Current Opinion in Oncology最新文献

Purpose of review: Small cell lung cancer (SCLC), particularly its transdifferentiated form, is highly aggressive and has a poor prognosis. The diagnosis of SCLC transdifferentiation is challenging, as repeat biopsies are often not clinically feasible and few noninvasive predictors of this neuroendocrine transformation have been identified to date.

Recent findings: Some retrospective studies and case reports have investigated this phenomenon. These studies indicate that it can occur in nonsmall cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, or rearranged during transfection (RET) fusions, typically following treatment with tyrosine kinase inhibitors. However, it has also been observed in cases of EGFR-wild type NSCLC after immunotherapy or radiation therapy.

Summary: Several molecular mechanisms that can drive SCLC transdifferentiation have been identified. The treatment of transdifferentiated SCLC remains a significant challenge, although promising new strategies are currently under investigation. This review summarizes the current understanding of SCLC transdifferentiation.

Purpose of review: Oligometastatic adrenocortical carcinoma (ACC) represents a distinct clinical subset of metastatic disease characterized by a limited tumor burden and potentially indolent biology. This review summarizes current evidence on its definition and management strategies.

Recent findings: Although mitotane and EDP-M chemotherapy remain the backbone of systemic therapy for advanced ACC, increasing evidence supports integrating local treatments - such as surgery, stereotactic body radiotherapy (SBRT), image-guided thermal ablation (IGT), and transarterial embolization (TACE/TARE) - in selected patients. Retrospective studies suggest that individuals with ≤5 metastases or lesions <3 cm, often classified as stage IVa, achieve higher disease control rates and prolonged survival when local and systemic therapies are combined. Decision-making should consider patient fitness, tumor biology (Ki-67 index, time to recurrence), and prior treatments within a multidisciplinary framework.

Summary: If a definition of oligometastatic ACC is required, a reasonable one would include stage IVa disease or up to five metastases <3 cm. Management should rely on a multidisciplinary approach in referral centers, integrating systemic and local therapies to optimize survival and quality of life.

Purpose of review: Lung cancer, the leading cause of cancer mortality, faces persistent challenges like resistance to targeted therapy and immunotherapy. This review comprehensively outlines the evolving role of bispecific antibodies (bsAbs), summarizing their mechanisms, clinical findings, and future directions. It is timely given emerging data and novel bsAbs that may reshape lung cancer treatment.

Recent findings: The article covers the development and clinical application of bsAbs in lung cancer, highlighting advancements in production technology and diverse formats. bsAbs are designed to simultaneously bind two different antigens, enabling mechanisms such as immune cell bridging and dual targeting of oncogenic pathways. Key themes include the use of bsAbs as first-line treatments, their role in second-line and later-line settings, and their application in neoadjuvant or adjuvant therapy.

Summary: The findings suggest that bsAbs represent a significant advancement in lung cancer treatment, offering new therapeutic strategies to address unmet needs. The development of next-generation bsAbs, including trispecific antibodies and conditional activation platforms, promises enhanced precision and safety. These innovations have the potential to improve outcomes for patients with advanced lung cancer. Future research should focus on optimizing patient selection through biomarker-driven approaches and exploring combination therapies to maximize the benefits of bsAbs.

Purpose of review: To examine the persistent global disparities in breast cancer outcomes, focusing on inequities in access to essential therapeutics, diagnostics, and emerging innovations, while highlighting current policy actions and international initiatives addressing these gaps.

Recent findings: Although survival rates for breast cancer have improved in high-income countries, significant inequalities remain in low- and middle-income settings. Access to timely diagnosis, standard treatments, and novel therapeutics such as targeted agents and immunotherapies is uneven. Recent global initiatives, including the WHO Global Breast Cancer Initiative, aim to enhance early detection, standardize care pathways, and improve access to affordable, quality-assured treatments. Policy frameworks are increasingly addressing issues of availability, affordability, and infrastructure, yet implementation remains inconsistent.

