Radiation Oncology

Laser acceleration of protons and heavy ions may in the future be used in radiation therapy. Laser-driven particle beams are pulsed and ultra high dose rates of >10⁹ Gy s^-1may be achieved. Here we compare the radiobiological effects of pulsed and continuous proton beams.

The ion microbeam SNAKE at the Munich tandem accelerator was used to directly compare a pulsed and a continuous 20 MeV proton beam, which delivered a dose of 3 Gy to a HeLa cell monolayer within < 1 ns or 100 ms, respectively. Investigated endpoints were G2 phase cell cycle arrest, apoptosis, and colony formation.

At 10 h after pulsed irradiation, the fraction of G2 cells was significantly lower than after irradiation with the continuous beam, while all other endpoints including colony formation were not significantly different. We determined the relative biological effectiveness (RBE) for pulsed and continuous proton beams relative to x-irradiation as 0.91 ± 0.26 and 0.86 ± 0.33 (mean and SD), respectively.

At the dose rates investigated here, which are expected to correspond to those in radiation therapy using laser-driven particles, the RBE of the pulsed and the (conventional) continuous irradiation mode do not differ significantly.

We performed this study to assess outcomes of patients with oropharyngeal cancer treated with modern therapy approaches. Demographics, treatments and outcomes of patients diagnosed with Stage 3- 4B squamous carcinoma of the oropharynx, between 2000 – 2007 were tabulated and analyzed. The cohort consisted of 1046 patients. The 5- year actuarial overall survival, recurrence-free survival and local-regional control rates for the entire cohort were 78%, 77% and 87% respectively. More advanced disease, increasing T-stage and smoking were associated with higher rates of local-regional recurrence and poorer survival. Patients with locally advanced oropharyngeal cancer have a relatively high survival rate. Patients’ demographics and primary tumor volume were very influential on these favorable outcomes. In particular, patients with small primary tumors did very well even when treatment was not intensified with the addition of chemotherapy.

To establish regression models of physical and equivalent dose in 2 Gy per fraction (EQD2) plan parameters of two kinds of hybrid planning for stage III NSCLC. Two kinds of hybrid plans named conventional fraction radiotherapy & stereotactic body radiotherapy (C&S) and conventional fraction radiotherapy & simultaneous integrated boost (C&SIB) were retrospectively made for 20 patients with stage III NSCLC. Prescription dose of C&S plans was 2 Gy × 30f for planning target volume of lymph node (PTVLN) and 12.5 Gy × 4f for planning target volume of primary tumor (PTVPT), while prescription dose of C&SIB plans was 2 Gy × 26f for PTVLN and sequential 2 Gy × 4f for PTVLN combined with 12.5 Gy × 4f for PTVPT. Regression models of physical and EQD2 plan parameters were established based on anatomical geometry features for two kinds of hybrid plans. The features were mainly characterized by volume ratio, min distance and overlapping slices thickness of two structures. The possibilities of regression models of EQD2 plan parameters were verified by spearman’s correlation coefficients between physical and EQD2 plan parameters, and the influence on the consistence of fitting goodness between physical and EQD2 models was investigated by the correlations between physical and EQD2 plan parameters. Finally, physical and EQD2 models predictions were compared with plan parameters for two new patients. Physical and EQD2 plan parameters of PTVLN CI60Gy have shown strong positive correlations with PTVLN volume and min distance(PT to LN), and strong negative correlations with PTVPT volume for two kinds of hybrid plans. PTV(PT+LN) CI60Gy is not only correlated with above three geometry features, but also negatively correlated with overlapping slices thickness(PT and LN). When neck lymph node metastasis was excluded from PTVLN volume, physical and EQD2 total lung V20 showed a high linear correlation with corrected volume ratio(LN to total lung). Meanwhile, physical total lung mean dose (MLD) had a high linear correlation with corrected volume ratio(LN to total lung), while EQD2 total lung MLD was not only affected by corrected volume ratio(LN to total lung) but also volume ratio(PT to total lung). Heart D5, D30 and mean dose (MHD) would be more susceptible to overlapping structure(heart and LN). Min distance(PT to ESO) may be an important feature for predicting EQD2 esophageal max dose for hybrid plans. It’s feasible for regression models of EQD2 plan parameters, and the consistence of the fitting goodness of physical and EQD2 models had a positive correlation with spearman’s correlation coefficients between physical and EQD2 plan parameters. For total lung V20, ipsilateral lung V20, and ipsilateral lung MLD, the models could predict that C&SIB plans were higher than C&S plans for two new patients. The regression models of physical and EQD2 plan parameters were established with at least moderate fitting goodness in this work, and the models have a potential to predict physical and EQD2 plan parameters for two kinds of hybrid planning.

