Featured
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Research Highlight |
ALND can be safely omitted for patients with sentinel-node macrometastases
- David Killock
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News & Views |
Lighting the torch: intratumoural T cell-to-stroma enrichment score as a predictor of immunotherapy response in urothelial carcinoma
T cell infiltration in the tumour microenvironment (TME) is a prerequisite for sustained antitumour immune responses. However, identifying predictive biomarkers that quantify T cell infiltration and the presence of proinflammatory TMEs associated with immune-checkpoint inhibitor (ICI) response for clinical implementation has proved challenging. Here, we highlight a study that validates a T cell-to-stroma enrichment score generated from RNA sequencing data as a novel biomarker for ICI response in patients with urothelial carcinoma.
- David H. Aggen
- & Jonathan E. Rosenberg
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News & Views |
Enhancing diagnostic precision in liver lesion analysis using a deep learning-based system: opportunities and challenges
A recent study reported the development and validation of the Liver Artificial Intelligence Diagnosis System (LiAIDS), a fully automated system that integrates deep learning for the diagnosis of liver lesions on the basis of contrast-enhanced CT scans and clinical information. This tool improved diagnostic precision, surpassed the accuracy of junior radiologists (and equalled that of senior radiologists) and streamlined patient triage. These advances underscore the potential of artificial intelligence to enhance hepatology care, although challenges to widespread clinical implementation remain.
- Jeong Min Lee
- & Jae Seok Bae
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Research Highlight |
IL-13Rα2-targeted CAR T cells show promise in patients with recurrent high-grade gliomas
- David Killock
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Review Article |
Targeting cuproplasia and cuproptosis in cancer
Copper is an essential trace element with inherent redox properties and fundamental roles in a diverse range of biological processes; therefore, maintaining copper homeostasis is crucial. In this Review, the authors discuss new insights into the mechanisms by which disrupted copper homeostasis contributes to tumour initiation and development, including the recently defined concepts of cuproplasia (copper-dependent cell growth and proliferation) and cuproptosis (a mitochondrial pathway of cell death triggered by excessive copper exposure). They also discuss potential strategies to exploit cuproplasia and cuproptosis for the treatment of cancer.
- Daolin Tang
- , Guido Kroemer
- & Rui Kang
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Research Highlight |
Non-inferiority of simple versus radical hysterectomy in low-risk cervical cancer
- Diana Romero
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Comment |
FDA approvals in 2023: biomarker-positive subsets, equipoise and verification of benefit
In 2023, the US FDA approved several new cancer drugs and biologic agents, including seven small-molecule inhibitors, four bispecific T cell engagers, two anti-PD-1 antibodies and one cell therapy product. Regulatory focus areas included analyses of biomarker-positive subgroups that drive efficacy, equipoise in randomized controlled trials and a new authority to require confirmatory trials be underway before accelerated approval.
- Kelly J. Norsworthy
- , Rosa J. Lee-Alonzo
- & Richard Pazdur
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Research Highlight |
Tabelecleucel is effective in EBV-positive lymphoproliferative disease
- Diana Romero
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Research Highlight |
Personalized neoantigen mRNA vaccine mitigates melanoma recurrence
- David Killock
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News & Views |
Combination strategies for advanced-stage urothelial carcinoma: a paradigm shift
Durable responses with first-line platinum-based chemotherapy for advanced-stage urothelial carcinoma are rare, and patient outcomes are poor. Recently, CheckMate 901 became the first phase III trial to establish a significant overall survival benefit from a combined chemoimmunotherapy approach in this disease setting. Herein, we discuss key findings from CheckMate 901 and their implications in the context of a rapidly evolving treatment landscape.
- Nimira Alimohamed
- & Srikala S. Sridhar
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Research Highlight |
PERSEUS triumphs — efficacy of daratumumab confirmed in transplant-eligible NDMM
- David Killock
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News & Views |
Pyrotinib in combination with first-line trastuzumab and docetaxel for patients with HER2-positive metastatic breast cancer: a new therapeutic option?
Recent results from the phase III PHILA trial demonstrate a benefit in terms of progression-free survival derived from the addition of pyrotinib to first-line chemotherapy plus trastuzumab in patients with metastatic HER2-positive breast cancer. Dual HER2 blockade with pyrotinib and trastuzumab is an effective therapeutic strategy but might increase the risk of gastrointestinal toxicity; therefore, the risk-to-benefit ratio should be carefully evaluated.
