RESUMEN
BACKGROUND: The purpose of this study is to test if functional multiparametric imaging with 18F-FDG-PET/MRI correlates spatially with immunohistochemical biomarker status within a lesion of head and neck squamous cell carcinoma (HNSCC), and also whether a biopsy with the highest FDG uptake was more likely to have the highest PD-L1 expression or the highest percentage of vital tumour cells (VTC) compared with a random biopsy. METHODS: Thirty-one patients with HNSCC were scanned on an integrated PET/MRI scanner with FDG prior to surgery in this prospective study. Imaging was quantified with SUV, ADC and Ktrans. A 3D-morphometric MRI scan of the specimen was used to co-register the patient and the specimen scans. All specimens were sectioned in consecutive slices, and slices from six different locations were selected randomly from each tumour. Core biopsies were performed to construct TMA blocks for IHC staining with the ten predefined biomarkers. The spatial correlation was assessed with a partial correlation analysis. RESULTS: Twenty-eight patients with a total of 33 lesions were eligible for further analysis. There were significant correlations between the three imaging biomarkers and some of the IHC biomarkers. Moreover, a biopsy taken from the most FDG-avid part of the tumour did not have a statistically significantly higher probability of higher PD-L1 expression or VTC, compared with a random biopsy. CONCLUSION: We found statistically significant correlations between functional imaging parameters and key molecular cancer markers.
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Biomarcadores de Tumor/genética , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Anciano , Antígeno B7-H1/genética , Antígeno B7-H1/aislamiento & purificación , Biopsia , Femenino , Fluorodesoxiglucosa F18/uso terapéutico , Humanos , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Estudios Prospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
Background: Dose-painting has recently been investigated in early-phase trials in head-and-neck cancer (HNC) with the aim of improving local tumor control. At the same time proton therapy has been reported as potentially capable of decreasing toxicity. Here, we investigate whether protons could be applied in a dose-painting setting by comparing proton dose distributions with delivered photon plans from a phase-I trial of FDG-PET based dose-painting at our institution.Material and methods: Eleven oropharynx (5), hypopharynx (2) and larynx cancer (4) patients from the recently conducted phase I trial were used for comparison of proton and photon dose-painting techniques. Robust optimization (3.5%/3 mm) was used for proton plans. Plan robustness and difference in dose metrics to targets and organs at risk were evaluated.Results: The proton plans met target dose constraints, while having lower non-target dose than photon plans (body-minus-CTV, mean dose 3.9 Gy vs 7.2 Gy, p = .004). Despite the use of robust proton planning for plan max dose, photon plan max doses were more robust (p = .006). Max dose to medulla, brainstem and mandible were lower in the proton plans, while there was no significant difference in mean dose to submandibular- and parotid glands.Conclusion: Proton dose-painting for HNC seems feasible and can reduce the non-target dose overall, however not significantly to certain organs close to the target, such as the salivary glands. Max dose in proton plans had a lower robustness compared to photons, requiring caution to avoid unintended hot spots in consideration of the risk of mucosal toxicity.
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Neoplasias de Cabeza y Cuello/radioterapia , Fotones/uso terapéutico , Terapia de Protones/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Ensayos Clínicos Fase I como Asunto , Simulación por Computador , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Humanos , Modelos Biológicos , Órganos en Riesgo/diagnóstico por imagen , Órganos en Riesgo/efectos de la radiación , Tomografía de Emisión de Positrones , Terapia de Protones/efectos adversos , Dosificación Radioterapéutica , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagenRESUMEN
Intratumor heterogeneity may contribute to the ambiguous clinical results on PD-L1 status as a predictor for immunotherapy response in patients with HNSCC. This decreases the utility of PD-L1 expression from single tumour biopsies as a predictive biomarker. In this prospective study, intratumor heterogeneity of PD-L1 expression in HNSCC was investigated with both Tumour Proportion Score (TPS) and Combined Positive Score (CPS). Thirty-three whole surgical specimens from 28 patients with HNSCC were included. PD-L1 expression in six random core biopsies from each surgical specimen was used to assess the concordance between multiple biopsies and the negative predictive value of a single negative core biopsy. With 1% cut off, 36% of the specimens were concordant with TPS and 52% with CPS. With a 50% cut-off value the concordance was 70% with TPS and 55% with CPS. Defining a tumour as positive if just a single-one of the biopsies was positive, the negative predictive value (NPV) of a single negative core biopsy was 38.9 and 0% (1% cut off), and 79.9% and 62.8% (50% cut off) for TPS and CPS, respectively. In conclusion, PD-L1 positivity varies markedly within the tumour, both with TPS and CPS, challenging the utility of this biomarker.
