Nature Reviews Clinical Oncology最新文献

Two multimodal treatment strategies, perioperative chemotherapy and preoperative chemoradiotherapy, have been shown to improve overall survival (OS) compared to surgery alone in patients with locally advanced oesophageal adenocarcinoma (EAC); however, the optimal approach has been unclear. Newly published results from the phase III ESOPEC trial demonstrate the superiority of the perioperative strategy.

In ESOPEC, 438 patients with resectable cT1–4aN+ or cT2–4aN0 EAC were randomly assigned (1:1) to receive four preoperative and four postoperative cycles of fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) or preoperative radiotherapy (41.4 Gy in 23 fractions) plus concurrent weekly carboplatin and paclitaxel. OS was the primary end point.

Surgical resection is the standard of care for patients with colorectal liver metastases. Thermal ablation has emerged as an alternative management approach for small lesions (≤3 cm diameter), although how it compares with surgery is unclear because most of the available evidence is from meta-analyses of retrospective studies. Now, results from the phase III COLLISION trial demonstrate that thermal ablation results in noninferior efficacy outcomes and has a superior safety profile relative to resection.

In this trial, 296 patients with colorectal liver metastases were randomly allocated (1:1) to undergo thermal ablation or resection of all target lesions (median 2, range 1–10). Of note, 18% and 35% of patients in the thermal ablation and resection groups, respectively, underwent both approaches. Overall survival (OS) was the primary end point.

Transarterial chemoembolization (TACE) is the standard-of-care treatment for patients with intermediate-stage hepatocellular carcinoma (HCC) who are not candidates for resection, ablation or transplantation, although disease recurrence is common. Now, early data from two phase III trials demonstrate that the addition of both an immune-checkpoint inhibitor (ICI) and an anti-angiogenic agent to TACE improves patient outcomes.

Both trials involved patients with Barcelona Clinic Liver Cancer stage A–C non-metastatic HCC amenable to TACE. In LEAP-012, 480 patients were randomly allocated (1:1) to TACE (with a maximum of two treatments per tumour) and either pembrolizumab plus lenvatinib or double placebo. In EMERALD-1, 616 patients were randomly allocated (1:1:1) to TACE (1–4 procedures) and either durvalumab plus bevacizumab, durvalumab plus placebo or placebo alone. The primary end point of both trials was progression-free survival (PFS).

Haematopoietic stem cell transplantation (HSCT) and CD19-targeted chimeric antigen receptor (CAR) T cells are potentially curative therapies for relapsed and/or refractory diffuse large B cell lymphoma (R/R DLBCL); however, many patients are unable to receive or have further relapse following these treatments. New data from the phase III ECHELON-3 trial demonstrate the promise of a novel combination regimen incorporating the anti-CD30 antibody–drug conjugate brentuximab vedotin (BV) for such patients.

In ECHELON-3, 230 patients with R/R DLBCL who had received ≥2 prior lines of therapy and were ineligible for HSCT or CAR T cell therapy were randomly assigned (1:1) to received lenalidomide and rituximab plus either BV or placebo. The primary end point was overall survival (OS).

Circulating tumour DNA (ctDNA) can be released by cancer cells into biological fluids through apoptosis, necrosis or active release. In patients with non-small-cell lung cancer (NSCLC), ctDNA levels correlate with clinical and pathological factors, including histology, tumour size and proliferative status. Currently, ctDNA analysis is recommended for molecular profiling in patients with advanced-stage NSCLC. In this Review, we summarize the increasing evidence suggesting that ctDNA has potential clinical applications in the management of patients with early stage and locally advanced NSCLC. In those with early stage NSCLC, detection of ctDNA before and/or after surgery is associated with a greater risk of disease recurrence. Longitudinal monitoring after surgery can further increase the prognostic value of ctDNA testing and enables detection of disease recurrence earlier than the assessment of clinical or radiological progression. In patients with locally advanced NSCLC, the detection of ctDNA after chemoradiotherapy is also associated with a greater risk of disease progression. Owing to the limited number of patients enrolled and the different technologies used for ctDNA testing in most of the clinical studies performed thus far, their results are not sufficient to currently support the routine clinical use of ctDNA monitoring in patients with early stage or locally advanced NSCLC. Therefore, we discuss the need for interventional studies to provide evidence for implementing ctDNA testing in this setting.

