Expert Review of Anticancer Therapy最新文献

Introduction: Chronic myeloid leukemia (CML) is effectively treated with tyrosine kinase inhibitors such as imatinib, though drug response varies among patients. Genetic polymorphisms in drug transporter genes ABCB1 and ABCG2 influence imatinib plasma trough concentrations (Ctrough).

Methods: Statistical analyses were performed using fixed-effect models and heterogeneity was assessed using I² statistic.

Results: This meta-analysis evaluated nine studies including 1,098 heterozygous patients, 519 variant carriers, and 896 wild-type individuals. Results showed significantly higher Ctrough in patients with the ABCB1 c.3435C>T TT genotype compared with CC with data of 7 studies (MD = 299.84; 95% CI: 208.06-391.62; P = 0.0097; I² = 77%). Similarly, ABCB1 c.2677G>T GT (MD = 327.62; 95% CI: 198.90-456.34; P = 0.0008; I² = 52%) and TT (MD = 289.22; 95% CI: 135.63-442.81; P < 0.001; I² = 12%) genotypes were associated with higher levels than GG, both assessed by 4 studies. Additionally, data from 5 studies observed that ABCG2 c.412C>A CA carriers had increased Ctrough versus CC (MD = 186.83; 95% CI: 67.11-306.56; P = 0.022; I² = 32%).

Conclusions: These findings support the role of pharmacogenetic screening in optimizing imatinib therapy, improving efficacy, and reducing risks of adverse outcomes.

Registration: PROSPERO (CRD42024574179).

Background: Hyperferritinaemia is common in cancer and may reflect tumor-associated macrophage activity and ferroptosis resistance, yet its prognostic value during immune checkpoint inhibitor (ICI) therapy is uncertain.

Methods: We retrospectively analyzed 262 patients with metastatic solid tumors treated with ICIs (January 2015-September 2024). An optimal serum ferritin (SF) cutoff stratified patients into low (<500 ng/mL) vs high (>500 ng/mL) groups. Outcomes were compared between SF groups, and SF was compared with other inflammatory markers - the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and C-reactive protein (CRP).

Results: Median overall survival (OS) was 6.0 months for high SF vs 23.9 months for low SF; median progression-free survival (PFS) was 2.7 vs 6.4 months (both p < 0.001). High SF independently predicted worse OS (hazard ratio [HR] 2.17) and PFS (HR 1.73). Subgroup interactions were largely non-significant; only age >65 years moderated the OS association (interaction p = 0.035). Across metrics, SF showed the highest C-indices and superior 12-, 24-, and 36-month OS area under the curve (AUC) values compared with NLR, PLR, LMR, and CRP.

Conclusions: Pretreatment hyperferritinaemia is an inexpensive, readily available biomarker that outperforms conventional inflammatory indices in predicting poor survival and diminished ICI benefit across diverse metastatic solid tumors.

Introduction: Immune checkpoint inhibitors (ICI) have become a cornerstone of cancer treatment and induce durable responses in many patients with advanced cancer. However, they cause immune-related adverse events (irAEs) which result in symptoms related to autoimmunity, chronic sequelae, and occasionally death. Balancing toxicity and efficacy considerations remains a major challenge in ICI treatment.

Areas covered: We provide an overview of the pathophysiology, risk factors, and clinical presentation of irAEs. Next, we discuss potential approaches to manage these events. Finally, we discuss novel strategies to detect, prevent, and mitigate severe irAEs and thus optimize the benefits of ICI therapy for patients with cancer.

Expert opinion: irAEs, along with lack of response, remain the major challenge in ICI therapy. These constraints are not unrelated, as more aggressive combinations result in higher response rates (at least in some tumors), but increase irAEs as well. Novel multidrug regimens with immune modulators may 'thread the needle' to optimize both response and toxicity concerns.

Introduction: Despite neck lymph node metastases occurring commonly in cases of papillary thyroid carcinoma (PTC), there has remained controversy regarding the thresholds that should be used for lymph node characteristics in predicting PTC recurrence risk.

