Browsing by Author "Adeberg, Sebastian"

Stereotactic radiosurgery (SRS) is an emerging treatment for patients with multiple brain metastases (BM). The present work compares the SRS of multiple brain metastases with whole-brain radiotherapy (WBRT).

(1) Background: The authors present the first results of active raster-scanned carbon ion radiotherapy (CIRT) for radioresistant laryngeal malignancies regarding efficacy and toxicity. (2) Methods: 15 patients with laryngeal adenoid cystic carcinoma (ACC; n = 8; 53.3%) or chondrosarcoma (CS; n = 7; 46.7%) who underwent radiotherapy with carbon ions (C12) at the Heidelberg Ion Beam Therapy Center (HIT) between 2013 and 2018 were identified retrospectively and analyzed for local control (LC), overall survival (OS), and distant progression-free survival using the Kaplan⁻Meier method. CIRT was applied either alone (n = 7, 46.7%) or in combination with intensity modulated radiotherapy (IMRT) (n = 8, 53.3%). The toxicity was assessed according to the Common Toxicity Terminology Criteria for Adverse Events (CTCAE) v4.03. (3). Results: the median follow-up was 24 months (range 5⁻61 months). Overall, the therapy was tolerated very well. No grade >3 acute and chronic toxicity could be identified. The most reported acute grade 3 side effects were acute dysphagia (n = 2; 13%) and acute odynophagia (n = 3; 20%), making supportive nutrition via gastric tube (n = 2; 13.3%) and via high caloric drinks (n = 1; 6.7%) necessary due to swallowing problems (n = 4; 27%). Overall, chronic grade 3 toxicity in the form of chronic hoarseness occurred in 7% of the patients (n = 1; 7%). At the last follow-up, all the patients were alive. No local or locoregional recurrence could be identified. Only one patient with laryngeal ACC developed lung metastases three years after the first diagnosis. (4) Conclusions: the accelerated hypofractionated active raster-scanned carbon ion radiotherapy for radioresistant laryngeal malignancies is feasible in practice with excellent local control rates and moderate acute and late toxicity. Further follow-ups are necessary to evaluate the long-term clinical outcome.

Due to its rarity, there are no randomized trials investigating the outcome of adjuvant radiotherapy in MBC. This study reports on patient and tumor characteristics of 41 consecutive MBC patients treated between 1990 and 2018 and on clinical outcomes after surgical resection of tumors and adjuvant radiotherapy of the chest wall or breast. Local control (LC), locoregional control (LRC), overall survival (OS), disease-free survival (DFS), and toxicity were evaluated. After a median follow-up of 80 months (95% CI: 14.6-213.8 months) there was only one recurrence, in a patient's locoregional lymph nodes 17 months after start of radiotherapy, resulting in an LC rate of 100% at 5 years and a 5-year LRC rate of 97.4% (standard deviation (SD): 0.025). Five-year DFS and OS rates were 64.6% (SD: 0.085) and 57.2% (SD: 0.082), respectively. Adjuvant radiotherapy was tolerated well without high-grade (CTCAE grade > II) adverse events. After tumor resection and adjuvant radiotherapy, LC and LRC rates in MBC patients are excellent and comparable to results found for female breast cancer (FBC) patients. However, as patients are often diagnosed with locally advanced, higher-risk tumors, distant recurrences remain the major failure pattern.

(1) Background: Esthesioneuroblastoma (ENB) is a rare tumor entity originating from the olfactory neuroepithelium. There is a scarcity of data about different treatment strategies. Intensity modulated radiotherapy (IMRT) and carbon ion radiotherapy (CIRT) are advanced radiation techniques that might improve local tumor control. (2) Methods: This retrospective analysis contained 17 patients with ENB (Kadish stage ≥ C: 88%; n = 15). Four patients had already undergone previous radiotherapy (RT). The treatment consisted of either IMRT (n = 5), CIRT (n = 4) or a combination of both techniques (n = 8). Median follow-up was 29 months. (3) Results: In patients that had not been irradiated before (n = 13), calculated overall survival (OS) and progression free survival (PFS) rates after 48 months were 100% and 81% respectively (Kaplan-Meier estimates). Two of four patients that underwent reirradiation died after RT, presumably due to tumor progression. Besides common toxicities, five patients (30%) showed mostly asymptomatic radiation-induced brain changes, most likely due to a disturbance of the blood-brain barrier. (4) Conclusions: Our results demonstrate that IMRT, CIRT, a combined approach of IMRT and CIRT as well as reirradiation with CIRT seem to be feasible and effective treatment methods in ENB.

