Radiotherapy and Oncology最新文献

Background and purpose: Although not validated as a standard treatment, high-intensity focused ultrasound (HIFU) is increasingly used in the management of localised prostate cancer (PCa). In case of recurrence after HIFU, treatment is currently not standardised. Our aim was to evaluate normofractionated (NFRT) and hypofractionated (HFRT) salvage radiotherapy (RT) using volumetric modulated arc therapy (s-VMAT) with doses used in first-line management of localised PCa.

Material and methods: We identified all patients with local or locoregional recurrence after HIFU treated with s-VMAT in 3 RT centres between 2014 and 2023. We evaluated acute and late toxicity and oncological outcomes.

Results: Fifty-six patients were identified. Median age at recurrence was 75 (70-80) years. Median time between HIFU and s-VMAT was 26.5 months (13.9-47.2). S-VMAT was delivered to the prostate only in 35 (62.5 %) patients and to the prostate and pelvis in 21 (37.5 %) patients. NFRT and HFRT were delivered in 46 (82.1 %) and 10 (17.9 %) patients, respectively. Androgen deprivation therapy (ADT) was given to 27 (48.2 %) patients. Eighteen (32 %) and four (7 %) patients reported an acute grade 2 genitourinary (GU) and gastrointestinal (GI) adverse event (AE), respectively. Two patients presented with a late grade 2 GU AE, and one with a late grade 2 GI AE. No grade 3+ toxicity was reported. With a median follow-up of 19.5 months (12 - 47), no patient had a biochemical, local or distant relapse.

Conclusions: This is the largest series of salvage RT after HIFU using VMAT and escalated doses (78-80 Gy/39-40Fr., or 60 Gy/20Fr.). Acute toxicity was acceptable and late AEs were few. Longer follow-up is required to assess efficacy. Overall, available series suggest that salvage RT could represent a valuable option in the treatment of relapses after HIFU.

Background and purpose: Atypical meningiomas are prevalent intracranial tumors with varied prognoses and recurrence rates. The role of adjuvant radiotherapy (ART) in atypical meningiomas remains debated. This study aimed to develop and validate a prognostic model incorporating machine learning techniques and clinical factors to predict progression-free survival (PFS) in patients with atypical meningiomas and assess the impact of ART.

Materials and methods: A retrospective review of 669 patients from five institutions in Korea and China was conducted. Cox proportional hazards, gradient boosting machine, and random survival forest models were employed for comparative analysis, utilizing both internal and external validation sets. Model performance was assessed using Harrell's concordance index and permutation feature importance.

Results: Of 581 eligible patients, age, post-operative platelet count, performance status, Simpson grade, and ART were identified as significant prognostic factors across all models. In the ART subgroup, age and tumor size were the top prognostic indicators. The Cox model outperformed other methods, achieving a training C-index of 0.73 (95 % CI: 0.72-0.73) and an external validation C-index of 0.74 (95 % CI: 0.73-0.74). The model effectively stratified patients into risk categories, revealing a differential impact of ART: low-risk patients in the active surveillance group showed a 5.6 % improvement in 5-year PFS with predicted ART addition, compared to a 15.9 % improvement in the high-risk group.

Conclusion: This multicenter study offers a validated prognostic model for atypical meningiomas, highlighting the need for tailored treatment plans. The model's ability to stratify patients into risk categories for PFS provides a valuable tool for clinical decision-making, potentially optimizing patient outcomes.

Purpose: To develop and validate a prognostic and predictive model integrating deep learning MRI features and clinical information in patients with stage II nasopharyngeal carcinoma (NPC) to identify patients with a low risk of progression for whom intensity-modulated radiotherapy (IMRT) alone is sufficient.

Methods: This multicenter, retrospective study enrolled 999 patients with stage II NPC from two centers. 3DResNet was used to extract deep learning MRI features and eXtreme Gradient Boosting model was employed to integrate the pre-trained features and clinical information to obtain an overall score for each patient. Based on the optimal cutoff value of the overall score, patients were stratified into high- and low- risk groups. Model performance was evaluated using concordance indexes (C-indexes), the area under the curve (AUC) values and calibration tests. Survival curves were used to analyze the clinical benefits of additional chemotherapy in each risk group.

