Daniel M Aebersold | Bern University (original) (raw)

Papers by Daniel M Aebersold

Radiotherapy and Oncology, 2017

High-throughput molecular profiling approaches have emerged as precious research tools in the fie... more High-throughput molecular profiling approaches have emerged as precious research tools in the field of head and neck translational oncology. Such approaches have identified and/or confirmed the role of several genes or pathways in the acquisition/maintenance of an invasive phenotype and the execution of cellular programs related to cell invasion. Recently published new-generation sequencing studies in head and neck squamous cell carcinoma (HNSCC) have unveiled prominent roles in carcinogenesis and cell invasion of mutations involving NOTCH1 and PI3K-patwhay components. Gene-expression profiling studies combined with systems biology approaches have allowed identifying and gaining further mechanistic understanding into pathways commonly enriched in invasive HNSCC. These pathways include antigen-presenting and leucocyte adhesion molecules, as well as genes involved in cell-extracellular matrix interactions. Here we review the major insights into invasiveness in head and neck cancer provided by high-throughput molecular profiling approaches.

Purpose: Pterygium is a common lesion affecting the population in countries with high levels of u... more Purpose: Pterygium is a common lesion affecting the population in countries with high levels of ultraviolet exposure. The final shape of a pterygium is the result of a growth pattern, which remains poorly understood. This manuscript provides a mathematical analysis as a tool to determine the shape of human pterygia. Materials and methods: Eighteen patients, all affected by nasal unilateral pterygia, were randomly selected from our patient database independently of sex, origin, or race. We included all primary or recurrent pterygia with signs of proliferation, dry eye, and induction of astigmatism. Pseudopterygia were excluded from this study. Pterygia were outlined and analyzed mathematically using a Cartesian coordinate system with two axes (X, Y) and five accurate landmarks of the pterygium. Results: In 13 patients (72%), the shape of the pterygia was hyperbolic and in five patients (28%), the shape was rather elliptical. Conclusion: This analysis gives a highly accurate mathematical description of the shape of human pterygia. This might help to better assess the clinical results and outcome of the great variety of therapeutic approaches concerning these lesions.

Background To analyze the impact of weight loss before and during chemoradiation on survival outc... more Background To analyze the impact of weight loss before and during chemoradiation on survival outcomes in patients with locally advanced head and neck cancer. Methods From 07/1994-07/2000 a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to either hyperfractionated radiation therapy alone or the same radiation therapy combined with two cycles of concomitant cisplatin. The primary endpoint was time to any treatment failure (TTF); secondary endpoints were locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Patient weight was measured 6 months before treatment, at treatment start and treatment end. Results The proportion of patients with >5% weight loss was 32% before, and 51% during treatment, and the proportion of patients with >10% weight loss was 12% before, and 17% during treatment. After a median follow-up of 9.5 years (range, 0.1 – 15.4 years) weight loss before treatment w...

Swiss Medical Forum ‒ Schweizerisches Medizin-Forum, 2009

Tailored total lymphoid irradiation in heart transplant patients: 10-years experience of one center

Physics in Medicine & Biology, 2021

Purpose. To develop a novel treatment planning process (TPP) with simultaneous optimization of mo... more Purpose. To develop a novel treatment planning process (TPP) with simultaneous optimization of modulated photon, electron and proton beams for improved treatment plan quality in radiotherapy. Methods. A framework for fluence map optimization of Monte Carlo (MC) calculated beamlet dose distributions is developed to generate treatment plans consisting of photon, electron and spot scanning proton fields. Initially, in-house intensity modulated proton therapy (IMPT) plans are compared to proton plans created by a commercial treatment planning system (TPS). A triple beam radiotherapy (TriB-RT) plan is generated for an exemplary academic case and the dose contributions of the three particle types are investigated. To investigate the dosimetric potential, a TriB-RT plan is compared to an in-house IMPT plan for two clinically motivated cases. Benefits of TriB-RT for a fixed proton beam line with a single proton field are investigated. Results. In-house optimized IMPT are of at least equal o...

Radiation Oncology, 2020

Background Current studies about percutaneous endoscopic gastrostomy (PEG) tube placement report ... more Background Current studies about percutaneous endoscopic gastrostomy (PEG) tube placement report equivalent patient outcomes with prophylactic PEG tubes (pPEGs) versus common nutritional support. Unreported was if omitting a pPEG is associated with an increased risk of complications leading to a treatment-related unplanned hospitalization (TRUH). Methods TRUHs were retrospectively analyzed in patients with advanced head and neck squamous cell carcinoma (n = 310) undergoing (chemo)radiotherapy with (pPEG) or without PEG (nPEG). Results In 88 patients (28%), TRUH was reported. One of the leading causes of TRUH in nPEG patients was inadequate oral intake (n = 16, 13%), and in pPEG patients, complications after PEG tube insertion (n = 12, 10%). Risk factors for TRUH were poor performance status, tobacco use, and surgical procedures. Conclusions Omitting pPEG tube placement without increasing the risk of an unplanned hospitalization due to dysphagia, dehydration or malnutrition, is an op...

