Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 127
Filtrar
3.
Med Phys ; 47(4): 1796-1806, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32037543

RESUMO

BACKGROUND AND PURPOSE: Proton treatment planning relies on an accurate determination of stopping-power ratio (SPR) from x-ray computed tomography (CT). A refinement of the heuristic CT-based SPR prediction using a state-of-the-art Hounsfield look-up table (HLUT) is proposed, which incorporates patient SPR information obtained from dual-energy CT (DECT) in a retrospective patient-cohort analysis. MATERIAL AND METHODS: SPR datasets of 25 brain-tumor patients, 25 prostate-cancer patients, and three nonsmall cell lung-cancer (NSCLC) patients were calculated from clinical DECT scans with the comprehensively validated DirectSPR approach. Based on the median frequency distribution of voxelwise correlations between CT number and SPR within the irradiated volume, a piecewise linear function was specified (DirectSPR-based adapted HLUT). Differences in dose distribution and proton range were assessed for the nonadapted and adapted HLUT in comparison to the DirectSPR method, which has been shown to be an accurate and reliable SPR estimation method. RESULTS: The application of the DirectSPR-based adapted HLUT instead of the nonadapted HLUT reduced the systematic proton range differences from 1.2% (1.1 mm) to -0.1% (0.0 mm) for brain-tumor patients, 1.7% (4.1 mm) to 0.2% (0.5 mm) for prostate-cancer patients, and 2.0% (2.9 mm) to -0.1% (0.0 mm) for NSCLC patients. Due to the large intra- and inter-patient tissue variability, range differences to DirectSPR larger than 1% remained for the adapted HLUT. CONCLUSIONS: The incorporation of patient-specific correlations between CT number and SPR, derived from a retrospective application of DirectSPR to a broad patient cohort, improves the SPR accuracy of the current state-of-the-art HLUT approach. The DirectSPR-based adapted HLUT has been clinically implemented at the University Proton Therapy Dresden (Dresden, Germany) in 2017. This already facilitates the benefits of an improved DECT-based tissue differentiation within clinical routine without changing the general approach for range prediction (HLUT), and represents a further step toward full integration of the DECT-based DirectSPR method for treatment planning in proton therapy.

5.
Br J Radiol ; 93(1107): 20190573, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31778315

RESUMO

OBJECTIVE: Classical robust optimization (cRO) in intensity-modulated proton therapy (IMPT) considers isocenter position and particle range uncertainties; anatomical robust optimization (aRO) aims to consider additional non-rigid positioning variations. This work compares the influence of different uncertainty sources on the robustness of cRO and aRO IMPT plans for head and neck squamous cell carcinoma (HNSCC). METHODS: Two IMPT plans were optimized for 20 HNSCC patients who received weekly control CTs (cCT): cRO, using solely the planning CT, and aRO, including 2 additional cCTs. The robustness of the plans in terms of clinical target volume (CTV) coverage and organ at risk (OAR) sparing was analyzed considering stepwise the influence of (1) non-rigid anatomical variations given by the weekly cCT, (2) with fraction-wise added rigid random setup errors and (3) additional systematic proton range uncertainties. RESULTS: cRO plans presented significantly higher nominal CTV coverage but are outperformed by aRO plans when considering non-rigid anatomical variations only, as cRO and aRO plans presented a median target coverage (D98%) decrease for the low-risk/high-risk CTV of 1.8/1.1 percentage points (pp) and -0.2 pp/-0.3 pp, respectively. Setup and range uncertainties had larger influence on cRO CTV coverage, but led to similar OAR dose changes in both plans. Considering all error sources, 10/2 cRO/aRO patients missed the CTV coverage and a limited number exceeded some OAR constraints in both plans. CONCLUSION: Non-rigid anatomical variations are mainly responsible for critical target coverage loss of cRO plans, whereas the aRO approach was robust against such variations. Both plans provide similar robustness of OAR parameters. ADVANCES IN KNOWLEDGE: The influence of different uncertainty sources was quantified for robust IMPT HNSCC plans.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Incerteza , Humanos , Órgãos em Risco/efeitos da radiação , Posicionamento do Paciente , Lesões por Radiação/prevenção & controle , Erros de Configuração em Radioterapia , Radioterapia de Intensidade Modulada/normas , Estudos Retrospectivos
6.
Br J Radiol ; 93(1107): 20190879, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31804145