In cases of simultaneous chemoradiotherapy (CRT), early recognition of toxic side effects is important, as drug discontinuation may prevent further injury. It appears favorable to undertake further steps to investigate whether patient subgroups behave differently depending on their toxicity profile.

There is no standard approach to differentiate cerebral radiation necrosis from tumor recurrence and no standard treatment pathway for symptomatic lesions. In addition, reports on histology-proven radiation necrosis and the underlying pathophysiology are scarce and highly relevant.

Background: In this analysis, we aimed to present the first results of carbon ion radiotherapy (CIRT), which is known for its conformal dose distribution and increased biological effectiveness in the treatment of high-risk nasopharyngeal carcinoma (NPC). Methods: We retrospectively analyzed twenty-six consecutive patients who had been treated at our center with CIRT for high-risk NPC between 2009 and 2018. Carbon ion (C12) boost was applied in a bimodal setting combined with intensity-modulated radiotherapy (IMRT) base plan. The median cumulative total dose was 74 Gy (RBE), and patients with inoperable (n = 17, 65%) or incompletely resected (n = 7, 27%) tumors were included in the analysis. Overall, 81% received concomitant chemotherapy (n = 21). Results: The median follow-up time was 40 months (range 10⁻97 months) for all patients. At the last follow-up, 92% of the patients were still alive. We could identify excellent tumor response with complete tumor remission (CR) in 60% (n = 15/25), partial tumor remission (PR) in 20% (n = 5/25), and stable disease (SD) in 12% (n = 3/25) of the patients according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Despite unfavorable tumor characteristics, only one patient showed a locally in-field recurrence after 56 months (4%) and another patient a locoregional recurrence in the unilateral cervical lymph nodes after 21 months (4%). The 2-year local control (LC), distant progression-free survival (DPFS), and overall survival (OS) were 95%, 93%, and 100% and the estimated 5-year LC, DPFS, and OS were 90%, 86%, and 86%, respectively. Overall, treatment was tolerated well with 20% acute and 16% chronic grade 3 side effects. No toxicity greater than grade 3 occurred. Conclusion: Bimodal radiotherapy including IMRT and active raster-scanning CIRT for high-risk nasopharyngeal cancer is a safe treatment method resulting in moderate toxicity and excellent local control. A larger patient number and longer follow-up time would be necessary to strengthen the current findings.

Treatment of patients with pelvic adenoid cystic carcinoma (ACC) remains a challenge owing to the rarity of the disease, the lack of data, and the relative radioresistance of these tumors.

This study aimed to assess the feasibility of carbon ion reirradiation (CIR) for recurrent head and neck cancer (HNC).

We evaluated treatment outcomes of CIRT in an active raster-scanning technique alone or in combination with IMRT for lacrimal gland tumors.

To prospectively investigate chemical exchange saturation transfer (CEST) MRI in glioblastoma patients as predictor of early tumor progression after first-line treatment.

