Current Opinion in Oncology最新文献

Purpose of review: This review aims to detail the characteristics and outcomes of duodenal-type follicular lymphoma (DTFL), a rare lymphoma variant. It focuses on integrating recent reports in treatment modalities and highlights emerging insights into the unique biological features of the disease.

Recent finding: Recent studies confirm the indolent nature of DTFL, with extended follow-up periods showing favorable outcomes under watchful waiting strategies and a notable proportion of patients experiencing spontaneous remission. Additionally, advancements in understanding the disease's biology revealed that the tumor microenvironment is marked by specific genomic expressions indicative of chronic inflammation.

Summary: The observations of spontaneous resolution and the generally favorable progression of DTFL call for a conservative approach in initiating treatment. Clinical management should judiciously consider the disease's typically benign course against the potential risks of intervention, promoting customized treatment protocols tailored for cases with clinical necessity. Additionally, the discovery of an inflammatory tumor microenvironment and molecular evidence suggesting an antigen-driven process highlight critical areas for future research.

Purpose of review: Patients with advanced breast cancer (aBC) treated with PARP inhibitors (PARPi) can eventually experience disease progression for emerging treatment resistance. This review aims to depict the treatment the molecular landscape, and the innovative therapies for patients with PARPi-resistant BRCA-mutated aBC.

Recent findings: No specific therapy is specifically available in the setting post-PARPi-failure, with antibody-drug conjugates or nonplatinum-based chemotherapy (PBC) representing the best treatment options in this setting. Mechanisms of on-target PARPi resistance can be classified in reversions (60%) and nonreversion (40%); reverse mutations restore PARP functions. According to the first evidence of clinical validity, these alterations are associated with lower efficacy of PARPi and PBC. However, their clinical utility needs to be assessed.

Summary: PARPi-resistant aBC represents a clinical unmet need due to the lack of specific targeted therapies and validated prognostic and predictive biomarkers. Constant efforts are required to better define the mechanisms of PARPi resistance and, consequently, develop biomarker-based treatment approach to prevent or overcame resistance.

Purpose of review: The past two decades have witnessed an impressive expansion in the treatment landscape of multiple myeloma, leading to significant improvements in progression-free; as well as overall survival. However, almost all patients still experience multiple relapses during their disease course, with biological and cytogenetic heterogeneity affecting response to subsequent treatments. The purpose of this review is to provide a historical background regarding the role of alkylating agents and an updated data regarding the use of peptide-drug conjugates such as melflufen for patients with multiple myeloma.

Recent findings: The combination of daratumumab-melflufen-dexamethasone evaluated in the LIGHTHOUSE study showed a statistically significant improvement in progression-free survival compared to single-agent daratumumab (not reached vs. 4.9 months respectively; P = 0.0032), with improvement in overall response rate to 59% vs. 30% respectively; P = 0.03.

Summary: There have been an interest in developing and utilizing peptide-drug conjugates such as melflufen for treatment of patients with multiple myeloma, especially in the relapsed setting given historical results with alkylating agents, the use of which has been limited by dose-related toxicities in a disease that remains largely incurable. Single agent melflufen initially showed promising results especially in specific subgroups of heavily pretreated patients before the decision to suspend all clinical trials evaluating this agent after results from the OCEAN phase 3 trial. Subsequent reported analyses especially for melflufen-based combinations appear promising and suggest a potential use of peptide-drug conjugates provided optimal patient selection, as well as identification of the best companion agent.

Purpose of review: The use of immunotherapy in recent years has changed the paradigm of treatment in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), improving outcomes in the relapsed/refractory setting. New strategies are incorporating immunotherapy into front-line regimens to reduce the toxicity of chemotherapy, prolong survival and increase the possibility of treating older patients. The aim of this review was to describe the new strategies, which have incorporated these drugs into front-line regimens for BCP-ALL patients.

Recent findings: Recent studies have demonstrated that immunotherapy can be included in front-line induction, consolidation and/or maintenance regimens for the treatment of BCP-ALL patients by its addition to chemotherapy, by substituting some chemotherapy cycles or even including immunotherapy in chemotherapy-free strategies.

Summary: The implications of these relevant findings will allow treating older patients, reducing the toxicity of chemotherapy and increasing patient outcomes. In addition, these findings have raised the possibility of avoiding the need for hematologic stem cell transplant in some selected patients.

Purpose of review: Significant advancements have been made in treating metastatic breast cancer (MBC) with antibody drug conjugates (ADCs). However, due to the development of resistance, patients experience disease progression. The aim of this review is to summarize current evidence on ADCs sequencing strategies and combination approaches in the treatment of MBC.

Recent findings: Concerning HER2 positive MBC, current evidence on the optimal ADC-sequencing is primarily about T-DXd, which demonstrated therapeutic value when used post-T-DM1. Conversely, data are limited about the reverse sequence. Similarly, in HER2-negative MBC, recent studies evaluated the sequential use of Sacituzumab Govitecan and T-DXd, which was associated with poor responses. Retrospective analyses have not demonstrated an optimal sequencing strategy for ADCs, and it is still very unclear whether switching the payload or targeting a different antigen may represent the best approach. Combinations may better overcome ADC resistance: interesting data associating immunotherapy or tyrosine kinase inhibitors to ADCs appear promising, albeit data are still immature.

Summary: In MBC, ADCs have expanded treatment options but their sequential use requires further study. Evidence suggests that sequencing ADCs with similar payloads is ineffective, though current data are inconclusive. More research is needed to optimize treatment strategies, including potential combination therapies.

