Therapeutic Advances in Medical Oncology最新文献

Background: Identification of hypopharyngeal cancer (HPC) patients at heightened risk for developing metachronous second primary esophageal cancer (MSPEC) is crucial for the optimization of screening protocols and thus survival improvement. Although mean corpuscular volume (MCV) is recognized as a biomarker for esophageal cancer, its association with MSPEC among HPC patients remains unexplored.

Objective: This study aimed to investigate the predictive value of MCV for MSPEC in HPC patients.

Design: In this 19-year retrospective, nested case-control study, HPC patients from the Chang Gung Research Database between January 2001, and December 2019, were examined.

Methods: A total of 114 HPC patients who developed MSPEC were matched with 1895 non-MSPEC controls in a 1:3 propensity score-matched analysis. Logistic regression models were deployed to assess the odds of MSPEC manifestation in relation to MCV levels.

Results: Matching for clinical characteristics and follow-up periods yielded 96 MSPEC patients and 288 matched controls. Elevated MCV levels were associated with an increased risk of MSPEC, indicating a dose-response relationship. Specifically, MCV ranges from 95 to 100 femtoliters (fL) and ⩾100 fL correlated with adjusted odds ratios for MSPEC of 2.37 (95% confidence interval (CI): 1.33-4.24) and 4.84 (95% CI: 2.62-8.95), respectively. Notably, an MCV ⩾100 fL was a more pronounced predictor of MSPEC among younger patients and those with advanced disease stages. Within the initial cohort of 2009 HPC patients, 31 (2.9%) of 1052 patients with MCV <95 fL developed MSPEC, and 46 (11.5%) of 401 patients with MCV ⩾100 fL experienced MSPEC.

Conclusion: Macrocytosis at HPC diagnosis is indicative of an escalated MSPEC risk, underscoring the imperative for intensive surveillance.

Background: Current biomarkers for predicting pathological response to neoadjuvant chemoimmunotherapy in esophageal squamous cell carcinoma (ESCC) remain limited.

Objective: This study investigates the potential of the pan-immune-inflammation value (PIV) as a biomarker for predicting pathological response after neoadjuvant chemoradiotherapy combined with anti-programmed death protein-1 (PD-1) therapy in ESCC.

Design: A multicenter, real-world, retrospective clinical study conducted across five centers in Southern China (January 2021-March 2024).

Methods: A multicenter retrospective study included 334 patients with ESCC, divided into pathological complete response (pCR) and non-pathological complete response (non-pCR) groups. Clinical and laboratory data were analyzed using univariate and multivariate logistic regression to evaluate the relationship between post-treatment PIV and pathological response. The threshold effect of PIV was explored using restricted cubic spline analysis.

Results: Subgroup analysis showed no significant interactions across clinical subgroups. Post-treatment PIV was positively associated with non-pCR risk (odds ratio = 1.002; 95% confidence interval: 1.001-1.003, p < 0.005). A positive association was observed in the high-PIV stratum (⩾280), where elevated PIV levels significantly correlated with increased non-pCR risk. Receiver operating characteristic analysis showed an area under the curve of 0.86 for predicting non-pCR, with a sensitivity of 86.6% and specificity of 72% at an optimal cutoff of 438.04. The high-PIV group exhibited inferior survival outcomes with significantly increased mortality risk.

Conclusion: Post-treatment PIV shows a nonlinear relationship with pathological response in patients receiving neoadjuvant chemoradiotherapy combined with anti-PD-1 therapy and may serve as a predictive biomarker.

Background: Docetaxel, following progression on immunotherapy and platinum-based chemotherapy, remains the standard of care for advanced non-small-cell lung cancer (NSCLC) but offers limited promise. Antibody-drug conjugates (ADCs) may improve outcomes in this population.

Objectives: Data from the literature, mainly randomized controlled trials (RCTs), have shown discrepancies. This report evaluates the efficacy and safety of ADCs versus docetaxel in previously treated advanced NSCLC.

Design: The systematic review and meta-analysis was conducted focusing on phase II/III RCTs to synthesize available evidence regarding efficacy outcomes and safety of ADCs compared to docetaxel.

Data resources and methods: Databases (PubMed (MEDLINE), EMBASE, and Cochrane Library), clinical trial registries, and proceedings of global oncology conferences from January 2015 to November 2024 were screened comparing ADC versus docetaxel. Two researchers independently completed data retrieval and screening work using Covidence. The Cochrane Risk of Bias Tool (RoB 2.0) was used to assess the methodological quality of the included RCTs. The primary outcomes include progression-free survival (PFS) and overall survival (OS), while the secondary outcomes include objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). The pooled hazard ratios (HRs) and odds ratios (ORs) were meta-analyzed using the appropriate generic variance and Mantel-Haenszel methods. Random-effect models were used to compute pooled estimates.

