Strahlentherapie und Onkologie最新文献

Purpose: To evaluate the outcome and prognostic factors for borderline resectable pancreatic cancer (BRPC) patients treated with neoadjuvant chemoradiotherapy using moderately hypofractionated intensity-modulated radiotherapy (NAC-MH-IMRT).

Methods: Patients with BRPC treated with NAC-MH-IMRT at 42 Gy in 15 fractions between February 2013 and June 2021 were evaluated. The overall survival (OS), progression-free survival (PFS), cumulative incidence of locoregional failure and distant metastases, association dose-volume indices, Evans grade for pathological response, and toxicities were evaluated.

Results: A total of 66 patients met the inclusion criteria, and the median follow-up period was 23.9 months. In all, 48 patients underwent pancreatectomy, and margin-negative resection was achieved in 44 patients (91.7%). The median survival and PFS times were 34.8 months and 12.0 months, respectively, for the whole cohort. The 2‑year cumulative incidences of locoregional recurrence and distant metastases in the resected group were 25.7 and 52.8%, respectively. From the Mann-Whitney U test, the minimum dose of the primary gross tumor volume (GTV_min) of the group with Evans grade ≥ 2b was statistically higher than that of the other group (38.6 Gy vs. 37.3 Gy, p = 0.005). However, this was not associated with reduced cumulative incidence of locoregional failure. No patient had grade ≥ 3 acute gastrointestinal toxicity.

Conclusion: NAC-MH-IMRT for BRPC resulted in good survival outcomes and margin-negative resection rates. High GTV_min was associated with good pathological response; however, improvement of local control requires further investigation.

Purpose: To evaluate the safety and efficacy of radiotherapy combined with chemoimmunotherapy (RCIT) versus chemoimmunotherapy (CIT) alone as first-line treatment for oligometastatic esophageal squamous cell carcinoma (OESCC) at initial diagnosis.

Methods: We retrospectively evaluated 140 patients newly diagnosed with OESCC who received RCIT or CIT as first-line treatment between June 2018 and December 2021. Among them, 76 patients were in the RCIT cohort and 64 patients in the CIT cohort. Propensity score matching (PSM) was used to simulate random allocation.

Results: After 1:1 PSM, 61 well-paired patients were selected. The median follow-up duration was 34.7 months (95%CI: 30.6-38.8 months). After PSM, the median PFS for the RCIT and CIT groups was 10.9 (95%CI: 9.4-12.4) months and 7.3 (95%CI: 6.0-8.7) months, respectively (P = 0.004). The median OS for the RCIT and CIT groups was 22.4 (95%CI: 17.5-27.4) months and 13.4 (95%CI: 10.9-15.9) months, respectively (P = 0.031). There were significant differences in PFS (median PFS: 12.9 vs. 8.6 vs. 7.3 months, P = 0.003) between the group receiving radiotherapy (RT) for all lesions, the group receiving RT for partial lesions, and the CIT group, while OS was on the threshold of significance (median OS: 29.4 vs. 17.3 vs. 13.4 months, P = 0.052). No significant differences in the incidence of grade 3 or higher (G3+) treatment-related adverse events (TRAEs) were observed between the two groups. However, the incidence of G3+ pneumonitis (13.1% vs 1.6%, P = 0.038) were higher in the RCIT group compared to the CIT group.

Conclusion: RCIT as first-line treatment for OESCC was safe and efficacious. RCIT improved PFS/OS compared to CIT without increasing the overall high grade toxicity rate. However, the increased incidence of pneumonitis due to RT implementation cannot be disregarded.

