Therapeutic Advances in Medical Oncology最新文献

Background: The current standard-of-care chemotherapy for treatment-naïve epithelial ovarian cancer is paclitaxel plus carboplatin.

Objectives: To compare the efficacy and safety of pegylated liposomal doxorubicin (PLD) plus carboplatin versus paclitaxel plus carboplatin as first-line treatment in patients with epithelial ovarian cancer.

Design: This was an investigator-initiated, multicenter, open-label, randomized, noninferiority trial.

Methods: This trial with a prespecified noninferiority margin (HR₀) of 1.2, was conducted in 20 clinic centers in China. Eligible patients were randomly assigned in a 1:1 ratio to receive either PLD (30 mg/m² on day 1) plus carboplatin (area under the curve (AUC) 5 on day 1; experimental group) or paclitaxel (175 mg/m² on day 1) plus carboplatin (AUC 5 on day 1; control group) for up to six cycles. The primary endpoint was progression-free survival (PFS). The key secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.

Results: Between March 21, 2019, and December 8, 2021, 395 eligible patients were enrolled, of whom 195 were randomly assigned to receive PLD-carboplatin and 196 received paclitaxel-carboplatin. Median PFS was 35.3 months (95% confidence interval (CI), 23.7-46.9) in the experimental group and 35.0 months (95% CI, 26.9-43.1) in the control group (hazard ratio = 0.99, 95% CI, 0.73-1.35; p = 0.94). There were no statistically significant differences between the two groups in median ORR (80.5% vs 79.2%), DCR (90.2% vs 83.3%), 2-year OS rate (96.2% vs 92.4%), or 4-year OS rate (87.6% vs 82.4%; all p > 0.05). In the experimental and control groups, 165 (84.6%) and 169 (86.2%) patients experienced at least one adverse event (AEs). Alopecia (9.2% vs 28.1%, p < 0.001), peripheral sensory neuropathy (2.1% vs 17.9%, p < 0.001), and febrile neutropenia (1.0% vs 6.1%, p = 0.01) were less common in the PLD-carboplatin group compared to the paclitaxel-carboplatin group.

Conclusion: The superior tolerability and comparable efficacy of PLD plus carboplatin over paclitaxel plus carboplatin as a first-line treatment for epithelial ovarian cancer suggest that substituting paclitaxel with PLD is both feasible and potentially more beneficial.

Trial registration: This trial is registered with ClinicalTrials.gov, NCT03794778.

Background: Brentuximab vedotin (BV) and polatuzumab vedotin (PV), CD30-specific and CD79b-specific monoclonal antibody conjugates, respectively, are used in the treatment of hematologic cancers. Both have been observed to cause gastrointestinal adverse events (GI AEs).

Objectives: We aimed to assess the clinical characteristics, disease course, treatment, and outcomes of patients who developed GI AEs following treatment with BV or PV.

Design: We retrospectively identified 879 adult cancer patients who received BV or PV therapy between March 1, 2016, and March 31, 2023, at our tertiary cancer center. Patients with alternate diagnoses were excluded.

Methods: Clinical characteristics, management, and outcomes of GI AEs were retrospectively evaluated and statistically analyzed.

Results: Sixty-four patients were included, and the median duration from therapy initiation to GI AE onset was 37 days. GI AEs occurred in the lower gastrointestinal tract (78%), upper gastrointestinal tract (45%), hepatobiliary system (11%), and pancreatic system (4.3%). Common symptoms were diarrhea (77%), nausea (61%), and abdominal pain (52%). Some patients had Common Terminology Criteria for Adverse Events grade ⩾3 toxicity (19% with diarrhea and 2.7% with colitis symptoms). Most patients (81%) received supportive care alone, and three received corticosteroids. Most patients (93%) achieved symptom resolution following treatment. Symptoms recurred in 37% of patients, and 41% of patients stopped BV/PV therapy due to GI AE.

