Publications by authors named "Maja Guberina"

17 Publications

  • Page 1 of 1

PROGNOSTIC VALUE OF POST-INDUCTION CHEMOTHERAPY VOLUMETRIC PET/CT PARAMETERS FOR STAGE IIIA/B NON-SMALL CELL LUNG CANCER PATIENTS RECEIVING DEFINITIVE CHEMORADIOTHERAPY.

J Nucl Med 2021 May 20. Epub 2021 May 20.

1. Department for Radiotherapy, University Hospital Essen, West German Cancer Center, University Duisburg-Essen, Essen, Germany 2. German Cancer Consortium, Partner Site University Hospital Essen, Essen, Germany.

The aim of this follow-up analysis of the ESPATUE phase-3 trial was to explore the prognostic value of post-induction chemotherapy PET metrics in patients with stage III non-small cell lung cancer (NSCLC) who were assigned to receive definitive chemoradiotherapy. All eligible patients stage IIIA (cN2) and stage IIIB of the trial received induction chemotherapy consisting of 3 cycles of cisplatin/paclitaxel and chemoradiotherapy up to 45 Gy/1.5 Gy per fraction twice-a-day, followed by a radiation-boost with 2 Gy once per day with concurrent cisplatin/vinorelbine. The protocol definition prescribed a total dose of 65-71 Gy. F-FDG-PET/CT (PETpre) was performed at study entry and before concurrent chemoradiotherapy (interim-PET; PETpost). Interim PETpost metrics and known prognostic clinical parameters were correlated in uni- and multivariable survival analyses. Leave-one-out cross-validation was used to show internal validity. Ninety-two patients who underwent F-FDG-PET/CT after induction chemotherapy were enrolled. Median MTVpost value was 5.9 ml. Altogether 85 patients completed the whole chemoradiation with the planned total dose of 60-71 Gy. In univariable proportional hazard analysis, each of the parameters MTVpost, SUV(post) and TLGmax(post) was associated with overall survival ( < 0.05). Multivariable survival analysis, including clinical and post-induction PET parameters, found TLGmax(post) (hazard ratio: 1.032 (95%-CI: 1.013-1.052) per 100 ml increase) and total radiation dose (hazard ratio: 0.930 (0.902-0.959) per Gray increase) significantly related with overall survival in the whole group of patients, and also in patients receiving a total dose ≥ 60 Gy. The best leave-one-out cross-validated 2 parameter classifier contained TLGmax(post) and total radiation dose. TLGmax(post) was associated with time to distant metastases ( = 0.0018), and SUV(post) with time to loco-regional relapse ( = 0.039) in multivariable analysis of patients receiving a total dose ≥ 60 Gy. Post-induction chemotherapy PET parameters demonstrated prognostic significance. Therefore, an interim F-FDG-PET/CT is a promising diagnostic modality for guiding individualized treatment intensification.
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http://dx.doi.org/10.2967/jnumed.120.260646DOI Listing
May 2021

Eye Tumors in Childhood as First Sign of Tumor Predisposition Syndromes: Insights from an Observational Study Conducted in Germany and Austria.

Cancers (Basel) 2021 Apr 14;13(8). Epub 2021 Apr 14.

Institute of Human Genetics, Medical Faculty, University Duisburg-Essen, 45122 Essen, Germany.

Retinoblastoma and other eye tumors in childhood are rare diseases. Many eye tumors are the first signs of a genetic tumor predisposition syndrome and the affected children carry a higher risk of developing other cancers later in life. Clinical and genetic data of all children with eye tumors diagnosed between 2013-2018 in Germany and Austria were collected in a multicenter prospective observational study. In five years, 300 children were recruited into the study: 287 with retinoblastoma, 7 uveal melanoma, 3 ciliary body medulloepithelioma, 2 retinal astrocytoma, 1 meningioma of the optic nerve extending into the eye. Heritable retinoblastoma was diagnosed in 44% of children with retinoblastoma. One child with meningioma of the optic nerve extending into the eye was diagnosed with neurofibromatosis 2. No pathogenic constitutional variant in was detected in a child with medulloepithelioma while two children did not receive genetic analysis. Because of the known association with tumor predisposition syndromes, genetic counseling should be offered to all children with eye tumors. Children with a genetic predisposition to cancer should receive a tailored surveillance including detailed history, physical examinations and, if indicated, imaging to screen for other cancer. Early detection of cancers may reduce mortality.
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http://dx.doi.org/10.3390/cancers13081876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070790PMC
April 2021

Scleral necrosis after brachytherapy for uveal melanoma: Analysis of risk factors.

