Therapeutic Advances in Medical Oncology最新文献

Background: The paradigm of adjuvant treatment for patients in pathological stages II and III of non-small-cell lung cancer has changed toward the adjuvant combination of chemotherapy and immune checkpoint inhibitors, neoadjuvant chemoimmunotherapy, or ultimately periadjuvant chemoimmunotherapy. The introduction of a new standard requires significant changes in preoperative assessment. A real description of its current state in Poland is required, which can form the basis for systemic changes.

Objectives: The aim of our study was to analyze the current standards for preoperative assessment in Poland.

Design: Observational study.

Methods: A comprehensive survey was conducted across seven thoracic surgery centers in Poland, focusing on preoperative pathological examination techniques, imaging methodologies, multidisciplinary team consultations, and the interval between imaging and surgical resection.

Results: The survey analyzed data from 459 patients who were operated between January 2024 and October 2024. The most common pathological diagnostic methods were intraoperative frozen section, and preoperative core biopsy. Almost all patients in stages pIA-IIIB had contrast-enhanced computerized tomography (CT) of the chest, positron emission tomography (PET/CT), and bronchoscopy before surgery. In Poland, brain imaging is not a standard part of the preoperative assessment, and brain scans are obtained only exceptionally (pooled median 0% of patients in stages IA-IIIB). The median time between the CT and surgery was 61 days (range 30-90 days), and between PET/CT and surgery 35 days (range 10-66 days). The median time between the surgery and pathological report was 17 days (range 5-30 days). Multidisciplinary tumor boards are organized in the postoperative period for all patients comparing to pooled median 50% in preoperative period. In the vast majority of cases, the expression status of Programmed Death Ligand-1 and next-generation sequencing were carried out only in postoperative samples.

Conclusion: Current compliance with perioperative assessment standards in Poland is inadequate. The consequence of this situation may be low availability of perioperative treatment protocols.

Background: Locoregionally advanced nasopharyngeal carcinoma (LANPC) is the predominant stage at diagnosis and is commonly treated with cisplatin-based chemoradiotherapy (CRT). Although this approach achieves excellent locoregional control, distant metastasis remains the leading cause of treatment failure. Immunotherapy with programmed cell death protein 1 (PD-1) inhibitors, supported by the immunogenicity of Epstein-Barr virus-associated disease, has emerged as a promising strategy.

Objectives: To synthesize evidence from phase III trials on the efficacy and safety of PD-1 blockade combined with definitive chemoradiotherapy in LANPC.

Design: Systematic review and meta-analysis of randomized controlled trials.

Data sources and methods: We systematically searched for phase III randomized controlled trials evaluating PD-1 blockade plus chemoradiotherapy versus chemoradiotherapy (with or without placebo) in previously untreated LANPC. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted for event-/failure-free survival (EFS/FFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS). Pooled effects were estimated with random-effects models, with heterogeneity assessed using I² and prediction intervals. Safety outcomes were summarized descriptively.

Results: Three trials including 1237 patients were identified. PD-1 blockade significantly improved EFS/FFS (HR 0.66, 95% CI: 0.49-0.89; I² = 18.6%; prediction interval 0.46-0.96), with the greatest effect on DMFS (HR 0.61, 95% CI: 0.43-0.85; I² = 0%). LRFS showed a nonsignificant trend toward benefit (HR 0.67, 95% CI: 0.41-1.11; I² = 43.6%), though a clear advantage was evident in cisplatin-based regimens (HR 0.53, 95% CI: 0.34-0.82). OS data were immature (HR 0.94, 95% CI: 0.60-1.48; I² = 0%). Rates of severe and fatal adverse events were comparable between groups.

Conclusion: This first meta-analysis of phase III evidence demonstrates that PD-1 blockade combined with cisplatin-based chemoradiotherapy improves disease control in LANPC without added toxicity. Longer follow-up from ongoing studies is needed to establish the OS benefit and optimize treatment strategies.

Trial registration: PROSPERO CRD-420251147756.

Background: Patients with perihilar cholangiocarcinoma (pCCA) have high postoperative mortality and a poor prognosis. A reliable preoperative marker is needed to determine whether these patients are likely to benefit from surgical treatment.

Objectives: This study aimed to verify the predictive value of preoperative albumin-bilirubin (ALBI) grades for 90-day mortality and long-term outcomes in these patients.

Methods and design: This retrospective, multicenter, cohort study included patients with pCCA, surgically treated between January 2012 and December 2023. Patients were divided into ALBI 1-2 and ALBI 3 groups according to preoperative ALBI grade. Logistic and Cox regression analyses evaluated risk factors for 90-day death and overall survival (OS), respectively.