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Antígeno B7-H1/genética , Heterogeneidad Genética , Receptor de Muerte Celular Programada 1/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Biopsia , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Transducción de Señal/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugíaRESUMEN
PURPOSE: The purpose of this study was to assess the use of 18F-FDG PET/CT scans for detecting distant metastases in patients with recurrent head and neck squamous cell carcinoma (HNSCC) and investigate the treatment and survival of patients with recurrence. METHODS: In this retrospective study, consecutive head and neck cancer patients referred for FDG PET/CT scan between 2012 and 2014 were included. Patient records were reviewed and only patients with recurrence of HNSCC were enrolled for further analysis. Information on distant metastases, surgery and survival was collected. A Kaplan-Meier analysis was used to report survival. RESULTS: Overall 275 PET/CT scans were performed due to suspected recurrence, and in 166 scans (144 patients), recurrence of HNSCC was confirmed, making them eligible for further analysis. Distant metastases were revealed in 29.8% of the scans (n = 51) and the proportion of revealed metastases remained constant at approximately 30% each year. Although the number of performed scans increased twofold each year, there was no statistically significant change in the proportion of scans with distant metastasis (p = 0.55). The distant metastases were most often seen in the lungs (n = 44) and bone (n = 15). A few patients had widespread dissemination to other areas. Salvage surgery was performed following 81 of the 166 PET/CT scans. Seven of the patients who underwent salvage surgery had M-site oligo-metastases. Patients who underwent salvage surgery had a median survival of 22 months whereas patients not treated with salvage surgery had a median survival of 6 months. After 5 years, 21% of the patients selected for salvage surgery were alive. CONCLUSIONS: Distant metastases occur frequently in patients with recurrent HNSCC disease and the proportion of revealed distant metastases remained the same (30%). Imaging with FDG PET/CT can be recommended in patients with recurrent HNSCC prior to putative salvage surgery.
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Neoplasias Óseas , Neoplasias de Cabeza y Cuello , Neoplasias Pulmonares , Recurrencia Local de Neoplasia/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello , Protocolos Antineoplásicos , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/secundario , Neoplasias Óseas/cirugía , Dinamarca/epidemiología , Femenino , Fluorodesoxiglucosa F18/farmacología , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Radiofármacos/farmacología , Estudios Retrospectivos , Terapia Recuperativa/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To identify a failure site-specific prognostic model by combining immunohistochemistry (IHC) and molecular imaging information to predict long-term failure type in squamous cell carcinoma of the head and neck. PATIENT AND METHODS: Tissue microarray blocks of 196 head and neck squamous cell carcinoma cases were stained for a panel of biomarkers using IHC. Gross tumor volume (GTV) from the PET/CT radiation treatment planning CT scan, maximal Standard Uptake Value (SUVmax) of fludeoxyglucose (FDG) and clinical information were included in the model building using Cox proportional hazards models, stratified for p16 status in oropharyngeal carcinomas. Separate models were built for time to locoregional failure and time to distant metastasis. RESULTS: Higher than median p53 expression on IHC tended toward a risk factor for locoregional failure but was protective for distant metastasis, χ2 for difference p = .003. The final model for locoregional failure included p53 (HR: 1.9; p: .055), concomitant cisplatin (HR: 0.41; p: .008), ß-tubulin-1 (HR: 1.8; p: .08), ß-tubulin-2 (HR: 0.49; p: .057) and SUVmax (HR: 2.1; p: .046). The final model for distant metastasis included p53 (HR: 0.23; p: .025), Bcl-2 (HR: 2.6; p: .08), SUVmax (HR: 3.5; p: .095) and GTV (HR: 1.7; p: .063). CONCLUSIONS: The models successfully distinguished between risk of locoregional failure and risk of distant metastasis, which is important information for clinical decision-making. High p53 expression has opposite prognostic effects for the two endpoints; increasing risk of locoregional failure, but decreasing the risk of metastatic failure, but external validation of this finding is needed.