Results: Of the 212 records screened, three RCTs involving 1597 patients were included. ADCs did not significantly improve PFS (pooled HR: 0.91, 95% CI: 0.73-1.13). For OS, the pooled HR was 0.88 (95% CI: 0.78-1.00, p = 0.06), reflecting a borderline significant trend favoring ADCs, with negligible heterogeneity (I ² = 0%). Furthermore, subgroup analysis demonstrated a significant OS benefit in the nonsquamous cohort (HR: 0.85, 95% CI: 0.74-0.98, p = 0.03). In addition, no difference was observed in ORR (OR: 1.16, 95% CI: 0.54-2.51) and DCR (OR: 1.39, 95% CI: 0.75-2.57). Grade ⩾ 3 treatment-related AEs were significantly lower (pooled OR: 0.49, 95% CI: 0.26-0.90, p = 0.02) with ADCs, despite high heterogeneity (I ² = 87%).

Conclusion: Overall, there was no difference between the docetaxel and the ADC treatment arms; however, our findings report a significant survival benefit in the subgroup of patients with nonsquamous NSCLC pathology treated with ADCs compared to docetaxel with a manageable safety profile. Further research is needed to address heterogeneity, refine patient selection, and obtain more mature survival data with predictive biomarkers.

Background: Neoadjuvant chemotherapy (NAC) plays a central role in the management of early breast cancer (BC), offering prognostic information and improving surgical outcomes. Blood-based biomarkers, including inflammatory markers-such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)-and circulating nucleic acids-such as circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), and cfDNA integrity index (cfDI)-have been investigated for their potential to predict treatment response.

Objectives: To systematically evaluate the prognostic value of inflammatory indices and circulating nucleic acids measured during NAC for predicting pathological complete response (pCR) in early BC.

Design: Systematic review with qualitative synthesis.

Data sources and methods: Twenty-four studies were included, examining changes in NLR, PLR, ctDNA, cfDNA, and cfDI during NAC. Study quality was assessed using the Newcastle-Ottawa Scale, and the strength of evidence was evaluated with a qualitative GRADE approach. Due to heterogeneity in biomarker definitions, sampling timepoints, and statistical methods, data were synthesized narratively.

Results: A reduction in PLR from baseline to mid-NAC (ΔPLR <0) was consistently associated with higher pCR rates. ctDNA clearance, particularly at mid- and post-NAC, was frequently linked to increased pCR and better overall survival. In contrast, findings on NLR dynamics were inconsistent. Evidence for cfDNA and cfDI was limited and mixed, with some studies suggesting lower cfDNA and higher cfDI may be associated with improved outcomes. Variability in biomarker thresholds and timepoints was a common limitation.

Conclusion: Mid-NAC PLR decrease and ctDNA clearance show moderate evidence as predictors of pCR and may help guide treatment decisions. The prognostic value of NLR, cfDNA, and cfDI remains uncertain and requires further prospective, standardized investigation.

Background: Breast phyllodes tumors (PT) are rare fibroepithelial tumors classified by the World Health Organization into benign, borderline, and malignant subtypes. Although surgery is the primary treatment, local recurrence remains a concern. The role of postoperative radiotherapy (PORT) in improving local control remains unclear.

Objectives: This study aimed to investigate the effect of PORT in patients with borderline PT (BoPT) and malignant PT (MPT) after R0 resection (complete resection without tumor margins) and to identify prognostic factors related to local recurrence-free survival (LRFS) and overall survival (OS).

Design: This was a retrospective multicenter study.

Methods: We retrospectively evaluated patients with BoPT and MPT who underwent R0 resection between January 2002 and October 2023. Propensity score matching was used to balance the covariates between the PORT (n = 37) and non-PORT (n = 83) groups. Kaplan-Meier curves were used to estimate the 5-year LRFS and OS, while Cox regression analyses were used to identify prognostic factors. Subgroup analysis was used to assess the potential benefits of radiotherapy.

Results: Of 480 patients, 438 (91.25%) underwent surgery alone and 42 (8.75%) received PORT. PORT did not improve the LRFS or OS. After matching, 5-year LRFS (71.42% vs 70.17%, p = 0.58) and OS (82.41% vs 80.02%, p = 0.82) were similar between the groups. Multivariate analysis of matched samples showed that axillary lymph node metastasis was significantly associated with LRFS and OS. Malignant heterologous elements were independent poor prognostic factors for LRFS. No subgroup benefited from radiotherapy.

Conclusion: In our study, PORT did not significantly improve LRFS or OS in patients with BoPT and MPT. Key prognostic factors may guide treatment decisions in these patients.