Clin Exp Ophthalmol 2021 Apr 17. Epub 2021 Apr 17.

Department of Ophthalmology, University Hospital of Essen, Essen, Germany.

Background: Radiation-induced scleral necrosis (RISN) is a rare, but a serious complication of brachytherapy for uveal melanoma. We aimed at analysing the incidence, timing and risk factors associated with development of RISN in a large institutional series.

Methods: All consecutive cases with brachytherapy for uveal melanoma treated by the Departments of Ophthalmology and Radiotherapy at University Hospital Essen between 1999 and 2016 were eligible. Development of RISN during the post-treatment follow-up was recorded. A 1:2 propensity score matched case-control study was performed for the evaluation of the prognostic value of different tumour- and treatment-associated parameters.

Results: RISN was documented in 115 (2.9%) of 3960 patients with uveal melanoma included in the final analysis, and occurred at the mean 30.3 months (range: 1.26-226 months) after brachytherapy. In the whole cohort, younger age (p = 0.042), plaque type (p = 0.001) and ciliary body involvement (p < 0.0001) were independently associated with the RISN occurrence. In the case-control study, multivariable weighted proportional hazard analysis discovered the association of the following additional tumour- and treatment-associated characteristics with RISN: posterior tumour margin anterior to equatorial region (p = 0.0003), extraocular tumour extension (p = <0.0001), scleral contact dose (p = <0.0001), conjunctival dehiscence after therapy (p = 0.0001), disinsertion of the superior rectus muscle (p = 0.001) and the glaucoma medication (p = 0.014).

Conclusions: Our study confirms RISN as a rare complication, which might occur even years later after the brachytherapy for uveal melanoma. Alongside with scleral dose five other tumour and therapy related factors predict the risk of RISN after brachytherapy for uveal melanoma were established.
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http://dx.doi.org/10.1111/ceo.13928DOI Listing
April 2021

Patterns of cervical lymph node metastasis in supraglottic laryngeal cancer and therapeutic implications of surgical staging of the neck.

Eur Arch Otorhinolaryngol 2021 Mar 27. Epub 2021 Mar 27.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.

Purpose: Accurate therapeutic management of the neck is a challenge in patients with supraglottic laryngeal cancer. Nodal metastasis is common at all disease stages, and treatment planning relies on clinical staging of the neck, for both surgical and non-surgical treatment. Here, we compared clinical and surgical staging results in supraglottic carcinoma patients treated with primary surgery to assess the accuracy of pre-therapeutic clinical staging and guide future treatment decisions.

Methods: Retrospective analysis of clinical, pathological, and oncologic outcome data of 70 patients treated with primary surgery and bilateral neck dissection for supraglottic laryngeal cancer. Patients where clinical and pathological neck staging results differed, were identified and analyzed in detail.

Results: On pathologic assessment, patients with early stage (pT1/2) primaries showed cervical lymph node metastases in 55% (n = 17/31) of cases, compared to 67% (n = 26/39) of patients with pT3/4 tumors. In 24% (n = 17/70) of all patients, cN status differed from pN status, resulting in an upstaging in 16% of cases (n = 11/70) and a downstaging in 9% (n = 6/70) of cases. 14% of patients with cN0 status had occult metastases (n = 5/30). As assessed by a retrospective tumor board, in case of a non-surgical treatment approach, the inaccurate clinical staging of the neck would have led to an over- or undertreatment of the neck in 20% (n = 14/70) of all patients.

Conclusion: Our data re-emphasize the high cervical metastasis rates of supraglottic laryngeal cancer across all stages. Inaccurate clinical staging of the neck is common and should be taken into consideration when planning treatment.
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http://dx.doi.org/10.1007/s00405-021-06753-1DOI Listing
March 2021

Impact of EBUS-TBNA in addition to [F]FDG-PET/CT imaging on target volume definition for radiochemotherapy in stage III NSCLC.

Eur J Nucl Med Mol Imaging 2021 Feb 5. Epub 2021 Feb 5.

Department of Radiotherapy, University Hospital Essen, West German Cancer Center, University Duisburg-Essen, Essen, Germany.

PURPOSE/INTRODUCTION: [F]FDG-PET/CT is the standard imaging-technique for radiation treatment (RT) planning in locally advanced non-small cell lung cancer (NSCLC). The purpose of this study was to examine the additional value of endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) to standard PET/CT for mediastinal lymph-node (LN) staging and its impact on clinical target volume (CTV).