Conclusion: GI AEs following the use of targeted antibody-drug conjugates can involve various gastrointestinal systems. In our patient cohort who received BV or PV, GI AEs were typically low grade and managed with supportive care or corticosteroids. Nonetheless, some patients experienced high-grade AEs or symptom recurrence and stopped BV/PV therapy. Future studies may provide clarification and guide clinical practice.

Background: Monocarboxylate transporters (MCTs) facilitate lactate transfer and support cancer cell survival and metastasis. MCT1 and MCT4 expression has been associated with poor prognosis and resistance to therapy with tyrosine kinase inhibitors.

Objectives: This pilot study examined the relevance of MCT1 and MCT4 expression in circulating tumour cells (CTCs) isolated from non-small cell lung cancer (NSCLC) patients during osimertinib treatment through single-cell analysis.

Design: Fifty-three NSCLC patients were enrolled at three different time points: baseline (n = 53), post-first cycle (n = 20) and progressive disease (PD; n = 21), to evaluate MCT1 and MCT4 expression in patients' samples.

Methods: CTCs were isolated with the ISET platform. MCT1/MCT4 expression was assessed using immunofluorescence triple staining experiments and confocal laser scanning microscopy.

Results: CTCs were detected in 75% (40/53), 40% (8/20) and 29% (6/21) of patients at baseline, post-first cycle and PD, respectively. Among cytokeratin (CK)-positive patients, MCT1 was overexpressed at all time points in a significant percentage: 67% (18/27) at baseline, 57% (4/7) at post-first cycle and 50% (2/4) at PD. Similarly, MCT4 was overexpressed in 55% (16/29), 50% (2/4) and 60% (3/5) of cases, respectively. Statistical analysis revealed that the (CK+MCT1-CD45-) phenotype was associated with worse progression-free survival [PFS; log rank, p = 0.041, hazard ratio (HR) = 1.971] and overall survival (log rank, p = 0.028; HR = 2.288) of the patients. Conversely, the presence of ⩾3 MCT4+ CTCs was correlated with poorer PFS (log rank, p = 0.042, HR = 4.189). Significant inverse correlations were observed between MCT1 and MCT4 expression, implying their distinct biological roles.

Conclusion: MCT1 and MCT4 are overexpressed in CTCs from NSCLC patients, supporting their potential as prognostic biomarkers and therapeutic targets.

Background: Spontaneous tumor rupture is a unique and life-threatening presentation of hepatocellular carcinoma (HCC). The optimal postoperative management of patients with spontaneously ruptured HCC (srHCC) remains controversial. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been proposed to reduce peritoneal dissemination, but its clinical benefit in srHCC is uncertain.

Objectives: This study aimed to evaluate the survival benefit and safety of postoperative HIPEC combined with hepatic resection in patients with srHCC.

Design: A retrospective multicenter cohort study was conducted, including patients with srHCC who underwent curative hepatectomy with or without postoperative HIPEC between 2018 and 2024.

Methods: A total of 208 srHCC patients from 4 institutions were enrolled and categorized into the resection group (R) and the resection plus HIPEC group (R-HIPEC). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to minimize baseline differences. The primary endpoint was recurrence-free survival (RFS), and the secondary endpoint was overall survival (OS). Survival outcomes were assessed using Kaplan-Meier analysis, Cox proportional hazards models, and subgroup analysis.

Results: Across the primary, PSM, and IPTW cohorts, patients in the R-HIPEC group achieved significantly longer median RFS (mRFS) and OS than those in the R group. The median OS was 45.6 versus 26.4 months in the primary cohort (p = 0.025), 48.2 versus 26.4 months in the PSM cohort (p = 0.025), and 42.9 versus 26.5 months in the IPTW cohort (p = 0.012). The mRFS was 15.5 versus 7.7 months (p = 0.002), 18.2 versus 8.3 months (p = 0.002), and 14.7 versus 7.4 months (p = 0.014), respectively. Subgroup analysis indicated that patients with Barcelona Clinic Liver Cancer stage 0/A derived significantly greater RFS benefit from HIPEC than those with stage B/C (interaction p = 0.0264). For OS, a significant interaction was observed with postoperative immunotherapy (interaction p = 0.0054). The R-HIPEC group showed a lower incidence of peritoneal implantation metastasis, without an increase in perioperative complications.

