Oncologist最新文献

Background: Sintilimab plus bevacizumab (Sin + Bev) is recommended as a first-line treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT); however, its efficacy remains limited. This study aimed to assess the efficacy and safety of stereotactic body radiotherapy (SBRT) combined with Sin + Bev for HCC with PVTT.

Patients and methods: This retrospective study included 69 HCC patients with PVTT treated at two centers in China from August 2021 to December 2022. Patients received either SBRT + Sin + Bev (n = 31) or Sin + Bev alone (n = 38). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and treatment-related adverse events (TRAEs).

Results: Baseline characteristics showed similar distributions between the two groups. SBRT + Sin + Bev group showed a significant increase in both median OS (18.9 vs 9.3 months, P < .001), median PFS (9.1 vs 4.7 months, P = .0015), and ORR (64.6% vs 26.3%, P = .031) compared to Sin + Bev group. TRAEs in SBRT + Sin + Bev group were mostly manageable and acceptable compared to Sin + Bev group. Multivariate analysis confirmed that SBRT + Sin + Bev was an independent prognostic factor for better OS (P < .001) and better PFS (P < .001).

Conclusion: SBRT combined with sintilimab plus bevacizumab appears to improve treatment efficacy and demonstrates a favorable safety and feasibility profile for HCC with PVTT.

Background: Medullary thyroid cancer (MTC) accounts for approximately 4% of thyroid carcinomas. Patients with unresectable, metastatic disease are candidates for approved agent-targeted therapies such as vandetanib, cabozantinib, or selpercatinib, but toxicity is often an issue. Preclinical data supported the potential use of immunotherapy targeting carcinoembryonic antigen (CEA) in this indolent disease.

Methods: Patients with advanced/recurrent MTC were randomly assigned in a 1:1 ratio to receive a Saccharomyces cerevisiae (yeast)-based immunotherapy (GI-6207) targeting CEA starting at the time of enrollment or 6 months after surveillance. The primary endpoint was to compare the calcitonin growth rate in the GI-6207 arm at 6 months with patients in the surveillance arm at 6 months.

Results: Between March 2013 and May 2018, 34 patients were randomly assigned to receive the yeast-CEA vaccine (GI-6207) starting at the time of enrollment or 6 months after surveillance. The mean age was 51 years, and 82% of patients were diagnosed with sporadic MTC. There was no significant change in the calcitonin growth rates at 6 months when the immunotherapy group was compared with the surveillance group (-2.490042 vs -2.526385; P = .3760). Treatment with GI-6207 was associated with increased peripheral CEA-specific CD4 and/or CD8 T cells, with 15/26 (58%) patients displaying increases after 3 months of treatment. One patient had a significant inflammatory event 17 months after the last vaccine at a known lymph node, perhaps related to a delayed immune response. There were no grade 3 or 4 adverse events. Grade 1 injection site reactions were most common.

Conclusion: The immunotherapy was well tolerated but did not have an impact on tumor growth rate at 6 months as measured by calcitonin kinetics.

Clinical trial identification: NCT01856920.

Background: Both hyperthermic intraperitoneal chemotherapy (HIPEC) and conventional intraperitoneal chemotherapy (IP) have shown survival benefits in ovarian cancer (OC), but direct comparisons between the two perfusion modalities are lacking. This study aimed to compare effectiveness and safety between HIPEC and conventional IP in OC.

Methods: This retrospective real-world study analyzed 606 patients with stages II-IV OC who received HIPEC or IP following cytoreductive surgery between 2013 and 2024. The primary endpoint was progression-free survival. Overall survival and adverse events were secondary endpoints. The study used inverse probability of treatment propensity-score weighting. We also conducted sensitivity analyses to evaluate result robustness and subgroup analyses to explore potential effect modification.

Results: After a median follow-up of 26 months, disease progression occurred in 40.6% of patients in the HIPEC group and 55.0% in the IP group (hazard ratio [HR] 0.79; P = .103). Mortality rates were 13.2% and 22.5%, respectively (HR 0.83; P = .434), showing no significant differences in progression and survival between the two groups. Exploratory subgroup analyses suggested a trend toward improved progression-free outcomes with HIPEC, particularly among patients with BRCA wild-type or BRCA1-mutated tumors and early postoperative perfusion. Hypoalbuminemia was the most common event in both groups (HIPEC 27.2%; IP 15.6%). HIPEC group had more abdominal distension and wound dehiscence, whereas IP patients experienced nausea and rash more frequently.

Conclusions: HIPEC did not significantly improve survival over conventional IP in the overall population, but showed greater benefit in specific subgroups, underscoring the importance of individualized intraperitoneal chemotherapy strategies in OC.

Purpose: Myelotoxicity is a well-known adverse effect of alkylating chemotherapy for glioblastoma. While risk factors during first-line therapy are established, little is known about myelotoxicity recurrence in second-line treatment. This study investigates whether first-line myelotoxicity therapy predisposes patients to recurrence in the second-line setting.