RESUMO

OBJECTIVE: Locally recurrent disease is of increasing concern in (non-)small cell lung cancer [(N)SCLC] patients. Local reirradiation with photons or particles may be of benefit to these patients. In this multicentre in silico trial performed within the Radiation Oncology Collaborative Comparison (ROCOCO) consortium, the doses to the target volumes and organs at risk (OARs) were compared when using several photon and proton techniques in patients with recurrent localised lung cancer scheduled to undergo reirradiation. METHODS: 24 consecutive patients with a second primary (N)SCLC or recurrent disease after curative-intent, standard fractionated radio(chemo)therapy were included in this study. The target volumes and OARs were centrally contoured and distributed to the participating ROCOCO sites. Remaining doses to the OARs were calculated on an individual patient's basis. Treatment planning was performed by the participating site using the clinical treatment planning system and associated beam characteristics. RESULTS: Treatment plans for all modalities (five photon and two proton plans per patient) were available for 22 patients (N = 154 plans). 3D-conformal photon therapy and double-scattered proton therapy delivered significantly lower doses to the target volumes. The highly conformal techniques, i.e., intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), CyberKnife, TomoTherapy and intensity-modulated proton therapy (IMPT), reached the highest doses in the target volumes. Of these, IMPT was able to statistically significantly decrease the radiation doses to the OARs. CONCLUSION: Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. They, however, significantly differ in the dose deposited in the OARs. The therapeutic options, i.e., reirradiation or systemic therapy, need to be carefully weighed and discussed with the patients. ADVANCES IN KNOWLEDGE: Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. In light of the abilities of the various highly conformal techniques to spare specific OARs, the therapeutic options need to be carefully weighed and patients included in the decision-making process.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Recidiva Local de Neoplasia/radioterapia , Órgãos em Risco/efeitos da radiação , Fótons/uso terapêutico , Terapia com Prótons/métodos , Reirradiação/métodos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Conjuntos de Dados como Assunto , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Órgãos em Risco/diagnóstico por imagem , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Radioterapia de Intensidade Modulada/métodos , Resultado do Tratamento
7.
Radiother Oncol ; 145: 45-48, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31887577

RESUMO

BACKGROUND: The role of prophylactic cranial irradiation (PCI) and thoracic radiotherapy (TRT) is unclear in resected small cell lung cancer (SCLC). METHODS: Thirteen European radiotherapy experts on SCLC were asked to describe their strategies on PCI and TRT for patients with resected SCLC. The treatment strategies were converted into decision trees and analyzed for consensus and discrepancies. RESULTS: For patients with resected SCLC and positive lymph nodes most experts recommend prophylactic cranial irradiation and thoracic radiotherapy. For elderly patients with resected node negative SCLC, most experts do not recommend thoracic radiotherapy or prophylactic cranial irradiation. CONCLUSION: PCI and TRT are considered in patients with resected SCLC and these treatments should be discussed with the patient in the context of shared decision-making.

11.
Acta Oncol ; 58(10): 1378-1385, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31271079

RESUMO

Introduction: Inter-observer variability (IOV) in target volume delineation is a well-documented source of geometric uncertainty in radiotherapy. Such variability has not yet been explored in the context of adaptive re-delineation based on imaging data acquired during treatment. We compared IOV in the pre- and mid-treatment setting using expert primary gross tumour volume (GTV) and clinical target volume (CTV) delineations in locoregionally advanced head-and-neck squamous cell carcinoma (HNSCC) and (non-)small cell lung cancer [(N)SCLC]. Material and methods: Five and six observers participated in the HNSCC and (N)SCLC arm, respectively, and provided delineations for five cases each. Imaging data consisted of CT studies partly complemented by FDG-PET and was provided in two separate phases for pre- and mid-treatment. Global delineation compatibility was assessed with a volume overlap metric (the Generalised Conformity Index), while local extremes of IOV were identified through the standard deviation of surface distances from observer delineations to a median consensus delineation. Details of delineation procedures, in particular, GTV to CTV expansion and adaptation strategies, were collected through a questionnaire. Results: Volume overlap analysis revealed a worsening of IOV in all but one case per disease site, which failed to reach significance in this small sample (p-value range .063-.125). Changes in agreement were propagated from GTV to CTV delineations, but correlation could not be formally demonstrated. Surface distance based analysis identified longitudinal target extent as a pervasive source of disagreement for HNSCC. High variability in (N)SCLC was often associated with tumours abutting consolidated lung tissue or potentially invading the mediastinum. Adaptation practices were variable between observers with fewer than half stating that they consistently adapted pre-treatment delineations during treatment. Conclusion: IOV in target volume delineation increases during treatment, where a disparity in institutional adaptation practices adds to the conventional causes of IOV. Consensus guidelines are urgently needed.