Summary: Bridging global breast cancer disparities demands coordinated action integrating health system strengthening, policy reform, and international collaboration. Equitable access to therapeutics and diagnostics must be prioritized to ensure that advancements in breast cancer care translate into improved outcomes worldwide.

Purpose of review: Reirradiation has emerged as a potentially valuable treatment strategy for recurrent glioblastoma, a disease characterized by inevitable local progression despite aggressive multimodal first-line therapy. Recent advances in radiotherapy techniques, improved patient selection, and evolving systemic treatment combinations have renewed clinical interest in this approach. This is reflected by recent publication of the first international consensus guidelines (ESTRO/EANO) and the initiation of an European phase III randomized trial on reirradiation of patients with recurrent glioblastoma.

Recent findings: Retrospective and early-phase prospective studies have demonstrated that reirradiation is feasible and well tolerated in selected patients, with median overall survival ranging from 7 to 13 months. The ESTRO/EANO guidelines on reirradiation of glioma provide standardized recommendations for patient selection, dose constraints, and target volume delineation. Meta-analyses suggest improved outcomes when reirradiation is combined with systemic therapies, such as bevacizumab or lomustine. The phase III EORTC-2227-BTG (LEGATO) trial will provide definitive data on survival benefit.

Summary: Reirradiation is gaining acceptance as a palliative yet potentially impactful treatment for recurrent glioblastoma. While current evidence supports its use in selected cases, results from ongoing phase III LEGATO trial will determine its future role in standard care and inform evidence-based clinical decision-making.

Purpose of review: Chimeric antigen receptor (CAR) T therapies hold potential as a new therapeutic approach for relapsed/refractory acute myeloid leukemia (R/R AML), but development has been challenging due to difficulty identifying the optimal targeting antigen. AML exhibits heterogenous and overlapping antigen expression with normal hematopoietic cells, raising concerns for poor efficacy and on-target/off-tumor hematotoxicity. However, it is not clear that these concerns have been fully borne out in available clinical data. Here, we review clinical studies of AML CAR T therapies with a focus on critically evaluating efficacy and toxicities.

Recent findings: Encouraging responses have been reported in a notable proportion of patients in published trials, especially when taking into consideration that patients have treatment-resistant disease after multiple lines of therapy. Rates of cytopenias after AML CAR T therapies vary and there are insufficient data to delineate whether they are due to on-target toxicity or off-target effects such as low marrow reserve and myelosuppressive inflammatory sequelae.

Summary: These studies highlight the need for continued optimization of CAR T design and treatment strategies to enhance efficacy and reduce toxicities in AML. Further studies are needed to better understand the frequency/severity of cytopenias after AML CAR T therapies and to clarify the underlying on-/off-target mechanisms.

Purpose of review: Vorasidenib has demonstrated efficacy in isocitrate dehydrogenase (IDH)-mutant grade 2 gliomas that do not require immediate oncological treatment. Here, we summarize open questions regarding its long-term benefit, its optimal use in IDH-mutant grade 2 gliomas as well as its potential use in grade 3 and 4 IDH-mutant gliomas.

Recent findings: In IDH-mutant grade 2 gliomas, vorasidenib may act as a differentiation therapy. Updated results from the INDIGO trial suggest an additional effect on seizure control. Volumetric analysis and amino acid PET imaging may improve response assessment. However, long-term follow-up and new clinical trials will be needed to determine whether first-line vorasidenib preserves cognition, quality of life and improves overall survival. Since contrast-enhancement rather than histological grade appears to be more closely associated with disease control, selected grade 3 IDH-mutant gliomas might also benefit from first-line vorasidenib. Ongoing trials are evaluating vorasidenib as maintenance therapy after radiochemotherapy, and in association with chemotherapy and different immunotherapies.