Neuro-Oncology, 2018

NEURO-ONCOLOGY • JUNE 2018 rospectively reviewed for patients (diagnosed with an iGCT (January 20... more NEURO-ONCOLOGY • JUNE 2018 rospectively reviewed for patients (diagnosed with an iGCT (January 2002-December 2011) from 6 centres [4 UK (n=45), 1 German (n=11) and 1 Canadian (n=31)]. Fisher's exact test used for comparisons (p<0.05 significant). RESULTS: Study cohort included 87 (58M:29F) patients [59 germinoma, and 28 non-germinoma] with tumours located in pineal (34), suprasellar (25), bifocal (24) and other area (4), of which 16 were metastatic. Median age at diagnosis was 11.5 years (0.6-22.6y). The time to diagnosis from first symptom (SI) ranged from 0-69 months (median 3m, mean 8.5m). A prolonged SI (> 6months) was observed in one third of patients (n=28) and significantly associated with metastatic disease (11/28 vs. 5/59, p=0.002) at diagnosis. In patients with a prolonged SI, endocrine symptoms, particularly diabetes insipidus (DI), were common (75%) but raised intracranial pressure (RICP) was infrequent (14%). In contrast, those with a SI <6 months frequently presented with RICP (84%, p<0.0001). CONCLUSIONS: One third of patients with an iGCT have symptoms >6 months prior to diagnosis. Delayed diagnosis is associated with metastatic disease. Early symptom recognition, particularly related to hormonal disturbances without RICP, may improve timely diagnosis, reduce frequency of metastatic disease and thus reduce the burden of treatment and late-effects.

Forum Médical Suisse ‒ Swiss Medical Forum, 2009

Swiss Medical Forum ‒ Schweizerisches Medizin-Forum, 2011

Abbildung 1 Darstellung eines tumorbefallenen parapharyngealen Lymphknotens in der FDG-PETmit ent... more Abbildung 1 Darstellung eines tumorbefallenen parapharyngealen Lymphknotens in der FDG-PETmit entsprechender Berücksichtigung in der Bestrahlungsplanung (Dosisaufsättigung, Bilder rechts).

Reports of Practical Oncology & Radiotherapy, 2019

Stereotactic body radiation therapy is an effective and safe treatment modality for bone metastas... more Stereotactic body radiation therapy is an effective and safe treatment modality for bone metastasis which allows clinicians to accurately target lesions to high doses while minimizing dose to organs at risk. The commercially available CyberKnife ® Xsight TM Spine Tracking System (Accuray, Inc., Sunnyvale, CA) tracks static skeletal structures and eliminates the need for implanted fiducial markers (FMs). However, the Xsight TM Spine Tracking system is not appropriate for bone metastases outside the spine, which are moving due to respiration and ,typically, FMs have to be implanted close to the lesion. These FMs will be used to track the dynamic target. For targets close to the surface, non-invasive fixation of the FMs to the patient's skin could be an option.

Molecular Cancer, 2018

Tumor metabolism is a thrilling discipline that focuses on mechanisms used by cancer cells to ear... more Tumor metabolism is a thrilling discipline that focuses on mechanisms used by cancer cells to earn crucial building blocks and energy to preserve growth and overcome resistance to various treatment modalities. At the same time, therapies directed specifically against aberrant signalling pathways driven by protein tyrosine kinases (TKs) involved in proliferation, metastasis and growth count for several years to promising anti-cancer approaches. In this respect, small molecule inhibitors are the most widely used clinically relevant means for targeted therapy, with a rising number of approvals for TKs inhibitors. In this review, we discuss recent observations related to TKs-associated metabolism and to metabolic feedback that is initialized as cellular response to particular TK-targeted therapies. These observations provide collective evidence that therapeutic responses are primarily linked to such pathways as regulation of lipid and amino acid metabolism, TCA cycle and glycolysis, advocating therefore the development of further effective targeted therapies against a broader spectrum of TKs to treat patients whose tumors display deregulated signalling driven by these proteins.

