Biological optimization for treatment planning in carbon ion therapy is currently based on the first version of the local effect model (LEM I). Further developments implemented in the latest version ...(LEM IV) allowed to predict more accurately the Relative Biological Effectiveness (RBE) in-vitro. The main goal of this study is to compare the LEM IV against LEM I under treatment-like conditions for idealized target geometries. Therefore, physical dose distributions resulting from the biological optimization with LEM I were used to recalculate the RBE-weighted dose distribution based on LEM IV. Input parameters representing the clinical endpoints late toxicity in the central nervous system and the tumor control for chordoma were chosen to investigate the impact of changes on the predicted isoeffective dose levels. The recalculated RBE-weighted dose distributions show an increase within the target region, and the mean RBE-weighted dose values are dependent on the geometry and decrease with increasing target dimension. The differences between predictions of LEM IV and LEM I are less than 10% for typical tumor volumes treated in the pilot project at GSI. Median RBE-weighted doses predicted by LEM IV in the target region are consistent with clinically observed dose-response behavior as demonstrated by comparison to the 5-year local control curve for skull base chordoma.
Background
Pancreatic cancer accounts for around 4.6% of cancers deaths worldwide per year. Despite many advances in treatment regimes, the prognosis is still poor. Only 20% of tumors are primarily ...resectable. Recurrences—both with distant metastasis as well as locoregional—are frequent. For patients with primary nonresectable localized disease or localized recurrences, we offered chemoradiation to achieve local control over a long period of time. We here report our results on combined chemoradiation of pancreatic tumors and local recurrences using proton beam therapy.
Materials and methods
We report on 25 patients with localized nonresectable pancreatic cancer (15 patients) or local recurrent disease (10 patients). All patients were treated with combined proton radiochemotherapy. Overall survival, progression-free survival, local control, and treatment-related toxicity were analyzed using statistically methods.
Results
Median RT dose was 54.0 Gy (RBE) for proton irradiation. The toxicity of treatment was acceptable. Four CTCAE grade III and IV adverse events (bone marrow disfunction, gastrointestinal GI disorders, stent dislocation, myocardial infarction) were recorded during or directly after the end of radiotherapy; two of them were related to combined chemoradiation (bone marrow disfunction, GI disorders). Six weeks after radiotherapy, one additional grade IV toxicity was reported (ileus, caused by peritoneal carcinomatosis, not treatment related). The median progression-free survival was 5.9 months and median overall survival was 11.0 months. The pretherapy CA19‑9 level was a statistically significant prognostic factor for enhanced overall survival. Local control at 6 months and 12 months were determined to be 86% and 80%, respectively.
Conclusion
Combined proton chemoradiation leads to high local control rates. Unfortunately, PFS and OS are driven by distant metastasis and were not improved compared to historical data and reports. With this in mind, enhanced chemotherapeutical regimes, in combination with local irradiation, should be evaluated.
Purpose
The prognosis for glioblastoma patients remains dismal despite intensive research on better treatment options. Molecular and immunohistochemical markers are increasingly being investigated as ...understanding of their role in disease progression grows. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been shown to have prognostic and therapeutic relevance for glioblastoma patients. Other markers implicated in tumor formation and/or malignancy are p53, Alpha thalassemia/mental retardation syndrome X-linked (ATRX), Epidermal Growth Factor Receptor splice variant III (EGFRvIII), and Ki-67, with loss of nuclear ATRX expression and lower Ki-67 index being associated with prolonged survival. For p53 and EGFRvIII the data are contradictory. Our aim was to investigate the markers mentioned above regarding progression-free (PFS) and overall survival (OS) to evaluate their viability as independent prognostic markers for our patient collective.
Methods
In this retrospective study, we collected data on patients undergoing radiotherapy due to isocitrate dehydrogenase (IDH) wildtype glioblastoma at a single university hospital between 2014 and 2020.
Results
Our findings confirm Ki-67 labeling index ≤ 20% as an independent prognostic factor for prolonged PFS as well as MGMT promoter methylation for both prolonged PFS and OS, in consideration of age and Eastern Cooperative Oncology Group (ECOG) status, chemotherapy treatment, and total radiation dose for PFS as well as additionally sex, resection status, and receipt of treatment for progression or recurrence for OS. Additionally, Ki-67 labeling index ≤ 20% showed a significant correlation with prolonged OS in univariate analysis. Modification of the recursive partitioning analysis (RPA) score to include Ki-67 labeling index resulted in a classification with the possible ability to distinguish long-term-survivors from patients with unfavorable prognosis.
Conclusion
MGMT promoter methylation and Ki-67 labeling index were independent predictors of survival in our collective. We see further studies pooling patient collectives to reach larger patient numbers concerning Ki-67 labeling index as being warranted.