Patients and methods: We conducted a retrospective cohort study of 589 patients with glioblastoma treated at the Brain Tumor Centre Amsterdam (2005-2022). Of these, 178 received second-line lomustine or rechallenge temozolomide. Myelotoxicity severity was predominantly assessed using nadir hematological values and its duration. A log-link generalized linear model evaluated associations between first-line and second-line myelotoxicity severity, adjusting for covariates. Cox proportional hazards models assessed time to myelotoxicity onset.

Results: We included 151 patients (mean age 57.1 ± 11.8 years; 66.9% male). Lomustine was given to 66.9%. Myelotoxicity occurred in 73.5% of patients, with 19.9% developing severe toxicity. First-line myelotoxicity severity was significantly associated with second-line severity (β = 1.3, P < .001). Lomustine correlated with higher myelotoxicity severity than temozolomide (β = 1.4, P = .002). Higher first-line myelotoxicity scores predicted earlier onset of any-grade (HR = 1.4, P < .001) and severe (HR =2.1, P < .001) myelotoxicity in second-line therapy.

Conclusion: First-line myelotoxicity for glioblastoma predicts its recurrence and earlier onset in second-line therapy. Patients with toxicity in first-line have an increased risk of severe hematological toxicity upon re-exposure. Lomustine carries a higher risk for myelotoxicity than temozolomide. These findings suggest an inherent predisposition to alkylating chemotherapy-induced myelotoxicity for a subgroup of patients. Integrating prior myelotoxicity history into second-line treatment decisions may improve risk stratification and guide monitoring.

Background: Invasive papillary breast cancer (IPC) is a rare cancer known to have a better prognosis than other breast cancers. This study aimed to explore whether patients with early-stage IPC can benefit from chemotherapy.

Materials and methods: IPC cases diagnosed between 2003 and 2021 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method and the Cox proportional hazard model were performed to identify significant prognostic factors. To eliminate selection bias and baseline characteristics, propensity score matching (PSM) was used. The primary endpoints were overall survival (OS) and breast cancer-specific survival (BCSS).

Results: A total of 1892 patients were enrolled, and 273 pairs were screened after PSM. Multivariable analysis showed that age under 50, married status, smaller tumor size, negative lymph node (LN) status, and receipt of surgery, chemotherapy or radiotherapy were independently associated with better OS. After PSM, patients receiving chemotherapy had significantly improved OS (P = .012), while BCSS showed no significant difference (P = .099). After stratified by tumor size and LN status, chemotherapy could significantly improve the OS of patients with LN-negative IPC with tumors ≥ 2.0 cm (P < .001). Among the patients with grade III or undifferentiated diseases, the OS of the chemotherapy group was significantly better than that of the non-chemotherapy group (P < .001).

Conclusions: For patients with LN-negative IPC with tumor ≥ 2.0 cm and patients with grade III or undifferentiated disease, chemotherapy significantly improved OS. Future randomized controlled trials are expected to validate the results.

Background: Financial toxicity (FT) refers to the negative effects of the economic burden of medical care on patients that potentially lead to poor well-being and quality of life. Individuals with breast cancer are especially prone to high out-of-pocket costs (OOPCs). We aimed to evaluate the FT rate of individuals with breast cancer and determine particularly vulnerable patients.

Methods: A comprehensive search of PubMed/Medline, Embase, Global Index Medicus, Web of Science (WOS), and EBSCO was performed from inception to July 28, 2025. Studies on FT in participants with breast cancer were included. Pooled estimates of FT rates with 95% confidence intervals (CIs) were calculated using the random-effects model. The primary outcome was FT. The secondary outcomes included the rates of participants in high-income countries (HICs), middle-income, and low-income countries (LMICs) who incurred FT based on income, OOPCs, or patient-reported impact of expenditures during diagnosis and treatment of breast cancer.

Results: Sixty-six studies involving 29 426 participants with breast cancer were enrolled in our study. Most studies were from HICs (46 studies), and the others were from LMICs (20 studies). The definition of FT was significant difference among these studies. The pooled FT rate was 39.3% (95% CI, 32.4%-46.6%) in HICs and 72.3% (95% CI, 56.8%-83.8%) in LMICs.

Conclusions: FT is a substantial burden among patients with breast cancer worldwide. While the burden of FT is still disproportionately higher in LMICs, nearly 40% of patients in HICs also experienced FT. However, the gap between the two settings may be narrowing.

Introduction: The rapid integration of immune checkpoint inhibitor (ICI) based combination therapies in first-line treatment of metastatic renal cell carcinoma (mRCC) is raising questions about next-line treatments and outcomes of ICI rechallenge.

Methods: We performed a meta-analysis using the results from the phase-III RCTs, CONTACT-03 and TiNivo-2, to evaluate the effect of adding a PD-1/PD-L1 inhibitor rechallenge to a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) vs a VEGF TKI alone in patients with mRCC who had progressed on ICI based combination therapy or ICI monotherapy.