Clinical and Translational Radiation Oncology, 2019

Background: Whole-ventricular radiotherapy (WV-RT) followed by a boost to the tumor bed (WV-RT/TB... more Background: Whole-ventricular radiotherapy (WV-RT) followed by a boost to the tumor bed (WV-RT/TB) is recommended for intracranial germ cell tumors (IGCT). As the critical brain areas are mainly in the target volume vicinity, it is unclear if protons indeed substantially spare neurofunctional organs at risk (NOAR). Therefore, a dosimetric comparison study of WV-RT/TB was conducted to assess whether proton or photon radiotherapy achieves better NOAR sparing. Methods: Eleven children with GCT received 24 Gy(RBE) WV-RT and a boost up to 40 Gy(RBE) in 25 fractions of 1.6 Gy(RBE) with pencil beam scanning proton therapy (PBS-PT). Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans were generated for these patients. NOAR were delineated and treatment plans were compared for target volume coverage (TVC), homogeneity index (HI), inhomogeneity coefficient (IC) and (N)OAR sparing. Results: TVC was comparable for all three modalities. Compared to IMRT and VMAT, PBS-PT showed statistically significant optimized IC, as well as dose reduction, among others, in mean and integral dose to the: normal brain (-35.2%,-32.7%; À35.2%,-33.0%, respectively), cerebellum (-53.7%,-33.1%;-53.6%,-32.7%) and right temporal lobe (-14.5%, À31.9%; À14.7%, À29.9%). The Willis' circle was better protected with PBS-PT than IMRT (À7.1%; À7.8%). The left hippocampus sparing was higher with IMRT. Compared to VMAT, the dose to the hippocampi, amygdalae and temporal lobes was significantly decreased in the IMRT plans. Conclusions: Dosimetric comparison of WV-RT/TB in IGCT suggests PBS-PT's advantage over photons in conformality and NOAR sparing, whereas IMRT's superiority over VMAT, thus potentially minimizing long-term sequelae.

Radiation Oncology, 2017

The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on... more The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements. Trends were evaluated using the autoregressive integrated moving average model. Two hundred sixteen (0.1%) trials were selected for further analysis. Academic centers (investigator initiated trials) were recorded as primary sponsors in 56.9% of trials, followed by industry 25.9%. Industry was the leading source of monetary support for the selected trials in 44.4%, followed by 25% of trials with primarily academic financial support. The number of newly initiated trials between 2005 and 2015 shows a positive trend, mainly through an increase in phase II trials, whereas phase III trials show a negative trend. The vast majority of trials evaluate forms of different systemic treatments (91.2%). In total, one hundred different molecular entities or biologicals were identified. Of those, 60% were involving drugs specifically designed for central nervous system malignancies. Trials that specifically address radiotherapy, surgery, imaging and other therapeutic or diagnostic methods appear to be rare. Current research in glioblastoma is mainly driven or sponsored by industry, academic medical oncologists and neuro-oncologists, with the majority of trials evaluating forms of systemic therapies. Few trials reach phase III. Imaging, radiation therapy and surgical procedures are underrepresented in current trials portfolios. Optimization in research portfolio for glioblastoma is needed.

International Journal of Radiation Oncology*Biology*Physics, 2016

To investigate whether current or prior smoking history had any impact on prostate cancer outcome... more To investigate whether current or prior smoking history had any impact on prostate cancer outcomes or toxicity in patients receiving dose escalated external beam radiation therapy (EBRT). Materials/Methods: Of the 500 patients treated with EBRT between 2003 and 2011, 444 had smoking histories recorded. Patients were classified as current smokers, former smokers, or never smokers. Toxicity was graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events and was compared between the groups via the Chi Square test. Biochemical failure-free survival (bFFS) and distant metastatic failure-free survival (DMFS) endpoints were compared by Kaplan Meier analysis. Multivariate Cox regression was used to determine whether smoking use had an impact on outcomes and multivariate logistic regression was used to analyze whether smoking use was associated with increased toxicity when accounting for covariables. Results: There were 176 men (39.6%) classified as never smokers, 169 as prior smokers (38.1%), and 99 as current smokers (22.3%). The median follow up was 76 months (range 9-146). The 8 year bFFS was 73.6% for never smokers, 80.2% for prior smokers, and 73.4% for current smokers, P Z 0.38. The 8 year DMFS was 92.8% for never smokers, 96.8% for prior smokers, and 95.3% for current smokers, P Z 0.54. On multivariate analysis neither prior smoking (HR 0.72, 95% CI 0.44-1.18, P Z 0.19), nor current smoking (HR 1.02, 95% CI 0.59-1.77, P Z 0.93) were associated with increased biochemical failure. Similarly, smoking use was not associated with an increased likelihood of distant metastatic disease on multivariate analysis (HR 0.71, 95% CI 0.25-2.00, P Z 0.51 for prior smokers, HR 1.41, 95% CI 0.50-3.96, P Z 0.52 for current smokers). On multivariate regression, prior or current smoking use was not associated with an increased likelihood of late grade 2 genitourinary (OR 1.33, 95% CI 0.69-2.58, P Z 0.39 for prior smokers, OR 1.10, 95% CI 0.46-2.63, P Z 0.84 for current smokers) or gastrointestinal toxicity (OR 1.20, 95% CI 0.74-1.96, P Z 0.46 for prior smokers, OR 0.73, 95% CI 0.38-1.41, P Z 0.35 for current smokers). Conclusion: Current or prior smoking use was not associated with inferior outcomes or increased toxicity in men undergoing dose escalated radiation therapy for prostate cancer.