Purpose of review: The purpose of this review is to provide a comprehensive overview of human epidermal growth factor receptor 2 (HER2) genomic tests, particularly focusing on the most recent developments and looking at the future prospects of this field, yet to be thoroughly explored.

Recent findings: HER2DX is a multifeatured assay, retrospectively proved to add prognostic information and to predict pathological complete response (pCR) in patients with HER2-positive early breast cancer (EBC) undergoing neoadjuvant treatment containing HER2-directed agents. Preliminary data have shown that the assay maintains its predictive capabilities even in the context of chemotherapy-free, anti-HER2 neoadjuvant regimens, potentially selecting patients suitable for treatment de-escalation, having highly HER2-driven malignancies.

Summary: Multigene prognostic assays have become essential tools in the management of EBC, providing crucial information for risk stratification.

Purpose of review: In the evolving landscape of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) management, liquid biopsy offers unprecedented opportunities for guiding clinical decisions. Here, we review the most recent findings on liquid biopsy applications in HER2-positive BC and its potential role in addressing challenges specific to this BC subtype.

Recent findings: Recent studies have highlighted the significance of liquid biopsy analytes, primarily circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), in stratifying patients' prognosis, predicting treatment response, and monitoring tumor evolution in both early and advanced stages of BC. Liquid biopsy holds promise in studying minimal residual disease to detect and potentially treat disease recurrence before it manifests clinically. Additionally, liquid biopsy may have significant implication in the management of brain metastasis, a major challenge in HER2-positive BC, and could redefine parameters for determining HER2 positivity. Combining ctDNA and CTCs is crucial for a comprehensive understanding of HER2-positive tumors, as they provide complementary insights.

Summary: Research efforts are needed to address analytical challenges, validate, and broaden the application of liquid biopsy in HER2-positive BC. This effort will ultimately facilitate its integration into clinical practice, optimizing the care of patients with HER2-positive tumors.

Purpose of review: Central nervous system (CNS) tumors represent a significant unmet medical need due to their enduring burden of high mortality and morbidity. Chimeric antigen receptor (CAR) T-cell therapy emerges as a groundbreaking approach, offering hope for improved treatment outcomes. However, despite its successes in hematological malignancies, its efficacy in solid tumors, including CNS tumors, remains limited. Challenges such as the intricate tumor microenvironment (TME), antigenic heterogeneity, and CAR T-cell exhaustion hinder its effectiveness. This review aims to explore the current landscape of CAR T-cell therapy for CNS tumors, highlighting recent advancements and addressing challenges in achieving therapeutic efficacy.

Recent findings: Innovative strategies aim to overcome the barriers posed by the TME and antigen diversity, prevent CAR T-cell exhaustion through engineering approaches and combination therapies with immune checkpoint inhibitors to improving treatment outcomes.

Summary: Researchers have been actively working to address these challenges. Moreover, addressing the unique challenges associated with neurotoxicity in CNS tumors requires specialized management strategies. These may include the development of grading systems, monitoring devices, alternative cell platforms and incorporation of suicide genes. Continued research efforts and clinical advancements are paramount to overcoming the existing challenges and realizing the full potential of CAR T-cell therapy in treating CNS tumors.

Purpose of review: Due to limited access to the tumor, there is an obvious clinical potential for liquid biopsy in patients with primary brain tumors. Here, we review current approaches, present limitations to be dealt with, and new promising data that may impact the field.

Recent findings: The value of circulating tumor cell-free DNA (ctDNA) in the cerebrospinal fluid (CSF) for the noninvasive diagnosis of primary brain tumors has been confirmed in several reports. The detection of ctDNA in the peripheral blood is desirable for patient follow-up but requires ultrasensitive methods to identify low mutant allelic frequencies. Digital PCR approaches and targeted gene panels have been used to identify recurrent hotspot mutations and copy number variations (CNVs) from CSF or plasma. Tumor classification from circulating methylomes in plasma has been actively pursued, although the need of advanced bioinformatics currently hampers clinical application. The use of focused ultrasounds to open the blood-brain barrier may represent a way to enrich of ctDNA the peripheral blood and enhance plasma-based liquid biopsy.

Summary: Monitoring CNVs and hotspot mutations by liquid biopsy is a promising tool to detect minimal residual disease and strengthen response assessment in patients with primary brain tumors. Novel methods to increase the relative and/or absolute amount of ctDNA can improve the clinical potential of plasma-based liquid biopsies.

Purpose of review: To provide up-to-date evidence on patient-reported outcomes (PROs) in neuro-oncology, with a focus on the core constructs of health-related quality of life (HRQoL) and the use of PROs in clinical trials and clinical practice.[Supplemental Digital Content: Video Abstract PROs in Neuro-Oncology.mov].

Recent findings: PROs are gaining importance in brain tumor research and medical care. For patients with a brain tumor, core PRO constructs are pain, difficulty communicating, perceived cognition, seizures, symptomatic adverse events, physical functioning and role and social functioning, which are assessed through patient-reported outcome measures (PROMs). Initiatives have been taken to improve the reliability and robustness of PRO data, including standardization of items included in clinical trial protocols (the SPIRIT-PRO extension) and formulation of PRO priority objectives for use in clinical trials (the SISAQOL-Innovative Medicines Initiative). In brain tumor patients with cognitive impairment, caregiver-reported outcomes may complement or replace PROs to increase accuracy. The next key challenge will be to widely implement PROs and apply PRO data in clinical practice to benefit patients with brain tumors.

Summary: PROs are clinically relevant endpoints providing information only known by the patient. Standardization of the use of PROs in clinical trials and wide implementation in clinical practice is needed to improve HRQoL of brain tumor patients.