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1.
Strahlenther Onkol ; 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33507331

RESUMO

Moderate hypofractionation is the standard of care for adjuvant whole-breast radiotherapy after breast-conserving surgery for breast cancer. Recently, 10-year results from the FAST and 5­year results from the FAST-Forward trial evaluating adjuvant whole-breast radiotherapy in 5 fractions over 5 weeks or 1 week have been published. This article summarizes recent data for moderate hypofractionation and results from the FAST and FAST-Forward trial on ultra-hypofractionation. While the FAST trial was not powered for comparison of local recurrence rates, FAST-Forward demonstrated non-inferiority for two ultra-hypofractionated regimens in terms of local control. In both trials, the higher-dose experimental arms resulted in elevated rates of late toxicity. For the lower dose experimental arms of 28.5 Gy over 5 weeks and 26 Gy over 1 week, moderate or marked late effects were similar in the majority of documented items compared to the respective standard arms, but significantly worse in some subdomains. The difference between the standard arm and the 26 Gy of the FAST-Forward trial concerning moderate or marked late effects increased with longer follow-up in disadvantage of the experimental arm for most items. For now, moderate hypofractionation with 40-42.5 Gy over 15-16 fractions remains the standard of care for the majority of patients with breast cancer who undergo whole-breast radiotherapy without regional nodal irradiation after breast-conserving surgery.

2.
Anticancer Res ; 41(1): 359-368, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419832

RESUMO

BACKGROUND/AIM: Surgical resection for soft tissue sarcomas (STSs) is the gold standard for a curative oncologic therapy in combination with neoadjuvant or adjuvant radiation therapy (NRT/ART). The aim of this study was to determine prognostic factors influencing the survival of patients with STS undergoing NRT or ART considering various parameters in a retrospective, single-centre analysis over 15 years. PATIENTS AND METHODS: We included 119 patients (male 59) and the median follow-up period was 69 months (4-197). The patients received NRT (n=64) or ART (n=55). We recorded the histopathologic subtype of STS, tumour grade, localization, tumour margins, complications, survival, local recurrence, and metastases. Survival analysis was performed using the Kaplan-Meier method. RESULTS: The overall survival rate was 68.9% at 5 years. The localization (epifascial/subfascial), resection margin and type of radiation therapy (NRT/ART) had no significant impact on survival. Tumour grade, tumour size, local recurrence and metastases were significantly correlated with patient survival (p<0.05). Local recurrence was significantly higher in patients with ART (p=0.044). CONCLUSION: Tumour grade and tumour size were independently associated with disease-specific survival, and patients with local recurrence and metastases had lower survival rates.


Assuntos
Sarcoma/mortalidade , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/cirurgia , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Retratamento , Estudos Retrospectivos , Sarcoma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Resultado do Tratamento
3.
Strahlenther Onkol ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33506347

RESUMO

BACKGROUND: Emerging moderately hypofractionated and ultra-hypofractionated schemes for radiotherapy (RT) of prostate cancer (PC) have resulted in various treatment options. The aim of this survey was to evaluate recent patterns of care of German-speaking radiation oncologists for RT of PC. METHODS: We developed an online survey which we distributed via e­mail to all registered members of the German Society of Radiation Oncology (DEGRO). The survey was completed by 109 participants between March 3 and April 3, 2020. For evaluation of radiation dose, we used the equivalent dose at fractionation of 2 Gy with α/ß = 1.5 Gy, equivalent dose (EQD2 [1.5 Gy]). RESULTS: Median EQD2(1.5 Gy) for definitive RT of the prostate is 77.60 Gy (range: 64.49-84.00) with median single doses (SD) of 2.00 Gy (range: 1.80-3.00), while for postoperative RT of the prostate bed, median EQD2(1.5 Gy) is 66.00 Gy (range: 60.00-74.00) with median SD of 2.00 Gy (range: 1.80-2.00). For definitive RT, the pelvic lymph nodes (LNs) are treated in case of suspect findings in imaging (82.6%) and/or according to risk formulas/tables (78.0%). In the postoperative setting, 78.9% use imaging and 78.0% use the postoperative tumor stage for LN irradiation. In the definitive and postoperative situation, LNs are irradiated with a median EQD2(1.5 Gy) of 47.52 Gy with a range of 42.43-66.00 and 41.76-62.79, respectively. CONCLUSION: German-speaking radiation oncologists' patterns of care for patients with PC are mainly in line with the published data and treatment recommendation guidelines. However, dose prescription is highly heterogenous for RT of the prostate/prostate bed, while the dose to the pelvic LNs is mainly consistent.