12.
Int J Radiat Oncol Biol Phys ; 105(3): 504-513, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31271828

RESUMO

PURPOSE: Range prediction in particle therapy is associated with an uncertainty originating from calculating the stopping-power ratio (SPR) based on x-ray computed tomography (CT). Here, we assessed the intra- and inter-patient variability of tissue properties in patients with primary brain tumor using dual-energy CT (DECT) and quantified its influence on current SPR prediction. METHODS AND MATERIALS: For 102 patients' DECT scans, SPR distributions were derived from a patient-specific DECT-based approach (DirectSPR). The impact of soft tissue diversity and age-related variations in bone composition on SPR were assessed. Tissue-specific and global deviations between this method and the state-of-the-art CT-number-to-SPR conversion applying a Hounsfield look-up table (HLUT) were quantified. To isolate systematic deviations between the two, the HLUT was also optimized using DECT information. RESULTS: An intra-patient ± inter-patient soft tissue diversity of 5.6% ± 0.7% in SPR (width of 95% confidence interval) was obtained including imaging- and model-related variations of up to 2.9%. This intra-patient SPR variability is associated with a mean absolute SPR deviation of 1.2% between the patient-specific DirectSPR approach and an optimal HLUT. Between adults and children younger than 6 years, age-related variations in bone composition resulted in a median SPR difference of approximately 5%. CONCLUSIONS: Accurate patient-specific DECT-based stopping-power prediction allows for improved handling of tissue mixtures and can intrinsically incorporate most of the SPR variability arising from tissue mixtures as well as inter-patient and intra-tissue variations. Since the state-of-the-art HLUT-even after cohort-specific optimization-cannot fully consider the broad tissue variability, patient-specific DECT-based stopping-power prediction is advisable in particle therapy.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Tecido Adiposo/diagnóstico por imagem , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Osso e Ossos/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Intervalos de Confiança , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Imagem Radiográfica a Partir de Emissão de Duplo Fóton , Estudos Retrospectivos , Razão Sinal-Ruído , Incerteza , Adulto Jovem
13.
PLoS One ; 14(6): e0217536, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31158263

RESUMO

BACKGROUND: Prognostic models based on individual patient characteristics can improve treatment decisions and outcome in the future. In many (radiomic) studies, small size and heterogeneity of datasets is a challenge that often limits performance and potential clinical applicability of these models. The current study is example of a retrospective multi-centric study with challenges and caveats. To highlight common issues and emphasize potential pitfalls, we aimed for an extensive analysis of these multi-center pre-treatment datasets, with an additional 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan acquired during treatment. METHODS: The dataset consisted of 138 stage II-IV non-small cell lung cancer (NSCLC) patients from four different cohorts acquired from three different institutes. The differences between the cohorts were compared in terms of clinical characteristics and using the so-called 'cohort differences model' approach. Moreover, the potential prognostic performances for overall survival of radiomic features extracted from CT or FDG-PET, or relative or absolute differences between the scans at the two time points, were assessed using the LASSO regression method. Furthermore, the performances of five different classifiers were evaluated for all image sets. RESULTS: The individual cohorts substantially differed in terms of patient characteristics. Moreover, the cohort differences model indicated statistically significant differences between the cohorts. Neither LASSO nor any of the tested classifiers resulted in a clinical relevant prognostic model that could be validated on the available datasets. CONCLUSION: The results imply that the study might have been influenced by a limited sample size, heterogeneous patient characteristics, and inconsistent imaging parameters. No prognostic performance of FDG-PET or CT based radiomics models can be reported. This study highlights the necessity of extensive evaluations of cohorts and of validation datasets, especially in retrospective multi-centric datasets.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Bases de Dados Factuais , Fluordesoxiglucose F18/administração & dosagem , Neoplasias Pulmonares , Modelos Biológicos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/terapia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
15.
Strahlenther Onkol ; 195(8): 756-763, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31143995