Purpose
Preoperative stereotactic radiosurgery (SRS) of brain metastases may achieve similar local control and better leptomeningeal control rates than postoperative fractionated stereotactic ...radiotherapy (FSRT) in patients treated with elective metastasectomy. To plan a multicentre trial of preoperative SRS compared with postoperative FSRT, a survey of experts was conducted to determine current practice.
Methods
A survey with 15 questions was distributed to the DEGRO Radiosurgery and Stereotactic Radiotherapy Working Group. Participants were asked under what circumstances they offered SRS, FSRT, partial and/or whole brain radiotherapy before or after resection of a brain metastasis, as well as the feasibility of preoperative stereotactic radiosurgery and neurosurgical resection within 6 days.
Results
Of 25 participants from 24 centres, 22 completed 100% of the questions. 24 respondents were radiation oncologists and 1 was a neurosurgeon. All 24 centres have one or more dedicated radiosurgery platform and all offer postoperative FSRT. Preoperative SRS is offered by 4/24 (16.7%) centres, and 9/24 (37.5%) sometimes recommend single-fraction postoperative SRS. Partial brain irradiation is offered by 8/24 (33.3%) centres and 12/24 (50%) occasionally recommend whole-brain irradiation. Two centres are participating in clinical trials of preoperative SRS. SRS techniques and fractionation varied between centres.
Conclusion
All responding centres currently offer postoperative FSRT after brain metastasectomy. Approximately one third offer single-fraction postoperative SRS and four already perform preoperative SRS. With regard to potential co-investigators, 18 were identified for the PREOP‑2 multicentre trial, which will randomise between preoperative SRS and postoperative FSRT.
Radiotherapy is frequently used in the therapy of lymphoma. Since lymphoma, for example Hodgkin's disease, frequently affect rather young patients, the induction of secondary cancer or other ...long-term adverse effects after irradiation are important issues to deal with. Especially for mediastinal manifestations numerous organs and substructures at risk play a role. The heart, its coronary vessels and cardiac valves, the lungs, the thyroid and, for female patients, the breast tissue are only the most important organs at risk. In this study we investigated if proton-radiotherapy might reduce the dose delivered to the organs at risk and thus minimize the therapy-associated toxicity.
In this work we compared the dose delivered to the heart, its coronary vessels and valves, the lungs, the thyroid gland and the breast tissue by different volumetric photon plans and a proton plan, all calculated for a dose of 28.8 Gy (EURO-NET-PHL-C2). Target Volumes have been defined by F18-FDG PET-positive areas, following a modified involved node approach. Data from ten young female patients with mediastinal lymphoma have been evaluated. Three different modern volumetric IMRT (VMAT) photon plans have been benchmarked against each other and against proton-irradiation concepts. For plan-evaluation conformity- and homogeneity-indices have been calculated as suggested in ICRU 83. The target volume coverage as well as the dose to important organs at risk as the heart with its substructures, the lungs, the breast tissue, the thyroid and the spinal cord were calculated and compared. For statistical evaluation mean doses to organs at risk were evaluated by non- parametric Kruskal-Wallis calculations with pairwise comparisons.
Proton-plans and three different volumetric photon-plans have been calculated. Proton irradiation results in significant lower doses delivered to organ at risk. The median doses and the mean doses could be decreased while PTV coverage is comparable. As well conformity as homogeneity are slightly better for proton plans. For several organs a risk reduction for secondary malignancies has been calculated using literature data as reference. According to the used data derived from literature especially the secondary breast cancer risk, the secondary lung cancer risk and the risk for ischemic cardiac insults can be reduced significantly by using protons for radiotherapy of mediastinal lymphomas.
Irradiation with protons for mediastinal Hodgkin-lymphoma results in significant lower doses for almost all organs at risk and is suitable to reduce long term side effects for pediatric and adolescent patients.
Purpose
Purpose of this study was to investigate overall survival in recurrent glioblastoma treated with either carbon ion reirradiation or photon reirradiation.
Materials and methods
In this ...retrospective study we evaluated 78 consecutive patients with recurrent IDH (Isocitrate dehydrogenase)-wildtype glioblastoma (38 patients carbon ion re-radiotherapy, 40 patients photon re-radiotherapy) treated with either carbon ion reirradiation or stereotactic photon reirradiation. 45 Gy (RBE; 15 fractions) carbon ion reirradiation (CIRT) or 39 Gy (13 fractions) photon reirradiation (FSRT) was administered, respectively. Overall survival was investigated with respect to histological, clinical, and epidemiological features. Kaplan–Meier and multivariate Cox statistics were calculated. A propensity score-matched analysis of the FSRT and CIRT groups using variables from a validated prognosis score was carried out.