Areas covered: This scoping review explored the prognostic significance of lymph node characteristics in predicting risk of PTC recurrence. Following the PRISMA guidelines, the PubMed, Embase, and Web of Science databases were searched and supplemented by hand searching reference lists to identify articles published from database inception until October 2024. A total of 172 studies were included. Most studies had a retrospective cohort design and were reported from South Korea, Japan, and China. In general, an increased number of metastatic lymph nodes (commonly >5), presence of extranodal cancer extension, larger size of metastatic lymph nodes (commonly >3 cm), higher lymph node ratio (commonly ≥0.3 or ≥0.4), and presence of lateral neck compartment nodal metastases were all associated with higher recurrence rates.

Expert opinion: The lack of standardized definitions and terminology make the interpretation of findings difficult and limit generalizability. Future studies must focus on exploring long-term recurrence risk, in an exclusively PTC patient population, while also incorporating standardized definitions and terminology for lymph node characteristics and recurrence.

Background: Metastasis is the leading cause of cancer-related death and involves biological processes such as genomic instability and immune evasion. Although metastatic tumors generally retain major alterations present in primary tumors, the extent of additional genomic divergence across cancer types remains insufficiently characterized.

Research design and methods: A pan-cancer analysis was performed using targeted sequencing data from 2846 patients with matched primary and metastatic tumors (5692 samples) from the AACR Project GENIE-v18.0 cohort. Comparisons between primary and metastatic samples included mutation count, fraction of genome altered (FGA), gene-level mutation frequencies, copy number alterations (CNA), and structural variants (SV).

Results: Metastatic tumors showed modest but statistically significant increases in mutation count (median 6 vs. 5) and FGA (0.186 vs. 0.140), with the largest differences observed in lung, breast, colorectal, pancreatic, and prostate cancers. Eleven genes, including KDM5A, CDKN2A, MYC, ESR1, and AR, were more frequently altered in metastases. Differences in CNA and SV patterns were also observed, particularly in genes involved in cell cycle control and DNA repair.

Conclusions: Compared with primary tumors, metastatic tumors demonstrated small but consistent genomic differences. These findings varied across cancer types and may reflect changes associated with the evolutionary transition from primary to metastatic disease.

Introduction: This meta-analysis sought to assess the efficacy and safety of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) as maintenance therapy for patients with newly diagnosed advanced ovarian cancer (OC).

Methods: A comprehensive search was conducted across the PubMed, Medline, EMBASE, Cochrane Library, and Web of Science databases, up to 30 January 2025. Both pairwise meta-analysis and Bayesian network meta-analysis were employed. The primary end points were progression-free survival (PFS) and adverse events (AEs).

Results: A total of seven randomized controlled trials, encompassing 11 studies and 3220 patients, were included. PARPi maintenance therapy significantly improved PFS in patients with newly diagnosed OC. Subgroup analysis revealed PFS benefits across BRCA mutations, BRCA wild-type (BRCAwt), homologous recombination deficiency (HRD), and homologous recombination proficiency patients. However, no overall survival (OS) benefit was observed with PARPi maintenance therapy in either the overall or HRD populations. Notably, senaparib showed superior PFS efficacy compared to veliparib and niraparib. Additionally, PARPi treatment was associated with a significantly higher incidence of grade ≥3 AEs.

Conclusions: PARPi showed efficacy in improving PFS as maintenance therapy for newly diagnosed advanced OC, although no OS advantage was observed.

Registration: PROSPERO (CRD420251020275).

Background: This study aimed to evaluate the impact of HPV vaccination at the time of treatment of cervical intraepithelial neoplasia (CIN) 2 or 3 on recurrence/persistence.

Research design and methods: Unvaccinated women with genital high-grade lesion(s) were offered vaccination (Gardasil 9®) at the time of treatment. Those with CIN2 or 3 were compared with a historical control group of unvaccinated women.

Results: Vaccination was accepted by 99.6% of women (267/268); 170 satisfied the inclusion criteria. CIN2+ recurrence/persistence rate up to 24 months in the vaccine group was 3.0% (5/164) vs. 7.1% (21/295) in the control group, p = 0.091. There were no differences in the time until diagnosis.Positive margins (HR [hazard ratio] 8.28; 95% CI 4.08 to 16.77, p < 0.001) and age > 45 years (HR 2.99; 95% IC 1.56 to 5.74, p < 0.001) were associated with increased risk of persistence/recurrence.There was no reduction in HPV detection at 6 months, but vaccinated women were more likely to become HPV negative (HR 0.689; CI 95% 0.54 to 0.89; p = 0.003) and earlier.

