RESUMEN
Objective.Deep learning shows promise in autosegmentation of head and neck cancer (HNC) primary tumours (GTV-T) and nodal metastases (GTV-N). However, errors such as including non-tumour regions or missing nodal metastases still occur. Conventional methods often make overconfident predictions, compromising reliability. Incorporating uncertainty estimation, which provides calibrated confidence intervals can address this issue. Our aim was to investigate the efficacy of various uncertainty estimation methods in improving segmentation reliability. We evaluated their confidence levels in voxel predictions and ability to reveal potential segmentation errors.Approach.We retrospectively collected data from 567 HNC patients with diverse cancer sites and multi-modality images (CT, PET, T1-, and T2-weighted MRI) along with their clinical GTV-T/N delineations. Using the nnUNet 3D segmentation pipeline, we compared seven uncertainty estimation methods, evaluating them based on segmentation accuracy (Dice similarity coefficient, DSC), confidence calibration (Expected Calibration Error, ECE), and their ability to reveal segmentation errors (Uncertainty-Error overlap using DSC, UE-DSC).Main results.Evaluated on the hold-out test dataset (n= 97), the median DSC scores for GTV-T and GTV-N segmentation across all uncertainty estimation methods had a narrow range, from 0.73 to 0.76 and 0.78 to 0.80, respectively. In contrast, the median ECE exhibited a wider range, from 0.30 to 0.12 for GTV-T and 0.25 to 0.09 for GTV-N. Similarly, the median UE-DSC also ranged broadly, from 0.21 to 0.38 for GTV-T and 0.22 to 0.36 for GTV-N. A probabilistic network-PhiSeg method consistently demonstrated the best performance in terms of ECE and UE-DSC.Significance.Our study highlights the importance of uncertainty estimation in enhancing the reliability of deep learning for autosegmentation of HNC GTV. The results show that while segmentation accuracy can be similar across methods, their reliability, measured by calibration error and uncertainty-error overlap, varies significantly. Used with visualisation maps, these methods may effectively pinpoint uncertainties and potential errors at the voxel level.
Asunto(s)
Aprendizaje Profundo , Neoplasias de Cabeza y Cuello , Procesamiento de Imagen Asistido por Computador , Humanos , Incertidumbre , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Reproducibilidad de los Resultados , Imagen Multimodal , Estudios RetrospectivosRESUMEN
PURPOSE: In the last decades FDG-PET/CT is increasingly used in combination with the standard diagnostic modalities (MRI + US-FNA) to identify residual neck disease (RND) after (chemo)radiotherapy for head-and-neck squamous cell carcinoma (HNSCC). The purpose of the current study is to identify the impact of increasing use of FDG-PET/CT on the accuracy of patient selection for salvage neck dissection (SND). MATERIALS AND METHODS: Between 2008 and 2022, 908 consecutive patients with node-positive HNSCC were treated with (chemo)radiotherapy in our institution. PRIMARY ENDPOINT: positive predictive value (PPV) of FDG-PET/CT for pathologic-confirmed RND (pRND) after SND, compared to the standard of care; MRI + US-FNA. Secondary endpoints: oncologic outcomes. RESULTS: Of the entire group, 130 patients (14 %) received SND. Of them only 53 patients (41 %) had pRND at the SND-specimens. The PPV of FDG-PET/CT for the detection of pRND was considerably better, compared to MRI + US-FNA; 89 % and 65 %, respectively. If FDG-PET/CT showed metabolic CR, these patients did not undergo SND. The NPV was 97.5 %, as only 2.5 % of these patients developed delayed regional failure. FDG-PET/CT considerably improved the accuracy of patient selection for SND, as significantly more patients treated in the second period, compared to first period of the study (n = 454 each) still had vital tumor at SND-specimen (53 % and 31 %, p = 0.008). Regional recurrence free-survival, DFS, OS and HNSCC-death were significantly worse in patients with pRND (p < 0.05) CONCLUSIONS: Incorporating FDG-PET/CT into the diagnostic pathway for the response evaluation after (chemo)radiotherapy significantly improved the accuracy of patient selection for SND and spared considerable number of patients (>20 %) from unnecessary SND. For patients with metabolic CR, SND can safely be omitted while for patients with no metabolic CR, SND is strongly advocated.
