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1.
Radiother Oncol ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32417350

RESUMO

BACKGROUND AND PURPOSE: Tumor hypoxia plays an important role in head and neck squamous cell carcinomas (HNSCC). Various positron emission tomography (PET) tracers promise non-invasive assessment of tumor hypoxia. So far, the applicability of hypoxia PET is hampered by monocentric imaging trials with few patients. MATERIALS AND METHODS: Multicenter individual patient data based meta-analysis of the original PET data from four prospective imaging trials was performed. All patients had localized disease and were treated with curatively intended radio(-chemo)therapy. Hypoxia PET imaging was performed with 18F-Fluoromisonidazole (FMISO, 102 patients) or 18F-Fluoroazomycin-arabinoside (FAZA, 51 patients). Impact of hypoxia PET parameters on loco-regional control (LRC) and overall survival (OS) was analyzed by uni- and multivariable Cox regression. RESULTS: Baseline characteristics between participating centers differed significantly, especially regarding T stage (p<0.001), tumor volume (p<0.001) and p16 status (p=0.009). The commonly used hypoxia parameters, maximal tumor-to-muscle ratio (TMRmax) and hypoxic volume with 1.6 threshold (HV1.6), showed a strong association with LRC (p=0.001) and OS (p<0.001). These findings were irrespective of the radiotracer and the same cut-off values could be applied for FMISO and FAZA (TMRmax>2.0 or HV1.6>1.5 ml). The effect size of TMRmax was similar for subgroups of patients defined by radiotracer, p16 status and FDG-PET parameters for LRC and OS, respectively. CONCLUSION: PET measured hypoxia is robust and has a strong impact on LRC and OS in HNSCC. The most commonly investigated tracers FMISO and FAZA can probably be used equivalently in multicenter trials. Optimal strategies to improve the dismal outcome of hypoxic tumors remain elusive.

2.
J Mol Diagn ; 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32247864

RESUMO

We compare the expression and applicability of biomarkers, from single genes and gene signatures, identified in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) using the GeneChip Human Transcriptome Array 2.0, nCounter, and real-time PCR analyses. Two multicenter, retrospective cohorts of patients with HNSCC from the German Cancer Consortium Radiation Oncology Group who received postoperative radiochemotherapy or primary radiochemotherapy were considered. Real-time PCR was performed for a limited number of 38 genes of the cohort who received postoperative radiochemotherapy only. Correlations between the methods were evaluated by the Spearman rank correlation coefficient. Patients were stratified based on the expression of putative cancer stem cell markers, hypoxia-associated gene signatures, and a previously developed seven-gene signature. Locoregional tumor control was compared between these patient subgroups using log-rank tests. Gene expressions obtained from nCounter analyses were moderately correlated to GeneChip analyses (median ρ= approximately 0.68). A higher correlation was obtained between nCounter analyses and real-time PCR (median ρ = 0.84). Significant associations with locoregional tumor control were observed for most of the considered biomarkers evaluated by GeneChip and nCounter analyses. In general, all applied biomarkers (single genes and gene signatures) classified approximately 70% to 85% of the patients similarly. Overall, gene signatures seem to be more robust and had a better transferability among different measurement methods.

3.
Mol Oncol ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32175659

RESUMO

Radiotherapy has been optimized over the last decades not only through technological advances, but also through the translation of biological knowledge into clinical treatment schedules. Optimization of fractionation schedules and/or the introduction of simultaneous combined systemic treatment have significantly improved tumour cure rates in several cancer types. With modern techniques, we are currently able to measure factors of radiation resistance or radiation sensitivity in patient tumours; the definition of new biomarkers is expected to further enable personalized treatments. In this Review article, we overview important translation paths and summarize the quality requirements for preclinical and translational studies that will help to avoid bias in trial results.