Summary: While vorasidenib is becoming the first-line treatment in the majority of IDH-mutant grade 2 gliomas, we are progressively learning how it works, how it should be used and in which contexts beyond grade 2 IDH-mutant gliomas it could be beneficial.

Purpose of review: To review the current evidence and inform clinical guidance on the implications of incomplete ovarian function suppression (OFS), the utility of serum estradiol (E2) monitoring, and appropriate management strategies in premenopausal women with early breast cancer (eBC) receiving adjuvant luteinizing hormone-releasing hormone agonist (LHRHa)-based therapy for OFS.

Recent findings: A universally accepted definition of incomplete OFS is currently lacking. Although biologically it is plausible that incomplete OFS may compromise the efficacy of endocrine therapy, its actual impact on clinical outcomes remains unclear. Currently, the reliability of E2 monitoring is limited by considerable variability in assay methods and reference ranges, raising concerns about its analytical validity. Notably, in a recent international survey of 205 oncologists managing patients with eBC, 43% reported routinely and 27% occasionally assessing E2 levels in premenopausal patients treated with LHRHa, suggesting inconsistent clinical practice. Standard immunoassays were the most frequently used (65%). However, interpretation of E2 values and subsequent management decisions varied widely, highlighting the absence of standardized clinical guidelines.

Summary: Although not currently supported by high-level evidence, serum E2 monitoring is widely adopted in clinical practice. Prospective studies and evidence-based recommendations are urgently needed. Emerging strategies to overcome incomplete OFS include LHRH antagonists (e.g., degarelix) and oral SERDs.

Purpose of review: Patients with acute promyelocytic leukemia (APL) who present with leukocytosis are considered high-risk due to lower relapse-free survival when treated with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. The discovery and incorporation of arsenic trioxide (ATO) in therapeutic regimens for high-risk patients have led to improved survival, but there is no consensus on the optimal treatment approach. This review addresses reduction in early death and explores questions of regimen selection, including the choice of induction, consolidation, and maintenance, as well as the use of prophylactic adjunctive therapies, while examining clinical trial and real-world evidence.

Recent findings: ATRA-ATO combined with idarubicin (IDA) or gemtuzumab ozogamicin are highly effective compared to ATRA-IDA-based chemotherapy in clinical trials and real-world studies. Improved survival and early death reduction can be seen in the randomized controlled APOLLO study and in data from the recently published HARMONY and HERO analyses.

Summary: ATRA-ATO-based combinations, including ATRA-ATO-IDA and ATRA-ATO-GO, are current standards of care in high-risk APL. Further studies should seek to clarify the choice between these and other regimens and to more clearly show the benefit of maintenance therapy and of additional therapies such as for differentiation syndrome and CNS prophylaxis with these highly effective induction/consolidation regimens.

Purpose of review: The aim of this study was to examine the role of proxy-reported outcomes in oncology, particularly in neuro-oncology, where cognitive impairment and disease progression often limit patients' ability to self-report. With increasing emphasis on patient-centered care and regulatory requirements for clinical outcome assessments (COAs), it is essential to understand when and how proxy reports can substitute or complement patient-reported outcomes (PROs), particularly in the assessment of health-related quality of life (HRQoL).

Recent findings: Use of proxy-reported outcomes in cancer clinical trials is common. Proxy reports can help reduce missing data and selection bias by replacing PROs in patients with a poor health condition. However, studies consistently show poor to moderate agreement between patient and proxy reports of HRQoL outcomes, with the lowest congruence in less observable areas such as emotional functioning. Most proxy reports rely on PRO instruments not validated for proxy use, and heterogeneity in statistical methods, proxy selection, and proxy instruction further complicates interpretation.

Summary: While proxy-reported outcomes should not replace PROs when patients can self-report, they offer valuable insights when self-report is not feasible. When standardized methods are followed, such as using validated instruments and clearly defining the reporting perspective, proxy reports can serve as a useful alternative in clinical trials and clinical practice.