4.
Int J Radiat Biol ; : 1-32, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33476246

RESUMO

PURPOSE: In a nuclear or radiological event, an early diagnostic or prognostic tool is needed to distinguish the worried well from low-exposed and those individuals who may later develop life-threatening hematologic acute radiation syndrome (H-ARS). In previous studies, we identified and validated genes in peripheral blood for this purpose. To gain a deeper understanding and to make methodological improvements, we examined the contribution of the peripheral blood´s cell populations on radiation-induced gene expression changes. MATERIALS AND METHODS: EDTA whole blood from six healthy donors was X-irradiated with 0 and 4 Gy, cultured in vitro for 24 h and cell populations of T-lymphocytes (CD3), B-lymphocytes (CD19), NK-cells (CD56) and granulocytes (CD15) were separated using immunomagnetic methods. Whole blood was used as a positive control to ensure the expected radiation-induced gene expression response based on previous examinations. Purity of cell separation and cell counts was validated using immunofluorescence imaging flow cytometry. After RNA isolation, gene expressions of FDXR, DDB2, POU2AF1 and WNT3 were examined in the cell populations and whole blood. RESULTS: The cell populations, on average, contributed to the total RNA amount with a ratio of 11.6 for T-lymphocytes: 1.2 for B-cells: 1.2 for NK-cells: 1.0 for granulocytes. In order to estimate the contribution of gene expression per cell population, the baseline (0 Gy) as well as the radiation-induced fold-change in gene expression relative to unexposed was considered for each gene. After considering all three parameters, the T-lymphocytes (74.8%/80.5%) contributed predominantly to the radiation-induced up-regulation observed for FDXR/DDB2 and the B-lymphocytes (97.1%/83.8%) for down-regulated POU2AF1/WNT3 with a similar effect on whole blood gene expression measurements reflecting a corresponding order of magnitude. CONCLUSIONS: T-lymphocytes and B-lymphocytes contributed predominantly to the radiation-induced up-regulation of FDXR/DDB2 and down-regulation of POU2AF1/WNT3. Further separation of cell populations will not increase the diagnostic sensitivity, but complicate an efficient workflow. Also, this study identifies undesired limitations of widely used whole blood in vitro models, but it still underlines the use of FDXR and DDB2 for biodosimetry purposes and POU2AF1 and WNT3 for effect prediction of acute health effects.