The purpose of this study is to investigate the potential to reduce exposure of the contralateral hippocampus in radiotherapy for glioblastoma using volumetric modulated arc therapy (VMAT). Datasets of 27 patients who had received 3D conformal radiotherapy (3D-CRT) for glioblastoma with a prescribed dose of 60Gy in fractions of 2Gy were included in this planning study. VMAT plans were optimized with the aim to reduce the dose to the contralateral hippocampus as much as possible without compromising other parameters. Hippocampal dose and treatment parameters were compared to the 3D-CRT plans using the Wilcoxon signed-rank test. The influence of tumour location and PTV size on the hippocampal dose was investigated with the Mann–Whitney-U-test and Spearman’s rank correlation coefficient. The median reduction of the contralateral hippocampus generalized equivalent uniform dose (gEUD) with VMAT was 36 % compared to the original 3D-CRT plans (p < 0.05). Other dose parameters were maintained or improved. The median V30Gy brain could be reduced by 17.9 % (p < 0.05). For VMAT, a parietal and a non-temporal tumour localisation as well as a larger PTV size were predictors for a higher hippocampal dose (p < 0.05). Using VMAT, a substantial reduction of the radiotherapy dose to the contralateral hippocampus for patients with glioblastoma is feasible without compromising other treatment parameters. For larger PTV sizes, less sparing can be achieved. Whether this approach is able to preserve the neurocognitive status without compromising the oncological outcome needs to be investigated in the setting of prospective clinical trials.

The aim of this study was to investigate if the flattening filter free (FFF) irradiation mode of a linear accelerator (linac) is advantageous as compared to the flat beam (FF) irradiation mode in intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for carcinoma of the hypopharynx / larynx. Four treatment plans were created for each of 10 patients for an Elekta Synergy linac with Agility collimating device, a dual arc VMAT and a nine field step and shoot IMRT each with and without flattening filter. Plan quality was compared considering target coverage and dose to the organs at risk. All plans were verified by a 2D–ionization-chamber-array and delivery times were compared. Peripheral point doses were determined as a measure of second cancer risk. The Wilcoxon test was used for statistical analysis with a significance level of 0.05. Plan quality was similar for all four treatment plans without statistically significant differences of clinical relevance. The clinical goals were met in all plans for the PTV-SIB (V95% > 95%), the spinal cord (D1ccm < 45 Gy) and the brain stem (D1ccm < 48 Gy). For the parotids, the goal of D50% < 30 Gy was met in 70% and 60% of the plans for the left and right parotid respectively, and the V95% of the SIB reached an average of 94%. Delivery times were similar for FF and FFF and significantly decreased by around 70% for VMAT as compared to IMRT. Peripheral doses were significantly reduced by 18% in FFF mode as compared to FF and by 26% for VMAT as compared to IMRT. Lowest peripheral doses were found for VMAT FFF, followed by VMAT FF. The FFF mode of a linear accelerator is advantageous for the treatment of hypopharynx/larynx carcinoma only with respect to reduction of second cancer induction in peripheral organs for the combination of Elekta Synergy linacs and Oncentra® External Beam v4.5 treatment planning system. This might be of interest in a therapy with curative intent.