Asunto(s)
Quimioradioterapia , Fluorodesoxiglucosa F18 , Neoplasias de Cabeza y Cuello , Disección del Cuello , Tomografía Computarizada por Tomografía de Emisión de Positrones , Terapia Recuperativa , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Terapia Recuperativa/métodos , Masculino , Femenino , Persona de Mediana Edad , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Anciano , Adulto , Radiofármacos , Neoplasia Residual , Anciano de 80 o más Años , Selección de PacienteRESUMEN
OBJECTIVE: This study aims to determine the added value of a geometrically accurate diffusion-weighted (DW-) MRI sequence on the accuracy of gross tumor volume (GTV) delineations, using pathological tumor delineations as a ground truth. METHODS: Sixteen patients with laryngeal or hypopharyngeal carcinoma were included. After total laryngectomy, the specimen was cut into slices. Photographs of these slices were stacked to create a 3D digital specimen reconstruction, which was registered to the in vivo imaging. The pathological tumor (tumorHE) was delineated on the specimen reconstruction. Six observers delineated all tumors twice: once with only anatomical MR imaging, and once (a few weeks later) when DW sequences were also provided. The majority voting delineation of session one (GTVMRI) and session two (GTVDW-MRI), as well as the clinical target volumes (CTVs), were compared to the tumorHE. RESULTS: The mean tumorHE volume was 11.1 cm3, compared to a mean GTVMRI volume of 18.5 cm3 and a mean GTVDW-MRI volume of 15.7 cm3. The median sensitivity (tumor coverage) was comparable between sessions: 0.93 (range: 0.61-0.99) for the GTVMRI and 0.91 (range: 0.53-1.00) for the GTVDW-MRI. The CTV volume also decreased when DWI was available, with a mean CTVMR of 47.1 cm3 and a mean CTVDW-MRI of 41.4 cm3. Complete tumor coverage was achieved in 15 and 14 tumors, respectively. CONCLUSION: GTV delineations based on anatomical MR imaging tend to overestimate the tumor volume. The availability of the geometrically accurate DW sequence reduces the GTV overestimation and thereby CTV volumes, while maintaining acceptable tumor coverage.
Asunto(s)
Imagen de Difusión por Resonancia Magnética , Neoplasias Hipofaríngeas , Neoplasias Laríngeas , Humanos , Neoplasias Hipofaríngeas/diagnóstico por imagen , Neoplasias Hipofaríngeas/patología , Neoplasias Laríngeas/diagnóstico por imagen , Neoplasias Laríngeas/patología , Imagen de Difusión por Resonancia Magnética/métodos , Masculino , Anciano , Persona de Mediana Edad , Femenino , Carga Tumoral , LaringectomíaRESUMEN
Purpose: To report on the late toxicity and local control (LC) of head and neck cancer patients treated with adaptive FDG-PET/CT response-guided radiotherapy (ADMIRE) with dose escalation (NCT03376386). Materials and methods: Between December 2017 and April 2019, 20 patients with stage II-IV squamous cell carcinoma of the larynx, hypopharynx or oropharynx were treated within the ADMIRE study where FDG-PET/CT response-guided (Week 2&4) dose escalation was applied (total dose 70-78 Gy). Cisplatin or cetuximab was added to radiotherapy in case of T3-4 and/or N2c disease. To compare the LC and late toxicity of the study population, we used an external control group (n = 67) consisting of all eligible patients for the study (but not participated). These patients were treated in our institution during the same period with the current standard of 70 Gy radiotherapy. To reduce the effect of confounding, logistic regression analyses was done using stabilized inverse probability of treatment weighting (SIPTW). Results: After median follow-up of 40 and 43 months for the ADMIRE and control groups, the 3-year LC-rates were 74% and 78%, respectively (adjusted HR after SIPTW 0.80, 95 %CI 0.25-2.52, p = 0.70). The incidences of any late G3 toxicity were 35% and 18%, respectively. The adjusted OR for any late G3 toxicity was 5.09 (95 %CI 1.64-15.8, p = 0.005), for any late G ≥ 2 toxicity was 3.67 (95 %CI 1.2-11.7, p = 0.02), for persistent laryngeal edema was 10.95 (95% CI 2.71-44.29, p = 0.001), for persistent mucosal ulcers was 4.67 (95% CI 1.23-17.7, p = 0.023), and for late G3 radionecrosis was 15.69 (95 %CI 2.43-101.39, p = 0.004). Conclusion: Given the comparable LC rates with increased late toxicity in the ADMIRE group, selection criteria for future adaptive dose escalation trials (preferably randomized) need to be refined to include only patients at higher risk of local failure and/or lower risk of severe late toxicity.
RESUMEN
BACKGROUND AND PURPOSE: The apparent diffusion coefficient (ADC), a potential imaging biomarker for radiotherapy response, needs to be reproducible before translation into clinical use. The aim of this study was to evaluate the multi-centre delineation- and calculation-related ADC variation and give recommendations to minimize it. MATERIALS AND METHODS: Nine centres received identical diffusion-weighted and anatomical magnetic resonance images of different cancerous tumours (adrenal gland, pelvic oligo metastasis, pancreas, and prostate). All centres delineated the gross tumour volume (GTV), clinical target volume (CTV), and viable tumour volume (VTV), and calculated ADCs using both their local calculation methods and each of the following calculation conditions: b-values 0-500 vs. 150-500 s/mm2, region-of-interest (ROI)-based vs. voxel-based calculation, and mean vs. median. ADC variation was assessed using the mean coefficient of variation across delineations (CVD) and calculation methods (CVC). Absolute ADC differences between calculation conditions were evaluated using Friedman's test. Recommendations for ADC calculation were formulated based on observations and discussions within the Elekta MRI-linac consortium image analysis working group. RESULTS: The median (range) CVD and CVC were 0.06 (0.02-0.32) and 0.17 (0.08-0.26), respectively. The ADC estimates differed 18% between b-value sets and 4% between ROI/voxel-based calculation (p-values < 0.01). No significant difference was observed between mean and median (p = 0.64). Aligning calculation conditions between centres reduced CVC to 0.04 (0.01-0.16). CVD was comparable between ROI types. CONCLUSION: Overall, calculation methods had a larger impact on ADC reproducibility compared to delineation. Based on the results, significant sources of variation were identified, which should be considered when initiating new studies, in particular multi-centre investigations.
Asunto(s)
Imagen por Resonancia Magnética , Neoplasias , Masculino , Humanos , Reproducibilidad de los Resultados , Imagen de Difusión por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Automatic image registration plays an important role in many aspects of the radiation oncology workflow ranging from treatment simulation, image guided and adaptive radiotherapy, motion management and response evaluation. Traditional automatic registration algorithms are often time-consuming and further improvements in registration accuracy are required. Recently, a variety of AI-driven strategies for automatic image registrations have been developed. In this review an overview of the many applications of automatic image registration in radiation oncology is provided. Different learning strategies and network architectures have been reviewed and the current status of AI based automatic image registration algorithms in radiation oncology has been described. AI based strategies for automatic image registration typically do not outperform traditional strategies yet. Various promising approaches to further improve AI based image registrations are being explored. Therefore AI based automatic image registration may be the method of choice in the foreseeable future.
Asunto(s)
Inteligencia Artificial , Oncología por Radiación , Algoritmos , HumanosRESUMEN
PURPOSE: Laborious and time-consuming tumor segmentations are one of the factors that impede adoption of radiomics in the clinical routine. This study investigates model performance using alternative tumor delineation strategies in models predictive of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Of 153 OPSCC patients, HPV status was determined using p16/p53 immunohistochemistry. MR-based radiomic features were extracted within 3D delineations by an inexperienced observer, experienced radiologist or radiation oncologist, and within a 2D delineation of the largest axial tumor diameter and 3D spheres within the tumor. First, logistic regression prediction models were constructed and tested separately for each of these six delineation strategies. Secondly, the model trained on experienced delineations was tested using these delineation strategies. The latter methodology was repeated with the omission of shape features. Model performance was evaluated using area under the curve (AUC), sensitivity and specificity. RESULTS: Models constructed and tested using single-slice delineations (AUC/Sensitivity/Specificity: 0.84/0.75/0.84) perform better compared to 3D experienced observer delineations (AUC/Sensitivity/Specificity: 0.76/0.76/0.71), where models based on 4 mm sphere delineations (AUC/Sensitivity/Specificity: 0.77/0.59/0.71) show similar performance. Similar performance was found when experienced and largest diameter delineations (AUC/Sens/Spec: 0.76/0.75/0.65 vs 0.76/0.69/0.69) was used to test the model constructed using experienced delineations without shape features. CONCLUSION: Alternative delineations can substitute labor and time intensive full tumor delineations in a model that predicts HPV status in OPSCC. These faster delineations may improve adoption of radiomics in the clinical setting. Future research should evaluate whether these alternative delineations are valid in other radiomics models.