5.
JMIR Mhealth Uhealth ; 9(1): e19727, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33427669

RESUMO

BACKGROUND: eHealth and mobile health (mHealth) are an evolving trend in the medical field. The acceptance of digital tools is high, and the need is growing. OBJECTIVE: Young adults (18-40 years) confronted with a cancer diagnosis present unique needs and require special care. They often have a strong affinity and are familiar with modern technology. On that account, we implemented a web-based symptom and quality of life (QoL) assessment to address patients' attitudes and willingness to use mHealth tools. The study also aims to evaluate sociodemographic parameters that could influence patients' opinions. METHODS: A total of 380 young patients aged 18-40 treated with radiotherapy between 2002 and 2017 were included in the trial. We assessed QoL via the European Organization for Research and Treatment of Cancer-Core 30 (EORTC C30) questionnaire and added general questions about mHealth technology. The added questions inquired patients' opinions regarding general aspects, including technical advances in medicine, mobile and app assistance during cancer treatment, data transfer, and app-specific features. The survey was conducted for 12 months. Participation was voluntary and pseudonymized; prior written consent was obtained. RESULTS: We achieved a participation rate of 57.6% (219/380) and a completion rate of 50.2% (110/219). The median age was 33 years (range 18-40). Of all participants, 89.1% (98/110) considered new technologies in medicine as positive; 10.9% (12/110) answered with neutral. Nearly all patients (96.4%, 106/110) stated that they would send further data via a web-based platform. Of all, 96.4% (106/110) considered the provided pseudonymization of their data as safe. We further asked the patients if they would use a mobile app for symptom and QoL assessment similar to the present web-based system: 74.5% (82/110) answered with yes and 25.5% (28/110) said they would not use a mobile app in the future. We tested the willingness to use an app on several sociodemographic parameters, such as age, gender, education, health insurance status, and cancer-related parameters: tumor stage, time since radiation treatment, and treatment intention. None of these parameters correlated with app use in this group of young adults. Patients who were generally positive regarding using an app rated several possible functions of a future app. The 3 most requested features were appointment reminders (89.0%, 73/82), contact overview of all involved clinics and physicians (87%, 71/82), and making an appointment via app (78%, 64/82). CONCLUSIONS: eHealth and mHealth tools should be available as an integrated part of a comprehensive cancer care approach. It provides automated, thorough documentation of health parameters during therapy and follow-up for doctors, medical staff, and tumor patients to optimize treatment. With this study, we could show that young adults are the ideal patient population to use eHealth/mHealth tools. Such tools offer further digital support and improve the patients' need for constant QoL during cancer care.

6.
Health Phys ; 120(4): 400-409, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315652

RESUMO

ABSTRACT: A suite of software tools has been developed for dose estimation (BAT, WinFRAT) and prediction of acute health effects (WinFRAT, H-Module) using clinical symptoms and/or changes in blood cell counts. We constructed a database of 191 ARS cases using the METREPOL (n = 167) and the SEARCH-database (n = 24). The cases ranged from unexposed (RC0), to mild (RC1), moderate (RC2), severe (RC3), and lethal ARS (RC4). From 2015-2019, radiobiology students and participants of two NATO meetings predicted clinical outcomes (RC, H-ARS, and hospitalization) based on clinical symptoms. We evaluated the prediction outcomes using the same input datasets with a total of 32 teams and 94 participants. We found that: (1) unexposed (RC0) and mildly exposed individuals (RC1) could not be discriminated; (2) the severity of RC2 and RC3 were systematically overestimated, but almost all lethal cases (RC4) were correctly predicted; (3) introducing a prior education component for non-physicians significantly increased the correct predictions of RC, ARS, and hospitalization by around 10% (p<0.005) with a threefold reduction in variance and a halving of the evaluation time per case; (4) correct outcome prediction was independent of the software tools used; and (5) comparing the dose estimates generated by the teams with H-ARS severity reflected known limitations of dose alone as a surrogate for H-ARS severity. We found inexperienced personnel can use software tools to make accurate diagnostic and treatment recommendations with up to 98% accuracy. Educational training improved the quality of decision making and enabled participants lacking a medical background to perform comparably to experts.

7.
Radiat Oncol ; 15(1): 276, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33303000

RESUMO

BACKGROUND: Local hypofractionated stereotactic radiotherapy (HFSRT) of the resection cavity is emerging as the standard of care in the treatment of patients with a limited number of brain metastases as it warrants less neurological impairment compared to whole brain radiotherapy. In periventricular metastases surgical resection can lead to an opening of the ventricles and subsequently carries a potential risk of cerebrospinal tumour cell dissemination. The aim of this study was to assess whether local radiotherapy of the resection cavity is viable in these cases. METHODS: From our institutional database we analyzed the data of 125 consecutive patients with resected brain metastases treated in our institution with HFSRT between 2009 and 2017. The incidence of LMD, overall survival (OS), local recurrence (LC) and distant recurrence were evaluated depending on ventricular opening (VO) during surgery. RESULTS: From all 125 patients, the ventricles were opened during surgery in 14 cases (11.2%). None of the patients with VO and 7 patients without VO during surgery developed LMD (p = 0.371). OS (p = 0.817), LC (p = 0.524) and distant recurrence (p = 0.488) did not differ in relation to VO during surgical resection. However, the incidence of distant intraventricular recurrence was slightly increased in patients with VO (14.3% vs. 2.7%, p < 0.01). CONCLUSION: VO during neurosurgical resection did not affect the outcome after HFSRT of the resection cavity in patients with brain metastases. Particularly, the incidence of LMD was not increased in patients receiving local HFSRT after VO. HFSRT can therefore be offered independently of VO as a local treatment of tumor bed after resection of brain metastases.