RESUMO

PURPOSE: To test the detectability of a liquid fiducial marker injected into ex vivo pancreas tumour tissue on magnetic resonance imaging (MRI) and computed tomography (CT). Furthermore, its injection performance using different needle sizes and its structural stability after fixation in formaldehyde were investigated. METHODS: Liquid fiducial markers with a volume of 20-100 µl were injected into freshly resected pancreas specimens of three patients with suspected adenocarcinoma. X­ray guided injection was performed using different needle sizes (18 G, 22 G, 25 G). The specimens were scanned on MRI and CT with clinical protocols. The markers were segmented on CT by signal thresholding. Marker detectability in MRI was assessed in the registered segmentations. Marker volume on CT was compared to the injected volume as a measure of backflow. RESULTS: Markers with a volume ≥20 µl were detected as hyperintensity on X­ray and CT. On T1- and T2-weighted 3T MRI, marker sizes ranging from 20-100 µl were visible as hypointensity. Since most markers were non-spherical, MRI detectability was poor and their differentiation from hypointensities caused by air cavities or surgical clips was only feasible with a reference CT. Marker backflow was only observed when using an 18-G needle. A volume decrease of 6.6 ± 13.0% was observed after 24 h in formaldehyde and, with the exception of one instance, no wash-out occurred. CONCLUSIONS: The liquid fiducial marker injected in ex vivo pancreatic resection specimen was visible as hyperintensity on kV X­ray and CT and as hypointensity on MRI. The marker's size was stable in formaldehyde. A marker volume of ≥50 µL is recommended in clinically used MRI sequences. In vivo injection is expected to improve the markers sphericity due to persisting metabolism and thereby enhance detectability on MRI.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Marcadores Fiduciais , Imagem por Ressonância Magnética , Neoplasias Pancreáticas/diagnóstico por imagem , Pancreaticoduodenectomia , Tomografia Computadorizada por Raios X , Adenocarcinoma/patologia , Idoso , Feminino , Formaldeído , Humanos , Injeções/instrumentação , Masculino , Agulhas , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Fixação de Tecidos
16.
J Appl Clin Med Phys ; 20(6): 111-119, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31120639

RESUMO

BACKGROUND AND PURPOSE: Abdominal organ motion seriously compromises the targeting accuracy for particle therapy in patients with pancreatic adenocarcinoma. This study compares three different abdominal corsets regarding their ability to reduce pancreatic motion and their potential usability in particle therapy. MATERIALS AND METHODS: A patient-individualized polyurethane (PU), a semi-individualized polyethylene (PE), and a patient-individualized three-dimensional-scan based polyethylene (3D-PE) corset were manufactured for one healthy volunteer. Time-resolved volumetric four-dimensional-magnetic resonance imaging (4D-MRI) and single-slice two-dimensional (2D) cine-MRI scans were acquired on two consecutive days to compare free-breathing motion patterns with and without corsets. The corset material properties, such as thickness variance, material homogeneity in Hounsfield units (HU) on computed tomography (CT) scans, and manufacturing features were compared. The water equivalent ratio (WER) of corset material samples was measured using a multi-layer ionization chamber for proton energies of 150 and 200 MeV. RESULTS: All corsets reduced the pancreatic motion on average by 9.6 mm in inferior-superior and by 3.2 mm in anterior-posterior direction. With corset, the breathing frequency was approximately doubled and the day-to-day motion variations were reduced. The WER measurements showed an average value of 0.993 and 0.956 for the PE and 3DPE corset, respectively, and of 0.298 for the PU corset. The PE and 3DPE corsets showed a constant thickness of 2.8 ± 0.2 and 3.8 ± 0.2 mm, respectively and a homogeneous material composition with a standard deviation (SD) of 31 and 32 HU, respectively. The PU corset showed a variable thickness of 4.2 - 25.6 mm and a heterogeneous structure with air inclusions with an SD of 113 HU. CONCLUSION: Abdominal corsets may be effective devices to reduce pancreatic motion. For particle therapy, PE-based corsets are preferred over PU-based corset due to their material homogeneity and constant thickness.