Results: Of the 828 included patients, 243 (29.3%) had ALBI grade 3. In total, 744 (89.9%) and 89 (10.1%) patients underwent radical resection and palliative surgery, respectively. The 90-day mortality rate was 8.9% for the entire cohort and 16.5% for patients with ALBI 3, higher than that of ALBI 1-2 (5.8%). Age, extended hemihepatectomy, and ALBI 3 were independent risk factors for 90-day mortality. Patients with ALBI 3 had a higher postoperative intra-abdominal bleeding, bile leakage, and acute organ dysfunction. The median OS of patients with ALBI 3 (21.0 months) was shorter than that of ALBI 1-2 (29.0 months). In the radical resection subgroup, the median OS of ALBI 3 was 23.0 months, poorer than that of ALBI 1-2 (33.0 months).

Conclusion: Preoperative ALBI grades can identify patients with pCCA who may benefit from surgical resection. Patients with ALBI 3 had a high risk of postoperative complications, 90-day mortality, and poorer long-term survival, and may benefit only marginally from surgical treatment.

Trial registration: ChiCTR2500102958 (Medical Research).

Background: Systemic therapy is standard treatment for postoperative recurrent or metastatic pancreatic adenocarcinoma, yet survival remains poor. While recurrence/metastasis-directed therapy (RDT/MDT) has shown benefits in other cancers, its role in pancreatic adenocarcinoma remains controversial.

Objectives: To evaluate whether adding RDT/MDT can enhance the efficacy of systemic therapy in patients with postoperative local recurrence or metastasis in pancreatic adenocarcinoma.

Methods: Patients with recurrence or metastasis of pancreatic adenocarcinoma following R0 resection between 2018 and 2024 at West China Hospital and Shang Jin Hospital were retrospectively enrolled. Patients were categorized into the RDT/MDT plus systemic therapy group versus the systemic therapy alone group. Propensity score matching (PSM; 1:1) was used to minimize selection bias. Survival outcomes were analyzed using Cox regression, with subgroup analyses based on postoperative recurrence/metastasis status. Clinical features and overall survival (OS) of patients receiving radiotherapy as RDT/MDT were also evaluated.

Results: A total of 203 eligible patients were enrolled. After 1:1 PSM, 76 patients from each group were analyzed for comparative survival outcomes. The median OS was 19.9 months in the RDT/MDT group versus 12.2 months in the systemic therapy group (hazard ratio 0.6, 95% confidence interval (CI): 0.4-0.8, p < 0.05). Subgroup analyses revealed significant survival advantages with RDT/MDT in patients with locoregional recurrence and widespread metastasis. In addition, a single-arm analysis of 64 patients who received radiotherapy as RDT/MDT (from the pre-PSM cohort) demonstrated a median OS of 20.1 months (95% CI: 17.5-28.5), with superior outcomes observed when radiotherapy was administered as first-line treatment.

Conclusion: This study suggested that adding RDT/MDT to systemic therapy may improve OS in pancreatic adenocarcinoma with postoperative recurrence and metastasis, with radiotherapy as a feasible option. Further randomized controlled trials are warranted.

Design: A multicenter, retrospective cohort study using PSM.

Background: Histopathological evaluation, TNM classification, and mediastinal staging via endobronchial ultrasound-guided transbronchial needle aspiration provide essential guidance for therapeutic decision-making in non-small cell lung cancer (NSCLC). Genomic profiles of primary tumors (PT) and matched mediastinal lymph nodes (MLN) can uncover occult metastases, refine recurrence risk assessment, and support personalized treatment strategies in lung adenocarcinoma (LUAD).

Objectives: The study aimed to investigate clinically relevant somatic variants in formalin-fixed, paraffin-embedded (FFPE) PT and scrapings of MLN cytological slide samples using next-generation sequencing (NGS) and correlated the findings with overall survival (OS).

Design: We retrospectively analyzed the genomic profile of PT and MLN from Brazilian LUAD patients between 2013 and 2020.

Methods: Genomic DNA (gDNA) was extracted from PT and MLN matched samples of 32 patients (n = 64). Targeted NGS was performed using the SureSelect XTHS2 panel. We analyzed OS using Kaplan-Meier curves, and risk factors for mortality using univariate and multivariate Cox regression models.

Results: Clinically significant or potentially significant variants were identified in 72% of PT and 75% of MLN, totaling 46 and 51 variants, respectively. The most frequent variants in PT involved EGFR (39.3%), TP53 (28.6%), ATM, and KRAS (21.4% in both), whereas in MLN, EGFR (35.7%), TP53 (32.1%), KRAS and BRAF (14.3% in both), and ATM (10.7%) have predominated. Co-mutations were detected in 31.3% of PT and 43.8% of MLN, with variant discordance between PT-MLN in 82.2% of cases.