Radiotherapy for cancer is a local treatment method that uses radiation to treat tumors. It is one of the main approaches for treating malignant tumors. Radiotherapy uses ionizing radiation on living organisms to cause necrosis of tumor cells. However, the DNA damage repair mechanisms of tumor cells and the hypoxic microenvironment of tumors limit the effectiveness of radiotherapy. Tumor cells can also achieve radioresistance through a variety of signaling pathways. The radiation tolerance of adjacent tissues also directly affects the effect of radiotherapy. Stimulation of tumor cells through physical methods such as ultrasound, light, heat, electricity, and magnetic fields can not only improve the hypoxic microenvironment of tumors and directly damage DNA but can also solve the problem of radioresistance by regulating a variety of signaling molecules. Physical stimulation therapy has high specificity and targeted effects, making it widely used in radiosensitization applications. However, the molecular mechanisms underlying the radiosensitizing effects of physical stimulation therapy are not fully understood at a practical level. In this review, we summarize the signaling pathways related to radioresistance as well as the established and potential molecular mechanisms responsible for radiosensitization induced by physical stimulation to provide insights for future radiosensitivity studies on physical stimulation therapies.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors worldwide. In this study, we aimed to investigate the pathophysiological mechanism through which F‑box and leucine-rich repeat protein 18 (FBXL18) promotes the progression of ESCC.

Methods: ESCC cell lines KYSE150 and TE‑1 were infected with PLVX-FBXL18 or shFBXL18-derived lentivirus to overexpress or knock down FBXL18. A Cell-Counting Kit 8 and colony-forming assay were used to assess cell viability and proliferation. Cells were irradiated with varying doses of X‑ray (IR) to determine whether FBXL18 influenced the radiosensitivity of ESCC cells. KYSE450 cells, stably transduced with shNC or shFBXL18-derived lentivirus, were injected into nude mice to assess whether FBXL18 affected ESCC tumor growth. KYSE150 and TE-1 cells overexpressing FBXL18 were lysed for Western blot analysis to evaluate protein expression.

Results: FBXL18 overexpression enhanced cell viability and colony formation, and proliferation of ESCC cells. In contrast, FBXL18 knockdown inhibited tumor growth in vivo. Additionally, FBXL18 overexpression reduced the radiosensitivity of ESCC cells. Mechanistically, FBXL18 was found to exert its effects by suppressing the expression of FBXL7 in ESCC cells.

Conclusion: FBXL18 promotes cell proliferation and diminishes radiosensitivity in ESCC cells. Most likely, it exerts its pro-tumorigenic effects by downregulating FBXL7.

Purpose: The oncological treatment of breast (BC) and head and neck cancer (H&NC) patients often includes radiotherapy. One serious side effect of this treatment is radiation-induced fibrosis (RIF), for which no established treatment currently exists. Studies have shown a potential effect of pentoxifylline and vitamin E on RIF. In this retrospective analysis, we investigate the effect of pentoxifylline and vitamin E on RIF in a cohort of BC and H&NC patients.

Methods: Consecutive BC and H&NC patients referred to the Department of Oncology, Aarhus University Hospital, Denmark, for treatment of severe and discomforting RIF during 2016-2023 were included. After initial evaluation, 61 patients-29 BC and 32 H&NC patients-started treatment with oral pentoxifylline 400 mg and vitamin E (290-350 mg) twice daily. In total, 54 patients-24 BC and 30 H&NC patients-were treated and finally evaluated. The endpoint was patient-reported and/or clinical treatment response.

Results: Overall, 18 BC (75%) and 7 H&NC patients (23%) reported subjective improvement following treatment. A clinical treatment response with partial or complete regression of RIF was seen in all patients with subjective effect, except in one BC and one H&NC patient.

Conclusion: Pentoxifylline and vitamin E might be an effective treatment for a selected group of patients with RIF. The therapeutic effect was more pronounced in BC patients compared to those with H&NC. Further randomized and blinded studies in larger populations are needed to validate the findings.

Background: Progression-free (PFS) and overall survival (OS) in UICC stage III non-small cell lung cancer (NSCLC) after definitive concurrent chemoradiotherapy (CRT) can be increased with consolidating immunotherapy. Recent studies have shown a strong predictive value of gross tumor volume (GTV) changes during CRT on OS. The TORCH trial investigated the prognostic impact of GTV changes during CRT as a predictor for a response to immunotherapy.

Methods: This retrospective non-interventional observational multicenter trial included n = 203 patients from 10 German university centers for radiation oncology with confirmed inoperable NSCLC in UICC stage III A-C. Patients had received CRT between 2015 and 2023 as a curative-intent treatment approach. Patient and tumor characteristics were collected anonymously via electronic case report forms. Initial GTVs before CRT (initial planning CT, GTV1) and at 40-50 Gy (re-planning CT for radiation boost, GTV2) were delineated. Absolute and relative GTV changes before/during CRT were correlated with OS to predict the response to CRT with sequential immunotherapy. Hazard ratios (HR) of survival analyses were estimated using adjusted Cox regression models.

Results: The mean GTV1 before radiation therapy (RT) was 145.29 ml with the 25th, 50th, and 75th percentiles being 61.36 ml, 145.29 ml, and 204.93 ml, respectively. Before initiation of the radiation boost, the mean GTV2 was 99.58 ml, with the 25th, 50th, and 75th percentiles at 32.93 ml, 70.45 ml, and 126.85 ml. The HR for the impact of GTV1 on survival was 0.99 per ml (95% confidence interval [CI] 0.99-1.00; p = 0.49). For the absolute volume change between GTV1 and GTV2, the HR was 1.004 per ml (95% CI 0.997-1.011; p = 0.26). In a subgroup analysis of patients who were treated with durvalumab, absolute volume changes between GTV1 and GTV2 were associated with longer OS (HR = 0.955 per ml; 95% CI 0.916-0.996; p = 0.03). Overall, durvalumab treatment was positively associated with OS, demonstrating an HR of 0.454 (95% CI 0.209-0.990; p = 0.047).

Conclusion: Pretreatment GTV and absolute GTV volume changes did not significantly correlate with OS. However, the absolute volume change between the pretreatment and replanning GTV was associated with longer OS in patients treated with durvalumab. Histological subtype, grading, UICC stage, age at onset, pulmonary comorbidities, and smoking status had no significant association with OS. Durvalumab treatment was associated with improved OS.

Purpose: The aim of this study was to evaluate the outcome, especially disease-free survival (DFS) and recurrence patterns, in patients with a maximum age of 45 years at first diagnosis of head and neck squamous cell carcinoma (HNSCC).

Methods: We retrospectively reviewed data from 79 patients with newly diagnosed HNSCC aged 45 or younger without distant metastasis who underwent postoperative or definitive radio(chemo)therapy in either the Department of Radiation Oncology at the University Hospital of Erlangen or the Department of Radiation Oncology at the University Hospital of Mainz between September 2006 and December 2023. The Kaplan-Meier method was used to calculate survival and recurrence rates. In univariate analysis, the log-rank test was used to correlate patient-/tumour- and treatment-related parameters to survival and recurrence rates.

Results: The overall survival rate was 79.7% at 2 years and 67.1% at 5 years. The DFS rate was 73.4% at 2 years and 67.1% at 5 years. Cumulatively, 14.6% of patients in the postoperative arm had locoregional recurrences at 2 years and 23.0% at 5 years, while 25.7% of patients in the definitive arm had local recurrences at 2 years and 33.1% at 5 years (p = 0.36). The rate of distant metastasis was 19.2% in the postoperative arm at 2 years and 21.6% at 5 years. In the definitive arm, the distant metastasis rate was 20.7% at 2 years and 28.6% at 5 years (p = 0.49). Disease-free survival was significantly improved in patients who drank little or no alcohol (p = 0.005) and in patients with a low UICC stage (p < 0.001). No differences in DFS were observed for different primary tumour locations or treatment modalities.

Conclusion: Locoregional recurrences were the most common site of recurrence, regardless of tumour location and treatment modality. Therefore, future study designs in this patient cohort should potentially investigate intensified treatment approaches.