8.
Radiother Oncol ; 156: 80-94, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33309848

RESUMO

BACKGROUND AND PURPOSE: For skull base tumors, target definition is the key to safe high-dose treatments because surrounding normal tissues are very sensitive to radiation. In the present work we established a joint ESTRO ACROP guideline for the target volume definition of skull base tumors. MATERIAL AND METHODS: A comprehensive literature search was conducted in PubMed using various combinations of the following medical subjects headings (MeSH) and free-text words: "radiation therapy" or "stereotactic radiosurgery" or "proton therapy" or "particle beam therapy" and "skull base neoplasms" "pituitary neoplasms", "meningioma", "craniopharyngioma", "chordoma", "chondrosarcoma", "acoustic neuroma/vestibular schwannoma", "organs at risk", "gross tumor volume", "clinical tumor volume", "planning tumor volume", "target volume", "target delineation", "dose constraints". The ACROP committee identified sixteen European experts in close interaction with the ESTRO clinical committee who analyzed and discussed the body of evidence concerning target delineation. RESULTS: All experts agree that magnetic resonance (MR) images with high three-dimensional spatial accuracy and tissue-contrast definition, both T2-weighted and volumetric T1-weighted sequences, are required to improve target delineation. In detail, several key issues were identified and discussed: i) radiation techniques and immobilization, ii) imaging techniques and target delineation, and iii) technical aspects of radiation treatments including planning techniques and dose-fractionation schedules. Specific target delineation issues with regard to different skull base tumors, including pituitary adenomas, meningiomas, craniopharyngiomas, acoustic neuromas, chordomas and chondrosarcomas are presented. CONCLUSIONS: This ESTRO ACROP guideline achieved detailed recommendations on target volume definition for skull base tumors, as well as comprehensive advice about imaging modalities and radiation techniques.

9.
Strahlenther Onkol ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230568

RESUMO

PURPOSE: Education as part of medical education is currently changing rapidly. Not least because of the corona crisis, more and more digital teaching formats and innovative teaching concepts such as the flipped classroom model are finding their way into teaching. We analyzed the acceptance and effectiveness of traditional teaching methods as well as the interest in innovative e­learning methods among medical students in the field of radiation oncology at the medical school of the Technical University of Munich. METHODS: We carried out an online-based survey as well as a knowledge test on all students from two terms who had completed the seminar series of radiation oncology. The survey comprised seven questions on the frequency of participation, acceptance, and judgment of the effectiveness in terms of learning and on a potential use of e­learning methods using a six-point Likert scale. The test consisted of 10 multiple-choice questions. RESULTS: Traditional teaching methods are largely accepted by students and most students consider the current learning format to be effective in terms of the teaching effect in the field of radiation oncology. However, only about 50% of all knowledge questions were answered correctly. The possible use of e­learning methods was judged critically or desired in roughly equal parts among the students. CONCLUSION: Traditional seminars enjoy a high level of acceptance among students. Effectiveness with regard to the internalization of content taught, however, should be increased. After all, the future seems to lie in the integration of e­learning in the form of educational videos and practical seminars.