Conclusion: HIPEC combined with resection for srHCC can effectively prolong survival time. Resection combined with HIPEC and targeted therapy may be a promising strategy for srHCC.

Background: Platinum-based chemotherapy is the first-line treatment choice for advanced thymic epithelial tumors (TETs), with the expected objective response rate (ORR) ≈of 50% in thymoma and ≈20% in thymic carcinoma.

Objective: To evaluate the impact of relative dose intensity (RDI) on first-line treatment outcomes in TET patients.

Design: Retrospective cohort referred between 2016 and 2022 at the University of Naples Federico II, Italy.

Methods: Advanced TETs treated with first-line platinum chemotherapy; RDI calculated as delivered/planned dose intensity and categorized as low (<85%) or high (⩾85%). Outcomes: ORR, time to next treatment (TTNT), overall survival (OS).

Results: Thirty-three patients (15 thymoma, 18 carcinoma); 22 low RDI, 11 high RDI. RDI was not associated with ORR. High RDI showed longer TTNT (6.6 vs 5.0 months; p = 0.042) and numerically longer OS (86.4 vs 32.2 months; p = 0.361).

Conclusion: Maintaining ⩾85% RDI during first-line platinum chemotherapy may offer clinical benefits and warrants further validation in larger cohorts.

Mesothelioma is a rare cancer that carries a poor prognosis. This malignancy has had few therapeutic advances prior to the introduction of immune checkpoint inhibitors. Immunotherapy is now a cornerstone of first-line treatment for pleural mesothelioma and has been shown to provide clinical benefit for relapsed or refractory patients treated with prior chemotherapy. This review article will discuss key immunotherapy trials in the scientific literature, along with challenges in the application of this therapy. We will also discuss future areas of immunotherapy research in the treatment of mesothelioma.

Background: The spleen, the largest secondary lymphoid organ, plays an essential role in systemic immune regulation. Its function in tumor progression and treatment response has gained increasing attention.

Objectives: This study aimed to evaluate the prognostic value of spleen volume (SV) change in patients with extensive-stage small-cell lung cancer (ES-SCLC) receiving first-line chemo-immunotherapy (CIT) and to explore its associations with tumor-infiltrating lymphocytes (TILs) and peripheral immune parameters.

Design: A single-center retrospective cohort study.

Methods: A total of 292 ES-SCLC patients who received first-line CIT were retrospectively analyzed. SV was measured on baseline and post-treatment CT scans, and the relative change was used to classify patients into increased or decreased SV groups. Cox proportional hazards regression models were used to assess the effects of SV metrics, immune-related indices, and clinicodemographic factors on overall survival (OS) and progression-free survival (PFS). Objective response rate (ORR) differences were tested using the chi-square test, and immune parameters were compared using Wilcoxon rank-sum tests and correlation analyses.

Results: Multivariate analysis identified increased SV after CIT as an independent adverse prognostic factor for both OS (hazard ratio (HR) = 1.561, 95% confidence interval (CI), 1.193-2.041, p = 0.001) and PFS (HR = 1.411, 95% CI, 1.106-1.800, p = 0.006). Patients with increased SV exhibited significantly shorter OS and PFS and a lower ORR (all p < 0.005). Increased SV was also associated with markedly lower total, CD4+, and CD8+ TIL densities and, at the systemic level, lower absolute lymphocyte count (ALC), and higher neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) (all p < 0.0001), indicating both local and systemic immune suppression.

Conclusion: SV change reflects both local and systemic immune remodeling during CIT in ES-SCLC. As a noninvasive and measurable imaging biomarker, SV change holds translational potential for immune monitoring and treatment response assessment.

