, and overall survival when neoadjuvant chemotherapy was combined with preoperative and postoperative pembrolizumab for patients with stage II–III triple-negative breast cancer. Consequently, the KEYNOTE regimen—a 24-week and four-drug polychemotherapy (carboplatin and paclitaxel followed by doxorubicin [or epirubicin] and cyclophosphamide)—has become the standard of care.

Against all odds, in a victory of data over opinion, and after the determined work of the Health and Social Care Select Committee in collecting and acting on the evidence, Wes Streeting (Secretary of State for Health and Social Care, UK) finally announced on Dec 19, 2024, the decision of the UK Government to publish a National Cancer Control Plan in 2025.1 The International Cancer Benchmarking Partnership (ICBP) has shown unequivocally that countries with consistent national cancer plans have better cancer outcomes than those that do not.

In their Article on primary lung tumour stereotactic body radiotherapy followed by concurrent mediastinal chemoradiotherapy and adjuvant immunotherapy for locally advanced non-small-cell lung cancer (NSCLC), John H Heinzerling and colleagues1 reported a 1-year progression-free survival of 62·7% (90% CI 51·2–73·2), which was not statistically significant when compared with the historical control from the PACIFIC trial. The inclusion of patients who did not receive consolidation durvalumab could confound comparisons.

We thank Zaoqu Liu and colleagues for their interest in our phase 2 trial on non-small-cell lung cancer (NSCLC).1 In their Correspondence, they raise concerns of confounding results due to some patients not receiving durvalumab consolidation. However, we listed outcomes for the whole cohort (n=61) and for the durvalumab subset (n=47). Liu and colleagues similarly question the reasons for 14 patients not receiving durvalumab, but, as stated in our Article, the reason was that the initial design and enrolment were before the US Food and Drug Administration approval of durvalumab consolidation.

The Series by M Saiful Huq and colleagues in The Lancet Oncology provides a comprehensive overview of cancer care in the eight South Asian Association for Regional Cooperation (SAARC) countries, including Afghanistan. Although the Series offers valuable insights, I would like to highlight some inaccuracies and omissions regarding cancer prevention and control in Afghanistan.

Clinically accessible images have substantial potential in constructing predictive models for cancer diagnosis and treatment. Based on the largest multicentre dataset yet, the DeepGEM model enables gene mutation prediction in lung cancer through pathological images and will profoundly affect precision medicine.1 However, some substantial optimisations should be contemplated in future research on artificial intelligence (AI) models.

Oliveira M, Pominchuk D, Nowecki Z, et al. Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): a multi-dose, open-label, randomised, phase 2 trial. Lancet Oncol 2024; 25: 1424–39—In this Article, in the penultimate paragraph of the Results, the first sentence (describing the onset of bradycardia) was an erroneous duplication of a sentence later in the paragraph and has been removed.

Access to critical medicines and technologies in low-income and middle-income countries (LMICs) remains a persistent challenge, particularly for cancer treatment. Despite numerous calls for action to governments and the private sector, substantial barriers continue to impede progress. The Access to Oncology Medicines Coalition (ATOM Coalition), led by the Union for International Cancer Control (UICC), offers innovative solutions to transform access to cancer medicines and technologies in LMICs.

On Jan 20, 2025, US President Donald Trump issued an executive order to withdraw the USA from WHO. The move could jeopardise public health care globally, including cancer care and prevention initiatives, particularly in lower-income regions such as Africa.

There is an urgent need to globally strengthen cancer-care systems considering projections that cancer cases will substantially increase during the coming years, said global leaders during a forum discussion on cancer care at the annual World Economic Forum in Davos, Switzerland, on Jan 22, 2025.

Most kidney cancer diagnoses in the UK are incidental and found as a result of unrelated medical interventions, according to a recent report by Kidney Cancer UK.

The French Parliament voted unanimously in favour of a law to expand free medical and supportive treatment for patients with breast cancer to items that cost an average of €1400 per case.

In a landmark judgement, the European Court of Human Rights (ECHR) has ruled that Italy is not protecting the right to life of 2·9 million people living in the southern provinces of Caserta and Naples. The ruling relates to the illegal dumping, burial, and burning of millions of tonnes of waste, including toxic and carcinogenic material, stretching back to at least the early 1980s. The affected area, which is made up of 90 municipalities, has become known as the Terra dei Fuochi (Land of Fires).