10.
Radiat Res ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33181834

RESUMO

In the event of a mass casualty radiological or nuclear scenario, it is important to distinguish between the unexposed (worried well), low-dose exposed individuals and those developing the hematological acute radiation syndrome (HARS) within the first three days postirradiation. In previous baboon studies, we identified altered gene expression changes after irradiation, which were predictive for the later developing HARS severity. Similar changes in the expression of four of these genes were observed using an in vitro human whole blood model. However, these studies have provided only limited information on the time frame of the changes after exposure in relationship to the development of HARS. In this study we analyzed the time-dependent changes in mRNA expression after in vitro irradiation of whole blood. Changes in the expression of informative mRNAs (FDXR, DBB2, POU2AF1 and WNT3) were determined in the blood of eight healthy donors (6 males, 2 females) after irradiation at 0 (control), 0.5, 2 and 4 Gy using qRT-PCR. FDXR expression was significantly upregulated (P < 0.001) 4 h after ≥0.5 Gy irradiation, with an 18-40-fold peak attained 4-12 h postirradiation which remained elevated (4-9-fold) at 72 h. DDB2 expression was upregulated after 4 h (fold change, 5-8, P < 0.001 at ≥ 0.5 Gy) and remained upregulated (3-4-fold) until 72 h (P < 0.001). The earliest time points showing a significant downregulation of POU2AF1 and WNT3 were 4 h (fold change = 0.4, P = 0.001, at 4 Gy) and 8 h (fold change = 0.3-0.5, P < 0.001, 2-4 Gy), respectively. These results indicate that the diagnostic window for detecting HARS-predictive changes in gene expression may be opened as early as 2 h for most (75%) and at 4 h postirradiation for all individuals examined. Depending on the RNA species studied this may continue for at least three days postirradiation.

11.
BMC Cancer ; 20(1): 1060, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33143683

RESUMO

BACKGROUND: Intraventricular neuroepithelial tumors (IVT) are rare lesions and comprise different pathological entities such as ependymomas, subependymomas and central neurocytomas. The treatment of choice is neurosurgical resection, which can be challenging due to their intraventricular location. Different surgical approaches to the ventricles are described. Here we report a large series of IVTs, its postoperative outcome at a single tertiary center and discuss suitable surgical approaches. METHODS: We performed a retrospective chart review at a single tertiary neurosurgical center between 03/2009-05/2019. We included patients that underwent resection of an IVT emphasizing on surgical approach, extent of resection, clinical outcome and postoperative complications. RESULTS: Forty five IVTs were resected from 03/2009 to 05/2019, 13 ependymomas, 21 subependymomas, 10 central neurocytomas and one glioependymal cyst. Median age was 52,5 years with 55.6% (25) male and 44.4% (20) female patients. Gross total resection was achieved in 93.3% (42/45). 84.6% (11/13) of ependymomas, 100% (12/21) of subependymomas, 90% (9/10) of central neurocytomas and one glioependymal cyst were completely removed. Postoperative rate of new neurological deficits was 26.6% (12/45). Postoperative new permanent cranial nerve deficits occurred in one case with 4th ventricle subependymoma and one in 4th ventricle ependymoma. Postoperative KPSS was 90% (IR 80-100). 31.1% of the patients improved in KPSS, 48.9% remained unchanged and 20% declined. Postoperative adverse events rate was 20.0%. Surgery-related mortality was 2.2%. The rate of shunt/cisternostomy-dependent hydrocephalus was 13.3% (6/45). 15.4% of resected ependymomas underwent adjuvant radiotherapy. Mean follow-up was 26,9 (±30.1) months. CONCLUSION: Our surgical findings emphasize satisfactory complete resection throughout all entities. Surgical treatment can remain feasible, if institutional experience is given. Satisfying long-term survival and cure is possible by complete removal. Gross total resection should always be performed under function-remaining aspects due to mostly benign or slow growing nature of IVTs. Further data is needed to evaluate standard of care and alternative therapy options in rare cases of tumor recurrence or in case of patient collective not suitable for operative resection.