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores/análisis , Carcinoma de Células Escamosas/patología , Toma de Decisiones Clínicas , Neoplasias de Cabeza y Cuello/patología , Imagen Molecular/métodos , Recurrencia Local de Neoplasia/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Femenino , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/terapia , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/terapia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: There is an exciting complementarity between the spatial resolution provided by molecular imaging of a single, often unspecific, biomarker on one hand and the more detailed biological profile achievable from a diagnostic biopsy using a panel of immunohistochemical (IHC) markers on the other. A number of previous studies have shown a relationship between glucose transport protein expression and 18F-Fludeoxyglucose (FDG) PET uptake. Here, FDG uptake is analyzed in relation to expression of a selected panel of IHC cancer biomarkers in head and neck squamous cell carcinomas (HNSCC). MATERIAL AND METHODS: IHC staining for Bcl-2, ß-tubulin-1 and 2, p53, EGFR, Ki-67, glutathione-S-transferase-π and p16 was performed on formalin-fixed paraffin embedded diagnostic biopsies from 102 HNSCC cases treated at Rigshospitalet during 2005-2009. The proportion of positive cells was used for analyses, except p16, which was scored according to EORTC guidelines. In all cases, maximal FDG standardized uptake value (SUV) metrics were extracted for the primary tumor, TSUVmax. Univariate linear regression and multiple linear regression of TSUVmax versus IHC markers were performed. RESULTS: In univariate analyses, TSUVmax showed negative associations with Bcl-2 (p = 0.002) and p16 (p = 0.005) indices and positive association with ß-tubulin-1 index (p = 0.003). On multivariate analysis, TSUVmax remained associated with ß-tubulin-1 (p = 0.009), Bcl-2 (p = 0.03) and p16 (p = 0.03). All correlations had r-squared < 0.3. CONCLUSION: Statistically significant correlations were observed between the expression of IHC biomarkers and maximum FDG uptake in the primary tumor.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/metabolismo , Biomarcadores de Tumor/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Receptores ErbB/metabolismo , Fluorodesoxiglucosa F18/farmacocinética , Glutatión Transferasa/metabolismo , Humanos , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Imagen Multimodal , Análisis Multivariante , Proteínas de Neoplasias/metabolismo , Tomografía de Emisión de Positrones , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Radiofármacos/farmacocinética , Tomografía Computarizada por Rayos X , Tubulina (Proteína)/metabolismo , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
BACKGROUND: The pre-treatment 18F-Fludeoxyglucose (FDG) avid subvolume of the tumor has shown promise as a potential target for dose painting in patients with in head and neck squamous cell carcinomas (HNSCC). PURPOSE: The purposes of this study are: 1) to assess the pre-treatment spatio-temporal variability of FDG PET/CT target volumes and 2) to assess the impact of this variability on dose distribution in dose painting plans in patients with HNSCC. MATERIAL AND METHODS: Thirty patients were enrolled and scanned twice, three days apart, days prior to treatment. Delineation of the FDG avid subvolume of the tumor and lymph nodes on both scans was performed by a specialist in nuclear medicine yielding GTVPET1 and GTVPET2 and segmentation based on SUV iso-contours were constructed yielding two metabolic target volumes, MTV1 and MTV2. Images were co-registered rigidly and dose painting plans with dose escalation up to 82 Gy to GTVPET1 were planned and GTVPET2 was copied from the co-registered images to the dose planning scan. Variation in dose to the target and modeled tumor control probability were assessed as measures of the impact of imaging variations in a dose painting scenario. RESULTS: Twenty-four patients were available for full analysis. The median mismatch between GTVPET1 and GTVPET2 was 14.2% (1.7 cm(3)). The median difference in dose to the FDG planning target volume was 0.3 Gy (PTVPET) and 0.4 Gy (PTVMTV). Median difference in the modeled tumor control probability (TCP) was < 0.2% and 23 of 24 patients had a difference in expected TCP < 1%. CONCLUSIONS: Pre-treatment FDG PET/CT target volumes were stable and day-to-day variability had no relevant impact on dose distribution and expected tumor control in dose painting plans.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/radioterapia , Fluorodesoxiglucosa F18 , Humanos , Imagen Multimodal , Tomografía de Emisión de Positrones , Radiofármacos , Dosificación Radioterapéutica , Tomografía Computarizada por Rayos XAsunto(s)