Assuntos
Abdome/diagnóstico por imagem , Adenocarcinoma/radioterapia , Imagem por Ressonância Magnética/métodos , Pâncreas/efeitos da radiação , Neoplasias Pancreáticas/radioterapia , Respiração , Técnicas de Imagem de Sincronização Respiratória/métodos , Abdome/patologia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Feminino , Tomografia Computadorizada Quadridimensional , Humanos , Masculino , Movimento , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia
17.
Radiother Oncol ; 133: 163-166, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30935574

RESUMO

BACKGROUND: Due to conflicting results between major trials the role of prophylactic cranial irradiation (PCI) in stage IV small cell lung cancer (SCLC) is controversial. METHODS: We obtained a list of 13 European experts from both the European Society for Therapeutic Radiation Oncology (ESTRO) and the International Association for the Study of Lung Cancer (IASLC). The strategies in decision making for PCI in stage IV SCLC were collected. Decision trees were created representing these strategies. Analysis of consensus was performed with the objective consensus methodology. RESULTS: The factors associated with the recommendation for the use of PCI included the fitness of the patient, young age and good response to chemotherapy. PCI was recommended by the majority of experts for non-elderly fit patients who had at least a partial response (PR) to chemotherapy (for complete remission (CR) 85% of radiation oncologists and 69% of medical oncologists, for PR: 85% of radiation oncologists and 54% of medical oncologists). For patients with stable disease after chemotherapy, PCI was recommended by 6 out of 13 (46%) radiation oncologists and only 3 out of 13 medical oncologists (23%). For elderly fit patients with CR, a majority recommended PCI (62%) and no consensus was reached for patients with PR. CONCLUSION: European radiation and medical oncologists specializing in lung cancer recommend PCI in selected patients and restrict its use primarily to fit, non-elderly patients who responded to chemotherapy.


Assuntos
Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/secundário , Irradiação Craniana/métodos , Neoplasias Pulmonares/radioterapia , Carcinoma de Pequenas Células do Pulmão/radioterapia , Adulto , Idoso , Neoplasias Encefálicas/radioterapia , Tomada de Decisões , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Intervalo Livre de Progressão , Radio-Oncologistas , Carcinoma de Pequenas Células do Pulmão/patologia
18.
Radiother Oncol ; 133: 28-34, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30935578

RESUMO

BACKGROUND AND PURPOSE: Oesophageal mobility relative to bony anatomy is a major source of geometrical uncertainty in proton radiotherapy of oesophageal carcinoma. To mitigate this uncertainty we investigated the use of implanted fiducial markers for direct target verification in terms of safety, visibility, and stability. MATERIALS AND METHODS: A total of 19 helical gold markers were endoscopically implanted in ten patients. Their placement at the proximal and distal tumour borders was compared to tumour demarcations derived from [18F]Fluorodeoxyglucose positron emission tomography, their visibility quantified via the contrast-to-noise ratio on daily orthogonal X-ray imaging, and their mobility relative to bony anatomy analysed by means of retrospective triangulation. RESULTS: Marker implantation proceeded without complications, but the distal tumour border could not be reached in two patients. Marker locations corresponded reasonably well with metabolic tumour edges (mean: 5.4 mm more distally). Marker visibility was limited but mostly sufficient (mean contrast-to-noise ratio: 1.5), and sixteen markers (84%) remained in situ until the end of treatment. Overall, marker excursions from their planned position were larger than 5(10) mm in 59(17)% of all analysed fractions. On one occasion severe target displacement was only identified via markers and was corrected before treatment delivery. CONCLUSION: Implanted helical gold fiducial markers are a safe and reliable method of providing target-centric positioning verification in proton beam therapy of oesophageal carcinoma.