Results: The combined model achieved a concordance index of 0.789 (95 % confidence interval [CI] 0.787-0.791), 0.768 (95 % CI 0.764-0.771), and 0.804 (95 % CI 0.801-0.807) for the training, internal validation, and external test cohorts, respectively, demonstrating a statistically significant improvement compared to the MRI model, T Stage, and N Stage. An overall score of < 0.405 in patients was significantly associated with a low risk of progression. In the low-risk group, patients treated with IMRT alone had comparable or even superior progression-free survival (PFS) compared to those who received additional chemotherapy.

Conclusion: The model demonstrated a satisfactory prognostic and predictive performance for PFS. Patients with stage II NPC were stratified into different risk groups to help identify optimal candidates who could benefit from IMRT alone.

Background & purpose: Deep learning (DL) based auto-segmentation has shown to be beneficial for online adaptive radiotherapy (OART). However, auto-segmentation of clinical target volumes (CTV) is complex, as clinical interpretations are crucial in their definition. The resulting variation between clinicians and institutes hampers the generalizability of DL networks. In OART the CTV is delineated during treatment preparation which makes the clinician intent explicitly available during treatment. We studied whether multicenter generalisability improves when using this prior clinical knowledge, the pre-treatment delineation, as a patient-specific prior for DL models for online auto-segmentation of the mesorectal CTV.

Material & methods: We included intermediate risk or locally advanced rectal cancer patients from three centers. Patient-specific weight maps were created by combining the patient-specific CTV delineation on the pre-treatment scan with population-based variation of likely inter-fraction mesorectal CTV deformations. We trained two models to auto-segment the mesorectal CTV on in-house data, one with (MRI + prior) and one without (MRI-only) priors. Both models were applied to two external datasets. An external baseline model was trained without priors from scratch for one external center. Performance was evaluated on the DSC, surface Dice, 95HD and MSD.

Results: For both external centers, the MRI + prior model outperformed the MRI-only model significantly on the segmentation metrics (p-values < 0.01). There was no significant difference between the external baseline model and the MRI + prior model.

Conclusion: Adding patient-specific weight maps makes the CTV segmentation model more robust to institutional preferences. Performance was comparable to a model trained locally from scratch. This makes this approach suitable for generalization to multiple centers.

Background: Patient Safety Indicators (PSIs) allow the evaluation of safety levels in healthcare settings. Despite their use in various medical fields, a specific and comprehensive PSI catalogue for radiation oncology (RO) is lacking. The Patient Safety in German Radiation Oncology (PaSaGeRO) study aims for the development of a specific PSI catalogue in radiation oncology.

Objectives: The primary objective of this systematic literature review as part of the PaSaGeRO study is to identify, formulate, and categorize PSIs specific to RO to bridge existing gaps in comprehensive patient safety evaluation.

Methods: An electronic search in PubMed included studies from 1989 onwards, in English or German, focusing on safety and quality indicators in RO, patient safety measures, or risk analyses. Exclusions were non-transferable, country-specific measures, techniques exclusive to specific departments, and legally mandated procedures. Additional sources were identified through reference tracking and professional society websites. Two experts independently extracted PSIs from the included references.

Results: Out of 157 included publications and nine secondary sources, we identified and formulated 145 PSIs. These were categorized into patient-specific processes (82, 56%), quality and risk management (42, 28%), human resources (15, 10%), and institutional culture (13, 9%).

Conclusion: The hereby developed PSIs provides a base for professionals to systematically evaluate and improve safety practices, addressing previously unmet needs in this field. By offering clear guidance on safety assessment, the catalogue has the potential to drive significant improvements in patient care and safety outcomes in RO. Funded by Deutsche Krebshilfe. Registered in the German Clinical Trials Register (DRKS00034690).