Asunto(s)
Alphapapillomavirus , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Humanos , Imagen por Resonancia Magnética/métodos , Neoplasias Orofaríngeas/diagnóstico por imagen , Papillomaviridae , Infecciones por Papillomavirus/patología , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello , Carga TumoralRESUMEN
BACKGROUND AND PURPOSE: Manual delineation of head and neck tumor contours for radiomics analyses is tedious and time consuming. This study investigates if fast or readily available tumor contours can substitute full tumor contours by an experienced observer for an MR-based radiomics model to predict locoregional control (LRC) in oropharyngeal squamous cell carcinoma (OPSCC) tumors. MATERIALS AND METHODS: Radiomic features were extracted from postcontrast T1-weighted MRIs of 177 OPSCC primary tumors using six different manual delineation strategies. LRC prediction models based on recursive feature elimination combined with logistic regression were built. Models were trained and tested on data from each separate delineation. Additionally, the model derived from segmentations from the experienced reader was tested by each of the alternative delineations. Complementary, this was repeated with removal of size and shape features. Model performance was evaluated using area under the curve (AUC). RESULTS: Prediction performance of the experienced radiologist tumor delineation (AUC: 0.74) was superior compared to all other delineations when trained and tested (AUCs: 0.41-0.56) or trained on experienced delineations and tested (AUC: 0.56-0.67) on alternative segmentations. Removal of size and shape features considerably decreases prediction performance (AUC: 0.54). Applying the model based on expert delineations to spherical or single slice delineations makes prediction worthless since these models predict one class. CONCLUSION: Fast or readily available contours cannot substitute full expert tumor delineations in radiomics models predictive of LRC in OPSCC.
Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Neoplasias Orofaríngeas/diagnóstico por imagen , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
OBJECTIVES: New markers are required to predict chemoradiation response in oropharyngeal squamous cell carcinoma (OPSCC) patients. This study evaluated the ability of magnetic resonance (MR) radiomics to predict locoregional control (LRC) and overall survival (OS) after chemoradiation and aimed to determine whether this has added value to traditional clinical outcome predictors. METHODS: 177 OPSCC patients were eligible for this study. Radiomic features were extracted from the primary tumor region in T1-weighted postcontrast MRI acquired before chemoradiation. Logistic regression models were created using either clinical variables (clinical model), radiomic features (radiomic model) or clinical and radiomic features combined (combined model) to predict LRC and OS 2-years posttreatment. Model performance was evaluated using area under the curve (AUC), 95 % confidence intervals were calculated using 500 iterations of bootstrap. All analyses were performed for the total population and the Human papillomavirus (HPV) negative tumor subgroup. RESULTS: A combined model predicted treatment outcome with a higher AUC (LRC: 0.745 [0.734-0.757], OS: 0.744 [0.735-0.753]) than the clinical model (LRC: 0.607 [0.594-0.620], OS: 0.708 [0.697-0.719]). Performance of the radiomic model was comparable to the combined model for LRC (AUC: 0.740 [0.729-0.750]), but not for OS prediction (AUC: 0.654 [0.646-0.662]). In HPV negative patients, the performance of all models was not sufficient with AUCs ranging from 0.587 to 0.660 for LRC and 0.559 to 0.600 for OS prediction. CONCLUSION: Predictive models that include clinical variables and radiomic tumor features derived from MR images of OPSCC better predict LRC after chemoradiation than models based on only clinical variables. Predictive models that include clinical variables perform better than models based on only radiomic features for the prediction of OS.
Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Humanos , Aprendizaje Automático , Imagen por Resonancia Magnética , Neoplasias Orofaríngeas/diagnóstico por imagen , Neoplasias Orofaríngeas/terapia , Estudios RetrospectivosRESUMEN
BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) have better prognosis and treatment response compared to HPV-negative OPSCC. This study aims to noninvasively predict HPV status of OPSCC using clinical and/or radiological variables. METHODS: Seventy-seven magnetic resonance radiomic features were extracted from T1-weighted postcontrast images of the primary tumor of 153 patients. Logistic regression models were created to predict HPV status, determined with immunohistochemistry, based on clinical variables, radiomic features, and its combination. Model performance was evaluated using area under the curve (AUC). RESULTS: Model performance showed AUCs of 0.794, 0.764, and 0.871 for the clinical, radiomic, and combined models, respectively. Smoking, higher T-classification (T3 and T4), larger, less round, and heterogeneous tumors were associated with HPV-negative tumors. CONCLUSION: Models based on clinical variables and/or radiomic tumor features can predict HPV status in OPSCC patients with good performance and can be considered when HPV testing is not available.
Asunto(s)
Alphapapillomavirus , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Humanos , Imagen por Resonancia Magnética , Neoplasias Orofaríngeas/diagnóstico por imagen , Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico por imagen , Pronóstico , Estudios RetrospectivosRESUMEN
PURPOSE: We investigated in a single-center prospective trial (NCT03376386) the use of serial fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) to determine the boost dose and to guide boost segmentation in head and neck cancer. METHODS AND MATERIALS: Patients were eligible when treated with curative radiation therapy with or without systemic treatment for T2-4 squamous cell carcinoma of the hypopharynx, larynx, or oropharynx (20 patients in total). FDG-PET/CT scans were made at baseline and for redelineation and replanning at the end of weeks 2 and 4 of radiation therapy. The metabolically active part of the primary tumor received a 4 Gy boost on top of the 70 Gy baseline dose per partial metabolic response. The study would be considered feasible when ≥80% of adaptations were successful and no Common Terminology Criteria for Adverse Events grade ≥4 acute toxicity occurred. RESULTS: One patient received 70 Gy after complete metabolic response in week 2, and 12 patients received 78 Gy because of partial metabolic response at weeks 2 and 4. Seven patients received 74 Gy, either because of complete metabolic response at week 4 (n = 3) or a missed FDG-PET/CT (n = 4). The patients missed their FDG-PET/CT scans because they did not fast (n = 2) or at patients' request (n = 2). In addition to the 4 missed FDG-PET/CT scans, 2 adaptive plans could not be finished successfully owing to logistical problems. In total, 85% of adaptations were completed correctly. No patient experienced grade ≥4 toxicity, and 40% had grade 3 dysphagia (tube feeding) during treatment. This decreased at 12 weeks posttreatment to 20%. CONCLUSIONS: This prospective trial demonstrates the feasibility of serial FDG-PET/CT scans for dose escalation and patient selection.
Asunto(s)
Neoplasias de Cabeza y Cuello/radioterapia , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radioterapia Guiada por Imagen/métodos , Radioterapia de Intensidad Modulada/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Anciano , Estudios de Factibilidad , Fluorodesoxiglucosa F18 , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Neoplasias Hipofaríngeas/diagnóstico por imagen , Neoplasias Hipofaríngeas/tratamiento farmacológico , Neoplasias Hipofaríngeas/radioterapia , Neoplasias Laríngeas/diagnóstico por imagen , Neoplasias Laríngeas/tratamiento farmacológico , Neoplasias Laríngeas/radioterapia , Persona de Mediana Edad , Neoplasias Orofaríngeas/diagnóstico por imagen , Neoplasias Orofaríngeas/tratamiento farmacológico , Neoplasias Orofaríngeas/radioterapia , Estudios Prospectivos , Radiofármacos , Dosificación Radioterapéutica , Radioterapia Guiada por Imagen/efectos adversos , Radioterapia de Intensidad Modulada/efectos adversos , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológicoRESUMEN
OBJECTIVE: The aim of the current study was to determine the incidence of organ function preservation failure (OFPF) in patients with head and neck squamous cell carcinoma (HNSCC) treated by (chemo)radiotherapy and to identify its risk factors. STUDY DESIGN: Retrospective cohort analysis. SETTING: Tertiary cancer care center. SUBJECTS AND METHODS: A single-center retrospective cohort analysis was done (n = 703) in which OFPF after (chemo)radiotherapy was assessed. OFPF was defined as local failure or pure functional failure in the absence of local failure because of major surgical intervention (total laryngectomy, commando resection, permanent tracheostomy) or feeding tube dependence >2 years. RESULTS: OFPF occurred in 153 patients (21.8%). Reasons for OFPF were local failure in 103 patients (14.6%) and functional