4.
Radiother Oncol ; 143: 108-116, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32044170

RESUMO

BACKGROUND: Neurocognitive function of adult patients with brain tumours may deteriorate after radiotherapy. Proton beam therapy (PBT) reduces the volume of irradiated healthy brain tissue and could potentially preserve neurocognition and quality of life (QoL). As present data are still limited, the impact of clinical factors and dosimetric parameters on neurocognitive function and QoL during recurrence-free follow-up after PBT is investigated. METHODS: The current study includes 62 brain tumour patients treated with PBT between 2015 and 2017. Neurocognition and QoL were assessed at baseline and every 3 months after PBT using the Montreal Cognitive Assessment (MoCA) test together with EORTC-QLQ-C30 and BN20 questionnaires, respectively. Objective and self-reported measures of neurocognitive functions were correlated. During two years of follow-up, the impact of clinical co-factors as well as dosimetric parameters of several brain structures were analysed using a mixed-model approach. RESULTS: At baseline, mean MoCA total score was 24.8/30 and self-reported cognitive function was 68.9/100. Both remained stable over time. Patients with impaired neurocognition on the MoCA test reported significantly lower global health status, cognitive, physical and role function as well as more fatigue, pain, headache and communication deficits compared to normal performing patients. For most follow-up time points, the majority of MoCA subitems correlated significantly to QoL items regarding neurocognition. Slight deterioration of the MoCA score was associated with tumours located in the left hemisphere and with an increase in relative volume of the anterior cerebellum that received doses of 30-40 Gy(RBE). CONCLUSION: Self-reported and objectively measured neurocognition and most other QoL domains remained largely stable over time during recurrence-free follow-up for brain tumour patients treated with PBT. The association between reduced cognitive function and irradiated volume of the anterior cerebellum requires validation in larger studies and comparison to patients treated with photon therapy.

5.
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
6.
Radiother Oncol ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31767470

RESUMO

BACKGROUND AND PURPOSE: Early radiation-induced esophageal toxicity (RIET) is one of the major side effects in patients with non-small cell lung cancer (NSCLC) and can be a reason for treatment interruptions. As the age of patients with NSCLC and corresponding comorbidities continue to increase, primary radiotherapy alone is a commonly used alternative treatment in these cases. The aim of the present study is to compare dosimetric and clinical parameters from the previously reported CHARTWEL trial for their ability to predict esophagitis and investigate potential differences in the accelerated and conventional fractionation arm. MATERIAL AND METHODS: 146 patients of the Dresden cohort of the randomized phase III CHARTWEL trial were included in this post-hoc analysis. Side effects were prospectively scored weekly during the first 8 weeks from start of radiotherapy. To compare both treatment arms, recorded dose-volume parameters were adjusted for the different fractionation schedules. Logistic regression was performed to predict early RIET for the entire study group as well as for the individual treatment arms. Different dosimetric and clinical parameters were tested. RESULTS: Patients receiving the accelerated CHARTWEL schedule experienced earlier and more severe esophagitis (e.g. 20.5% vs. 9.6% ≥grade 2 at week 3, respectively). In contrast, the median time period for recovery of grade 1 esophagitis was significantly longer for patients with conventional fractionation compared to the CHARTWEL group (median [range]: 21 [12-49] days vs. 15 [7-84] days, p = 0.028). In univariable logistic regression none of the dose-volume parameters showed a significant correlation with early RIET grade ≥ 2 in the conventional irradiation group. In contrast, for patients receiving CHARTWEL, the physical dose-volumes parameters V40 and V50; and re-scaled values VEQD2,50 and VEQD2,60 were significant predictors of early RIET grade ≥ 2. Dose-volume parameters remained different between CHARTWEL and conventional fractionation even after biological rescaling. CONCLUSION: Our results show a more dominant dose-volume effect in the CHARTWEL arm compared to conventional fractionation, especially for higher esophageal doses. These findings support the notion that dose-volume parameters for radiation esophagitis determined in a specific and time dependent setting of field arrangements can not be easily transferred to another setting. In clinical practice esophageal volumes receiving 40 Gy or more should be strictly limited in hyperfractionated-accelerated fraction schemes.

7.
Cancers (Basel) ; 11(9)2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31480456

RESUMO

The development of new radiotherapy technologies is a long-term process, which requires proof of the general concept. However, clinical requirements with respect to beam quality and controlled dose delivery may not yet be fulfilled. Exemplarily, the necessary radiobiological experiments with laser-accelerated electrons are challenged by fluctuating beam intensities. Based on tumour-growth data and dose values obtained in an in vivo trial comparing the biological efficacy of laser-driven and conventional clinical Linac electrons, different statistical approaches for analysis were compared. In addition to the classical averaging per dose point, which excludes animals with high dose deviations, multivariable linear regression, Cox regression and a Monte-Carlo-based approach were tested as alternatives that include all animals in statistical analysis. The four methods were compared based on experimental and simulated data. All applied statistical approaches revealed a comparable radiobiological efficacy of laser-driven and conventional Linac electrons, confirming the experimental conclusion. In the simulation study, significant differences in dose response were detected by all methods except for the conventional method, which showed the lowest power. Thereby, the alternative statistical approaches may allow for reducing the total number of required animals in future pre-clinical trials.