Background and purpose: The 90-day mortality following lung cancer treatment is a common performance indicator. The aim of this study was to investigate 90-day mortality following (chemo)radiotherapy for stage I-III lung cancer to evaluate the applicability of this outcome indicator in this patient population.

Materials and methods: The Netherlands National Cancer Registry was queried for this retrospective population-based study. Early mortality rates from the start and end of radiotherapy are reported with 95% confidence intervals (CI). The association between clinical characteristics and 90-day mortality was evaluated with multivariable logistic regression analysis.

Results: 18,355 Patients treated between 2015 and 2020 were included. The 90-day mortality was 2.56% in stages I-II and 4.60% in stage III, was significantly higher in males, elderly patients and patients with a poor performance status and independent of facility volume. In stage I-II, 90-day mortality was lower after stereotactic versus conventional radiotherapy (2.0% versus 5.25%, OR 0.5 (95%CI 0.4-0.7)). In stage III, mortality decreased from 5.26% in 2015-2016 to 3.73% in 2019-2020 (OR 0.7 (95% CI 0.5-0.9)) and was lower after concurrent versus sequential chemoradiotherapy (3.4% versus 5.9%, OR 1.5 (95%CI 1.2-1.9)). Early mortality increased to 3.20% in stages I-II and 6.70% in stage III when calculated from the end of radiotherapy.

Conclusion: Short-term mortality rates following curative intent radiotherapy for lung cancer in the Netherlands are low and independent of facility volume. It was demonstrated that 90-day mortality is an arguable indicator to monitor radiotherapy quality and that standardization of definitions and relevant case-mix factors is warranted.

Background: Guidelines recommend elective irradiation of the external iliac and upper pelvic lymph nodes (LNs) regardless of clinical stage, but the supporting evidence for this recommendation is limited.

Methods: We conducted a retrospective analysis of 68 consecutive patients with squamous cell carcinoma of the anal canal who underwent volumetric modulated arc therapy chemoradiation, excluding external iliac LNs from elective irradiation. In patients with negative bilateral inguinal LNs, both external iliac regions were omitted, while in those with unilateral positive inguinal LNs, only the ipsilateral external iliac region was included and the contralateral side was omitted. For patients with early-stage tumours, the cranial border of elective irradiation was located in the inferior aspect of the sacroiliac joints.

Results: The median follow-up was 4.0 years. Six patients (9 %) experienced recurrence of the primary tumour and three (4 %) developed distant metastases. No isolated nodal recurrences were seen in the LNs that were positive at baseline, or in or outside electively irradiated regions. Notably, no recurrences were seen in any of the 124 external iliac regions omitted from elective irradiation across the 68 patients, or in the upper pelvic region among the subgroup of 33 patients where the cranial irradiation border was at the bottom of the sacroiliac joint. Reducing the elective irradiation volume significantly decreased the dose-volume parameters for organs-at-risk.

Conclusions: The present findings suggest that omitting the external iliac and upper pelvic LNs from elective irradiation is safe for selected patients and allows dose reduction in organs-at-risk.

Background and purpose: Tumor hypoxia is the principal cause of clinical radioresistance. Despite its established role as radiosensitizer, hydrogen peroxide (H₂O₂) encounters clinical limitations due to stability and toxicity concerns. Recent advancements in drug delivery combine H₂O₂ with sodium hyaluronate (SH), enabling intratumoral administration of H₂O₂. This study investigates the radiomodulatory pathways of Kochi Oxydol-Radiation for Unresectable Carcinomas (KORTUC) (H₂O₂ + SH) under hypoxia.

Materials and methods: CT26 and 4T1 tumor cells were exposed to H₂O_2, SH and KORTUC under hypoxic conditions. Toxicity levels were determined using MTT and live-cell analysis. KORTUC's radiomodulatory properties were evaluated by colony formation assay and in spheroids. Reactive oxygen species (ROS) levels, DNA damage, apoptosis and ferroptosis were analyzed using flow cytometry. Oxygen consumption rate (OCR) and mitochondrial complex activity were assessed by Seahorse Analyzer. Oxygen levels were investigated using fiber-optic sensors. The in vitro findings were validated in CT26-bearing mice.