failure in 50 patients (7.2%). Evidence of functional failure included need for total laryngectomy (n = 9, 1.3%), commando resection (n = 2, 0.3%), permanent tracheostomy (n = 16, 2.3%), and/or long-term feeding tube for functional reasons (n = 23, 3.3%). In a Cox proportional hazards model, OFPF was worse for patients with T4 tumors (hazard ratio [HR] <0.5 and P < .001 for all other stages), for laryngeal vs oropharyngeal cancer (HR, 1.83; 95% confidence interval [CI], 1.20-2.79, P = .005, hypopharyngeal not significant), and for smokers (HR, 1.68; 95% CI, 1.10-2.56, P = .015). Exploratory multivariate analysis by tumor site showed that T4 tumor and pretreatment tracheostomy were the strongest predictive factors for OFPF in laryngeal and hypopharyngeal carcinoma while T4 tumor and smoking were predictive for poor OFPF in oropharyngeal carcinoma. CONCLUSION: This work shows a detrimental effect of smoking on functional outcomes after (chemo-)radiotherapy for HNSCC. Moreover, T4 tumor, laryngeal subsite, and pretreatment tracheostomy are strong predictors of OFPF.
Asunto(s)
Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Neoplasias Hipofaríngeas/terapia , Neoplasias Laríngeas/terapia , Neoplasias Orofaríngeas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Laringectomía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Traqueostomía , Insuficiencia del TratamientoRESUMEN
PURPOSE: Oropharynx cancer (OPC) is heterogeneous; human papillomavirus (HPV)-positive and HPV tumors represent 2 disease entities with a different prognosis. Earlier studies investigating the prognostic value of pretreatment F-FDG PET in OPC are small or included patients with unknown HPV status. This study assessed the prognostic value of PET variables, in a large cohort with balanced HPV status. METHODS: Retrospectively, primary tumor SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were extracted from baseline FDG PET/CT of patients with OPC treated with (chemo)radiation. The Pearson correlation between the PET variables was calculated. With linear regression, the correlation between the PET variables and HPV status, age, smoking status, T stage, N stage, and American Joint Committee on Cancer stage was calculated. Univariable and multivariable Cox models analyzed local control, overall survival, and disease-free survival (DFS). RESULTS: Of 201 patients, 109 were HPV. Metabolic tumor volume and TLG correlated (r = 0.96), as did SUVpeak and SUVmax (r = 0.97). The PET variables correlated strongest with HPV status and T stage. These two accounted for 40% of the variance of MTV and 33% of TLG. Human papillomavirus-negative tumors had a significantly higher SUVmax, SUVpeak, MTV, and TLG. In univariable analysis, all PET variables were significantly associated with local control, overall survival, and DFS. In multivariable analysis, TLG was significantly associated to DFS in patients with HPV OPC (hazard ratio, 1.005; 95% confidence interval, 1.001-1.010; P = 0.03). However, we did not observe this in HPV patients. CONCLUSIONS: Increased baseline TLG is associated with worse DFS in HPV OPC and might be used as biomarker for risk stratification in these patients. Interestingly, we could not identify this association in HPV patients.
Asunto(s)
Neoplasias Orofaríngeas/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/normas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/epidemiología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Valor Predictivo de las Pruebas , RadiofármacosRESUMEN
PURPOSE: Early detection of residual disease (RD) after (chemo)radiation for oropharyngeal (OPC) is crucial. Surveillance of neck nodes with FDG-PET/CT has been studied extensively, whereas its value for local RD remains less clear. We aim to evaluate the diagnostic value of post-treatment FDG-PET/CT in detecting local RD and the outcome of patients with local RD. METHODS: A cohort (n = 352) of consecutively treated OPC patients at our institute between 2010 and 2017 was evaluated. Patients that underwent FDG-PET/CT at 3 months post-treatment (n = 94) were classified as having complete (CMR) or partial metabolic response (PMR). PMR was defined as visually detectable metabolic activity above the background of surrounding normal tissues. Primary endpoint was diagnostic accuracy in detecting local RD. RESULTS: Local RD was seen in 19/352 patients (5%), all of them were HPV negative. The FDG-PET/CT had a sensitivity of 100% (8/8), specificity 85% (73/86), PPV 38% (8/21), NPV 100% (73/73), and accuracy 86%. Patients with local RD had significantly worse OS at 2 years, compared to those without (10 versus 88%, P < 0.001). In multivariable analysis, local RD remained a significant predictive factor for death with a hazard ratio of 11.9 (95% CI 5.8-24.3). The number of patients that underwent PET/CT increased over time (P < 0.001), whereas the number of patients that underwent EUA declined (P = 0.072). CONCLUSION: FDG-PET/CT has excellent performance for the detection of RD, with the sensitivity and negative predictive value approaching 100%. Due to these excellent results is examination under anaesthesia today in the vast majority of the PET-negative cases not necessary anymore.