8.
Haematologica ; 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467130

RESUMO

Extramedullary disease in patients with acute myeloid leukemia is a known phenomenon. Since the prevalence of extramedullary acute myeloid leukemia has so far been only clinically determined on examination, we performed a prospective study in patients with acute myeloid leukemia. The goal of this prospective study was to determine the prevalence of metabolically active extramedullary acute myeloid leukemia using total body 18FDG-PET/CT imaging at diagnosis prior to initiation of therapy. In order, to define the dynamics of extramedullary acute myeloid leukemia throughout treatment, PET-positive patients underwent a second 18FDG-PET/CT imaging series during follow-up by the time of remission assessment. Findings: A total of 93 patients with acute myeloid leukemia underwent 18FDG-PET/CT scans at diagnosis. The prevalence of PET-positive extramedullary acute myeloid leukemia was 19% in our study with a total of 65 EM AML manifestations and a median number of two extramedullary manifestations per patient (range, 1-12) with a median SUVmax of 6.1 (range, 2-51.4), respectively. When adding those three patients with histologically confirmed extramedullary acute myeloid leukemia who were 18FDG-PET/CT negative in the 18FDG-PET/CT at diagnosis, the combined prevalence for extramedullary acute myeloid leukemia in this study was 22%, resulting in a sensitivity and specificity of 77% and 97%, respectively. Importantly, 60% (6 of 10) patients with histologically confirmed extramedullary acute myeloid leukemia still had active extramedullary disease in their follow-up 18FDG-PET/CT. 18FDG-PET/CT reveals a high prevalence of metabolically active extramedullary disease in acute myeloid leukemia patients. Metabolic activity in extramedullary acute myeloid leukemia may persist even beyond the time-point of hematologic remission, a finding that merits further prospective investigation with respect to its prognostic relevance. This trial is registered at www.clinicaltrials.gov as #NCT01278069.

9.
Nuklearmedizin ; 58(5): 352-362, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31443113

RESUMO

AIM: 68Ga-PSMA-11 is the gold standard for molecular imaging of prostate cancer. However, recurrent tumor manifestations or metastases cannot be detected in every case. Therefore, we investigated if there is an additive value of the gastrin-releasing peptide receptor (GRP-R) ligand 68Ga-RM2 compared to the well-established 68Ga-PSMA-11 in patients with (Group 1) and without (Group 2) pathologic PSMA-expression in different tumor stages. PATIENTS AND METHODS: Sixteen men (median age: 74 years, range 50-80 years) with prostate cancer in different stages who had a recent negative (n = 8) or pathologic (n = 8) PSMA PET underwent a subsequent 68Ga-RM2 PET. Both examinations were analyzed qualitatively and quantitatively and compared in terms of pathologic and physiologic tracer distribution. RESULTS: None of the PSMA-negative patients showed any pathological RM2-accumulation. Pathologic PSMA-uptake was observed in 8 patients of whom 5 had pathologic RM2-uptake. The number of patients with a local recurrence was equal in both scans (n = 3). Bone metastases and lymph node metastases were detected in less patients in RM2 PET compared to PSMA PET (n = 4 vs. 7 and n = 2 vs. 5, respectively). In one patient, PSMA-positive liver metastases were not detected in RM2. RM2 PET revealed two additional lesions indicative for bone metastases in two patients with multiple PSMA-positive bone metastases, which had no therapeutic consequence. CONCLUSION: At least in our small and heterogeneous patient population, 68Ga-RM2 showed no clinically relevant, additional benefit compared to 68Ga-PSMA-11 PET.

10.
Radiother Oncol ; 139: 94-100, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31445839

RESUMO

PURPOSE: a) To investigate if an ex vivo cultured and irradiated tumor biopsy reflects and predicts the radiation response of the corresponding in vivo irradiated tumor measured with the DNA double strand break marker γH2AX foci. MATERIALS AND METHODS: Five human head and neck squamous cell carcinoma (hHNSCC) xenograft models were used. Fine needle biopsies were taken from anesthetized tumor-bearing NMRI nude mice prior to in vivo single dose irradiation (0, 2, 4, or 8 Gy) under ambient blood flow. Biopsies were ex vivo reoxygenated and irradiated with equivalent doses. Tumors and biopsies were fixed 24 h post irradiation, and γH2AX foci were assessed in oxygenated tumor regions. RESULTS: Linear regression analysis showed comparable slopes of the residual γH2AX foci dose-response curves in four out of five hHNSCC models when in vivo and ex vivo cohorts were compared. The slopes from ex vivo biopsies and in vivo tumors could classify the respective tumor model as sensitive or resistant according to the intrinsic radiation sensitivity (TCD50). CONCLUSION: The ability of ex vivo irradiated tumor biopsies to reflect and predict the intrinsic radiation response of in vivo tumors increases the translational potential of the ex vivo γH2AX foci assay as a diagnostic tool for clinical practice.

11.
Clin Transl Radiat Oncol ; 18: 113-119, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31341986

RESUMO

Background and purpose: Previous MRI studies have shown a substantial decrease in normal-tissue uptake of a hepatobiliary-directed contrast agent 6-9 weeks after liver irradiation. In this prospective clinical study, we investigated whether this effect is detectable during the course of proton therapy. Material and methods: Gd-EOB-DTPA enhanced MRI was performed twice during hypo-fractionated proton therapy of liver lesions in 9 patients (plus two patients with only one scan available). Dose-correlated signal changes were qualitatively scored based on difference images from the two scans. We evaluated the correlation between the MRI signal change with the planned dose map. The GTV was excluded from all analyses. In addition, were examined timing, irradiated liver volume, changes in liver function parameters as well as circulating biomarkers of inflammation. Results: Strong, moderate or no dose-correlated signal changes were detected for 2, 3 and 5 patients, respectively. Qualitative scoring was consistent with the quantitative dose to signal change correlation. In an exploratory analysis, the strongest correlation was found between the qualitative scoring and pretreatment IL-6 concentration. For all patients, a clear dose-correlated signal decrease was seen in late follow-up scans. Conclusion: Radiation-induced effects can be detected with Gd-EOB-DTPA enhanced MRI in a subgroup of patients within a few days after proton irradiation. The reason for the large inter-patient variations is not yet understood and will require validation in larger studies.

12.
Radiother Oncol ; 137: 24-31, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31048234

RESUMO

BACKGROUND AND PURPOSE: Predictive biomarkers can be instrumental to treatment individualisation of cancer patients and improve therapy outcome. Residual γH2AX foci represent a promising biomarker to predict tumour radiosensitivity. In this pre-clinical study, the slope of the dose-response curve was evaluated for its predictive relevance in head and neck squamous cell carcinoma xenografts (HNSCC). Additionally, the feasibility of the translated assay was tested in a clinical setting in patient derived HNSCC samples, and associations between residual γH2AX foci and clinical parameters were analysed. MATERIALS AND METHODS: Seven HNSCC xenografts models (FaDu, SAS, SKX, UT-SCC-5, UT-SCC-14, UT-SCC-45, XF354) were used. Tumour bearing NMRI nude mice were randomly distributed to five treatment arms (0-8 Gy). Residual γH2AX foci (24 h post irradiation) were counted by visual scoring in a micromilieu dependent manner (assessed with BrdU and pimonidazole). The local tumour control values measured as TCD50 (tumour control dose 50%) have previously been published. Patient derived HNSCC biopsies were cultivated ex vivo for 24 h including 4 h of pimonidazole and BrdU treatment, subsequently irradiated with 0-8 Gy and fixed after 24 h. RESULTS: In the pre-clinical study, the dose-response curve slopes negatively correlated with the tumour control dose after fractionated irradiation (TCD50,fx, R2 = 0.63, p = 0.032) and after single dose irradiation under homogeneous hypoxia (TCD50,SD,clamp, R2 = 0.66, p = 0.027). The γH2AX assay in clinical HNSCC samples showed a dose-response relationship, with the values of the slopes ranging from 0.099 Gy-1 to 0.920 Gy-1 (coefficient of variation = 52.8%). Slopes derived from patients were in the same ranges as the sensitive, moderate and resistant models of the pre-clinical study. Statistical analysis revealed a significant negative correlation between the slope and the patients' age (R2 = 0.65, p = 0.001). CONCLUSION: These results further support the promise of the slope of the residual γH2AX foci dose-response as a biomarker for radiosensitivity. In the clinical samples, the variation in the slopes reveals patients' specific repair capacities, which could hold potential value for treatment individualisation.

13.
Clin Transl Radiat Oncol ; 16: 40-47, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30993218

RESUMO

Objective: To independently validate the impact of tumour volume, p16 status, cancer stem cell (CSC) marker expression and hypoxia-associated gene signatures as potential prognostic biomarkers for patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who underwent primary radiotherapy or radiochemotherapy (RCTx). These markers have previously been reported in a study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG) (Linge et al., 2016). Materials and methods: In this retrospective monocentric study, 92 patients with locally advanced HNSCC were included. Univariable and multivariable logistic regressions and Cox models presented in the study of the DKTK-ROG were validated using the area under the curve (AUC) and the concordance index (ci), respectively. The primary endpoint of this study was loco-regional tumour control (LRC) after primary RCTx. Results: Although both cohorts significantly differed in the proportion of the tumour subsites, the parameters tumour volume, p16 status and N stage could be validated regarding LRC and overall survival (OS) using multivariable Cox regression (LRC ci: 0.59, OS ci: 0.63). These models were slightly improved by combination with the putative CSC marker CD44 (LRC ci: 0.61, OS ci: 0.69). The logistic regression model for 2-year LRC based on tumour volume, p16 status and CD44 protein was validated with an AUC of 0.64. The patient stratification based on hypoxia-associated gene signatures status was similar to the original study but without significant differences in LRC and OS. Conclusions: In this validation study, the inclusion of the putative CSC marker CD44 slightly improved the prognostic performance of the baseline parameters tumour volume, p16 status and N stage. No improvement was observed when including expressions of the hypoxia-associated gene signatures. Prospective validation on a larger cohort is warranted to assess the clinical relevance of these markers.

14.
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.

15.
Clin Transl Radiat Oncol ; 15: 108-112, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30834349

RESUMO

Purpose: This secondary analysis of the prospective study on repeat [18F]fluoromisonidazole (FMISO)-PET in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) assessed the correlation of hypoxia in the primary tumour and lymph node metastases (LN) prior to and during primary radiochemotherapy. Methods: This analysis included forty-five LN-positive HNSCC patients having undergone FMISO-PET/CTs at baseline, and at week 1, 2 and 5 of radiochemotherapy. The quantitative FMISO-PET/CT parameters maximum standardised uptake value (SUVmax, corrected for partial volume effect) and peak tumour-to-background ratio (TBRpeak) were estimated in the primary tumour as well as in index and large LN, respectively. Statistical analysis was performed using the Spearman correlation coefficient ρ. Results: In 15 patients with large LN (FDG-PET positive volume >5 ml), there was a significant correlation between the hypoxia measured in the primary tumour and the large LN at three out of four time-points using the TBRpeak (baseline: ρ = 0.57, p = 0.006; week 2: ρ = 0.64, p = 0.003 and week 5: ρ = 0.68, p = 0.001). For the entire cohort (N = 45) only assessed prior to the treatment, there was a statistically significant, though weak correlation between FMISO-SUVmax of the primary tumour and the index LN (ρ = 0.36, p = 0.015). Conclusions: We observed a significant correlation between FMISO-based hypoxia in the primary tumour and large lymph node(s) in advanced stage HNSCC patients. However, since most patients only had relatively small hypoxic lymph node metastases, a comprehensive assessment of the primary tumour and lymph node hypoxia is essential.