Materials And Methods: All consecutive patients with primary stage III NSCLC who underwent [F]FDG-PET/CT and EBUS-TBNA prior to RT were analyzed from 12/2011 to 06/2018. LN-stations were assessed by an expert-radiologist and a nuclear medicine-physician. CTV was evaluated by two independent radiation oncologists. LNs were grouped with increasing distance along the lymphatic chains from primary tumor into echelon-1 (ipsilateral hilum), echelon-2 (LN-station 7 and ipsilateral 4), and echelon-3 (remaining mediastinum and contralateral hilum).

Results: A total of 675 LN-stations of which 291 were positive for tumor-cells, were sampled by EBUS-TBNA in 180 patients. The rate of EBUS-positive LNs was 43% among all sampled LNs. EBUS-positivity in EBUS-probed LNs decreased from 85.8% in echelon-1 LNs to 42.4%/ 9.6% in echelon-2/ -3 LNs, respectively (p < 0.0001, Fisher's exact test). The false discovery rate of PET in comparison with EBUS results rose from 5.3% in echelon-1 to 32.9%/ 69.1% in echelon-2/ -3 LNs, respectively (p < 0.0001, Fisher's exact test). Sensitivity and specificity of FDG-PET/CT ranged from 85 to 99% and 67 to 80% for the different echelons. In 22.2% patients, EBUS-TBNA finding triggered changes of the treated CTV, compared with contouring algorithms based on FDG-avidity as the sole criterion for inclusion. CTV was enlarged in 6.7% patients due to EBUS-positivity in PET-negative LN-station and reduced in 15.5% by exclusion of an EBUS-negative but PET-positive LN-station.

Conclusion: The false discovery rate of [F]FDG-PET/CT increased markedly with distance from the primary tumor. Inclusion of systematic mediastinal LN mapping by EBUS-TBNA in addition to PET/CT has the potential to increase accuracy of target volume definition, particularly in echelon-3 LNs. EBUS-TBNA is recommended as integral part of staging for radiochemotherapy in stage III NSCLC.
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http://dx.doi.org/10.1007/s00259-021-05204-7DOI Listing
February 2021

Dosimetric impact of the positioning variation of tumor treating field electrodes in the PriCoTTF-phase I/II trial.

J Appl Clin Med Phys 2021 Jan 3;22(1):242-250. Epub 2021 Jan 3.

Department of Radiotherapy, West German Cancer Center, University Hospital Essen, University of Duisburg, Essen, Germany.

Purpose: The aim of the present study based on the PriCoTTF-phase I/II trial is the quantification of skin-normal tissue complication probabilities of patients with newly diagnosed glioblastoma multiforme treated with Tumor Treating Field (TTField) electrodes, concurrent radiotherapy, and temozolomide. Furthermore, the skin-sparing effect by the clinically applied strategy of repetitive transducer array fixation around their center position shall be examined.

Material And Methods: Low-dose cone-beam computed tomography (CBCT) scans of all fractions of the first seven patients of the PriCoTTF-phase I/II trial, used for image guidance, were applied for the dosimetric analysis, for precise TTField transducer array positioning and contour delineation. Within this trial, array positioning was varied from fixation-to-fixation period with a standard deviation of 1.1 cm in the direction of the largest variation of positioning and 0.7 cm in the perpendicular direction. Physical TTField electrode composition was examined and a respective Hounsfield Unit attributed to the TTField electrodes. Dose distributions in the planning CT with TTField electrodes in place, as derived from prefraction CBCTs, were calculated and accumulated with the algorithm Acuros XB. Dose-volume histograms were obtained for the first and second 2 mm scalp layer with and without migrating electrodes and compared with those with fixed electrodes in an average position. Skin toxicity was quantified according to Lyman's model. Minimum doses in hot-spots of 0.05 cm and 25 cm ( D , D ) size in the superficial skin layers were analyzed.

Results: Normal tissue complication probabilities (NTCPs) for skin necrosis ranged from 0.005% to 1.474% (median 0.111%) for the different patients without electrodes. NTCP logarithms were significantly dependent on patient (P < 0.0001) and scenario (P < 0.0001) as classification variables. Fixed positioning of TTField arrays increased skin-NTCP by a factor of 5.50 (95%, CI: 3.66-8.27). The variation of array positioning increased skin-NTCP by a factor of only 3.54 (95%, CI: 2.36-5.32) (P < 0.0001, comparison to irradiation without electrodes; P = 0.036, comparison to irradiation with fixed electrodes). NTCP showed a significant rank correlation with D25cm over all patients and scenarios (r  = 0.76; P < 0.0001).