Conclusion: Cox regression analysis demonstrated that the presence of co-mutations in MLN was a co-factor associated with poorer OS, while no significant associations were observed for PT variants. These findings highlight distinct genomic profiles between PT and MLN. Integrating the molecular profile of MLN into staging may improve prognostic accuracy and guide treatment decisions in LUAD patients.

Background: Metastatic gastric cancer (GC) is biologically heterogeneous; however, current staging classifies all metastatic cases as stage IV without reflecting this variability. Circulating tumor DNA (ctDNA)-derived biomarkers, including maximum somatic allele frequency (MSAF), may serve as surrogates for tumor burden and underlying tumor biology.

Objectives: This study aimed to evaluate the prognostic significance of baseline MSAF in patients with metastatic GC receiving first-line palliative chemo or chemoimmunotherapy.

Design: This was a retrospective, single-center cohort study of consecutively tested patients.

Methods: We analyzed 108 patients with pathologically confirmed metastatic gastric adenocarcinoma who underwent baseline ctDNA next-generation sequencing prior to first-line systemic therapy between December 2022 and April 2024. MSAF was defined as the highest variant allele frequency detected in ctDNA and evaluated as both a continuous and categorical variable. Patients were stratified into MSAF-high and MSAF-low groups using the cohort mean (12.31%) as the cutoff. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier estimation and Cox proportional hazards regression analyses.

Results: The MSAF-high group (n = 41) demonstrated significantly inferior OS compared with the MSAF-low group (n = 67; median OS, 10.0 vs 17.6 months; log-rank p = 0.006). PFS showed a nonsignificant trend favoring the MSAF-low group (median PFS, 4.5 vs 8.0 months; p = 0.1). In multivariate analysis (complete-case analysis, n = 70), high MSAF remained independently associated with worse OS (hazard ratio, 2.14; 95% confidence interval: 1.04-4.41; p = 0.039), along with older age and multiple metastatic sites. Tumors in the MSAF-high group more frequently exhibited molecular features such as deficient mismatch repair and high tumor mutational burden.

Conclusion: Baseline MSAF is an independent prognostic biomarker in metastatic GC and may reflect underlying biological aggressiveness. Incorporating MSAF into risk stratification frameworks could enhance prognostic classification and inform personalized treatment strategies.

Background: For metastatic colorectal cancer (mCRC) patients whose disease is refractory to standard therapies, treatment with regorafenib, fruquintinib, or trifluridine/tipiracil (FTD/TPI; also known as TAS-102) with or without bevacizumab is recommended. Recent clinical trial evidence indicates that FTD/TPI + bevacizumab has superior efficacy to FTD/TPI for these patients, although its relative efficacy compared with other treatment regimens requires further evidence.

Objectives: A systematic literature review (SLR) and network meta-analysis (NMA) were performed to evaluate the relative efficacy of treatments for patients with refractory mCRC.

Design: SLR and NMA.

Data sources and methods: Databases were searched for clinical trials evaluating treatments for refractory mCRC patients. NMA using random- and fixed-effects models was performed to estimate the relative treatment effects of FTD/TPI + bevacizumab compared with other treatment regimens on overall survival (OS) and progression-free survival (PFS).

Results: Twenty-eight randomized controlled trials evaluating treatment regimens in patients with refractory mCRC were identified. Of these, 16 trials connected in a network with FTD/TPI + bevacizumab. NMA including these trials using random-effects models showed that the efficacy of FTD/TPI + bevacizumab was statistically favorable relative to that of other treatment regimens including placebo/best supportive care (hazard ratio (95% credible interval); OS: 0.41 (0.28, 0.58), PFS: 0.21 (0.14, 0.31)), FTD/TPI monotherapy (OS: 0.59 (0.43, 0.79), PFS: 0.46 (0.34, 0.64)), cetuximab (OS: 0.47 (0.29, 0.73), PFS: 0.32 (0.20, 0.53)), cetuximab + irinotecan (PFS: 0.43 (0.19, 0.98), panitumumab (OS: 0.46 (0.28, 0.72), PFS: 0.35 (0.22, 0.59)), regorafenib (OS: 0.60 (0.38, 0.95), PFS: 0.49 (0.31, 0.84)), and fruquintinib (OS: 0.62 (0.39, 0.94)).

Conclusion: NMA results suggest that FTD/TPI + bevacizumab confers clinically relevant improvements in OS and PFS compared with other treatment regimens for refractory mCRC patients, supporting the use of this combination therapy in the third-line treatment setting.