12.
Eur Radiol ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33211140

RESUMO

OBJECTIVE: Assessing the advantage of x-ray dark-field contrast over x-ray transmission contrast in radiography for the detection of developing radiation-induced lung damage in mice. METHODS: Two groups of female C57BL/6 mice (irradiated and control) were imaged obtaining both contrasts monthly for 28 weeks post irradiation. Six mice received 20 Gy of irradiation to the entire right lung sparing the left lung. The control group of six mice was not irradiated. A total of 88 radiographs of both contrasts were evaluated for both groups based on average values for two regions of interest, covering (irradiated) right lung and healthy left lung. The ratio of these average values, R, was distinguished between healthy and damaged lungs for both contrasts. The time-point when deviations of R from healthy lung exceeded 3σ was determined and compared among contrasts. The Wilcoxon-Mann-Whitney test was used to test against the null hypothesis that there is no difference between both groups. A selection of 32 radiographs was assessed by radiologists. Sensitivity and specificity were determined in order to compare the diagnostic potential of both contrasts. Inter-reader and intra-reader accuracy were rated with Cohen's kappa. RESULTS: Radiation-induced morphological changes of lung tissue caused deviations from the control group that were measured on average 10 weeks earlier with x-ray dark-field contrast than with x-ray transmission contrast. Sensitivity, specificity, and accuracy doubled using dark-field radiography. CONCLUSION: X-ray dark-field radiography detects morphological changes of lung tissue associated with radiation-induced damage earlier than transmission radiography in a pre-clinical mouse model. KEY POINTS: • Significant deviations from healthy lung due to irradiation were measured after 16 weeks with x-ray dark-field radiography (p = 0.004). • Significant deviations occur on average 10 weeks earlier for x-ray dark-field radiography in comparison to x-ray transmission radiography. • Sensitivity and specificity doubled when using x-ray dark-field radiography instead of x-ray transmission radiography.

13.
Int J Radiat Biol ; : 1-11, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33211606

RESUMO

PURPOSE: The MSc Radiation Biology course is a highly interdisciplinary degree program placing radiation biology at the interface between biology, medicine, and physics, as well as their associated technologies. The goal was to establish an internationally acknowledged program with diverse and heterogeneous student cohorts, who benefit from each other academically as well as culturally. We have completed a Five-Year evaluation of the program to assess our qualification profile and the further direction we want to take. MATERIALS AND METHODS: We evaluated the student cohort's data from the last 5 years regarding gender, age, and nationality as well as the highest degree before applying and career path after graduation. RESULTS: Data shows a great diversity regarding nationalty as well as undergraduate background. Cohort sizes could be increased and future prospects mainly aimed to a PhD. Measures after regular quality meetings and students' feedback led to improving the curriculum and workload, teacher's training, and changes to examination regulations. CONCLUSIONS: After 5 years, statistics show that our expectations have been met exceedingly. All graduates had excellent career opportunities reflecting the necessity of this MSc and its topics. We are continuously working on improving the program and adapting the curriculum to the requirements in radiation sciences. The future vision includes an expansion of the program as well as undergraduate education opportunities in this field.

14.
Radiat Oncol ; 15(1): 253, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33138837

RESUMO

BACKGROUND: The ESCALOX trial was designed as a multicenter, randomized prospective dose escalation study for head and neck cancer. Therefore, feasibility of treatment planning via different treatment planning systems (TPS) and radiotherapy (RT) techniques is essential. We hypothesized the comparability of dose distributions for simultaneous integrated boost (SIB) volumes respecting the constraints by different TPS and RT techniques. METHODS: CT data sets of the first six patients (all male, mean age: 61.3 years) of the pre-study (up to 77 Gy) were used for comparison of IMRT, VMAT, and helical tomotherapy (HT). Oropharynx was the primary tumor location. Normalization of the three step SIB (77 Gy, 70 Gy, 56 Gy) was D95% = 77 Gy. Coverage (CVF), healthy tissue conformity index (HTCI), conformation number (CN), and dose homogeneity (HI) were compared for PTVs and conformation index (COIN) for parotids. RESULTS: All RT techniques achieved good coverage. For SIB77Gy, CVF was best for IMRT and VMAT, HT achieved highest CN followed by VMAT and IMRT. HT reached good HTCI value, and HI compared to both other techniques. For SIB70Gy, CVF was best by IMRT. HTCI favored HT, consequently CN as well. HI was slightly better for HT. For SIB56Gy, CVF resulted comparably. Conformity favors VMAT as seen by HTCI and CN. Dmean of ipsilateral and contralateral parotids favor HT. CONCLUSION: Different TPS for dose escalation reliably achieved high plan quality. Despite the very good results of HT planning for coverage, conformity, and homogeneity, the TPS also achieved acceptable results for IMRT and VMAT. Trial registration ClinicalTrials.gov Identifier: NCT01212354, EudraCT-No.: 2010-021139-15. ARO: ARO 14-01.