Conclusion: Skin-NTCP calculation uncovers significant interpatient heterogeneity and may be used to stratify patients into high- and low-risk groups of skin toxicity. Array position variation may mitigate about one-third of the increase in surface dose and skin-NTCP by the TTField electrodes.
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http://dx.doi.org/10.1002/acm2.13144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856507PMC
January 2021

Spatial and dosimetric evaluation of residual distortions of prostate and seminal vesicle bed after image-guided definitive and postoperative radiotherapy of prostate cancer with endorectal balloon.

J Appl Clin Med Phys 2021 Jan 30;22(1):226-241. Epub 2020 Dec 30.

Department of Radiotherapy, University Hospital Essen, Essen, Germany.

Purpose: To quantify daily residual deviations from the planned geometry after image-guided prostate radiotherapy with endorectal balloon and to evaluate their effect on the delivered dose distribution.

Methods: Daily kV-CBCT imaging was used for online setup-correction in six degrees of freedom (6-dof) for 24 patients receiving definitive (12 RT patients) or postoperative (12 RT patients) radiotherapy with endorectal balloon (overall 739 CBCTs). Residual deviations were evaluated using several spatial and dosimetric variables, including: (a) posterior Hausdorff distance HD (=maximum distance between planned and daily CTV contour), (b) point P with largest HD over all fractions, (c) equivalent uniform dose using a cell survival model (EUD ) and the generalized EUD concept (gEUD with parameter a = -7 and a = -20). EUD values were determined for planned ( ), daily ( ), and delivered dose distributions ( ) for plans with 6 mm (=clinical plans) and 2 mm CTV-to-PTV margin. Time series analyses of interfractional spatial and dosimetric deviations were conducted.

Results: Large HD values ≥ 12.5 mm (≥15 mm) were observed in 20/739 (5/739) fractions distributed across 7 (3) patients. Points P were predominantly located at the posterior CTV boundary in the seminal vesicle region (16/24 patients, 6/7 patients with HD  ≥ 12.5 mm). Time series analyses revealed a stationary white noise characteristic of HD and relative dose at P . The EUD difference between planned and accumulated dose distributions was < 5.4% for all 6-mm plans. Evaluating 2-mm plans, EUD deteriorated by < 10% (<5%) in 75% (58.5%) of the patients. was well described by the median value of the distribution. PTV margin calculation at P yielded 8.8 mm.

Conclusions: Accumulated dose distributions in prostate radiotherapy with endorectal balloon are forgiving of considerable residual distortions after 6-dof patient setup if they are observed in a minority of fractions and the median value of determined per fraction stays within 95% of prescribed dose. Common PTV margin calculations are overly conservative because after online correction of translational and rotational errors only residual deformations need to be included. These results provide guidelines regarding online navigation, margin optimization, and treatment adaptation strategies.
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http://dx.doi.org/10.1002/acm2.13138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856505PMC
January 2021

Comprehensive Analysis of Tumour Sub-Volumes for Radiomic Risk Modelling in Locally Advanced HNSCC.

Cancers (Basel) 2020 Oct 19;12(10). Epub 2020 Oct 19.

OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, 01307 Dresden, Germany.

Imaging features for radiomic analyses are commonly calculated from the entire gross tumour volume (GTV ). However, tumours are biologically complex and the consideration of different tumour regions in radiomic models may lead to an improved outcome prediction. Therefore, we investigated the prognostic value of radiomic analyses based on different tumour sub-volumes using computed tomography imaging of patients with locally advanced head and neck squamous cell carcinoma. The GTV  was cropped by different margins to define the rim and the corresponding core sub-volumes of the tumour. Subsequently, the best performing tumour rim sub-volume was extended into surrounding tissue with different margins. Radiomic risk models were developed and validated using a retrospective cohort consisting of 291 patients in one of the six Partner Sites of the German Cancer Consortium Radiation Oncology Group treated between 2005 and 2013. The validation concordance index (C-index) averaged over all applied learning algorithms and feature selection methods using the GTVentire achieved a moderate prognostic performance for loco-regional tumour control (C-index: 0.61 ± 0.04 (mean ± std)). The models based on the 5 mm tumour rim and on the 3 mm extended rim sub-volume showed higher median performances (C-index: 0.65 ± 0.02 and 0.64 ± 0.05, respectively), while models based on the corresponding tumour core volumes performed less (C-index: 0.59 ± 0.01). The difference in C-index between the 5 mm tumour rim and the corresponding core volume showed a statistical trend ( = 0.10). After additional prospective validation, the consideration of tumour sub-volumes may be a promising way to improve prognostic radiomic risk models.
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http://dx.doi.org/10.3390/cancers12103047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589463PMC
October 2020

2D and 3D convolutional neural networks for outcome modelling of locally advanced head and neck squamous cell carcinoma.