Radiotherapy and Oncology, 2013

Materials and Methods: Fourteen patients treated atour facility with passively scattered proton b... more Materials and Methods: Fourteen patients treated atour facility with passively scattered proton beams were selected. Aperture areas ranged from ~3 to ~35 cm 2. Aperture sizes < 3 cm 2 were not considered in this study because aperture scattering effects might outweigh effects from patient heterogeneities. Dose distributions predicted by our pencil beam (PB) algorithm were verified against MC dose calculations using TOPAS-a TOol for PArticle Simulation layered on top of GEANT4. Open field dosimetry was corrected based on the clinical guidelines for small fields to consider aperture scattering and dose equilibrium. DVHs were analyzed and differences in the dose to the 50% of the GTV (D50) were assessed on a field-by-field basis. We developed a simple and fast methodology to quantify the tissue inhomogeneity traversed by a single beam using a heterogeneity index (HI). The implementation was based on the dose calculation approach taken by our PB algorithm. Finally, we evaluated the potential correlation between the errors made by our PB algorithm in D50 for each field and the level of tissue heterogeneity traversed by the proton beam given by HI. Results: Discrepancies up to 5.4% were found in D50 ([D50 PB-D50 MC ]/ D50 MC). The discrepancies found for each field exhibited a strong correlation to their associated HI-values (Spearman's ρ = 0.8, p <0.0001); the higher the level of tissue heterogeneities for a particular field, the larger the dosimetric error by the analytical algorithm. With the established correlation a threshold for HI could be set by choosing a tolerance level; requiring an absolute difference for D50 < 2.5% for clinical routines suggests recalculation ofpatient treatments for HI t >> 1.7. Conclusions: The HI as defined in this study appeared to be a good indicator for theaccuracy of proton field delivery in terms of GTV prescription dose coverage. Each HI-value was obtained in less than 3 minutes allowing the implementation of this methodology in the clinical routine. For HI-values exceeding the threshold, either a change in beam direction (if feasible) or a recalculationof the dose with Monte Carlo would be highly recommended. OC-0438 Experimental validation of monte carlo pencil beam scanning model in heterogeneous media for proton therapy.

International Journal of Radiation Oncology*Biology*Physics, 2014

regarding RT utilization was evaluated over this timeframe. Geographic variation in RT usage was ... more regarding RT utilization was evaluated over this timeframe. Geographic variation in RT usage was categorically compared based on northeast, southeast, midwest, southwest, and west (including Hawaii) regions. All P-values were two-sided, with 0.05 being statistically significant. Results: We identified 64,614 and 20,675 pts diagnosed with colon and rectal cancers, respectively. The overall RT utilization rates were 3.3 and 34.7% (colon vs rectal cancer). IMRT represented 4.5% of all RT cases (about equal rates for both malignancies). Older age was related to decreased use of RT. More stage III-IV rectal cancer pts utilized RT compared to stage I-II (45 vs 34%). Majority of patients were either treated with chemotherapy and/or surgery, with no appreciable difference by RT modality (see Table). Compared with the RT utilization in the period of 1997-2002, a 7.8-fold increase of IMRT usage was observed for all colorectal cancer pts in 2003-2007 (0.9 vs 7.2%, P<0.0001), while the rates of chemotherapeutic and surgical intervention remained stable over time. West region had the highest rate of IMRT utilization for both colon and rectal cancers, representing about half of the nation's cases over the survey period. Conclusions: In rectal cancer, there has been an increasing adoption of IMRT; however, geographic variation exists nationally. Given the increased rates of use, appropriate utilization, outcomes, and cost-effectiveness associated with IMRT will receive greater visibility in the future.

European Urology Supplements, 2013