Background: Despite significant advancements in treatment, patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) continue to face the challenge of drug resistance, highlighting the need to develop new drugs and treatment strategies. Pyrotinib has exhibited notable efficacy in managing HER2-positive MBC, especially in individuals with brain metastasis (BM). However, real-world evidence on the effectiveness of pyrotinib re-treatment remains limited.

Objectives: This study aims to assess the efficacy of pyrotinib re-treatment-including treatment beyond progression (TBP) and rechallenge-in patients with HER2-positive MBC, particularly those with BMs, in a real-world clinical setting.

Design: A retrospective, multicenter, real-world study.

Methods: Patients with HER2-positive MBC who experienced progression during pyrotinib treatment and subsequently continued or resumed pyrotinib-based regimens were enrolled. Patients were divided into two groups according to the re-treatment pattern: the pyrotinib TBP group and the pyrotinib rechallenge group. The endpoints were progression-free survival (PFS) and overall survival (OS).

Results: A total of 226 participants received pyrotinib TBP, whereas 33 received pyrotinib rechallenge. The median PFS of pyrotinib re-treatment (7.2 vs 6.3 months, p = 0.31) and the median OS, measured from the start of pyrotinib re-treatment (31.6 vs 21.0 months, p = 0.062), were comparable between the two groups. Among patients with BMs before pyrotinib re-treatment, the median PFS for pyrotinib re-treatment was 7.2 months, and the median OS was 25.2 months.

Conclusion: Pyrotinib TBP and pyrotinib rechallenge both demonstrate potential benefits for patients with HER2-positive MBC, including those with BM.

Background: Regorafenib targets tumor angiogenesis and oncogenic signaling by inhibiting multiple kinases involved in angiogenesis, oncogenesis, and the tumor microenvironment. Chemotherapy of FOLFIRI causes direct cytotoxic damage to tumor cells.

Objectives: We evaluated the efficacy and safety of regorafenib plus FOLFIRI with uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping-guided irinotecan dose escalation in patients with metastatic colorectal cancer (mCRC) who had received second- or third-line systemic therapy.

Design: A total of 153 patients were randomized (at a ratio of 2:1) to receive either regorafenib plus FOLFIRI (experimental group, 102 patients) or regorafenib alone (control group, 51 patients).

Methods: Both groups received regorafenib (120 mg daily) for 21 consecutive days in 28-day cycles. In addition, the experimental group received FOLFIRI with UGT1A1 genotyping-guided irinotecan dose escalation. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), disease control rate (DCR), and adverse events.

Results: The final cohort included 116 patients. The experimental group exhibited significant improvement in PFS (p = 0.016) but marginally significant improvements in DCR (p = 0.055). Specifically, PFS improved significantly for experimental group patients carrying wild-type rat sarcoma virus (RAS; p = 0.003) and those carrying left-sided colon tumors (p = 0.015). A trend toward improved OS was noted in experimental group patients carrying wild-type RAS (p = 0.096). No significant between-group difference was observed in the incidence of severe adverse events (all p > 0.05).

Conclusion: Our findings suggest that regorafenib plus FOLFIRI significantly improved PFS in patients with mCRC and offers a safety profile similar to that of regorafenib alone. This regimen may be particularly beneficial for patients with mCRC carrying wild-type RAS and those carrying left-sided tumors. However, larger phase III randomized controlled trials are necessary to confirm the efficacy and safety of this combination therapy before adoption into standard practice.

Trial registration: ClinicalTrials.gov registry: NCT03880877 (https://clinicaltrials.gov/search?cond=NCT03880877).

Background: Alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) are classical tumor markers in clinical practice. However, the relationship between tumor markers and prognosis in hepatocellular carcinoma (HCC) patients receiving immune checkpoint inhibitor (ICI) therapy remains unclear.

Objectives: This study aims to explore the prognostic value of AFP and PIVKA-II in HCC patients treated with ICIs.

Design: This study was a single-center, retrospective investigation aimed to assess the prognostic value of AFP and PIVKA-II in HCC patients receiving immune checkpoint inhibitors.

Methods: This retrospective study included HCC patients who received ICIs treatment at Wuhan Union Hospital between July 2020 and March 2024. Serum AFP and PIVKA-II levels were collected before treatment. Patients were stratified into two groups based on AFP ⩾ 400 μg/L (yes = 1, no = 0) and PIVKA-II ⩾ 40 mAU/mL (yes = 1, no = 0). A total of 61% (114/186) of patients scored ⩽ 1, while 39% (72/186) scored 2. The objective response rate (ORR) and disease control rate (DCR) were calculated for both groups. Kaplan-Meier survival curves and Cox regression models were used to analyze overall survival (OS) and progression-free survival (PFS). Receiver operating characteristic curves were generated to demonstrate the predictive ability of combined independent prognostic factors for long-term survival.