Purpose: The aim of the current evaluation was to assess central nervous system necrosis (CNSN) after re-irradiation with carbon ions (CR) in two-hundred seventeen (n = 217) patients with recurrent head-and-neck cancer (HNC). Methods: Thirty-six (n = 36) patients with CNSN were assessed retrospectively regarding clinical symptoms and radiographic response. Results: CNSN were classified according to clinical management in line with the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. At a median follow-up of 25.3 months (range 3.3⁻79.9 months), the median time interval until occurrence of grade I, II, and III CNSN was 9.2 months (range 2.8⁻75.0 months), 10.2 months (range 2.3⁻60.5 months), and 16.6 months (range 8.7⁻32.5 months), respectively. In one patient with an adenocarcinoma infiltrating the frontal lobe, an extensive CNSN grade IV was suspected but the patient declined surgical intervention. Radiographic response after treatment of CNSN grade I, II, and III, defined as ≥25% reduction of the T2 alteration on Magnetic Resonance Imaging (MRI), was observed in 4 (16.0%), 5 (29.4%), and 4 (80%) patients, respectively. Conclusion: CNSN occurred late and frequent after re-irradiation with carbon ions in patients with HNC infiltrating the base of skull. The clinical outcome with adequate treatment was encouraging but correct diagnosis of CNSN remains challenging.

The PACIFC trial demonstrated a significant benefit of durvalumab consolidation immunotherapy (CIT) after definitive platinum-based chemoradiotherapy (P-CRT) for survival in stage III non-small cell lung cancer (NSCLC). It is unknown how many patients are eligible in clinical practice to receive CIT according to PACIFIC criteria compared to real administration rates and what influencing factors are.

To assess radiotherapy (RT) outcomes in patients with gingival carcinoma and growth up to or involvement of the lower jaw bone.

Background and Purpose. The reasons for the inevitable glioblastoma recurrence are yet understood. However, recent data suggest that tumor cancer stem cells (CSCs) in the stem-cell niches, with self-renewing capacities, might be responsible for tumor initiation, propagation, and recurrence. We aimed to analyze the effect of higher radiation doses to the stem-cell niches on progression-free survival (PFS) and overall survival (OS) in glioblastoma patients. Materials and Methods. Sixty-five patients with primary glioblastoma treated with radiation therapy were included in this retrospective analysis. The SVZ and DG were segmented on treatment planning magnetic resonance imaging, and the dose distributions to the structures were calculated. The relationship of dosimetry data and survival was evaluated using the Cox regression analysis. Results. Conventionally fractionated patients (n = 54) who received higher doses (D mean ≥ 40 Gy) to the IL SVZ showed improved PFS (8.5 versus 5.2 months; p = 0.013). Furthermore, higher doses (D mean ≥ 30 Gy) to the CL SVZ were associated with increased PFS (10.1 versus 6.9 months; p = 0.025). Conclusion. Moderate higher IL SVZ doses (≥40 Gy) and CL SVZ doses (≥30 Gy) are associated with improved PFS. Higher doses to the DG, the second stem-cell niche, did not influence the survival. Targeting the potential cancer stem cells in the SVZ might be a promising treatment approach for glioblastoma and should be addressed in a prospective randomized trial.

Background: Carbon ion re-irradiation (CIR) was evaluated to investigate treatment planning and the consequences of individual risk-benefit evaluations concerning dose-limiting organs at risk (OAR). Methods: A total of 115 consecutive patients with recurrent head and neck cancer (HNC) were analyzed after initial radiotherapy and CIR at the same anatomical site. Toxicities were evaluated in line with the Common Terminology Criteria for Adverse Events 4.03. Results: The median maximum cumulative equivalent doses applied in fractions of 2 Gy (EQD2) to the brainstem, optic chiasm, ipsilateral optic nerve, and spinal cord were 56.8 Gy (range 0.94-103.9), 51.4 Gy (range 0-120.3 Gy), 63.6 Gy (range 0-146.1 Gy), and 28.8 Gy (range 0.2-87.7 Gy). The median follow up after CIR was 24.0 months (range 2.5-72.0 months). The cumulative rates of acute and late severe (≥grade III) side effects after CIR were 1.8% and 14.3%. Conclusion: In recurrent HNC, an individual risk-benefit tradeoff is frequently inevitable due to unfavorable location of tumors in close proximity to vital OAR. There are uncertainties about the dose tolerance of OAR after CIR, which warrant increased awareness about the potential treatment toxicity and further studies on heavy ion re-irradiation.