Background: The optimal treatment approach for lacrimal gland adenoid cystic carcinoma (LGACC) remains controversial.

Objectives: We aim to demonstrate the value of radiotherapy (RT) in the multidisciplinary treatment of LGACC.

Design: This was a retrospective cohort study.

Methods: This study was conducted on 90 patients with LGACC treated from 2002 to 2023. We compared the overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) between those treated with surgery alone versus surgery plus postoperative radiotherapy (PORT). In addition, the ipsilateral visual outcome and ocular complications were evaluated.

Results: The addition of radiotherapy significantly improved the 5-year RFS (63.4% vs 31.1%, p = 0.014) and PFS (56.8% vs 31.1%, p = 0.036) while showing no improvement in OS (79.7% vs 85.6%, p = 0.98) and DMFS (67.3% vs 70.1%, p = 0.70) compared to surgery alone. Further analysis indicated that, compared to the photon-RT group, the proton/carbon-ion group showed no significant differences in 5-year OS (p = 0.7), RFS (p = 0.37), PFS (p = 0.45), and DMFS (p = 0.57). Univariate (odds ratio (OR) = 0.14, 95% confidence interval (CI): 0.04-0.49, p = 0.002) and multivariate (OR = 0.16, 95% CI: 0.04-0.62, p = 0.008) logistic regression indicated that radiotherapy was a protective factor for local recurrence. Furthermore, among the long follow-up of 35 patients accepting eye-sparing surgery plus PORT, 13 patients (37.1%) had best-corrected visual acuity (⩾20/40) and 14 (40.0%) had severe vision loss (<20/200); furthermore, dry eye disease (100%, 35/35) and cataract progression (45.7%,16/35) are the most common ocular complications.

Conclusion: Surgery plus radiotherapy is a safe and effective multidisciplinary treatment in improving local control with tolerable long-term ocular toxicity, but of limited impact on OS for LGACC.

Background: Induction chemotherapy (IC) regimens such as gemcitabine plus cisplatin (GP), docetaxel plus cisplatin plus fluorouracil (TPF), and paclitaxel plus cisplatin (TP) are optional clinical options for locoregionally advanced nasopharyngeal carcinoma (LA-NPC).

Objectives: This study aims to evaluate the efficacy and toxicity profiles of the GP, TPF, and TP induction regimens in LA-NPC.

Design: This was a retrospective study.

Methods: This multicenter retrospective study enrolled 722 patients with stage III-IVA LA-NPC who received GP, TPF, or TP IC. Propensity score matching (PSM) was performed before comparing survival outcomes and acute grades 3-4 toxicities among the three groups. Survival outcomes included the overall survival (OS), failure-free survival (FFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS).

Results: The original cohort comprised 722 patients (247 in the GP group, 240 in the TPF group, and 235 in the TP group). After PSM analysis, the GP group showed a better 3-year OS rate than the TP group (p = 0.019), while the 3-year OS rate revealed no difference between the GP group and TPF group and between the TPF group and TP group. There were no significant differences in the 3-year FFS, 3-year LRFS, and 3-year DMFS rates between and within the three groups. During the induction period, the toxicity of the three regimens was generally acceptable and manageable.

Conclusion: The GP induction regimen demonstrated superior efficacy in terms of OS, with its favorable safety profile. Compared with the TPF and TP regimens, the GP induction regimen represents a more clinically advantageous treatment option for LA-NPC.

Background: Circulating tumor DNA (ctDNA) is predictive of recurrence in resected stage III melanoma, yet its role in the neoadjuvant setting for clinical stage III (cSIII) is unclear.

Objective: Assess the association between ctDNA and outcomes following neoadjuvant immunotherapy (IO) + targeted therapy (TT) in cSIII melanoma.

Design: Patients in the NeoACTIVATE study were treated with neoadjuvant IO + TT, underwent lymphadenectomy, and received adjuvant immunotherapy.

Methods: Patients with ctDNA testing performed at baseline, pre- and post-operation were analyzed. Baseline positron emission tomography-computed tomography volumetrics and surgical, major pathological responses (MPR) were assessed.

Results: Thirteen patients had serial ctDNA, 10 (77%) were detectable at baseline, and 9/10 (90%) had ctDNA clearance. Seven (54%) achieved MPR, all with undetectable preoperative ctDNA, yet 3/7 (43%) had disease recurrence.

Conclusion: ctDNA and MPR are poor predictors of recurrence following neoadjuvant IO + TT for cSIII melanoma patients. Further studies are warranted to define the role of ctDNA in this setting.