Assuntos
Neoplasias Esofágicas/radioterapia , Marcadores Fiduciais , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Idoso , Estudos de Coortes , Neoplasias Esofágicas/diagnóstico por imagem , Fluordesoxiglucose F18 , Ouro , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Prótons , Compostos Radiofarmacêuticos , Planejamento da Radioterapia Assistida por Computador/instrumentação , Radioterapia Guiada por Imagem/instrumentação , Radioterapia Guiada por Imagem/métodos , Estudos Retrospectivos
19.
Front Immunol ; 10: 602, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984181

RESUMO

Neoadjuvant radiochemotherapy (nRCT) can significantly influence the tumor immune architecture that plays a pivotal role in regulating tumor growth. Whereas, various studies have investigated the effect of nRCT on tumor-infiltrating T cells, little is known about its impact on the frequency and activation status of human dendritic cells (DCs). Plasmacytoid DCs (pDCs) essentially contribute to the regulation of innate and adaptive immunity and may profoundly influence tumor progression. Recent studies have revealed that higher pDC numbers are associated with poor prognosis in cancer patients. 6-sulfo LacNAc-expressing monocytes (slanMo) represent a particular proinflammatory subset of human non-classical blood monocytes that can differentiate into DCs. Recently, we have reported that activated slanMo produce various proinflammatory cytokines and efficiently stimulate natural killer cells and T lymphocytes. slanMo were also shown to accumulate in clear cell renal cell carcinoma (ccRCC) and in metastatic lymph nodes from cancer patients. Here, we investigated the influence of nRCT on the frequency of rectal cancer-infiltrating pDCs and slanMo. When evaluating rectal cancer tissues obtained from patients after nRCT, a significantly higher density of pDCs in comparison to pre-nRCT tissue samples was found. In contrast, the density of slanMo was not significantly altered by nRCT. Further studies revealed that nRCT significantly enhances the proportion of rectal cancer-infiltrating CD8+ T cells expressing the cytotoxic effector molecule granzyme B. When exploring the impact of nRCT on the phenotype of rectal cancer-infiltrating pDCs and slanMo, we observed that nRCT markedly enhances the percentage of inducible nitric oxide synthase (iNOS)- or tumor necrosis factor (TNF) alpha-producing slanMo. Furthermore, nRCT significantly increased the percentage of mature CD83+ pDCs in rectal cancer tissues. Moreover, the proportion of pDCs locally expressing interferon-alpha, which plays a major role in antitumor immunity, was significantly higher in post-nRCT tissues compared to pre-nRCT tumor specimens. These novel findings indicate that nRCT significantly influences the frequency and/or phenotype of pDCs, slanMo, and CD8+ T cells, which may influence the clinical response of rectal cancer patients to nRCT.

20.
Radiother Oncol ; 135: 43-50, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31015169

RESUMO

BACKGROUND: Hypoxia is an important factor of tumour resistance to radiotherapy, chemotherapy and potentially immunotherapy. It can be measured e.g. by positron emission tomography (PET) imaging or hypoxia-associated gene expressions from tumour biopsies. Here we correlate [18F]fluoromisonidazole (FMISO)-PET/CT imaging with hypoxia-associated gene expressions on a cohort of 50 head and neck squamous cell carcinoma (HNSCC) patients and compare their prognostic value for response to radiochemotherapy (RCTx). METHODS: FMISO-PET/CT images of 50 HNSCC patients were acquired at four time-points before and during RCTx. For 42 of these patients, hypoxia-associated gene expressions were evaluated by nanoString technology based on a biopsy obtained before any treatment. The FMISO-PET parameters tumour-to-background ratio and hypoxic volume were correlated to the expressions of 58 hypoxia-associated genes using the Spearman correlation coefficient ρ. Three hypoxia-associated gene signatures were compared regarding their correlation with the FMISO-PET parameters using their median expression. In addition, the correlation with tumour volume was analysed. The impact of both hypoxia measurement methods on loco-regional tumour control (LRC) and overall survival (OS) was assessed by Cox regression. RESULTS: The median expression of hypoxia-associated genes was weakly correlated to hypoxia measured by FMISO-PET imaging (ρ ≤ 0.43), with higher correlations to imaging after weeks 1 and 2 of treatment (p < 0.001). Moderate correlations were obtained between FMISO-PET imaging and tumour volume (ρ ≤ 0.69). Prognostic models for LRC and OS based on the FMISO-PET parameters could not be improved by including hypoxia classifiers. CONCLUSION: We observed low correlations between hypoxia FMISO-PET parameters and expressions of hypoxia-associated genes. Since FMISO-PET showed a superior patient stratification, it may be the preferred biomarker over hypoxia-associated genes for stratifying patients with locally advanced HNSCC treated by primary RCTx.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA