Strahlentherapie und Onkologie最新文献

Purpose: Micro ribonucleic acids (miRNAs) are short non-coding RNA molecules that control the expression of target mRNAs. Many miRNAs are dysregulated in various cancers, acting as tumor suppressors or oncogenes. This study aims to investigate the regulatory status of miRNA-320a-3p and miRNA-136-5p in cervical cancer development as well as their predictive significance for treatment response and disease recurrence.

Materials and methods: Included in the study were 51 cervical cancer patients and 19 healthy controls. Expression levels of miRNA-320a-3p and miRNA-136-5p were detected using miRNA-specific quantitative real-time polymerase chain reaction (PCR). The relative expression of miRNAs was calculated using the 2^-∆∆Ct method.

Results: miRNA-136-5p was downregulated in the cervical cancer patients compared to the controls (fold change: -3.06, p = 0.000239). In the case group, upregulation of miRNA-320a-3p was significantly associated with a poor treatment response (fold change: 1.88, p = 0.0264). Additionally, higher expression of miRNA-320a-3p was observed in patients with locoregionally confined recurrence both in the evaluation based on initial recurrence patterns (fold change: 1.38, p = 0.0341) and at last follow-up (fold change: 2.56, p = 0.000582).

Conclusion: miRNA-136-5p can be proposed as a biomarker in cervical tumorigenesis, while miRNA-320a-3p can be used for treatment response and locoregional recurrence prediction.

Purpose: Financial toxicity (FT) associated with cancer and its treatment has become increasingly important. This study investigated factors associated with the development of FT during radiation therapy (RT). SOCOFIN was the first longitudinal prospective study to systematically evaluate FT in the context of RT.

Methods: Financial toxicity was measured with the Comprehensive Score for Financial Toxicity (COST-12) at RT initiation, completion, and at 3 months afterwards. Secondary endpoints included socioeconomic factors, health-related quality of life (EORTC QLQ-C30), depression (PHQ-9), coping mechanisms, and sense of coherence. The data were collected digitally; missing data were estimated using multiple imputation with chained equations.

Results: Between July 2023 and June 2024, 230 patients were recruited. Analyses were performed on 170 records. During RT, FT did not increase; a slight overall decrease was descriptively observed. Of seven tumor groups, the highest difference in FT at baseline was measured between prostate (median 33) and pelvic cancer patients (median 19), reaching statistical significance (Kruskal-Wallis test, p = 0.01). Nonetheless, tumor entity was not found to be a significant predictor of FT following RT in multivariate linear regression models. While factors associated with FT differed between timepoints, financial difficulties at baseline predicted the occurrence of FT most strongly (p < 10^-13) and persistently.

Conclusion: Predictors of FT were predominantly socioeconomic, such as baseline financial difficulties, net income, employment stability, and sense of coherence, which superseded tumor- or treatment-specific variables. The findings of this study underscore the necessity of multifactorial, early screening before RT to mitigate FT among radiation oncology patients.

Purpose: Lymphedema of the arm and reduced shoulder mobility are common complications of breast cancer treatment. We aim to establish whether the radiation dose received by the area of the axillary lateral thoracic artery vessel juncture (ALTJ) and the shoulder joint-affect the development of the mentioned side effects.

Methods: In this retrospective study, 298 patients with early breast cancer treated surgically and with adjuvant radiation therapy, were included. Clinical data from the prospective database were used. Physiotherapists evaluated lymphedema and shoulder mobility at diagnosis, 6 and 12 months afterwards. The ALTJ, humeral head, and humeral head with a safety margin were delineated on a CT scan, and irradiation parameters were obtained from dose-volume histograms.

Results: Multivariate analysis confirmed a correlation between higher mean (Dmean) and near-minimum (D98) radiation doses received by ALTJ and the incidence of lymphedema 12 months post-diagnosis (p = 0.016 and p = 0.002, respectively). No significant association was found between the radiation dose to the humeral head and reduced mobility.