Background: The efficacy of immunochemotherapy (ICT) remains poor in patients with polymetastases from esophageal squamous cell carcinoma (ESCC). While radiation therapy (RT) has shown promise in oligometastatic settings, its role when combined with ICT for polymetastatic ESCC (with >5 metastatic lesions) remains unclear.

Objective: This study evaluated the efficacy and value of RT in patients with polymetastatic ESCC who received ICT as first-line treatment.

Design: This multi-center cohort study was conducted at 20 hospitals in China.

Methods: In total, 331 patients who received at least one cycle of first-line ICT between January 2019 and December 2021 were enrolled. Among them, 88 received ICT plus RT (RT group), and 243 received ICT alone (non-RT group). Propensity score matching (PSM) was performed to control for potential confounders (75 patients/group). Outcomes included overall survival (OS), progression-free survival, objective response rate (ORR), symptom control, and safety. This study was registered at the Clinicaltrials.gov registry (identification number NCT05142709).

Results: Both before and after PSM, no significant OS benefit was observed with RT group (median OS: 15.2 vs 12.2 months, hazard ratio (HR) 0.80 (0.60-1.07), p = 0.14; 15.0 vs 11.0 months, HR 0.80 (0.55-1.15), p = 0.23, respectively), though pre-PSM ORR favored RT (59.1% vs 40.3%, p = 0.003). RT demonstrated superior symptom control, with significantly higher rates of dysphagia improvement (63.3% vs 36.4%, p = 0.0006) and meaningful pain reduction (59.4% vs 40.0%, p = 0.007). Grade ⩾3 treatment-related adverse events were comparable between groups (38 vs 40 cases post-PSM, p = 0.74), with equivalent grade 5 toxicities (1.3% each).

Conclusion: For polymetastatic ESCC, RT combined with ICT enhanced symptom control without severe toxicity, though it did not improve survival. This supports its personalized use for quality of life in symptomatic patients.

Background: In oral tongue squamous cell carcinoma (OTSCC) patients, cervical lymph node metastasis profoundly influences prognoses and is central to guiding surgical strategies. Mapping the likelihood of lymph node metastasis across different cervical nodal levels is essential for achieving precise surgical planning.

Purpose: OTSCC is a prevalent head and neck malignancy. Accurate MRI-based tumor segmentation and prognostic prediction are essential for detecting lymph node metastasis and improving patient survival rates. However, the potential of deep learning techniques has been underexplored in this context.

Design: This retrospective pilot study included 136 OTSCC patients with non-lymph node metastasis and lymph node metastasis who underwent primary and cervical lymph node dissection following baseline MRI. The development of a machine learning approach, incorporating an automatically segmented approach, enables the creation of a model capable of predicting cervical lymph node metastasis based on primary site tumors.

Methods: We propose a two-stage OTSCC diagnostic workflow. First, a multiparametric fusion network (MobileNetV2 U-Net) was implemented using TensorFlow to integrate features from contrast-enhanced T1-weighted (CE-T1WI), T2-weighted (T2WI), and T1-weighted (T1WI) MRI sequences and automatically segment primary tumors. Next, radiomic models were constructed to predict cervical lymph node metastasis from these automated segmentations. A fusion nomogram combining radiomic features and clinical data was developed to predict metastasis status. For comparison, a radiomics model using manually segmented CE-T1WIs was also evaluated.

Results: Data from 136 patients (mean age 50.29 ± 12.25 years; 100 men, 36 women) showed that the MobileNetV2 U-Net achieved a Dice similarity coefficient (DSC) of 85% and a mean intersection over union (IoU) of 76% on the training set, and a DSC 87% and an IoU 79% on the independent test set. The fusion nomogram achieved areas under the ROC curves of 0.98 and 0.93 on the training and test sets, respectively, when using the automated segmentation masks. The automated segmentation nomogram performed comparably to the model using manual segmentations for predicting lymph node metastasis.

Conclusion: Our TensorFlow-based MobileNetV2 U-Net provides clinicians with an automated tool to delineate OTSCC tumors and predict cervical lymph node metastasis, potentially aiding personalized surgical planning.