Results: KORTUC demonstrated less cytotoxicity than H₂O₂-alone. KORTUC radiosensitized hypoxic tumor cells in a dose-dependent manner with enhancement ratios of 3.1 (CT26) and 2.7 (4T1). Dose-dependent OCR reduction following KORTUC exposure correlated with complex I and II inhibition, accompanied by mitochondrial ROS elevation. KORTUC injection into a 2D hypoxic tumor model surged O₂ levels. KORTUC radiosensitized CT26-tumors, delaying growth by 14 days.

Conclusions: SH in KORTUC mitigates H₂O₂ cytotoxicity. We demonstrate that KORTUC overcomes hypoxia-induced radioresistance through inhibition of OCR, via complex I- and II-blockade, leading to tumor reoxygenation. Understanding KORTUC's pathways is essential for developing effective cancer combination therapies.

Background and purpose: Interferon (IFN) signaling plays an important role in antitumor immune responses. Inhibitors of the DNA damage response, such as ATR inhibitors, can increase IFN signaling upon conventional radiotherapy with X-rays. However, it is not known whether such inhibitors also enhance IFN signaling after irradiation with high linear energy transfer (LET) particles.

Materials and methods: Human glioblastoma U-251 and T98G cells were irradiated with X-rays, protons (LET: 4.8 and 41.9 keV/µm) and carbon ions (LET: 28 and 73 keV/µm), with and without ATR inhibitor (VE-822) or ATM inhibitor (AZD1390). DNA damage signaling and cell cycle distribution were analyzed by immunoblotting and flow cytometry, and radiosensitivity was assessed by clonogenic survival assay. IFN-β secretion was measured by ELISA, and STAT1 activation was examined by immunoblotting.

Results: High-LET protons and carbon ions caused stronger activation of the DNA damage response compared to low-LET protons and X-rays at similar radiation doses. G2 checkpoint arrest was abrogated by the ATR inhibitor and prolonged by the ATM inhibitor after all radiation types. The inhibitors increased radiosensitivity, as measured after X- and carbon ion irradiation. ATR inhibition increased IFN signaling following both low-LET and high-LET irradiation. ATM inhibition also increased IFN signaling, but to a lesser extent. Notably, both cell lines secreted significantly more IFN-β when the inhibitors were combined with high-LET compared to low-LET irradiation.

Conclusion: These findings indicate that DNA damage response inhibitors can enhance IFN signaling following X-, proton and carbon ion irradiation, with a strong positive dependency on LET.

Purpose: To assess the feasibility and benefit of NTCP optimized aspiration-prevention treatment planning by sparing specific aspiration related organs at risk, and to assess the impact of baseline complaints on the planning results.

Materials and methods: This in silico planning study included 30 HNC patients who were previously treated with definitive radiotherapy. New fully automated plans, allowing for sparing specific aspiration related organs at risk, were optimised directly on normal tissue complication probability (NTCP) models for common toxicities: xerostomia and dysphagia. Optimisation was performed with and without aspiration-prevention, i.e., with and without specific sparing of recently identified aspiration-related muscles, and with and without the assumption of existing baseline complaints.

Results: All plans complied with the pre-defined treatment planning quality criteria and were successful in limiting the risk of xerostomia and dysphagia. Aspiration-prevention VMAT, optimized using the additional NTCP model for aspiration, significantly reduced the estimated risk of late aspiration (p < 0.001) in all 30 patients when compared to plans without NTCP optimisation for late aspiration. The predicted risk of late aspiration was reduced even further when baseline aspiration was assumed present during optimisation, resulting in an average risk reduction of 13.3 % versus 8.3 % in plans assuming no aspiration at baseline. Aspiration-prevention did not reduce overall plan quality and maintained NTCP values obtained for various other toxicities.

Conclusion: Sparing specific aspiration-related organs at risk has the potential to significantly reduce the risk of late RT-induced aspiration, especially in patients who experience aspiration already at baseline.