Conclusion: There was a non-significant trend toward lower risk of recurrence/persistence of CIN2+ after treatment in vaccinated women; vaccination did not impact the short-term HPV detection but increased the likelihood of becoming undetectable.

Introduction: This systematic review and meta-analysis evaluated whether compression therapy prevents chemotherapy-induced peripheral neuropathy (CIPN) in breast cancer patients receiving taxanes.

Methods: Randomized controlled trials (RCTs) including breast cancer patients treated with taxanes and reporting CTCAE-graded CIPN were eligible. The primary outcome was grade ≥2 CIPN incidence. Odds ratios (OR) were pooled with a random-effects model; heterogeneity was assessed with I², and bias with the Cochrane RoB 2.0 tool.

Results: Three RCTs (n = 195) met criteria. Pooled analysis showed compression therapy significantly lowered CIPN incidence versus control (OR 0.33, 95% CI 0.15-0.71, p = 0.004; I² = 31%). Compared with standard care, compression markedly reduced CIPN (OR 0.24, 95% CI 0.11-0.49, p = 0.0001). No significant benefit was observed versus sham compression (OR 0.76, 95% CI 0.23-2.54, p = 0.66).

Conclusions: Compression therapy reduced grade ≥2 CIPN in breast cancer patients receiving taxanes, with benefits over standard care but not sham compression, suggesting placebo contributions. Limitations include the small number of available trials and participants. Larger, rigorously sham-controlled studies are required to confirm effectiveness and establish standardized timing and pressure protocols.

Registration: PROSPERO (CRD420251055184).

Introduction: Residual lesions after transurethral resection of bladder tumor (TURBT) are a major contributor to recurrence in bladder cancer. Advances in diagnostic technology are shifting postoperative management from conventional macroscopic evaluation toward molecular-level assessment.

Areas covered: A systematic search of PubMed, Web of Science and Embase from January 2000 to September 2025 identified studies on postoperative residual disease detection in non-muscle invasive bladder cancer (NMIBC). At the macroscopic level, enhanced cystoscopic modalities and artificial intelligence have improved visualization and recognition of subtle urothelial abnormalities. At the microscopic level, liquid biopsy approaches such as urinary tumor DNA, plasma circulating tumor DNA and exosome-based biomarkers enable more sensitive detection of minimal residual disease and dynamic molecular risk stratification beyond traditional cystoscopy and cytology. Integration of imaging findings with molecular profiling provides a more comprehensive basis for individualized surveillance and early therapeutic intervention in NMIBC.

Expert opinion: Future priorities include standardizing diagnostic workflows, improving multi-omics integration and validating MRD-guided strategies in prospective studies. These developments may refine risk stratification, reduce recurrence, and support more personalized postoperative management in bladder cancer.

Background: Chemotherapy-induced neutropenia (CIN) may reflect higher pharmacodynamic exposure and relate to improved outcomes, but its clinical relevance in pancreatic cancer remains uncertain.

Methods: PROSPERO-registered, PRISMA-compliant systematic review and meta-analysis. PubMed, Embase, and CENTRAL were searched to 18 August 2025. Eligible studies compared OS in CIN ≥G3 vs 

Results: Eight observational studies met inclusion; five (all advanced disease) were meta-analyzed. CIN ≥G3 was associated with better OS (grouped HR 0.50; 95% CI 0.40-0.62; I² = 0%), with consistent direction across studies. Sensitivity analyses confirmed robustness. ROBINS-I rated four studies at serious and four at moderate risk of bias; GRADE certainty for the pooled OS effect was moderate.

Conclusions: In advanced pancreatic cancer, CIN ≥G3 is associated with improved OS, supporting its role as a cohort-level prognostic/pharmacodynamic marker. Generalizability is limited by predominantly Japanese cohorts. Prospective multicenter studies with time-dependent modeling and control of relative dose intensity.

Registration: www.crd.york.ac.uk/prospero, identifier CRD420251005347.