Conclusion: In our cohort of patients, irradiation of the ALTJ region is associated with the occurrence of clinically-assessed lymphedema, while irradiation of the humeral head is not linked to limited mobility of the shoulder after breast cancer treatment.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by supramaximal immune activation. Although rare, HLH has been increasingly recognized as an immune-related adverse event in patients undergoing immune checkpoint inhibitor (ICI) therapy.

Case presentation: We report the case of a female patient treated with concomitant radio-chemo-immunotherapy for cervical cancer (according to the KEYNOTE-A18 trial). She developed HLH following a single dose of pembrolizumab, presenting initially with immune-mediated pneumonitis and subsequently with fever, prolonged pancytopenia, and elevated inflammatory markers. After intensive diagnostics, broad-spectrum anti-infective treatment and granulocyte colony-stimulating factor (G-CSF) stimulation was started, without improvement. The diagnosis was finally made by HLH-2004 criteria, strongly indicated by an H‑score of 251 (> 99% probability of HLH). The HLH was successfully treated with corticosteroids alone.

Conclusion: This case highlights the importance of early recognition and aggressive management of HLH secondary to immunotherapy, particularly in patients presenting with unexplained fever, G‑CSF-refractory cytopenia, and hyperferritinemia.

Chemo-/radiotherapy-induced cardiomyopathy is a clinical challenge for patients with cancer, characterized by detrimental effects on cardiac structure and function. To date, numerous experimental and clinical investigations have revealed that numerous mechanisms, such as oxidative damage, contribute to chemo-/radiotherapy-induced cardiomyopathy. Chronic oxidative stress and reactive oxygen species (ROS) production following damage to mitochondria and the endoplasmic reticulum (ER) play a fundamental role in the progression of cell death, inflammation, and fibrosis, leading to heart failure and unusual changes in the heart structure. This review delves into the mechanisms of cardiotoxicity induced by chemotherapy and radiotherapy, highlighting the pivotal role of mitochondrial dysfunction and subsequent oxidative stress and cell death. The interplay between mitochondrial and ER dysfunction can also be offered as a paramount factor in the development of cardiomyopathy. We review how damage to these organelles may trigger cardiac injury through crosstalk with other mechanisms such as activation of pro-oxidant enzymes, inflammation, fibrosis, and other important processes.

Background: 5‑Aminolevulinic acid (5-ALA) is a keto-carbon amino acid frequently used in glioma surgery for fluorescence-guided resection. Additionally, cytotoxic properties of 5‑ALA can be induced via stimulation with laser light in photodynamic therapy (PDT). Preclinical in vitro and in vivo trials have also demonstrated this effect to be inducible by photon irradiation as used in radiation treatment. This makes 5‑ALA a potential sensitizer for radiation therapy whose capabilities and limitations have not yet been fully evaluated. In this article, we present results from a systematic literature review regarding the evidence of 5‑ALA's radiosensitizing properties and the context of its use. We discuss these findings in terms of the underlying mechanisms, their limitations, and the questions to be addressed in future clinical trials.

Methods: A systematic review in the PubMed database was performed via a specifically designed search term, including all search results that featured the combination of 5‑ALA with ionizing radiation. The last date of search was November 13, 2024. Risk of bias among study data was assessed individually according to the study setup after full-text analysis. The results were synthesized based on the underlying tumor entity.

Results: A total of 31 articles were included that examined the combination of 5‑ALA with radiotherapy (RT) in glioma (n = 12), melanoma (n = 6), breast (n = 3), lung (n = 2), prostate (n = 4), and colorectal (n = 1) cancer as well as in sarcoma (n = 2) and primary CNS lymphoma (n = 1). The radiosensitizing effect of 5‑ALA varies among these entities, with glioma and melanoma presenting the strongest body of evidence.

Conclusion: These results imply a basis for 5‑ALA as a possible radiosensitizer for RT, but several questions remain unanswered, as limitations arise from the fact that data are predominantly based on in vitro or rodent in vivo trials, with only two ongoing clinical trials and one case report involving human patients. Moreover, trial setups varied in terms of ALA dose and application timing.

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.