Results: A total of 865 patients with mRCC were included in this meta-analysis. The meta-analysis showed no difference in progression free survival between ICI plus VEFG TKI combination and TKI monotherapy groups (HR = 0.96, 95% CI, 0.76-1.21; P = .75) in patients previously progressing on ICI. Furthermore, adding ICI to anti-VEGF TKI therapy was not associated with improve overall survival (HR = 1.06, 95% CI, 0.89-1.25; P = .52).

Conclusion: In summary, PD-1/PD-L1 inhibitor rechallenge with a VEGF TKI in mRCC does not improve survival outcomes and should not be used in patients with prior progression to ICI. Understanding both intrinsic and acquired resistance mechanisms to ICI therapy is crucial for developing effective initial and sequential immunotherapy strategies in RCC.

In February 2025, the European Commission granted approval for belzutifan (Welireg) as a treatment for certain von Hippel-Lindau (VHL) disease-associated tumors. This is the first medicinal product in Europe for pharmacological management of VHL, a rare, hereditary condition characterized by the development of multiple tumors across various organs. Belzutifan is an oral inhibitor of hypoxia-inducible factor-2α (HIF-2α), a protein involved in the pathogenesis of VHL-associated tumors. This approval, which is based on the results of the pivotal phase 2 clinical trial MK-6482-004 (LITESPARK-004) offers a therapeutic approach to managing certain VHL disease-associated tumors. This article describes the clinical data supporting belzutifan approval in the EU, focusing on the VHL disease indication and its mechanism of action.

Background: Trastuzumab deruxtecan (T-DXd) reshaped clinical practice in human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC). The impact of clinical characteristics and drug-drug interactions (DDIs) on outcomes in patients receiving T-DXd is still under investigation.

Methods: We retrospectively analyzed data of patients from the Italian DE-REAL study. Clinical features including age, body mass index (BMI), toxicity and DDIs were assessed and correlated with clinical outcomes. The Drug-PIN software was used to evaluate DDIs.

Results: Among 143 patients, age did not significantly affect progression-free survival (PFS) but influenced overall survival (OS), with younger patients (<65 years) showing better outcomes (median overall survival [mOS]: 12 vs. 10 months, P = 0.02). Patients with BMI >25 demonstrated significantly longer PFS (11 vs. 9 months, P = 0.04), which was confirmed as independent predictor of better PFS at multivariate analysis (P ≤0.05), but experienced higher toxicity rates, particularly nausea (P = 0.019). Drug-PIN classification showed no impact on survival outcomes, although patients with high-risk DDIs experienced more nausea and asthenia compared to those with low-risk interactions (P = 0.0018 and P = 0.003, respectively).

Conclusion: T-DXd efficacy appears consistent across different age groups, although elderly patients showed reduced OS. Higher BMI was associated with improved PFS but increased toxicity. While DDIs did not affect survival outcomes, they influenced specific adverse events. Our results reinforce the efficacy and favorable safety profile of T-DXd in a broad real-world population, including patients with polypharmacy or comorbidities, while highlighting that personalized monitoring and supportive care strategies may be particularly beneficial for elderly patients and those with higher BMI.

Background: This study describes clinical characteristics, treatment patterns as well as safety outcomes of NSCLC patients harboring PD-L1 ≥ 50% who received adjuvant atezolizumab within the Italian real-world scenario.

Methods: Patients with surgically resected NSCLC harboring EGFR/ALK wild type disease and PD-L1 TPS ≥ 50%, who received at least one cycle of adjuvant atezolizumab were included. Clinical-pathological and molecular data, safety and efficacy outcomes were collected from the Italian ATLAS real-world registry.

Results: A total of 132 patients were included across 45 Italian centers between July 2022 and August 2024. Lobectomy was performed in 81.1% of cases, with 8.3% pathological stage IIA, 40.2% stage IIB, 43.9% stage IIIA, and 7.6% stage IIIB, according to the eighth TNM staging edition. The median number of atezolizumab cycles was 12.5 (range: 1-20). Treatment related adverse events (TRAEs) during atezolizumab were reported in 44 patients (33.3%), including 11 (8.3%) who experienced multiple TRAEs. Grade ≥ 3 TRAEs were reported in 21 cases (15.9%), leading to treatment discontinuation in 18 (13.6%). The median time to the first onset of TRAEs was 89 days (range: 3-390 days). 15 patients experienced a disease recurrence, including 6 locoregional-only and 9 distant relapses, with a median time since surgery of 13.3 months.

Conclusion: This study showed that the safety profile of adjuvant atezolizumab outside of a clinical trial context was comparable to the IMPower-010 study, highlighting the value of the Italian ATLAS registry as source of real-word evidence to optimize the clinical management of NSCLC patients.