Carcinoma de Células Escamosas/mortalidad , Neoplasias de Cabeza y Cuello/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Estudios de Cohortes , Terapia Combinada , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Humanos , Modelos Estadísticos , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Assessment of target dose conformity in multi-dose-level treatment plans is challenging due to inevitable over/underdosage at the border zone between dose levels. Here, we evaluate different target dose prescription planning aims and approaches to evaluate the relative merit of such plans. A quality volume histogram (QVH) tool for history-based evaluation is proposed. MATERIAL AND METHODS: Twenty head and neck cancer dose-painting plans with five prescription levels were evaluated, as well as clinically delivered simultaneous integrated boost (SIB) plans from 2010 and 2012. The QVH tool was used for target dose comparison between groups of plans, and to identify and improve a suboptimal dose-painting plan. RESULTS: Comparison of 2010 and 2012 treatment plans with the QVH tool demonstrated that 2012 plans have decreased underdosed volume at the expense of increased overdosed volume relative to the 2010 plans. This shift had not been detected previously. One suboptimal dose-painting plan was compared to the 'normal zone' of the QVH tool and could be improved by re-optimization. CONCLUSION: The QVH tool provides a method to assess target dose conformity in dose-painting and multi-dose-level plans. The tool can be useful for quality assurance of multi-center trials, and for visualizing the development of treatment planning in routine clinical practice.
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Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Humanos , Dosificación RadioterapéuticaRESUMEN
BACKGROUND: Uncertainty persists regarding clinical and treatment variations crucial to consider when comparing high human papillomavirus (HPV)-prevalence oropharyngeal squamous cell carcinoma (OPSCC) cohorts for accurate patient stratification and replicability of clinical trials across different geographical areas. METHODS: OPSCC patients were included from The University of Texas MD Anderson Cancer Center (UTMDACC), USA and from The University Hospital of Copenhagen, Denmark from 2015-2020, (n = 2484). Outcomes were 3-year overall survival (OS) and recurrence-free interval (RFI). Subgroup analyses were made for low-risk OPSCC patients (T1-2N0M0) and high-risk patients (UICC8 III-IV). RESULTS: There were significantly more HPV-positive (88.2 % vs. 63.1 %), males (89.4 % vs. 74.1 %), never-smokers (52.1 % vs. 23.7 %), lower UICC8-stage (I/II: 79.3 % vs. 68 %), and fewer patients treated with radiotherapy (RT) alone (14.8 % vs. 30.3 %) in the UTMDACC cohort. No difference in the adjusted OS was observed (hazard ratio [HR] 1.21, p = 0.23), but a significantly increased RFI HR was observed for the Copenhagen cohort (HR: 1.74, p = 0.003). Subgroup analyses of low- and high-risk patients revealed significant clinical and treatment differences. No difference in prognosis was observed for low-risk patients, but the prognosis for high-risk patients in the Copenhagen cohort was worse (OS HR 2.20, p = 0.004, RFI HR 2.80, p = 0.002). CONCLUSIONS: We identified significant differences in clinical characteristics, treatment modalities, and prognosis between a Northern European and Northern American OPSCC population. These differences are important to consider when comparing outcomes and for patient stratification in clinical trials, as reproducibility might be challenging.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Masculino , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/epidemiología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Pronóstico , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/terapia , Virus del Papiloma Humano , Neoplasias Orofaríngeas/epidemiología , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/patología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/patología , Prevalencia , Reproducibilidad de los Resultados , Dinamarca/epidemiología , PapillomaviridaeRESUMEN