The UK's National Health Service (NHS) has launched the world's largest prospective trial of using artificial intelligence (AI) to assess routine mammogram screenings. Nearly 700 000 women who have booked routine screenings in the UK will be invited to participate from April, 2025.

On Feb 3, 2025, the Pan American Health Organization (PAHO) issued a statement calling on countries in Latin America and the Caribbean to prioritise access to essential cancer medicines. The statement noted that there are more than 4 million new cases of cancer every year in the Americas and over 1·4 million deaths. Patients do not always get the treatment they need, however. PAHO gave the example of childhood cancer. Every year, around 30 000 people younger than 19 years of age are diagnosed with cancer in Latin America and the Caribbean.

Activists in US farm states are stepping up their battle against proposed bills that would block legal claims for disease or injury against pesticide companies. Under the proposed legislation, people would not be able to bring lawsuits against companies if the labels on their products were approved by the Environmental Protection Agency (EPA).

The number of patients with cancer who are experiencing treatment delays has almost quadrupled in recent years, according to analysis by Cancer Research UK published last week in The Guardian.

On Feb 11, 2025, the Global Platform for Access to Childhood Cancer Medicines (known as the Global Platform) announced that it had started distributing drugs to the six countries participating in the pilot phase of the initiative. The platform is a partnership between WHO and St Jude Children's Research Hospital, which is providing technical support and US$200 million in funding. The short-term goal is to deliver enough quality-assured paediatric cancer medication to treat some 120 000 children in 50 or so low-income and middle-income countries (LMICs) within the next 5–7 years.

Breast cancer is the most common cancer and the leading cause of cancer death for women in the Philippines, a large lower middle-income income country of 115 million people.1,2 Although 5-year survival rates in high-income countries exceed 90%, the 5-year survival rate is only 44% in the Philippines.3

As a television news journalist at the height of his career, Glenn Campbell spends his days breaking some of the biggest news stories as well as asking questions of government ministers and elected representatives as BBC Scotland's political editor. Yet, over the past 2 years, Campbell has gone from reporting stories to becoming the story after being diagnosed with an oligodendroglioma, a rare type of brain tumour. Campbell shared his experience of diagnosis and treatment during a 30-minute documentary entitled My Brain Tumour and Me, which was broadcast on BBC One Scotland on Nov 20, 2024.

The addition of [177Lu] Lu-PSMA-617 to enzalutamide was associated with improved survival and some aspects of HRQOL in patients with high-risk metastatic castration-resistant prostate cancer. Our findings warrant phase 3 evaluation of adaptive-dosed [177Lu] Lu-PSMA-617 in combination with androgen receptor pathway inhibitors in people with metastatic prostate cancer.

To our knowledge, the RADIOSA trial represents the first randomised trial in the metachronous oligometastatic hormone-sensitive prostate cancer setting to report improved clinical progression-free survival with the combination of SBRT and a short course of ADT, although carefully selected patients might still benefit from SBRT alone. By demonstrating improved clinical progression-free survival, the RADIOSA trial reinforces the role of metastasis-directed therapy in delaying systemic treatment escalation.

Consistent with the initial analysis of 3-year disease-free survival, the extended 5-year overall survival analysis from the RESOLVE trial confirmed the survival advantage of perioperative-SOX and adjuvant-SOX compared with the standard adjuvant-CapOx regimen. The SOX regimen, given perioperatively or as an adjuvant treatment, emerges as a potential standard treatment modality for locally advanced gastric or gastro-oesophageal junction cancer management in Asian patients.

Our findings suggest that ipilimumab plus nivolumab maintains efficacy to at least 7 years in patients with active asymptomatic brain metastasis. Upfront ipilimumab plus nivolumab should be the standard of care for patients with melanoma brain metastasis; a trial investigating the role of stereotactic surgery in this new paradigm is ongoing.

In previously untreated advanced thymic carcinoma, the addition of atezolizumab to carboplatin and paclitaxel conferred clinically meaningful antitumour activity with a manageable safety profile. Thus, atezolizumab plus carboplatin and paclitaxel might become a viable treatment option for previously untreated advanced or recurrent thymic carcinoma.

With extended follow-up, palbociclib plus exemestane with ovarian function suppression continued to show a significant benefit in progression-free survival compared with capecitabine in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer who had been previously treated with tamoxifen; however, no improvement in overall survival was seen. Given the progression-free survival benefit, the upfront use of palbociclib plus endocrine therapy is the preferred option for premenopausal women, although a capecitabine-first strategy might be an alternative treatment strategy for maintaining overall survival in resource-limited settings.

This study did not reach its prespecified endpoint for darolutamide activity in patients with triple-negative breast cancer selected on the basis of immunohistochemistry for AR. Further studies selecting patients based on RNA profiling might allow better identification of tumours sensitive to anti-androgens.

While this study did not support the hypothesis that lead-in nivolumab before chemotherapy was associated with a pathological complete response advantage, high pathological complete response rates were reached supporting shorter duration, non-anthracycline regimens in patients with newly diagnosed triple-negative breast cancer. Future trials are warranted to compare this regimen with the current standards of care.

Acute toxicity following prostate radiotherapy was statistically significantly associated with late toxicity and with decrement in patient-reported QOL metrics. These data support efforts to evaluate whether interventions that reduce acute toxicity ultimately reduce the risk of late toxicity.

All investigated ablative methods continue to represent effective treatment choices in renal cell carcinoma, and these findings support multi-disciplinary discussions of these treatment methods, along with surgery and surveillance, to individualise treatment decisions in these patients. Future research should aim to conduct randomised controlled trials across larger patient populations to further elucidate the long-term oncological and survival outcomes associated with these treatments.

The Eastern Mediterranean region covers a population of more than 700 million individuals and 22 countries and territories, sharing histories, culture, and languages. The countries and territories of this region also have large differences in demographics and human development. Population ageing and growth is predicted to more than double the number of new cancer cases in the region over the next few decades, from 782 000 in 2022 to close to 1·8 million by the year 2050. At the same time, cancer control capacity is low, with large inequalities between and within countries, further aggravated by political instability and conflicts.

Histological diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2) has traditionally been the cutoff for local surgical treatment, due to a substantial risk of cancer development. However, evidence from the past decade suggests 50–60% of CIN2 lesions spontaneously regress, and active surveillance (or conservative management—ie, leaving the lesion untreated) might be justified in some cases. Active surveillance of CIN2 lesions is now practised widely, although clear recommendations on eligibility, frequency of surveillance, threshold for treatment, and criteria for return to routine recall are insufficient in most countries.

Radiotherapy both promotes and antagonises tumour immune recognition. Some clinical studies show improved patient outcomes when immunotherapies are integrated with radiotherapy. Safe, greater than additive, clinical response to the combination is limited to a subset of patients, however, and how radiotherapy can best be combined with immunotherapies remains unclear. The National Cancer Institute–Immuno-Oncology Translational Network–Society for Immunotherapy of Cancer–American Association of Immunology Workshop on Combining Immunotherapy with Radiotherapy was convened to identify and prioritise opportunities and challenges for radiotherapy and immunotherapy combinations.

Access to many cancer medicines on WHO's Essential Medicines List (EML) is restricted because of price, especially in low-income and middle-income countries (LMICs). Other cancer medicines that have been shown to improve survival, such as immune checkpoint inhibitors for lung cancer, are not included on the EML because approved doses and schedules exceed affordable prices in LMICs. Multiple strategies are therefore needed to reduce medicine costs or circumvent these problems, such as optimising doses and schedules.

A 66-year-old male patient underwent surgery for prostate cancer 4 years ago. His initial prostate-specific antigen (PSA) level was 6·98 ng/mL and a preoperative MRI scan revealed bilateral pubic, left ischial, and sacral metastases. Postoperative pathology showed a Gleason score of 4+5=9, a WHO/ISUP grade of 5/5, and a clinical stage of T3N0M1. 3 months post-surgery, radiotherapy (5000 cGy given in 25 fractions over 36 days) was administered to the pelvic metastases, accompanied by an 18-month course of endocrine therapy (leuprorelin and bicalutamide).

March 8 marks International Women's Day. The campaign theme, Accelerate Action, is a worldwide call to acknowledge and support strategies, resources, and activities that positively impact women's advancement. The current forecast from the World Economic Forum indicates that, at the current rate of progress, it will take over 120 years or roughly five generations before the world reaches full gender parity. Therefore, there is an urgent need to address the systemic barriers and biases that women face.

5 years have passed since the WHO declared the start of the COVID-19 pandemic. Although patients with haematological malignancies have greatly benefited from SARS-CoV-2 vaccines, the risk of infection outcomes after a third dose in this group requires further assessment.

The introduction of regular transfusion and modern approaches for iron monitoring and chelation have prolonged survival in patients with transfusion-dependent β-thalassaemia.1 In resource-limited settings, suboptimal control of anaemia and iron overload are the key drivers for persistently high morbidity rates.2 In regions with adequate access to care, lifelong treatment needs and increased health-care resource utilisation are associated with considerable clinical and economic burden on the patient and health-care system.

Allogeneic haematopoietic stem cell transplantation is a curative treatment for a various haematological disorders, but finding HLA-matched donors is challenging. Therefore, HLA-mismatched haploidentical family donors and unrelated umbilical cord blood are now widely used as alternative stem cell sources. Donor T cells must be depleted ex vivo or in vivo to decrease severe graft-versus-host disease (GVHD) in HLA-mismatched transplantation. Sufficient ex vivo T-cell depletion has been achieved with CD34+ cell selection, resulting in less than 10% incidence of acute or chronic GVHD.

In The Lancet Hematology, Jorge E Cortes and colleagues1 report a phase 1/2 study on vodobatinib in patients with resistance or intolerance mainly to third-line or later lines of therapy. Vodabatinib (developed by Sun Pharma, Mumbai, India) is structurally similar to ponatinib, the most potent TKI for treatment of patients with chronic myeloid leukaemia. Compared with ponatinib, vodabatinib does not inhibit vascular endothelial growth factors, which have been implicated in the development of hypertension and atherothrombotic events that complicate treatment with ponatinib.

Newborns treated with intrauterine transfusions (IUT) for severe haemolytic disease of the fetus and newborn (HDFN) have a high transfusion dependency after birth. Antenatal transfusions with consequently an inhibition of erythropoiesis, combined with continued haemolysis postnatally, can cause anaemia after birth.1 Up to approximately 90% of affected newborns require at least one erythrocyte transfusion and a median of two erythrocyte transfusions during the first 3 months of life.2 Transfusion dependency in preterm neonates has been shown to affect neurodevelopment, showing increasingly worse long-term outcome with increasing number of transfusions.

The editorial team at The Lancet Haematology would like to extend our thanks to the many experts who offered their time and expertise to help us make decisions on and improve papers in 2024, which marked the 10-year anniversary of the journal. In this issue we publish a list of clinical and statistical peer reviewers—we hope that some small recognition of an important academic task can be given to those who give their time, knowledge, and expertise. The Journal's success was partially reflected in our 2023 Impact Factor of 15·4 and Scopus CiteScore of 26·0.

Skeith L, Malinowski AK, El-Chaâr D, et al. Low-dose aspirin versus placebo in postpartum venous thromboembolism: a multi-national, pilot, randomised, placebo-controlled trial. Lancet Haematol 2025; 12: e109–19—In this Article, Suzanne Dubois's affiliation should have been “CanVECTOR Research Network, The Ottawa Hospital, Ottawa, ON, Canada”. This correction has been made as of Feb 3, 2025.

Yu S, Huang, F, Xu N, et al. Haploidentical peripheral blood stem cells combined with bone marrow or unrelated cord blood as grafts for haematological malignancies: an open-label, multicentre,randomised, phase 3 trial. Lancet Haematology 2025; 12: e190–200—In this Article, Na Xu's affiliations should have been “Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China” and “Clinical Medical Research Center of Hematology Diseases of Guangdong Province, Guangzhou, China”.

Idowu M, Otieno L, Dumitriu B, et al. Safety and efficacy of mitapivat in sickle cell disease (RISE UP): results from the phase 2 portion of a global, double-blind, randomised, placebo-controlled trial. Lancet Haematol 2024; 12: e35–44—In figure 3 of this Article, the number of patients at week 4 in the mitapivat 50 mg twice daily group should have been 19. This correction has been made as of Feb 12, 2025.

Sickle cell disease is a life-threatening inherited blood disorder affecting more than 100 000 Americans and millions worldwide. The sickle mutation originated in sub-Saharan Africa as a protective measure against malaria and has been distributed across the world. Therefore, most individuals living with sickle cell disease in the USA and Europe are Black or Latinx with shared African ancestry. Sickle cell disease is arguably the most egregious example of racial health inequity with innumerable disparities in access to and quality of care, research funding, and lack of prioritisation and inadequate treatment within healthcare systems and funding organizations.

The provision of a good paediatric haematopoietic stem-cell transplantation (HSCT) service requires significant skill and a coordinated team effort. The acquisition of this expertise has been shown to be heterogeneous both in terms of the pathway to become a paediatric haematologist and the way in which knowledge is acquired. This heterogeneity was depicted in our previous publication from the European Society for Blood and Marrow transplantation Trainee Committee (EBMTTC), where substantial variation in training duration was shown worldwide.

These long-term results affirm luspatercept's efficacy in addressing key unmet needs of patients with transfusion-dependent β-thalassaemia with a manageable safety profile.

Transplantation of haploidentical PBSCs plus unrelated cord blood achieved superior 1-year disease-free survival compared with transplantation of haploidentical PBSCs plus bone marrow in patients with haematological malignancies, with a more satisfactory safety profile. Our results suggest that combining haploidentical PBSCs with unrelated cord blood, rather than with bone marrow, could be a better treatment option for this population.

Pooled analysis of the phase 1 and 2 studies showed clinically meaningful antileukaemic activity of vodobatinib and a tolerable safety profile in patients with advanced chronic myeloid leukaemia who previously received multiple TKIs, including ponatinib and asciminib, addressing an otherwise unmet clinical need. The phase 2 study was statistically underpowered and warrants further investigation in a phase 3, randomised controlled trial and in an earlier treatment setting of the disease.

Graft-versus-host disease (GVHD) is a complication of hematopoietic cell transplantation (HCT) that has a low chance of complete remission and a substantial effect on morbidity and mortality. To better understand how to improve the field of GVHD research, management, and care, the cGVHD Eurograft Initiative organised a European community advisory board of patient advocates, with the assistance of the Lymphoma Coalition, to identify unmet needs. We present the results of this project in this Viewpoint, which identify unmet GVHD needs from the patient advocates’ perspectives and provide five key actionable themes to improve GVHD management and care.

The growing use of measurable residual disease (MRD) assays across haematology–oncology creates an urgent need for clinicians and researchers to reflect on the biological and clinical rationale of this class of biomarkers. In this Viewpoint, we critically examine two premises behind MRD's use in haematology–oncology, focusing on its biological plausibility as a predictive biomarker and surrogate endpoint, and the evidence needed for it to influence decision making in haematological cancers. Examining these premises leads us to advocate for the establishment of more robust biological and clinical evidence to ensure the clinically useful and safe application of MRD.

In November, 2019, a 44-year-old woman presented with complaints of dyspnoea, night sweats, 15 kilograms of weight loss, cough, abdominal pain, and paraesthesia. Physical examination revealed a 5 × 3 cm purple tumour on the skin of the right leg, with no lymphadenopathy detected at any level; the rest of the examination was normal.

Obesity was associated with improved 5‐year OS after treatment with ICI across various solid tumor malignancies in this electronic health record–based big data study. Further investigation is warranted to understand the mechanism of this association.

This large study of the prospective association between the oral microbiome and CRC risk showed numerous site‐specific associations, including multiple associations with distal colon and rectal cancer risk.

In summary, the authors identified gliomas that had mutational signatures associated with haloalkane exposure that were enriched in firefighters and other occupations.

iSleep youth is effective in treating insomnia and concurrent fatigue in adolescents and young adults after childhood cancer and should be implemented.

Lower health literacy was associated with higher all‐cause mortality among patients with 12 different types of cancer, varying by cancer type and stage.

Between 2009 and 2021, there was increasing use of EBRT and SBRT, whereas use of RP remained stable. Although BT was the least costly, its utilization as monotherapy and combined with EBRT declined.

The consumption of alcohol has been associated with increased cancer risk, but red wine has been perceived by some as a healthier choice compared to white wine and other types of alcohol. Investigators evaluated whether the anticancer properties of red wine were greater in a recent study published...

In a study reported in the Journal of Clinical Oncology, Veenstra et al found that pathogenic variants (PVs) in ATM, CHEK2, or PALB2 were not associated with significant differences in mortality from breast, colorectal, or pancreatic cancer compared with the absence of such PVs.

Recent findings from the Human Papillomavirus (HPV) Vaccine Impact Monitoring Project (HPV-IMPACT), which were published by Gargano et al in the Morbidity and Mortality Weekly Report, revealed decreased incidences of cervical intraepithelial neoplasia (CIN)2+ and CIN3+ lesions among young women.

Researchers have uncovered a novel combination therapy leveraging the U.S. Food and Drug Administration (FDA)-approved KRAS inhibitor sotorasib and an experimental drug called FGTI-2734, which could improve the efficacy of precision medicine in patients with KRAS-mutated non–small cell lung cancer...

The PD-1 inhibitor nivolumab plus the tyrosine kinase inhibitor cabozantinib continues to demonstrate a significant survival advantage over sunitinib alone in patients with previously untreated advanced renal cell carcinoma, according to data presented at the 2025 ASCO Genitourinary Cancers...

In previously untreated patients with locally advanced or metastatic urothelial carcinoma, use of the antibody-drug conjugate enfortumab vedotin-ejfv in combination with the PD-1 inhibitor pembrolizumab continues to demonstrate a significant survival benefit over chemotherapy, according to updated...

In an analysis reported as a letter to the editor in The New England Journal of Medicine, Rousseau et al found a relationship between the duration of neoadjuvant immunotherapy and the likelihood of pathologic complete response in patients with localized mismatch repair–deficient (MMRd) colorectal...

Among patients with gliomas, gene mutations related to exposure to certain chemical compounds may be more common in firefighters than in those with other occupations, according to a recent study published by Cannataro et al in Cancer.

Taking more daily steps and engaging in moderate-to-vigorous physical activity may both be associated with a reduced risk of cardiovascular disease–related mortality among postmenopausal women with a history of cancer, according to preliminary findings presented by Hyde et al at the American Heart...

Studies have shown that not only does exposure to wildfire smoke, which contains fine particulate matter, increase the risk of developing lung cancer, it can also significantly reduce survival rates among patients recovering from lung cancer surgery.

In a retrospective cohort study reported in JAMA Network Open, Podany et al identified differences in circulating tumor DNA (ctDNA) profiles, targeted therapy use, and survival outcomes in Black vs White patients with metastatic breast cancer.

As reported in the Journal of Clinical Oncology by Petrylak et al, the phase III KEYNOTE-921 trial showed no benefit in outcomes with the addition of pembrolizumab to docetaxel in patients with previously treated metastatic castration-resistant prostate cancer.

Over the past 20 years, the investment in research and development of cancer therapies has been unprecedented, and the pace of new drug development has been accelerating. To illustrate this trajectory, the U.S. Food and Drug Administration (FDA) approved 71 treatments for solid cancers in adults...

Investigators may have identified new strategies for use in the primary care setting to improve the detection of cancer-susceptibility genes, according to a recent study published by Swisher et al in JAMA Network Open.

The use of a circulating tumor DNA (ctDNA) liquid biopsy to guide colorectal cancer treatment in the adjuvant setting may not compromise outcomes despite allowing many patients to avoid chemotherapy, according to a recent study published by Tie et al in Nature Medicine.

In an Italian single-center phase II trial (RADIOSA) reported in The Lancet Oncology, Marvaso et al found that the addition of androgen-deprivation therapy (ADT) to stereotactic body radiotherapy (SBRT) improved progression-free survival in patients with hormone-sensitive oligorecurrent prostate...

In a study reported in The Lancet Oncology, Dee et al identified cancer incidence and mortality rates for 2022 in the countries of southeast Asia.

In recognition of her commitment to tackling the complexities and challenges of cancer, the American Cancer Society (ACS) awarded the 2025 Medal of Honor to W. Kimryn Rathmell, MD, PhD, MMHC. The Medal of Honor is the American Cancer Society’s most prestigious award given to distinguished...

The investigational drug formulation rhenium (Re)-186 obisbemeda (RNL-186) may extend survival in patients with glioblastoma, according to a recent study published by Brenner et al in Nature Communications.

Combining the PD-1 inhibitor nivolumab and chemotherapy, and following that regimen with response-adapted chemoradiation, may an effective treatment for advanced human papillomavirus (HPV)-negative head and neck squamous cell carcinoma, according to a recent study published by Rosenberg et al in...

In a Children’s Oncology Group (COG) study reported in the Journal of Clinical Oncology, Berko et al identified the spectrum and clinical significance of clonal and subclonal pathogenic alterations in high-risk neuroblastoma.

In JAMA, Lee et al provided a concise, evidence-based summary to help clinicians discuss information regarding breast density and implement shared decision-making with patients following the U.S. Food and Drug Administration (FDA) Mammography Quality Standards Act mandate. Since September 2024,...

A 5-year study on men that had primary partial-gland cryoablation shows that the procedure averted cancer recurrence in most patients while preserving urinary and sexual function.

Catharine Young, PhD, has spent the past decade of her career focused on cancer policy and advocacy. A native of Johannesburg, South Africa, Dr. Young served as Senior Director of Science Policy at the Biden Cancer Initiative, which began in 2017 by then former Vice President Joe Biden. There she...

Investigators have found that the consumption of plant-based oils instead of butter may provide beneficial health effects and potentially reduce the risk of premature mortality, according to recent findings presented at the American Heart Association Epidemiology, Prevention, Lifestyle &...

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.

Reduced-volume radiotherapy for locally advanced NPC improves QOL without compromising efficacy

First-line treatment of advanced-stage classic Hodgkin lymphoma (HL) has successfully entered the era of targeted agents based on results from the phase III German Hodgkin Study Group HD21 and US intergroup S1826 trials. Although these trials bring about important advances, many uncertainties remain and the outcomes of all patients with HL can be further improved.

Advanced-stage hepatocellular carcinoma is currently treated with various anti-PD-(L)1 antibody-containing regimens. Now, a triplet combining the anti-TIGIT antibody tiragolumab with one of these regimens has demonstrated promising efficacy in a phase Ib/II trial, although these data will need to be confirmed. This study highlights the value of umbrella trials while also raising questions regarding the most effective immune-targeting strategies in patients with this disease.

SOX superior to CAPOX in resectable G/GEJ cancer

Immunotherapies, predominantly immune-checkpoint inhibitors and chimaeric antigen receptor T cells, have transformed oncology. Nonetheless, these systemically administered agents have several limitations, including the risk of off-target toxicities and a lack of activity owing to an inability to overcome an immunosuppressive tumour microenvironment (TME). In this Review, the authors describe the potential to overcome these challenges using functionalized nanomaterials that are designed to release a wide range of immunotherapeutic cargoes in response to specific TME characteristics, including hypoxia, differences in pH, the presence of specific enzymes, reactive oxygen species and/or high levels of extracellular ATP.

Patients with advanced-stage cancer seek treatments that prolong survival and improve quality of life. We analysed new anticancer drug indications approved by the FDA and EMA between 2020 and 2023 using the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale quality-of-life checklist. Our findings highlight critical gaps in the availability and reliability of quality-of-life outcomes from the pivotal trials that support these approvals.

Single-cell RNA sequencing has transformed our understanding of the biology of cancer cells and that of nonmalignant cells present in the tumour microenvironment. However, how this new knowledge can be translated into improved outcomes for patients often remains uncertain. In this Review, the authors describe the results of single-cell RNA analyses of samples from patients with cancer with an emphasis on how the findings of these studies have, or are anticipated to lead to, improved patient outcomes, with a focus on four key aspects: refinement of tumour subtyping, characterization of treatment-induced changes, identification of gene expression programmes predictive of treatment response and resistance, and the discovery of novel therapeutic targets.

In a recently reported study, a novel engineered oncolytic Newcastle disease virus encoding porcine α1,3-galactosyltransferase was evaluated in monkeys with CRISPR-induced primary hepatocellular carcinoma and in a phase I clinical trial. The virus induced hyperacute tumour rejection and an objective response rate of 35% in 20 evaluable patients. This approach highlights the promises and challenges of oncolytic virus drug development.

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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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

On 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.

On January 16, 2025, the Food and Drug Administration approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for adult patients with KRAS G12C-mutated metastatic colorectal cancer (mCRC), as determined by an FDA-approved test, who have received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. 

On January 16, 2025, the Food and Drug Administration granted traditional approval to acalabrutinib (Calquence, AstraZeneca) with bendamustine and rituximab for adults with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT).

On December 27, 2024, the Food and Drug Administration approved nivolumab and hyaluronidase-nvhy (Opdivo Qvantig, Bristol Myers Squibb Company) for subcutaneous injection across approved adult, solid tumor nivolumab (Opdivo, Bristol Myers Squibb Company) indications as monotherapy, monotherapy maintenance following completion of Opdivo plus Yervoy (ipilimumab) combination therapy, or in combination with chemotherapy or cabozantinib.

On December 20, 2024, the Food and Drug Administration granted accelerated approval to encorafenib (Braftovi, Array BioPharma Inc., a subsidiary of Pfizer Inc.) with cetuximab and mFOLFOX6 for patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by an FDA-approved test.

On December 18, 2024, the Food and Drug Administration approved remestemcel-L-rknd (Ryoncil, Mesoblast, Inc.), an allogeneic bone marrow-derived mesenchymal stromal cell (MSC) therapy, for steroid-refractory acute graft versus host disease (SR-aGVHD) in pediatric patients 2 months of age and older. Ryoncil is the first FDA-approved MSC therapy.

On December 18, 2024, the Food and Drug Administration approved ensartinib (Ensacove, Xcovery Holdings, Inc.) for adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not previously received an ALK-inhibitor.

On December 13, 2024, the Food and Drug Administration approved cosibelimab-ipdl (Unloxcyt, Checkpoint Therapeutics, Inc.), a programmed death ligand-1 (PD-L1) blocking antibody, for adults with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation. 

On December 4, 2024, the Food and Drug Administration approved durvalumab (Imfinzi, AstraZeneca) for adults with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

On November 20, 2024, the Food and Drug Administration granted accelerated approval to zanidatamab-hrii (Ziihera, Jazz Pharmaceuticals, Inc.), a bispecific HER2-directed antibody, for previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.

On November 19, 2024, the Food and Drug Administration approved updated drug labeling for fludarabine phosphate (Fludarabine Phosphate Injection, Sandoz) under Project Renewal, an Oncology Center of Excellence (OCE) initiative aimed at updating labeling information for certain older oncology drugs to ensure information is clinically meaningful and scientifically up to date.

On November 15, 2024, the Food and Drug Administration approved revumenib (Revuforj, Syndax Pharmaceuticals, Inc.), a menin inhibitor, for relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients 1 year and older.

On November 8, 2024, the Food and Drug Administration approved obecabtagene autoleucel (Aucatzyl, Autolus Inc.), a CD19-directed genetically modified autologous T cell immunotherapy, for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

On October 29, 2024, the Food and Drug Administration granted accelerated approval to asciminib (Scemblix, Novartis AG) for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP).

On October 18, 2024, the Food and Drug Administration approved zolbetuximab-clzb (Vyloy, Astellas Pharma US, Inc.), a claudin 18.2 (CLDN18.2)-directed cytolytic antibody, with fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLDN18.2 positive, as determined by an FDA-approved test.

On October 10, 2024, the Food and Drug Administration approved inavolisib (Itovebi, Genentech, Inc.) with palbociclib and fulvestrant for adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth-factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy.

On October 3, 2024, the Food and Drug Administration approved nivolumab (Opdivo, Bristol Myers Squibb Company) with platinum-doublet chemotherapy as neoadjuvant treatment, followed by single-agent nivolumab after surgery as adjuvant treatment, for adults with resectable (tumors ≥ 4 cm and/or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. 

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