Immune-checkpoint inhibitors (ICIs) have improved clinical outcomes across several solid tumour types. Prominent efforts have focused on understanding the anticancer mechanisms of these agents, identifying biomarkers of response and uncovering resistance mechanisms to develop new immunotherapeutic approaches. This research has underscored the crucial roles of the tumour microenvironment and, particularly, tumour-infiltrating lymphocytes (TILs) in immune-mediated tumour elimination. Numerous studies have evaluated the prognostic and predictive value of TILs and the mechanisms that govern T cell dysfunction, fuelled by technical developments in single-cell transcriptomics, proteomics, high-dimensional spatial platforms and advanced computational models. However, questions remain regarding the definition of TILs, optimal strategies to study them, specific roles of different TIL subpopulations and their clinical implications in different treatment contexts. Additionally, most studies have focused on the abundance of major TIL subpopulations but have not developed standardized quantification strategies or analysed other crucial aspects such as their functional profile, spatial distribution and/or arrangement, tumour antigen-reactivity, clonal diversity and heterogeneity. In this Review, we discuss a conceptual framework for the systematic study of TILs and summarize the evidence regarding their biological properties and biomarker potential for ICI therapy. We also highlight opportunities, challenges and strategies to support future developments in this field.

Immune-checkpoint inhibitors (ICIs) have transformed the treatment paradigm for advanced-stage squamous non-small-cell lung cancer (LUSC), a histological subtype associated with inferior outcomes compared with lung adenocarcinoma. However, only a subset of patients derive durable clinical benefit. In the first-line setting, multiple ICI regimens are available, including anti-PD-(L)1 antibodies as monotherapy, in combination with chemotherapy, or with an anti-CTLA4 antibody with or without chemotherapy. Several important questions persist regarding the optimal regimen for individual patients, particularly how to identify patients who might benefit from adding chemotherapy and/or anti-CTLA4 antibodies to anti-PD-(L)1 antibodies. An urgent need exists for predictive biomarkers beyond PD-L1 to better guide precision oncology approaches. Deeper knowledge of the underlying molecular biology of LUSC and its implications for response to ICIs will be important in this regard. Integration of this knowledge into multi-omics methods coupled with artificial intelligence might enable the development of more robust biomarkers. Finally, several novel therapeutic strategies, including novel ICIs, bispecific antibodies and personalized cancer vaccines, are emerging. Addressing these unresolved questions through innovative clinical trials and translational research will be crucial to further improving the outcomes of patients with LUSC. In this Review, we provide a comprehensive overview of current immunotherapeutic approaches, unresolved challenges and emerging strategies for patients with LUSC.

Cervical cancer is preventable with screening and vaccination approaches; however, access to these preventative measures is limited both nationally and globally and thus many women will still develop cervical cancer. Novel treatments and practice-changing research have improved cervical cancer outcomes over the past few decades. In this Review, we discuss clinical trials that have refined or redefined the treatment of cervical cancers across the early stage, locally advanced, persistent, recurrent and/or metastatic disease settings. Advances for patients with early stage disease have been achieved through trials evaluating less extensive and fertility-preserving surgeries, different surgical approaches (open versus minimally invasive), and sentinel versus full pelvic lymph node dissection. We also discuss results from trials testing the use of neoadjuvant, induction and adjuvant chemotherapy as well as immune-checkpoint inhibitors in patients with locally advanced disease. Finally, we review the progress made with systemic chemotherapy and novel therapeutics, including anti-angiogenic agents, immune-checkpoint inhibitors and antibody–drug conjugates, in the setting of metastatic and/or recurrent cervical cancer. The advances highlighted in this manuscript have reduced morbidity and improved overall survival for patients with this challenging-to-treat disease, while also inspiring additional research and trials in the field.