- Pier Paolo M. Berton Giachetti
- & Giuseppe Curigliano
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Research Highlight |
From CHRYSALIS to PAPILLON: the metamorphosis of amivantamab into frontline therapy for NSCLC
- David Killock
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Review Article |
Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy
Hepatocellular carcinoma (HCC) is among the most common causes of cancer-related death globally, and despite improvements in prevention and treatment strategies, continued increases in HCC incidence and mortality are predicted. Cirrhosis remains the major risk factor for HCC, although the underlying aetiology is shifting from virus-related to non-viral liver diseases. In this Review, the authors discuss the changing trends in HCC epidemiology and their implications for screening, prevention and therapy, including opportunities to further improve the management of patients with, or at high risk of, HCC.
- Amit G. Singal
- , Fasiha Kanwal
- & Josep M. Llovet
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News & Views |
Digital symptom assessment tools: the next frontier in financial toxicity screening
PRO-TECT is a randomized trial that innovatively integrated financial toxicity screening into a pre-existing digital symptom-monitoring programme, enabling longitudinal detection of financial toxicity. Such a strategy provides an unobtrusive and cost-effective method for early detection and mitigation of financial toxicity by aligning the needs of patients and carers with the resources available in community clinical practices.
- Christopher T. Su
- & Veena Shankaran
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Review Article |
Molecular tumour boards — current and future considerations for precision oncology
According to the precision oncology paradigm, cancer therapies are increasingly being matched to specific sensitizing alterations using a biomarker-directed approach. However, the criteria for determining the actionability of molecular alterations and selecting matched treatments evolve over time. Molecular tumour boards (MTBs) have emerged as means to capitalize on the collective knowledge of various experts to interpret molecular-profiling data and to eliminate subjectivity in treatment selection. This Review describes the components, processes and increasingly important role of MTBs in optimizing the implementation of precision oncology in both clinical trials and clinical practice, as well as current and future considerations for ensuring the sustainability of MTBs and expanding their outreach to underserved populations.
- Apostolia M. Tsimberidou
- , Michael Kahle
- & Funda Meric-Bernstam
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News & Views |
Harnessing potent therapies with care: enfortumab vedotin plus pembrolizumab for advanced-stage urothelial carcinoma
Following the recent FDA Accelerated Approval of enfortumab vedotin (EV) plus pembrolizumab for patients with advanced-stage urothelial carcinoma who are cisplatin-ineligible, herein we highlight key clinical outcomes with this combination based on results from Cohort K of the pivotal phase Ib/II EV-103 trial. We also discuss treatment sequencing, de-escalation strategies and toxicity management as EV–pembrolizumab becomes widely used in clinical practice.
- Pooja Ghatalia
- & Elizabeth R. Plimack
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Research Highlight |
First-line pembrolizumab plus lenvatinib is effective in non-clear-cell RCC
- Diana Romero
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Review Article |
The global burden of lung cancer: current status and future trends
Lung cancer is the commonest cancer globally. Reflecting patterns of smoking and other risk factor exposures, both the incidence of and mortality from lung cancer are highest in economically developed countries. Nonetheless, developing and less economically developed countries are likely to have the biggest increases in lung cancer in the coming years. In this Review, the authors describe the global epidemiology of lung cancer, and how changes in exposures, socioeconomic status, public health interventions and better treatment strategies are influencing both the incidence of and mortality from lung cancer.
- Amanda Leiter
- , Rajwanth R. Veluswamy
- & Juan P. Wisnivesky
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Comment |
Problematic crossovers in cancer drug trials
Crossover in a randomized trial can skew the interpretation of the efficacy of a cancer drug. In this Comment, I use examples from clinical trials presented at the 2023 ASCO annual meeting to highlight why ‘allowing’ crossover in randomized trials testing cancer drugs is problematic, and propose that crossovers should either be mandated or prohibited depending on the context.
- Bishal Gyawali
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News & Views |
A critical appraisal of the ATLAS trial of maintenance therapy for multiple myeloma: end points, censoring and equipoise
A recent report from the ATLAS trial comparing different maintenance strategies following haematopoeitic stem cell transplantation for multiple myeloma provides an opportunity to explore various themes of critical appraisal, including end points, the equipoise of trial design, and the part censoring can play in the validity of results.