BACKGROUND AND PURPOSE: In cancer treatment precise definition of the tumor volume is essential, but despite development in imaging modalities, this remains a challenge. Here, pathological tumor volumes from the surgical specimens were obtained and compared to tumor volumes defined from modern PET/MRI hybrid imaging. The purpose is to evaluate mismatch between the volumes defined from imaging and pathology was estimated and potential clinical impact. METHODS AND MATERIALS: Twenty-five patients with head and neck squamous cell carcinoma were scanned on an integrated PET/MRI system prior to surgery. Three gross tumor volumes (GTVs) from the primary tumor site were delineated defined from MRI (GTVMRI), PET (GTVPET) and one by utilizing both anatomical images and clinical information (GTVONCO). Twenty-five primary tumor specimens were extracted en bloc, scanned with PET/MRI and co-registered to the patient images. Each specimen was sectioned in blocks, sliced and stained with haematoxylin and eosin. All slices were digitalized and tumor delineated by a head and neck pathologist. The pathological tumor areas in all slices were interpolated yielding a pathological 3D tumor volume (GTVPATO). GTVPATOwas compared with the imaging GTV's and potential mismatch was estimated. RESULTS: Thirteen patients were included. The mean volume of GTVONCOwas larger than the GTV's defined from PET or MRI. The mean mismatch of the GTVPATOcompared to the GTVPET, GTVMRIand GTVONCOwas 31.9 %, 54.5 % and 27.9 % respectively, and the entire GTVPATO was only fully encompassed in GTVONCO in 1 of 13 patients. However, after the addition of a clinical 5 mm margin the GTVPATO was fully encompassed in GTVONCO in 11 out of 13 patients. CONCLUSIONS: Despite modern hybrid imaging modalities, a mismatch between imaging and pathological defined tumor volumes was observed in all patients.A 5 mm clinical margin was sufficient to ensure inclusion of the entire pathological volume in 11 out of 13 patients.
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Neoplasias de Cabeza y Cuello , Tomografía Computarizada por Rayos X , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Carga Tumoral , Tomografía Computarizada por Rayos X/métodos , Tomografía de Emisión de Positrones/métodos , Imagen por Resonancia Magnética/métodos , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Fluorodesoxiglucosa F18 , RadiofármacosRESUMEN
BACKGROUND: Quantitative whole-body PET/MRI relies on accurate patient-specific MRI-based attenuation correction (AC) of PET, which is a non-trivial challenge, especially for the anatomically complex head and neck region. We used a deep learning model developed for dose planning in radiation oncology to derive MRI-based attenuation maps of head and neck cancer patients and evaluated its performance on PET AC. METHODS: Eleven head and neck cancer patients, referred for radiotherapy, underwent CT followed by PET/MRI with acquisition of Dixon MRI. Both scans were performed in radiotherapy position. PET AC was performed with three different patient-specific attenuation maps derived from: (1) Dixon MRI using a deep learning network (PETDeep). (2) Dixon MRI using the vendor-provided atlas-based method (PETAtlas). (3) CT, serving as reference (PETCT). We analyzed the effect of the MRI-based AC methods on PET quantification by assessing the average voxelwise error within the entire body, and the error as a function of distance to bone/air. The error in mean uptake within anatomical regions of interest and the tumor was also assessed. RESULTS: The average (± standard deviation) PET voxel error was 0.0 ± 11.4% for PETDeep and -1.3 ± 21.8% for PETAtlas. The error in mean PET uptake in bone/air was much lower for PETDeep (-4%/12%) than for PETAtlas (-15%/84%) and PETDeep also demonstrated a more rapidly decreasing error with distance to bone/air affecting only the immediate surroundings (less than 1 cm). The regions with the largest error in mean uptake were those containing bone (mandible) and air (larynx) for both methods, and the error in tumor mean uptake was -0.6 ± 2.0% for PETDeep and -3.5 ± 4.6% for PETAtlas. CONCLUSION: The deep learning network for deriving MRI-based attenuation maps of head and neck cancer patients demonstrated accurate AC and exceeded the performance of the vendor-provided atlas-based method both overall, on a lesion-level, and in vicinity of challenging regions such as bone and air.