16.
Acta Oncol ; 58(6): 916-925, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30882264

RESUMO

Purpose: To compare early and late toxicities, dosimetric parameters and quality of life (QoL) between conventionally fractionated proton beam therapy (PBT) and intensity-modulated radiation therapy (IMRT) in prostate cancer (PCA) patients. Methods: Eighty-eight patients with localized PCA treated between 2013 and 2017 with either definitive PBT (31) or IMRT (57) were matched using propensity score matching on PCA risk group, transurethral resection of the prostate, prostate volume, diabetes mellitus and administration of anticoagulants resulting in 29 matched pairs. Early and late genitourinary (GU) and gastrointestinal (GI) toxicities according to Common Terminology Criteria for Adverse Events (CTCAE) and QoL based on EORTC-QLQ-C30/PR25 questionnaires were collected prospectively until 12 months after radiotherapy (RT). Associations between toxicities and dose-volume parameters in corresponding organs at risk (OARs) were modeled by logistic regression. Results: There were no significant differences in GI and GU toxicities between both treatment groups except for late urinary urgency, which was significantly lower after PBT (IMRT: 25.0%, PBT: 0%, p = .047). Late GU toxicities and obstruction grade ≥2 were significantly associated with the relative volume of the anterior bladder wall receiving 70 Gy and the entire bladder receiving 60 Gy, respectively. The majority of patients in both groups reported high functioning and low symptom scores for the QoL questionnaires before and after RT. No or little changes were observed for most items between baseline and 3 or 12 months after RT, respectively. Global health status increased more at 12 months after IMRT (p = .040) compared to PBT, while the change of constipation was significantly better at 3 months after PBT compared to IMRT (p = .034). Conclusions: Overall, IMRT and PBT were well tolerated. Despite the superiority of PBT in early constipation and IMRT in late global health status compared to baseline, overall QoL and the risks of early and late GU and GI toxicities were similar for conventionally fractionated IMRT and PBT.


Assuntos
Neoplasias da Próstata/radioterapia , Terapia com Prótons/efeitos adversos , Terapia com Prótons/mortalidade , Qualidade de Vida , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Seguimentos , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Pelve/efeitos da radiação , Prognóstico , Estudos Prospectivos , Dosagem Radioterapêutica , Reto/efeitos da radiação , Taxa de Sobrevida , Sistema Urogenital
17.
Nuklearmedizin ; 58(2): 93-100, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30917398

RESUMO

AIM: Retrospective evaluation of serial FDG-PET/CT scans in head and neck squamous cell cancer (HNSCC) patient's follow-up after primary radiochemotherapy (RCTx), to assess the diagnostic accuracy of an experienced observer vs. an objective classification compared to standard clinical follow-up examinations. METHODS: Sixty-nine patients with locally advanced HNSCC were included, who received curative RCTx. Follow-up included serial FDG-PET/CT at the following time intervals t1: ≤ 270 d, t2: 271-540 d, t3: > 540 d after curative RCTx. The likelihood to detect local recurrences, nodal and distant metastases were compared between (i) experienced observer, (ii) an objective classification system by Zundel et al. 25, and (iii) routine clinical follow-up examinations. RESULTS: Twenty-two local recurrences, 7 nodal and 17 distant metastases were recorded during the follow-up. The diagnostic accuracy for local recurrence of the experienced observer vs. objective classification was 78 % vs. 77 % for t1, 83 % vs. 79 % for t2 and 100 % vs. 84 % for t3.The classification (ii) and the conventional follow-up (iii) resulted in a relatively high amount of equivocal findings reducing the diagnostic accuracy. CONCLUSION: Evaluation of FDG-PET/CT by an experienced observer in follow-up of HNSCC patients after curative RCTx resulted in the highest diagnostic accuracy in comparison to an objective classification and to routine clinical examination.HNSCC is a malignant tumor with a high likelihood of recurrence, especially in the first two years after curative RCTx. Early detection of recurrence is of high clinical importance, since there are several effective second line therapies that may have curative potential in some patients.


Assuntos
Quimiorradioterapia , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Interpretação de Imagem Assistida por Computador/métodos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adulto , Idoso , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos
18.
Radiother Oncol ; 131: 120-126, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30773178