Sci Rep 2020 09 24;10(1):15625. Epub 2020 Sep 24.

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany.

For treatment individualisation of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with primary radiochemotherapy, we explored the capabilities of different deep learning approaches for predicting loco-regional tumour control (LRC) from treatment-planning computed tomography images. Based on multicentre cohorts for exploration (206 patients) and independent validation (85 patients), multiple deep learning strategies including training of 3D- and 2D-convolutional neural networks (CNN) from scratch, transfer learning and extraction of deep autoencoder features were assessed and compared to a clinical model. Analyses were based on Cox proportional hazards regression and model performances were assessed by the concordance index (C-index) and the model's ability to stratify patients based on predicted hazards of LRC. Among all models, an ensemble of 3D-CNNs achieved the best performance (C-index 0.31) with a significant association to LRC on the independent validation cohort. It performed better than the clinical model including the tumour volume (C-index 0.39). Significant differences in LRC were observed between patient groups at low or high risk of tumour recurrence as predicted by the model ([Formula: see text]). This 3D-CNN ensemble will be further evaluated in a currently ongoing prospective validation study once follow-up is complete.
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http://dx.doi.org/10.1038/s41598-020-70542-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518264PMC
September 2020

Comparison of early tumour-associated versus late deaths in patients with central or >7 cm T4 N0/1 M0 non-small-cell lung-cancer undergoing trimodal treatment: Only few risks left to improve.

Eur J Cancer 2020 10 2;138:156-168. Epub 2020 Sep 2.

Department of Oncology, West German Cancer Center, University Hospital Essen, Germany; Division of Thoracic Oncology, University Medicine Essen - Ruhrlandklinik, Essen, Germany.

Background: The optimal treatment for patients with locally advanced non-small-cell lung-cancer (NSCLC) cT4 cN0/1 cM0 is still under debate. The purpose of this study was to examine the long-term survival of cT4 cN0/1 cM0 NSCLC patients undergoing induction chemotherapy and concurrent radiochemotherapy before surgery.

Methods: All consecutive patients with confirmed NSCLC (cT4 cN0/1 cM0) treated with neoadjuvant chemotherapy, concurrent radiochemotherapy (RT/CTx) (45-46 Gy) and surgical resection between 2000 and 2015 were included. According to the UICC guidelines (8th edition), T4 stage was reanalysed by an expert radiologist. The mediastinal staging was performed by systematic EBUS-TBNA or mediastinoscopy. The primary end-point was overall-survival (OS). The power to detect an increase of early tumour-associated mortality (hazard ratio > 3.5) within the first 5 years after treatment in comparison to late deaths beyond 96 months was >80%.

Results: Overall, 67 patients were treated with concurrent RT/CTx. T4 criteria were fulfilled by all patients, and multiple T4 criteria by 53 patients. Seventy percent of patients had an initial PET/CT staging. The median follow-up period was 134 months. OS rates at 2, 5, 10 and 15 years were 83.6 ± 4.5%, 65.4 ± 5.9%, 53.3 ± 6.3% and 36.6 ± 6.8%, respectively. A total of 44.8% of patients achieved a pathologic complete response. In multivariable analysis, ypT category was the most predictive factor. OS at 5 years for ypT0 (n = 31) was 80.5%, and ypT1 (n = 11) was 62.5%. Main sites of failure were brain and pulmonary metastases in seven and three patients, respectively. The intercurrent annual death rate was estimated from the survival curve beyond 96 months and was found to be 4.75% (95% CI 2.40-9.27%). No significant increased mortality was observed during the first 5 years (annual death rate: 8.31% [95% CI 5.60-12.24%], hazard-ratio = 1.72 [95% CI 0.81-3.65]).

Conclusions: The effectiveness of this trimodality schedule is high in patients with cT4 cN0/1 cM0 NSCLC with excellent local control rates. Considering the annual death rate beyond 8 years of survival as an intercurrent death rate due to comorbidity, this treatment schedule reduces annual mortality to background even in the first 5 years after therapy.
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http://dx.doi.org/10.1016/j.ejca.2020.07.025DOI Listing
October 2020

Estimation of radiation exposure of children undergoing superselective intra-arterial chemotherapy for retinoblastoma treatment: assessment of local diagnostic reference levels as a function of age, sex, and interventional success.