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RATIONALE: Tumor biopsy cannot detect heterogeneity and an association between heterogeneity in functional imaging and molecular biology will have an impact on both diagnostics and treatment possibilities. PURPOSE: Multiparametric imaging can provide 3D information on functional aspects of a tumor and may be suitable for predicting intratumor heterogeneity. Here, we investigate the correlation between intratumor heterogeneity assessed with multiparametric imaging and multiple-biopsy immunohistochemistry. METHODS: In this prospective study, patients with primary or recurrent head and neck squamous cell carcinoma (HNSCC) underwent PET/MRI scanning prior to surgery. Tumors were removed en bloc and six core biopsies were used for immunohistochemical (IHC) staining with a predefined list of biomarkers: p40, p53, EGFR, Ki-67, GLUT1, VEGF, Bcl-2, CAIX, PD-L1. Intratumor heterogeneity of each IHC biomarker was quantified by calculating the coefficient of variation (CV) in tumor proportion score among the six core biopsies within each tumor lesion. The heterogeneity in the imaging biomarkers was assessed by calculating CV in 18F-fluorodeoxyglucose (FDG)-uptake, diffusion and perfusion. Concordance of the two variance measures was quantified using Spearman's rank correlation RESULTS: Twenty-eight patients with a total of 33 lesions were included. There was considerable heterogeneity in most of the IHC biomarkers especially in GLUT1, PD-L1, Ki-67, CAIX and p53, however we only observed a correlation between the heterogeneity in GLUT1 and p53 and between Ki-67 and EGFR. Heterogeneity in FDG uptake and diffusion correlated with heterogeneity in cell density. CONCLUSION: Considerable heterogeneity of IHC biomarkers was found, however, only few and weak correlations between the studied IHC markers were observed. The studied functional imaging biomarkers showed weak associations with heterogeneity in some of the IHC biomarkers. Thus, biological heterogeneity is not a general tumor characteristic but depends on the specific biomarker or imaging modality.
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Neoplasias de Cabeza y Cuello , Tomografía de Emisión de Positrones , Biomarcadores , Biomarcadores de Tumor , Fluorodesoxiglucosa F18 , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Humanos , Recurrencia Local de Neoplasia , Estudios Prospectivos , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
PURPOSE: Radiotherapy planning based only on positron emission tomography/magnetic resonance imaging (PET/MRI) lacks computed tomography (CT) information required for dose calculations. In this study, a previously developed deep learning model for creating synthetic CT (sCT) from MRI in patients with head and neck cancer was evaluated in 2 scenarios: (1) using an independent external dataset, and (2) using a local dataset after an update of the model related to scanner software-induced changes to the input MRI. METHODS AND MATERIALS: Six patients from an external site and 17 patients from a local cohort were analyzed separately. Each patient underwent a CT and a PET/MRI with a Dixon MRI sequence over either one (external) or 2 (local) bed positions. For the external cohort, a previously developed deep learning model for deriving sCT from Dixon MRI was directly applied. For the local cohort, we adapted the model for an upgraded MRI acquisition using transfer learning and evaluated it in a leave-one-out process. The sCT mean absolute error for each patient was assessed. Radiotherapy dose plans based on sCT and CT were compared by assessing relevant absorbed dose differences in target volumes and organs at risk. RESULTS: The MAEs were 78 ± 13 HU and 76 ± 12 HU for the external and local cohort, respectively. For the external cohort, absorbed dose differences in target volumes were within ± 2.3% and within ± 1% in 95% of the cases. Differences in organs at risk were <2%. Similar results were obtained for the local cohort. CONCLUSIONS: We have demonstrated a robust performance of a deep learning model for deriving sCT from MRI when applied to an independent external dataset. We updated the model to accommodate a larger axial field of view and software-induced changes to the input MRI. In both scenarios dose calculations based on sCT were similar to those of CT suggesting a robust and reliable method.