15.
Cancers (Basel) ; 12(10)2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33086761

RESUMO

Imaging features for radiomic analyses are commonly calculated from the entire gross tumour volume (GTV entire). 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 entire 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 (p = 0.10). After additional prospective validation, the consideration of tumour sub-volumes may be a promising way to improve prognostic radiomic risk models.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33038461

RESUMO

PURPOSE: Microbeam radiation therapy is a preclinical concept in radiation oncology. It spares normal tissue more effectively than conventional radiation therapy at equal tumor control. The radiation field consists of peak regions with doses of several hundred gray, whereas doses between the peaks (valleys) are below the tissue tolerance level. Widths and distances of the beams are in the submillimeter range for microbeam radiation therapy. A similar alternative concept with beam widths and distances in the millimeter range is presented by minibeam radiation therapy. Although both methods were developed at large synchrotron facilities, compact alternative sources have been proposed recently. METHODS AND MATERIALS: A small-animal irradiator was fitted with a special 3-layered collimator that is used for preclinical research and produces microbeams of flexible width of up to 100 µm. Film dosimetry provided measurements of the dose distributions and was compared with Monte Carlo dose predictions. Moreover, the micronucleus assay in Chinese hamster CHO-K1 cells was used as a biological dosimeter. The focal spot size and beam emission angle of the x-ray tube were modified to optimize peak dose rate, peak-to-valley dose ratio (PVDR), beam shape, and field homogeneity. An equivalent collimator with slit widths of up to 500 µm produced minibeams and allowed for comparison of microbeam and minibeam field characteristics. RESULTS: The setup achieved peak entrance dose rates of 8 Gy/min and PVDRs >30 for microbeams. Agreement between Monte Carlo simulations and film dosimetry is generally better for larger beam widths; qualitative measurements validated Monte Carlo predicted results. A smaller focal spot enhances PVDRs and reduces beam penumbras but substantially reduces the dose rate. A reduction of the beam emission angle improves the PVDR, beam penumbras, and dose rate without impairing field homogeneity. Minibeams showed similar field characteristics compared with microbeams at the same ratio of beam width and distance but had better agreement with simulations. CONCLUSION: The developed setup is already in use for in vitro experiments and soon for in vivo irradiations. Deviations between Monte Carlo simulations and film dosimetry are attributed to scattering at the collimator surface and manufacturing inaccuracies and are a matter of ongoing research.

18.
Cancers (Basel) ; 12(10)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066251

RESUMO

Tumor heterogeneity is considered to be a hallmark of glioblastoma (GBM). Only more recently, it has become apparent that GBM is not only heterogeneous between patients (intertumoral heterogeneity) but more importantly, also within individual patients (intratumoral heterogeneity). In this study, we focused on assessing intratumoral heterogeneity. For this purpose, the heterogeneity of 38 treatment-naïve GBM was characterized by immunohistochemistry. Perceptible areas were rated for ALDH1A3, EGFR, GFAP, Iba1, Olig2, p53, and Mib1. By clustering methods, two distinct groups similar to subtypes described in literature were detected. The classical subtype featured a strong EGFR and Olig2 positivity, whereas the mesenchymal subtype displayed a strong ALDH1A3 expression and a high fraction of Iba1-positive microglia. 18 tumors exhibited both subtypes and were classified as "subtype-heterogeneous", whereas the areas of the other tumors were all assigned to the same cluster and named "subtype-dominant". Results of epigenomic analyses corroborated these findings. Strikingly, the subtype-heterogeneous tumors showed a clearly shorter overall survival compared to subtype-dominant tumors. Furthermore, 21 corresponding pairs of primary and recurrent GBM were compared, showing a dominance of the mesenchymal subtype in the recurrent tumors. Our study confirms the prognostic impact of intratumoral heterogeneity in GBM, and more importantly, makes this hallmark assessable by routine diagnostics.