How to protect the ovarian function during radiotherapy is uncertain. The purpose of this study was to explore the association between the location of the transposed ovary and the ovarian dose in patients with cervical cancer received radical hysterectomy, ovarian transposition, and postoperative pelvic radiotherapy. A retrospective analysis was conducted of 150 young patients with cervical cancer who received radical hysterectomy, intraoperative ovarian transposition, and postoperative adjuvant radiotherapy in Zhejiang Cancer Hospital. Association between location of the transposed ovaries and ovarian dose was evaluated. The transposed position of ovaries with a satisfactory dose was explored using a receiver operator characteristic curve (ROC) analysis. Patients’ ovarian function was followed up 3 months and 1 year after radiotherapy. A total of 32/214 (15%) transposed ovaries were higher than the upper boundary of the planning target volume (PTV). The optimum cutoff value of > 1.12 cm above the iliac crest plane was significantly associated with ovaries above the upper PTV boundary. When the ovaries were below the upper boundary of PTV, the optimum cutoff value of transverse distance > 3.265 cm between the ovary and PTV was significantly associated with ovarian max dose (Dmax) ≤ 4Gy, and the optimum cutoff value of transverse distance > 2.391 cm was significantly associated with ovarian Dmax≤5Gy. A total of 77 patients had received complete follow-up, and 56 patients (72.7%) showed preserved ovarian function 1 year after radiotherapy, which was significantly increased compared with 3 months (44.2%) after radiotherapy. The location of transposed ovaries in patients with cervical cancer is significantly correlated with ovarian dose in adjuvant radiotherapy. We recommend transposition of ovaries > 1.12 cm higher than the iliac crest plane to obtain ovarian location above PTV. When the transposed ovary is below the upper boundary of PTV, ovarian Dmax ≤4Gy may be obtained when the transverse distance between the ovary and PTV was > 3.265 cm, and the ovarian Dmax≤5Gy may be obtained when the transverse distance was > 2.391 cm.

Conventional treatment of pulmonary metastatic sarcoma primarily involves surgery, with systemic therapy added in select patients. However, broader applications of radiation therapy techniques have prompted investigation into the use of stereotactic body radiotherapy (SBRT) for treatment of metastatic sarcoma, an attractive non-invasive intervention with potential for lower rates of adverse events than surgery. Current data are limited to retrospective analyses. This study analyzed 2-year local control and overall survival and adverse events in patients prospectively treated with SBRT to pulmonary sarcoma metastases. Patients prospectively treated with SBRT to the lung for biopsy-proven metastatic sarcoma at a single institution from 2010 to 2022 were included. SBRT dose/fractionation treatment regimens ranged from 34 to 54 Gy in 1–10 fractions using photons. Local recurrence, local progression-free survival (LPFS) and overall survival (OS) were calculated from the end of SBRT. Univariable analysis (UVA) was performed using the log-rank test. Multivariable analysis (MVA) was performed using the Cox proportional hazards model. Adverse events due to SBRT were graded based on the Common Terminology Criteria for Adverse Events, version 4.0. Eighteen patients with metastatic sarcoma were treated to 26 pulmonary metastases. The median local progression-free survival was not met. The median overall survival was not met. The local control rate at 2 years was 96%. 2-year LPFS was 95.5% and OS was 74%. Three patients (16.7%) developed grade 1 adverse events from SBRT. There were no adverse events attributed to radiation that were grade 2 or higher. We report prospective data demonstrating that SBRT for sarcoma pulmonary metastases affords a high rate of local control and low toxicity, consistent with prior sarcoma SBRT retrospective data. This study adds to the wealth of information on SBRT in a radioresistant tumor. Though largely limited to retrospective reviews, current data indicate high rates of local control with favorable toxicity profiles. Therefore, SBRT for pulmonary sarcoma metastases may be considered for properly selected patients.