Neuroradiology 2021 Mar 29;63(3):391-398. Epub 2020 Aug 29.

Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.

Purpose: This study aims to determine local diagnostic reference levels (LDRLs) of intra-arterial chemotherapy (IAC) procedures of pediatric patients with retinoblastoma (RB) to provide data for establishing diagnostic reference levels (DRLs) in pediatric interventional radiology (IR).

Methods: In a retrospective study design, LDRLs and achievable dose (AD) were assessed for children undergoing superselective IAC for RB treatment. All procedures were performed at the flat-panel angiography systems (I) ArtisQ biplane (Siemens Healthineers) and (II) Allura Xper (Philips Healthcare). Patients were differentiated according to age (A1: 1-3 months; A2: 4-12 months; A3: 13-72 months; A4: 73 months-10 years; A5: > 10 years), sex, conducted or not-conducted chemotherapy.

Results: 248 neurointerventional procedures of 130 pediatric patients (median age 14.5 months, range 5-127 months) with RB (68 unilateral, 62 bilateral) could be included between January 2010 and March 2020. The following diagnostic reference values, AD, and mean values could be determined: (A2) DRL 3.9 Gy cm, AD 2.9 Gy cm, mean 3.5 Gy cm; (A3) DRL 7.0 Gy cm, AD 4.3 Gy cm, mean 6.0 Gy cm; (A4) DRL 14.5 Gy cm, AD 10.7 Gy cm, mean 10.8 Gy cm; (A5) AD 8.8 Gy cm, mean 8.8 Gy cm. Kruskal-Wallis-test confirmed a significant dose difference between the examined age groups (A2-A5) (p < 0.001). There was no statistical difference considering sex (p = 0.076) and conducted or not-conducted chemotherapy (p = 0.627). A successful procedure was achieved in 207/248 cases.

Conclusion: We report on radiation exposure during superselective IAC of a pediatric cohort at the German Retinoblastoma Referral Centre. Although an IAC formally represents a therapeutic procedure, our results confirm that radiation exposure lies within the exposure of a diagnostic interventional procedure. DRLs for superselective IAC are substantially lower compared with DRLs of more complex endovascular interventions.
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http://dx.doi.org/10.1007/s00234-020-02540-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880957PMC
March 2021

ERCC2 gene single-nucleotide polymorphism as a prognostic factor for locally advanced head and neck carcinomas after definitive cisplatin-based radiochemotherapy.

Pharmacogenomics J 2021 02 16;21(1):37-46. Epub 2020 Jun 16.

Department of Radiotherapy, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Identifying patients with locally advanced head and neck carcinoma on high risk of recurrence after definitive concurrent radiochemotherapy is of key importance for the selection for consolidation therapy and for individualized treatment intensification. In this multicenter study we analyzed recurrence-associated single-nucleotide polymorphisms (SNPs) in DNA repair genes in tumor DNA from 132 patients with locally advanced head and neck carcinoma (LadHnSCC). Patients were treated with definitive radiotherapy and simultaneous cisplatin-based chemotherapy at six partner sites of the German Cancer Consortium (DKTK) Radiation Oncology Group from 2005 to 2011. For validation, a group of 20 patients was available. Score selection method using proportional hazard analysis and leave-one-out cross-validation were performed to identify markers associated with outcome. The SNPs rs1799793 and rs13181 were associated with survival and the same SNPs and in addition rs17655 with freedom from loco-regional relapse (ffLRR) in the trainings datasets from all patients. The homozygote major rs1799793 genotype at the ERCC2 gene was associated with better (Hazard ratio (HR): 0.418 (0.234-0.744), p = 0.003) and the homozygote minor rs13181 genotype at ERCC2 with worse survival (HR: 2.074, 95% CI (1.177-3.658), p = 0.017) in comparison to the other genotypes. At the ffLRR endpoint, rs1799793 and rs13181 had comparable prognostic value. The rs1799793 and rs13181 genotypes passed the leave-one-out cross-validation procedure and associated with survival and ffLRR in patients with LadHnSCC treated with definitive radiochemotherapy. While findings were confirmed in a small validation dataset, further validation is underway within a prospective biomarker study of the DKTK.
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http://dx.doi.org/10.1038/s41397-020-0174-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840506PMC
February 2021

Pretreatment metabolic tumour volume in stage IIIA/B non-small-cell lung cancer uncovers differences in effectiveness of definitive radiochemotherapy schedules: analysis of the ESPATUE randomized phase 3 trial.

