Strahlentherapie und Onkologie最新文献

Purpose: In locally advanced cervical cancer (LACC), chemoradiotherapy (CRT) represents the standard of care. The aim of this narrative review is to investigate the prognostic role of metabolic response of ¹⁸F-FDG PET-CT after CRT in LACC patients.

Methods: We reviewed the literature according to the PRISMA guidelines to identify studies up to December 2023. The literature search was performed on PubMed and Scopus, using the following combination of medical subject headings (MeSH) and keywords "Uterine Cervical Neoplasms", "¹⁸F-FDG PET-CT", "locally advanced cervical cancer", "chemoradiotherapy". Studies assessing metabolic response after CRT in LACC were included. All abstracts and full-text articles were screened independently by four authors. Discrepancies were resolved through discussion with a third party.

Results: After the literature research, 9 studies fulfilled the inclusion criteria and were included in this review. Metabolic response after radical CRT treatment was significantly related to better clinical outcomes and to lower local relapse. Incomplete metabolic response could be considered a predictive factor for distant metastasis and cancer related deaths.

Conclusion: Current data highlight the potential role of metabolic response of ¹⁸F-FDG PET-CT after CRT to predict survival outcomes. LACC patients are likely to benefit from this imaging technique in the follow up management. Patients with incomplete metabolic response could be addressed to further additional therapeutic strategies.

Purpose: The aim of the study was to evaluate the clinical efficacy and side effects of stereotactic body radiotherapy (SBRT) using a gantry-based linear accelerator (LINAC) or robotic technique in a large cohort of consecutively treated medically inoperable early-stage lung cancer patients.

Methods: Between March 2015 and February 2023, 401 early-stage (T1-2 N0 M0) primary lung cancer patients were treated using either LINACs (Varian VitalBeam® and TrueBeam®; Varian, Palo Alto, CA, USA) or CyberKnife® (Accuray, Madison, WI, USA). Median age was 70 years (range 44-90). Diagnosis was based on biopsy for 37.4% of patients, while pathological confirmation was unavailable due to high risk for 62.6%. ¹⁸F‑fluorodeoxyglucose positron-emission tomography (18-FDG-PET) was part of the pretreatment diagnostic workup in 96% (n = 386) of the total cohort. Tumor stage distribution was T1a in 32 (8%), T1b in 179 (44.6%), T1c in 112 (27.9%), T2a in 67 (16.7%), and T2b in 11 (2.7%) patients. Applied dose schemes were identical for both LINAC and CyberKnife treatments, using risk-adapted doses of 45-60 Gy in 3 to 8 fractions, (biologically effective dose ranging from 86 to 151.2 Gy BED₁₀).

Results: At a median follow-up of 32 months (range 2-104), the crude survival rate was 58%. Median overall survival (OS) was 63 months (95% CI: 51.1-74.8) the 2‑, 3‑, and 4‑year OS rates were 79, 68, and 56%, respectively. Actuarial local control (LC) rates were 94% at 2 years, 90% at 3 years, and 87% at 4 years. Median LC was not reached. Median local progression-free survival (LPFS) and progression-free survival (PFS) rates were 49.5 months (95% CI: 42.8-56.3) and 37 months (95% CI: 31.2.-42.8), respectively. Actuarial 2‑, 3‑, and 4‑year LPFS and PFS rates were 75, 60, and 51% and 66, 51, and 42%, respectively. On multivariate analysis, BED₁₀ ≥ 132 Gy predicted improved LPFS, while earlier tumor stage and better ECOG performance status were associated with improved OS. No grade 3 or higher acute side effects were observed. Grade 3 late side effects occurred in 4 patients (1%), including grade 3 late pulmonary fibrosis in 3 cases and potentially treatment-related grade 3 pneumothorax in 1 patient. Rib fracture was observed in 14 cases (3%).

Conclusion: Clinical results after SBRT at a national comprehensive cancer center demonstrate high LC and LPFS rates and favorable PFS and OS, comparable to published studies. Application of a BED₁₀ of 132 Gy or higher shows a potential benefit in terms of LPFS and may thus be recommended in the absence of conflict with organ at risk constraints. SBRT with either LINAC or CK is proven to be a well-tolerated but still highly effective treatment for the elderly, medically inoperable early-stage lung cancer population.

Background: Ventricular tachycardia (VT) is a life-threatening condition, and standard treatments are not suitable for many affected patients. Stereotactic arrhythmia radioablation (STAR) has emerged as a promising experimental last-resort treatment for patients with refractory VT, but it lacks clinical standardization. To address this issue, the STOPSTORM.eu consortium aims to collect data on patients treated with STAR via the development of a multicentric patient registry. The Ethics & Regulations Working Group (ERG) provides support addressing ethical and regulatory challenges.

Methods: The ERG conducted a survey to assess how prospective data on STAR are collected at the partner centres and to explore potential ethical concerns. Responses were analysed to evaluate clinical trial approval processes, adherence to STOPSTORM guidelines, and emerging ethical issues.

Results: Among the 28 partners, there were 13 interventional clinical trials-ongoing or concluded-across seven countries; centres without ongoing trials enrolled patients under compassionate use. Most trials were single arm, with few exceptions (a randomized trial and dose escalation studies). Most ethics committees approved STAR trials without major objections, but regulatory inconsistencies were observed, resulting in approval denial or delay. Ethical concerns included potential therapeutic misconception among patients, autonomy issues due to the vulnerability of VT patients, and inequities in access to STAR. The heterogeneity in trial designs, endpoints, and follow-up strategies among participating centres posed challenges for data standardization, but using a registry to collect data from multiple local clinical trials offers an innovative approach to overcoming logistical and financial barriers in research on rare diseases.

Conclusion: Multicentric non-pharmaceutical trials on STAR may present ethical, regulatory, and organizational challenges. The open registry model facilitates large-scale data collection and supports future protocol standardization. However, greater intercentre collaboration and regulatory harmonization are needed to optimize STAR's integration into clinical practice while upholding ethical standards in patient care and research.

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.

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.

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.