Neoadjuvant radiotherapy (RT) has been shown to improve local control; however, whether it can improve overall survival (OS) in locally advanced rectal cancer (LARC) patients remains controversial. We therefore aimed to examine the benefits of surgery alone, neoadjuvant radiotherapy (RT), adjuvant RT, and surgery plus chemotherapy in stage II (T3/4N0M0) and III (any T and N + M0) on the OS of rectal cancer patients. Date from the Surveillance, Epidemiology, and End Results (SEER) database diagnosed between 2004 and 2016 were used. Kaplan-Meier analyses were used to compare patient prognoses across different treatment modalities. Cox hazard regression analysis were used to identify independent predictors of OS. For stage T3/4N0M0 patients, neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy resulted in similar OS (all p > 0.05; mean survival, 115.89 months (M), 111.97 M, and 117.22 M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p < 0.001, mean survival, 88.96 M). For stage T1/2N + M0 patients, neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy resulted in similar OS (all p > 0.05; mean survival, 121.50 M, 124.25 M, and 121.20 M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p < 0.001, mean survival 83.81 M). For stage T3/4N + M0 patients, neoadjuvant RT (HR = 0.436; 95% CI, 0.396~0.478; p < 0.001) resulted in significantly longer OS than adjuvant RT and surgery plus chemotherapy (mean survival, 104.47 M, 93.94 M, and 93.62 M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p < 0.001, mean survival 54.87 M). Older age (> 60 years), black race, unmarried status, high tumour grade, and tumour size > 5 cm were all associated with a poor prognosis (all p < 0.05). Neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy results in better OS than surgery alone in LARC patients. Neoadjuvant RT has the potential to be highly recommended over adjuvant RT and surgery plus chemotherapy for T3/4N + M0 patients; however, it showed no OS advantage over adjuvant RT or surgery plus chemotherapy for T3/4N0M0 and T1/2N + M0 patients.

Prognostic biomarkers identifying patients with early tumor progression after local ablative therapy remain an unmet clinical need. The aim of this study was to investigate circulating miR-21 and miR-210 levels as prognostic biomarkers of HCC treated by CT-guided high-dose rate brachytherapy (HDR-BT). 24 consecutive HCC patients (BCLC A and B) treated with CT-guided HDR-BT (1 × 15 Gy) were included in this prospective IRB-approved study. RT-PCR was performed to quantify miR-21 and miR-210 levels in blood samples acquired prior to and 2 d after HDR-BT. Follow-up imaging (contrast-enhanced liver MRI and whole-body CT) was performed in 3 months follow-up intervals. Therapy response was assessed with patients classified as either responders or non-responders (12 each). Responders were defined as having no local or diffuse systemic progression within 6 months and no diffuse systemic progression exceeding 3 nodules/nodule diameter > 3 cm from 6 months to 2 years. Non-responders had recurrence within 6 months and/or tumor progression with > 3 nodules or individual lesion diameter > 3 cm or extrahepatic disease within two years, respectively. Biostatistics included parametric and non-parametric testing (Mann–Whitney-U-test), as well as Kaplan–Meier curve construction. The responder group demonstrated significantly decreasing miR-21 values 2 d post therapy compared to non-responders (median miR-21 2−ΔΔCт: responders 0.73 [IQR 0.34], non-responders 1.53 [IQR 1.48]; p = 0.0102). miR-210 did not show any significant difference between responders and non-responders (median miR-210 2−ΔΔCт: responders 0.74 [IQR 0.45], non-responders 0.99 [IQR 1.13]; p = 0.8399). Kaplan–Meier curves demonstrated significantly shorter time to systemic progression for increased miR-21 (p = 0.0095) but not miR-210 (p = 0.7412), with events accumulating > 1 year post therapy in non-responders (median time to systemic progression 397 days). Increasing circulating miR-21 levels are associated with poor response and shorter time to systemic progression in HDR-BT-treated HCC. This proof-of-concept study provides a basis for further investigation of miR-21 as a prognostic biomarker and potential stratifier in future clinical trials of interventional oncology therapies. Trial registration: In this monocentric clinical study, we analyzed prospectively acquired data of 24 patients from the “ESTIMATE” patient cohort (Studiennummer: DRKS00010587, Deutsches Register Klinischer Studien). Ethical approval was provided by the ethics committee “Ethikkommission bei der LMU München” (reference number “17-346”) on June 20, 2017 and August 26, 2020.