Eur J Nucl Med Mol Imaging 2019 Jul 1;46(7):1439-1447. Epub 2019 Feb 1.

Department of Radiation Oncology, West German Cancer Center, University of Duisburg-Essen Medical School, Hufelandstr. 55, 45122, Essen, Germany.

Purpose: According to the ACRIN 6668/RTOG 0235 trial, pretreatment metabolic tumour volume (MTV) as detected by F-fluorodeoxyglucose PET/CT is a prognostic factor in patients with stage III non-small-cell lung cancer (NSCLC) after definitive radiochemotherapy (RCT). To validate the prognostic value of MTV in patients with stage III NSCLC after RCT, we analysed mature survival data from the German phase III trial ESPATUE.

Methods: This analysis included patients who were staged by PET/CT and who were enrolled in the ESPATUE trial, a randomized study comparing definitive RCT (arm A) with surgery (arm B) after induction chemotherapy and RCT in patients with resectable stage IIIA/IIIB NSCLC. Patients refusing surgery and those with nonresectable disease were scheduled to receive definitive RCT. MTV was measured using a fixed threshold-based approach and a model-based iterative volume thresholding approach. Data were analysed using proportional hazards models and Kaplan-Meier survival functions.

Results: MTV as a continuous variable did not reveal differences in survival between the 117 patients scheduled to receive definitive RCT and all 169 enrolled patients who underwent pretreatment PET/CT (p > 0.5). Five-year survival rates were 33% (95% CI 17-49%) in patients scheduled for definitive RCT with a high MTV (>95.4 ml) and 32% (95% CI: 22-42%) in those with a low MTV. The hazard ratio for survival was 0.997 (95% CI 0.973-1.022) per 10-ml increase in MTV and the slope was significantly shallower than that in the ACRIN 6668/RTOG 0235 trial (random effects model, p = 0.002). There were no differences in MTV size distributions between the ACRIN and ESPATUE trials (p = 0.97).

Conclusion: Patients with stage III NSCLC and a large MTV in whom definitive RCT had a particularly good survival in the ESPATUE trial. Treatment individualization according to MTV is not supported by this study. The ESPATUE and ACRIN trials differed by the use of cisplatin-containing induction chemotherapy and an intensified radiotherapy regimen that were particularly effective in patients with large MTV disease.
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http://dx.doi.org/10.1007/s00259-019-4270-xDOI Listing
July 2019

Re-irradiation of recurrent gliomas: pooled analysis and validation of an established prognostic score-report of the Radiation Oncology Group (ROG) of the German Cancer Consortium (DKTK).

Cancer Med 2018 05 23;7(5):1742-1749. Epub 2018 Mar 23.

Department of Radiation Oncology, Technical University Munich (TUM), Munich, Germany.

The heterogeneity of high-grade glioma recurrences remains an ongoing challenge for the interdisciplinary neurooncology team. Response to re-irradiation (re-RT) is heterogeneous, and survival data depend on prognostic factors such as tumor volume, primary histology, age, the possibility of reresection, or time between primary diagnosis and initial RT and re-RT. In the present pooled analysis, we gathered data from radiooncology centers of the DKTK Consortium and used it to validate the established prognostic score by Combs et al. and its modification by Kessel et al. Data consisted of a large independent, multicenter cohort of 565 high-grade glioma patients treated with re-RT from 1997 to 2016 and a median dose of 36 Gy. Primary RT was between 1986 and 2015 with a median dose of 60 Gy. Median age was 54 years; median follow-up was 7.1 months. Median OS after re-RT was 7.5, 9.5, and 13.8 months for WHO IV, III, and I/II gliomas, respectively. All six prognostic factors were tested for their significance on OS. Aside from the time from primary RT to re-RT (P = 0.074) and the reresection status (P = 0.101), all factors (primary histology, age, KPS, and tumor volume) were significant. Both the original and new score showed a highly significant influence on survival with P < 0.001. Both prognostic scores successfully predict survival after re-RT and can easily be applied in the routine clinical workflow. Now, further prognostic features need to be found to even improve treatment decisions regarding neurooncological interventions for recurrent glioma patients.
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http://dx.doi.org/10.1002/cam4.1425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943421PMC
May 2018

Independent validation of a new reirradiation risk score (RRRS) for glioma patients predicting post-recurrence survival: A multicenter DKTK/ROG analysis.

Radiother Oncol 2018 04 9;127(1):121-127. Epub 2018 Feb 9.

German Cancer Consortium (DKTK), partner sites Munich, Heidelberg, Berlin, Frankfurt, Tübingen, Freiburg, Dresden, Essen; and German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Radiation Oncology, Heidelberg Ion Therapy Center (HIT), Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Research in Oncology (NCRO), University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Germany.

Background And Purpose: Reirradiation (reRT) is a valid option with considerable efficacy in patients with recurrent high-grade glioma, but it is still not known which patients might be optimal candidates for a second course of irradiation. This study validated a newly developed prognostic score independently in an external patient cohort.

Material And Methods: The reRT risk score (RRRS) is based on a linear combination of initial histology, clinical performance status, and age derived from a multivariable model of 353 patients. This score can predict post-recurrence survival (PRS) after reRT. The validation dataset consisted of 212 patients.

Results: The RRRS differentiates three prognostic groups. Discrimination and calibration were maintained in the validation group. Median PRS times in the development cohort for the good/intermediate/poor risk categories were 14.2, 9.1, and 5.3 months, respectively. The respective groups within the validation cohort displayed median PRS times of 13.8, 8.8, and 3.8 months, respectively. Uno's C for development data was 0.64 (CI: 0.60-0.69) and for validation data 0.63 (CI: 0.58-0.68).

Conclusions: The RRRS has been successfully validated in an independent patient cohort. This linear combination of three easily determined clinicopathological factors allows for a reliable classification of patients and may be used as stratification factor for future trials.
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http://dx.doi.org/10.1016/j.radonc.2018.01.011DOI Listing
April 2018

Standardized Uptake Decrease on [18F]-Fluorodeoxyglucose Positron Emission Tomography After Neoadjuvant Chemotherapy Is a Prognostic Classifier for Long-Term Outcome After Multimodality Treatment: Secondary Analysis of a Randomized Trial for Resectable Stage IIIA/B Non-Small-Cell Lung Cancer.

J Clin Oncol 2016 07 31;34(21):2526-33. Epub 2016 May 31.

Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.

Purpose: A confirmatory analysis was performed to determine the prognostic value of metabolic response during induction chemotherapy followed by bimodality/trimodality treatment of patients with operable locally advanced non-small-cell lung cancer.

Patients And Methods: Patients with potentially operable stage IIIA(N2) or selected stage IIIB non-small-cell lung cancer received three cycles of cisplatin/paclitaxel (induction chemotherapy) followed by neoadjuvant radiochemotherapy (RCT) to 45 Gy (1.5 Gy twice per day concurrent cisplatin/vinorelbine) within the ESPATUE (Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA[N2] and Selected IIIB Non-Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy) trial. Positron emission tomography scans were recommended before (t0) and after (t2) induction chemotherapy. Patients who were eligible for surgery after neoadjuvant RCT were randomly assigned to definitive RCT or surgery. The prognostic value of percentage of maximum standardized uptake value (%SUVmax) remaining in the primary tumor after induction chemotherapy-%SUVremaining = SUVmax(t2)/SUVmax(t0)-was assessed by proportional hazard analysis and receiver operating characteristic analysis.

Results: Overall, 161 patients were randomly assigned (155 from the Essen and Tübingen centers), and 124 of these received positron emission tomography scans at t0 and t2. %SUVremaining as a continuous variable was prognostic for the three end points of overall survival, progression-free survival, and freedom from extracerebral progression in univariable and multivariable analysis (P < .016). The respective hazard ratios per 50% increase in %SUVremaining from multivariable analysis were 2.3 (95% CI, 1.5 to 3.4; P < .001), 1.8 (95% CI, 1.3 to 2.5; P < .001), and 1.8 (95% CI, 1.2 to 2.7; P = .006) for the three end points. %SUVremaining dichotomized at a cut point of maximum sum of sensitivity and specificity from receiver operating characteristic analysis at 36 months was also prognostic. Exploratory analysis revealed that %SUVremaining was likewise prognostic for overall survival in both treatment arms and was more closely associated with extracerebral distant metastases (P = .016) than with isolated locoregional relapses (P = .97).

Conclusion: %SUVremaining is a predictor for survival and other end points after multimodality treatment and can serve as a parameter for treatment stratification after induction chemotherapy or for evaluation of adjuvant new systemic treatment options for high-risk patients.
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http://dx.doi.org/10.1200/JCO.2015.65.5167DOI Listing
July 2016