Asunto(s)
Quimioradioterapia , Fluorodesoxiglucosa F18 , Neoplasias Orofaríngeas/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Adulto , Anciano , Anciano de 80 o más Años , Anestesia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Residual , Neoplasias Orofaríngeas/terapia , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
OBJECTIVES: To study the prognostic value of abnormalities in baseline complete blood count in patients with oropharyngeal cancer (OPC) treated with (chemo) radiation. METHODS AND MATERIALS: The prognostic value of baseline complete blood count on outcome in 234 patients with OPC treated between 2010 and 2015 was examined in multivariate analysis together with other conventional prognostic variables including HPV-status, tumor stage, tumor and nodal size. RESULTS: The 3-year overall survival (OS), disease-free survival (DFS), locoregional control (LRC), and distant control (DC) of the whole group were 74%, 64%, 79%, and 88%, respectively. Leukocytosis and HPV-status were the only significant prognosticators for OS and DFS at the multivariate analysis. Patients without leukocytosis had a significantly better DC compared to those with leukocytosis (92% and 70%, respectively, pâ¯<â¯0.001). Patients with HPV-negative OPC had significantly worse LRC compared to HPV-positive patients (67% and 90%, respectively, pâ¯<â¯0.001). The 3-year OS in HPV-positive group with leukocytosis compared to those without leukocytosis were 69% and 95%, respectively (pâ¯<â¯0.001). The figures for HPV-negative patients were 41% vs. 61%, respectively (pâ¯=â¯0.010). CONCLUSIONS: This is the first study to date reporting the independent impact of leukocytosis and HPV-status on outcome of patients with OPC. The poor outcome of patients with leukocytosis is mainly caused by the worse DC. The significant impact of leukocytosis on outcome was even more pronounced in HPV-positive patients. These biomarkers could help identifying patients with poor prognosis at baseline requiring intensification of local and/or systemic treatment while treatment de-intensification might be offered to the low-risk group.
Asunto(s)
Alphapapillomavirus/aislamiento & purificación , Biomarcadores de Tumor/sangre , Leucocitosis/sangre , Neoplasias Orofaríngeas/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/virología , PronósticoRESUMEN
BACKGROUND AND PURPOSE: Early detection of Residual disease (RD) is vital for salvage possibilities after (chemo) radiatiotherapy for oropharyngeal carcinoma (OPC). We standardized clinical investigation to test its added value to MRI response evaluation and investigated the benefit of FDG-PET/CT. MATERIALS AND METHODS: Radiological response evaluation using Ojiri-score was done for 234 patients with OPC, using MRI 12 weeks after (chemo) radiotherapy between 2010 and 2014. The presence of mucosal lesions and/or major complaints (still completely tube feeding-dependent and/or opiate-dependent because of swallowing problems) was scored as clinical suspicion (CS). Retrospectively, the performance of Ojiri to predict RD was compared to CS and both combined using Pearson Chi-squared. Of the whole group, FDG-PET/CT metabolic response (MR) was available in 50 patients. RESULTS: Twelve out of 234 patients (5.1%) had RD. Ojiri and CS had excellent negative predictive value (NPV) (98% and 100% respectively). The combination of CS and Ojiri reduced false positives by 32% (38-26 patients) without lowering NPV (98%). No patients with complete MR (n = 39) at the FDG-PET/CT had RD compared to 5 (45%) with partial MR. CONCLUSION: For response evaluation in OPC, the combination of CS and Ojiri-score improved the predictive accuracy by reducing false positives compared to them individually. FDG-PET/CT is promising to further reduce false positives.