19.
JAMA Oncol ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057566

RESUMO

Importance: For brain metastases, the combination of neurosurgical resection and postoperative hypofractionated stereotactic radiotherapy (HSRT) is an emerging therapeutic approach preferred to the prior practice of postoperative whole-brain radiotherapy. However, mature large-scale outcome data are lacking. Objective: To evaluate outcomes and prognostic factors after HSRT to the resection cavity in patients with brain metastases. Design, Setting, and Participants: An international, multi-institutional cohort study was performed in 558 patients with resected brain metastases and postoperative HSRT treated between December 1, 2003, and October 31, 2019, in 1 of 6 participating centers. Exclusion criteria were prior cranial radiotherapy (including whole-brain radiotherapy) and early termination of treatment. Exposures: A median total dose of 30 Gy (range, 18-35 Gy) and a dose per fraction of 6 Gy (range, 5-10.7 Gy) were applied. Main Outcomes and Measures: The primary end points were overall survival, local control (LC), and the analysis of prognostic factors associated with overall survival and LC. Secondary end points included distant intracranial failure, distant progression, and the incidence of neurologic toxicity. Results: A total of 558 patients (mean [SD] age, 61 [0.50] years; 301 [53.9%] female) with 581 resected cavities were analyzed. The median follow-up was 12.3 months (interquartile range, 5.0-25.3 months). Overall survival was 65% at 1 year, 46% at 2 years, and 33% at 3 years, whereas LC was 84% at 1 year, 75% at 2 years, and 71% at 3 years. Radiation necrosis was present in 48 patients (8.6%) and leptomeningeal disease in 73 patients (13.1%). Neurologic toxic events according to the Common Terminology Criteria for Adverse Events grade 3 or higher occurred in 16 patients (2.8%) less than 6 months and 24 patients (4.1%) greater than 6 months after treatment. Multivariate analysis identified a Karnofsky Performance Status score of 80% or greater (hazard ratio [HR], 0.61; 95% CI, 0.46-0.82; P < .001), 22 to 33 days between resection and radiotherapy (HR, 1.50; 95% CI, 1.07-2.10; P = .02), and a controlled primary tumor (HR, 0.69; 95% CI, 0.52-0.90; P = .007) as prognostic factors associated with overall survival. For LC, a single brain metastasis (HR, 0.57; 95% CI, 0.35-0.93; P = .03) and a controlled primary tumor (HR, 0.59; 95% CI, 0.39-0.92; P = .02) were significant in the multivariate analysis. Conclusions and Relevance: To date, this cohort study includes one of the largest series of patients with brain metastases and postoperative HSRT and appears to confirm an excellent risk-benefit profile of local HSRT to the resection cavity. Additional studies will help determine radiation dose-volume parameters and provide a better understanding of synergistic effects with systemic and immunotherapies.

20.
Clin Cancer Res ; 26(20): 5368-5379, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32873573

RESUMO

PURPOSE: Non-small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK) cells. Patients with advanced mHsp70-positive NSCLC may therefore benefit from a therapeutic intervention involving mHsp70-targeting NK cells. The randomized phase II clinical trial (EudraCT2008-002130-30) explores tolerability and efficacy of ex vivo-activated NK cells in patients with NSCLC after radiochemotherapy (RCT). PATIENTS AND METHODS: Patients with unresectable, mHsp70-positive NSCLC (stage IIIa/b) received 4 cycles of autologous NK cells activated ex vivo with TKD/IL2 [interventional arm (INT)] after RCT (60-70 Gy, platinum-based chemotherapy) or RCT alone [control arm (CTRL)]. The primary objective was progression-free survival (PFS), and secondary objectives were the assessment of quality of life (QoL, QLQ-LC13), toxicity, and immunobiological responses. RESULTS: The NK-cell therapy after RCT was well tolerated, and no differences in QoL parameters between the two study arms were detected. Estimated 1-year probabilities for PFS were 67% [95% confidence interval (CI), 19%-90%] for the INT arm and 33% (95% CI, 5%-68%) for the CTRL arm (P = 0.36, 1-sided log-rank test). Clinical responses in the INT group were associated with an increase in the prevalence of activated NK cells in their peripheral blood. CONCLUSIONS: Ex vivo TKD/IL2-activated, autologous NK cells are well tolerated and deliver positive clinical responses in patients with advanced NSCLC after RCT.

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