Results: The cohort consisted of 186 patients, divided into the low-risk group (n = 114) and the high-risk group (n = 72). Among all patients, 34.4% (64/186) achieved complete or partial response. Concurrent elevation of AFP and PIVKA-II was inversely associated with ORR (p = 0.012). The high-risk group exhibited significantly shorter OS (adjusted HR: 2.226 (95% CI: 1.410-3.513); p < 0.001) compared to the low-risk group. The integrated model combining AFP, PIVKA-II, and Barcelona Clinic liver cancer stage demonstrated moderate to good predictive capability for long-term risk stratification, with time-dependent area under the curves of 0.78 (9-month), 0.68 (12-month), and 0.63 (15-month).

Conclusion: Concurrent elevation of AFP and PIVKA-II is significantly associated with shorter survival outcomes in HCC patients following ICI therapy.

Background: Liver metastases (LM) in advanced non-small-cell lung cancer (NSCLC) are associated with poor clinical outcomes. The tolerogenic immune microenvironment in the liver may contribute to inferior response to immune checkpoint inhibitors (ICIs). We hypothesized that the presence of LM may be associated with an expanded peripheral myeloid population, using the neutrophil-to-lymphocyte ratio (NLR) as a surrogate in patients treated with ICIs.

Objectives: We evaluated the impact of LM and NLR on clinical outcomes in patients with advanced NSCLC treated with ICIs.

Design: This was a retrospective analysis conducted at a single cancer center.

Methods: We reviewed the records of 324 patients with advanced NSCLC treated with programmed death ligand-1 (PD-L1) inhibitors as monotherapy or in combination with cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors. Clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were evaluated among patients with and without LM in NLR-High (NLR ⩾ 5) and NLR-Low (NLR < 5) subgroups.

Results: Patients with LM had significantly higher median NLR compared to patients without LM (median 7.3 vs 4.5, p < 0.001). Patients with LM had significantly shorter median PFS (HR 1.54, p = 0.006) and median OS (HR 1.56, p = 0.014). Patients with LM who were NLR-High (LM+ NLR-H) had shorter median PFS and median OS (2.0 months and 5.4 months, respectively) compared to patients who had LM and were NLR-Low (LM+ NLR-L, median PFS 4.0 months and median OS 13.3 months). This trend was also observed within the PD-L1 > 50% subgroup. In 42 patients with evaluable response and LM, 25/42 (59.5%) of patients had concordant responses in the liver and extra-hepatic sites.

Conclusion: Patients with LM who are NLR-High had the poorest clinical outcomes to ICI, and this appeared to be irrespective of PD-L1 status. Ongoing translational work will provide further insight into tumor myeloid subpopulations that may correlate with treatment resistance.

Solitary fibrous tumours (SFT) are fibroblastic mesenchymal tumours that can develop virtually at any site. It usually affects adults, and its incidence is estimated as 1 new case per million people per year. SFT is characterized by a gene fusion involving NAB2 (NGFI-A-binding protein 2) and STAT6 (signal transducer and activator of transcription 6); a higher nuclear STAT6 immunostaining can be seen in SFT cells, and it is considered an excellent marker for immunohistochemical diagnosis. The 2020 WHO classification defines two categories for SFT: intermediate (rarely metastasizing) and malignant. Many risk stratification models have been proposed to predict the behaviour of these tumour identities. In case of localized SFTs, the cornerstone of the treatment remains surgery with the aim of negative margins (R0) when technically feasible. In intermediate/high-risk SFTs with positive margins (R1/R2) with no possibility to re-resection or in meningeal high-risk SFTs, adjuvant radiotherapy (RT) could be performed. Neoadjuvant RT could also have a role in both extra-meningeal and meningeal localizations. Sole RT could have a role in managing non-resectable SFTs even in a curative intent. Medical therapy plays an important role in the metastatic/advanced SFTs. Conventional chemotherapy may be used, with doxorubicin and dacarbazine being active though yielding poor responses. Other active drugs with currently ongoing studies in SFT are eribulin and trabectedin. Antiangiogenetic treatments have also been shown to provide benefit in this histological subtype. An area of recent investigation is immunotherapy, with an ongoing randomized trial comparing nivolumab + ipilimumab versus pazopanib in advanced rare soft tissue sarcomas, including SFTs. Despite its rarity and therefore the difficulty in performing prospective randomized trials with a large number of patients, many promising results in perioperative (radiotherapy) or in the metastatic (medical therapy) setting have been obtained. This review overviews the main characteristics and provides the current knowledge on standard therapies.