Therapeutic Advances in Medical Oncology最新文献

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.

Background: Postoperative early recurrence (PER) remains a major challenge to long-term survival after successful conversion therapy and curative resection for initially unresectable colorectal liver metastases (CRLM). Existing prediction models rely heavily on clinicopathological parameters and lack molecular biomarkers, limiting their predictive accuracy.

Objectives: To define the optimal recurrence-free survival (RFS) cutoff for PER and develop a comprehensive predictive nomogram incorporating molecular and clinical variables to predict PER in patients with initially unresectable CRLM who undergo curative resection following conversion therapy.

Design: Retrospective cohort study.

Methods: Clinicopathological and molecular data from 411 patients with initially unresectable CRLM undergoing curative resection after conversion therapy were analyzed. The minimum p value approach determined the optimal RFS cutoff for PER. Least absolute shrinkage and selection operator regression identified significant predictors, followed by multivariate logistic regression to build a nomogram. Model performance was assessed using the area under the curve (AUC), calibration curves, and decision curve analysis (DCA).

Results: PER was defined as recurrence within 4 months postoperatively. Independent predictors included dual preoperative positivity for CEA and CA19-9 (odds ratio (OR) = 2.437, p < 0.001), number of liver metastases (OR = 1.061, p < 0.001), tumor progression during the chemotherapy-to-surgery interval (OR = 2.837, p = 0.003), KRAS exon 2 mutations (OR = 1.927, p = 0.006), and BRAF V600E mutations (OR = 2.410, p = 0.002). An AUC of 0.703 (95% confidence intervals (CI): 0.650-0.756) was achieved, with an internal validation AUC of 0.697 (95% CI: 0.670-0.723). Calibration curves showed good agreement (p > 0.05), and DCA indicated clinical benefit at recurrence risk thresholds above 30%.

Conclusion: We identified 4 months as the optimal RFS threshold for PER and proposed a novel nomogram integrating molecular and clinical factors for perioperative decision-making in patients with initially unresectable CRLM.

Background: The benefit of adding immunotherapy to induction chemotherapy before definitive chemoradiotherapy (CRT) in older patients with unresectable stage III non-small-cell lung cancer (NSCLC) remains unclear.

Objectives: This real-world study aimed to evaluate the efficacy and safety of induction chemoimmunotherapy followed by CRT in this patient population.

Design: A real-world multicenter study.

Methods: In this retrospective, multicenter study, we enrolled patients aged ⩾65 years with unresectable stage III NSCLC who received CRT between January 2014 and June 2024. Patients were stratified into two groups: the induction chemoimmunotherapy group (I-CRT), who received PD-1/PD-L1 inhibitors plus chemotherapy before CRT, and the control group (Non-I-CRT), who received CRT without any prior immunotherapy. Propensity score matching (PSM) was used to balance baseline characteristics. The primary endpoints were progression-free survival (PFS) and overall survival (OS).

Results: Among 260 patients, 141 received I-CRT and 119 constituted the Non-I-CRT control group. After 1:1 PSM (97 patients per group), the I-CRT group showed significantly improved outcomes compared to the Non-I-CRT group: median PFS was 23.4 versus 11.6 months (p < 0.001), and median OS was 46.0 versus 24.4 months (p = 0.009). The incidence of Grade 3/4 adverse events was comparable between the matched groups (20.6% vs 28.9%, p = 0.52).

Conclusion: Induction chemoimmunotherapy before CRT is feasible in selected older NSCLC patients, offering survival benefits without significant safety concerns.