Results
The type of reirradiation (CIRT vs. FSRT) significantly influenced overall survival—8.0 months vs. 6.5 months (univariate:
p
= 0.046)—and remained an independent prognostic factor in multivariate analysis (
p
= 0.017). Propensity score-adjusted analysis with CIRT versus FSRT as the dependent variable yielded a significant overall survival advantage for the CIRT group (median OS 8.9 versus 7.2 months,
p
= 0.041, 1‑year survival 29 versus 10%). Adverse events (AE) were evaluated for both subgroups. For the FSRT group no toxicity ≥ grade 4 occurred. For the CIRT subgroup no grade 5 AE occurred, but 1 patient developed a grade 4 radionecrosis. We encountered 4 grade 3 toxicities. One patient developed a zoster at the trunk, 2 progressed in their paresis, and 1 featured progressive dysesthesia.
Conclusion
In conclusion, carbon ion treatment is a safe and feasible treatment option for recurrent glioblastoma. Due to the retrospective nature of the study and two different dose levels for CIRT or FSRT, the improved outcome in CIRT reirradiation might be an effect of higher biological impact from carbon ions or a simple dose-escalation effect. This hypothesis needs prospective testing in larger patient cohorts. A prospective phase III randomized trial is in preparation at our center.
Purpose
The coronavirus pandemic is affecting global health systems, endangering daily patient care. Hemato-oncological patients are particularly vulnerable to infection, requiring decisive ...recommendations on treatment and triage. The aim of this survey amongst experts on radiation therapy (RT) for lymphoma and leukemia is to delineate typical clinical scenarios and to provide counsel for high-quality care.
Methods
A multi-item questionnaire containing multiple-choice and free-text questions was developed in a peer-reviewed process and sent to members of the radiation oncology panels of the German Hodgkin Study Group and the German Lymphoma Alliance. Answers were assessed online and analyzed centrally.
Results
Omission of RT was only considered in a minority of cases if alternative treatment options were available. Hypofractionated regimens and reduced dosages may be used for indolent lymphoma and fractures due to multiple myeloma. Overall, there was a tendency to shorten RT rather than to postpone or omit it. Even in case of critical resource shortage, panelists agreed to start emergency RT for typical indications (intracranial pressure, spinal compression, superior vena cava syndrome) within 24 h. Possible criteria to consider for patient triage are the availability of (systemic) options, the underlying disease dynamic, and the treatment rationale (curative/palliative).
Conclusion
RT for hemato-oncological patients receives high-priority and should be maintained even in later stages of the pandemic. Hypofractionation and shortened treatment schedules are feasible options for well-defined constellations, but have to be discussed in the clinical context.
Scanned ion beam delivery enables the highest degree of target dose conformation attainable in external beam radiotherapy. Nominal pencil beam widths (spot sizes) are recorded during treatment ...planning system commissioning. Due to changes in the beam-line optics, the actual spot sizes may differ from these commissioning values, leading to differences between planned and delivered dose. The purpose of this study was to analyse the dosimetric consequences of spot size variations in particle therapy treatment plans. For 12 patients with skull base tumours and 12 patients with prostate carcinoma, scanned-beam carbon ion and proton treatment plans were prepared and recomputed simulating spot size changes of (1) ±10% to simulate the typical magnitude of fluctuations, (2) ±25% representing the worst-case scenario and (3) ±50% as a part of a risk analysis in case of fault conditions. The primary effect of the spot size variation was a dose deterioration affecting the target edge: loss of target coverage and broadening of the lateral penumbra (increased spot size) or overdosage and contraction of the lateral penumbra (reduced spot size). For changes 25%, the resulting planning target volume mean 95%-isodose line coverage (CI-95%) deterioration was ranging from negligible to moderate. In some cases changes in the dose to adjoining critical structures were observed.
Purpose:
Verifying an algorithm to reconstruct relative initial photon fluence for clinical use. Clinical EPID and CT images were acquired to reconstruct an external photon radiation treatment field. ...The reconstructed initial photon fluence could be used to verify the treatment or calculate the applied dose to the patient.
Methods:
The acquired EPID images were corrected for scatter caused by the patient and the EPID with an iterative reconstruction algorithm. The transmitted photon fluence behind the patient was calculated subsequently. Based on the transmitted fluence the initial photon fluence was calculated using a back-projection algorithm which takes the patient geometry and its energy dependent linear attenuation into account. This attenuation was gained from the acquired cone-beam CT or the planning CT by calculating a water-equivalent radiological thickness for each irradiation direction. To verify the algorithm an inhomogeneous phantom consisting of three inhomogeneities was irradiated by a static 6 MV photon field and compared to a reference flood field image.
Results:
The mean deviation between the reconstructed relative photon fluence for the inhomogeneous phantom and the flood field EPID image was 3% rising up to 7% for off-axis fluence. This was probably caused by the used clinical EPID calibration, which flattens the inhomogeneous fluence profile of the beam.
Conclusion:
In this clinical experiment the algorithm achieved good results in the center of the field while it showed high deviation of the lateral fluence. This could be reduced by optimizing the EPID calibration, considering the off-axis differential energy response. In further progress this and other aspects of the EPID, eg. field size dependency, CT and dose calibration have to be studied to realize a clinical acceptable accuracy of 2%.
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