RESUMO

BACKGROUND AND PURPOSE: The aim was to investigate the incidence of isolated regional failure following stereotactic ablative radiotherapy (SABR) and risk factors for recurrence. MATERIALS AND METHODS: Early stage non-small cell lung cancer (NSCLC) patients treated with SABR were included in this retrospective cohort study, with isolated regional recurrence (IRR) as primary endpoint, distant recurrence (DR) and overall survival (OS) as secondary endpoints. Survival analyses were performed using the cumulative incidence function (IRR and DR) or the Kaplan-Meier method (OS) and Cox proportional hazards modelling for univariate and multivariate analyses. The prognostic effect of contact between the tumour and the pleura was investigated using the CT scans used for SABR planning. RESULTS: A total of 554 patients were included, of whom 494 could be analysed for IRR. The median follow-up for surviving patients was 48.1 months. Twenty-one patients developed an IRR (4%). The cumulative incidence of IRR and DR after 1-, 2-, and 5 years was 2%, 3%, 7% and 8%, 15% and 21%, respectively. Two year OS was 71%. The presence and type of pleural contact was not associated with any of the studied outcomes. CONCLUSION: The presence, type and length of pleural contact as surrogate for visceral pleural invasion were not predictive for outcome. Further studies focussing on risk factors for occult nodal involvement, (I)RR, distant metastases and mortality in early stage NSCLC are warranted for the development of risk adapted diagnostic, treatment and follow-up strategies as more younger, operable and fitter patients receive SABR.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Recidiva Local de Neoplasia/patologia , Pleura/patologia , Neoplasias Pleurais/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Pleura/diagnóstico por imagem , Neoplasias Pleurais/diagnóstico por imagem , Prognóstico , Radiocirurgia/métodos , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Eur J Cancer ; 110: 11-20, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30739835

RESUMO

BACKGROUND: Combining stereotactic radiosurgery (SRS) and active systemic therapies (STs) achieved favourable survival outcomes in patients with melanoma brain metastases (MBMs) in retrospective analyses. However, several aspects of this treatment strategy remain poorly understood. We report on the overall survival (OS) of patients with MBM treated with a combination of radiotherapy (RT) and ST as well as the impact of the v-Raf murine sarcoma viral oncogene homolog B (BRAF)-V600 mutation (BRAFmut) status, types of RT and ST and their sequence. PATIENTS AND METHODS: Data of 208 patients treated with SRS or whole brain radiation therapy (WBRT) and either immunotherapy (IT) or targeted therapy (TT) within a 6-week interval to RT were analysed retrospectively. OS was calculated from RT to death or last follow-up. Univariate and multivariate Cox proportional hazard analyses were performed to determine prognostic features associated with OS. RESULTS: The median follow-up was 7.3 months. 139 patients received IT, 67 received TT and 2 received IT and TT within 6 weeks to RT (WBRT 45%; SRS 55%). One-year Kaplan-Meier OS rates were 69%, 65%, 33% and 18% (P < .001) for SRS with IT, SRS with TT, WBRT with IT and WBRT with TT, respectively. Patients with a BRAFmut receiving IT combined with RT experienced higher OS rates (88%, 65%, 50% and 18%). TT following RT or started before and continued thereafter was associated with improved median OS compared with TT solely before RT (12.2 [95% confidence interval {CI} 9.3-15.1]; 9.8 [95% CI 6.9-12.6] versus 5.1 [95% CI 2.7-7.5]; P = .03). CONCLUSION: SRS and IT achieved the highest OS rates. A BRAFmut appears to be a favourable prognostic factor for OS. For the combination of RT and TT, the sequence appears to be crucial. Combinations of WBRT and ST achieved unprecedentedly high OS rates and warrant further studies.

20.
Sci Rep ; 9(1): 614, 2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30679599

RESUMO

Image features need to be robust against differences in positioning, acquisition and segmentation to ensure reproducibility. Radiomic models that only include robust features can be used to analyse new images, whereas models with non-robust features may fail to predict the outcome of interest accurately. Test-retest imaging is recommended to assess robustness, but may not be available for the phenotype of interest. We therefore investigated 18 combinations of image perturbations to determine feature robustness, based on noise addition (N), translation (T), rotation (R), volume growth/shrinkage (V) and supervoxel-based contour randomisation (C). Test-retest and perturbation robustness were compared for combined total of 4032 morphological, statistical and texture features that were computed from the gross tumour volume in two cohorts with computed tomography imaging: I) 31 non-small-cell lung cancer (NSCLC) patients; II): 19 head-and-neck squamous cell carcinoma (HNSCC) patients. Robustness was determined using the 95% confidence interval (CI) of the intraclass correlation coefficient (1, 1). Features with CI ≥ 0:90 were considered robust. The NTCV, TCV, RNCV and RCV perturbation chain produced similar results and identified the fewest false positive robust features (NSCLC: 0.2-0.9%; HNSCC: 1.7-1.9%). Thus, these perturbation chains may be used as an alternative to test-retest imaging to assess feature robustness.

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