- Ghulam Rehman Mohyuddin
- & Tomer Meirson
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Comment |
National value-based pricing negotiation for oncology drugs — lessons from China
Between 2016 and 2022, 83 previously approved oncology drugs were covered and reimbursed in China through a value-based pricing negotiation programme, which resulted in substantial price cuts but did not improve the correlation between drug cost and clinical benefit. Herein, we call for an improved, transparent value-based pricing model to better account for high-value innovation in oncology drugs.
- Jing Yuan
- , Minghui Li
- & Z. Kevin Lu
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Review Article |
Improving outcomes in patients with oesophageal cancer
Oesophageal cancer is one of the most common malignancies worldwide and is associated with considerable morbidity and mortality. In this Review, the authors highlight advances made across the disease continuum that have improved the management and outcomes of patients with oesophageal cancer. These advances include an increased understanding of the disease biology, improvements in screening, the development of minimally invasive endoscopic monitoring and management technologies, refinement of surgical techniques and perioperative management, and novel radiotherapy and systemic therapy approaches. Continual multidisciplinary efforts across all these aspects of care will further improve patient outcomes.
- Manish A. Shah
- , Nasser Altorki
- & Julian A. Abrams
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Comment |
Envisioning trans-inclusive and trans-specific cancer care
Transgender patients are a marginalized group for whom current standards of oncology have yet to be optimized. In this Comment, we highlight opportunities for transgender-inclusive and transgender-specific practices across the cancer care continuum and identify evidence gaps that will need to be filled to attain optimal care for transgender populations.
- Elle Lett
- , Joannie M. Ivory
- & Mya L. Roberson
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News & Views |
Combination immunomodulation for immune-checkpoint-inhibitor-associated myocarditis
Immune-checkpoint-inhibitor-associated myocarditis has a high fatality rate, warranting the development of more-effective treatment strategies. Herein, we discuss a recent report of a series of patients who were managed using a novel approach that involved personalized abatacept dosing, ruxolitinib and close respiratory monitoring, which was associated with low mortality.
- Douglas B. Johnson
- & Alexander M. Menzies
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Review Article |
Neoadjuvant therapy for pancreatic cancer
Advances in surgical technique and chemotherapy regimens have improved the survival outcomes of patients with pancreatic cancer, although these remain dismal relative to most other solid tumours. Attempts to further improve outcomes have led to increasing research interest in neoadjuvant therapy, which is beginning to improve the outcomes of certain subgroups of patients. In this Review, the authors provide an overview of the various neoadjuvant therapy approaches for patients with pancreatic cancer, including discussions of several promising future research directions
- Christoph Springfeld
- , Cristina R. Ferrone
- & John Neoptolemos
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Research Highlight |
Recurrent nasopharyngeal carcinoma: hyperfractionation of IMRT improves outcomes
- David Killock
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Comment |
Approvals in 2022: overall survival, dose optimization, new approvals and beyond
In 2022, the FDA approved numerous new drug and biologic agents, including targeted small molecules, immunotherapeutics, a gene therapy and a radiopharmaceutical. Several drug development challenges were also addressed, and key focus areas for the FDA Oncology Center of Excellence included ongoing monitoring of the Accelerated Approval programme and drug dose optimization.
- Deepti Telaraja
- , Nicole Gormley
- & Richard Pazdur
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Research Highlight |
Sublobar resection is non-inferior to lobectomy in very early stage NSCLC
- Diana Romero
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Review Article |
Protein degraders enter the clinic — a new approach to cancer therapy
Protein degraders constitute a new class of agents that eliminate, rather than just inhibit, their target proteins. These novel agents have recently entered testing in oncology trials, with initial data providing clinical proof of concept for the mechanism of action as well as the antitumour activity of heterobifunctional protein degraders. In this Review, the authors outline the progress in the development of such protein degraders for the treatment of cancer and consider prospects and potential challenges for these agents.
- Deborah Chirnomas
- , Keith R. Hornberger
- & Craig M. Crews
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Research Highlight |
Docetaxel-based CRT improves survival in cisplatin-ineligible patients
- David Killock
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Research Highlight |
Early MRD predicts disease recurrence and benefit from adjuvant chemotherapy in CRC
- David Killock
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Research Highlight |
Targeted biopsy reduces detection of clinically insignificant cancer
- Diana Romero
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