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BACKGROUND: Isolated regional recurrences following head-neck squamous-cell carcinomas (HNSCC) are often accessible for curatively intended salvage treatment. Factors prognostic for outcome were investigated in a large cohort of HNSCC patients. METHODS: In total, 1811 patients receiving curatively intended radiotherapy from 2007 to 2017 were reviewed and isolated cervical nodal recurrences were identified. Factors associated with survival and second recurrence were investigated using univariate and multivariate analyses. RESULTS: Isolated regional recurrence was seen in 95/1811 (5.2%) patients. Eighty of 95 patients (84%) received salvage surgery. Two-year survival after isolated regional recurrence was 40%. Overall survival (OS) and time to second recurrence were associated with resection status of the salvage surgery and presence of extranodal spread (ENS), while p16-positive oropharyngeal squamous-cell carcinoma (OPSCC) was associated with better OS. CONCLUSION: Long-term survival after regional recurrence in HNSCC is possible. p16-positive OPSCC, complete salvage surgery, and lack of ENS are associated with better outcome.
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Neoplasias de Cabeza y Cuello , Recurrencia Local de Neoplasia , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Pronóstico , Estudios Retrospectivos , Terapia Recuperativa , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugíaRESUMEN
PURPOSE: Multiparametric positron emission tomography (PET)/magnetic resonance imaging (MRI) as a one-stop shop for radiation therapy (RT) planning has great potential but is technically challenging. We studied the feasibility of performing multiparametric PET/MRI of patients with head and neck cancer (HNC) in RT treatment position. As a step toward planning RT based solely on PET/MRI, a deep learning approach was employed to generate synthetic computed tomography (sCT) from MRI. This was subsequently evaluated for dose calculation and PET attenuation correction (AC). METHODS AND MATERIALS: Eleven patients, including 3 pilot patients referred for RT of HNC, underwent PET/MRI in treatment position after a routine fluorodeoxyglucose-PET/CT planning scan. The PET/MRI scan protocol included multiparametric imaging. A convolutional neural network was trained in a leave-one-out process to predict sCT from the Dixon MRI. The clinical CT-based dose plans were recalculated on sCT, and the plans were compared in terms of relative differences in mean, maximum, near-maximum, and near-minimum absorbed doses for different volumes of interest. Comparisons between PET with sCT-based AC and PET with CT-based AC were assessed based on the relative differences in mean and maximum standardized uptake values (SUVmean and SUVmax) from the PET-positive volumes. RESULTS: All 11 patients underwent PET/MRI in RT treatment position. Apart from the 3 pilots, full multiparametric imaging was completed in 45 minutes for 7 out of 8 patients. One patient terminated the examination after 30 minutes. With the exception of 1 patient with an inserted tracheostomy tube, all dosimetric parameters of the sCT-based dose plans were within ±1% of the CT-based dose plans. For PET, the mean difference was 0.4 ± 1.2% for SUVmean and -0.5 ± 1.0% for SUVmax. CONCLUSIONS: Performing multiparametric PET/MRI of patients with HNC in RT treatment position was clinically feasible. The sCT generation resulted in AC of PET and dose calculations sufficiently accurate for clinical use. These results are an important step toward using multiparametric PET/MRI as a one-stop shop for personalized RT planning.
Asunto(s)
Aprendizaje Profundo , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Imagen Multimodal/métodos , Tomografía de Emisión de Positrones/métodos , Estudios de Factibilidad , Fluorodesoxiglucosa F18 , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Redes Neurales de la Computación , Posicionamiento del Paciente , Estudios Prospectivos , Radiofármacos , Dosificación Radioterapéutica , Radioterapia Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodosRESUMEN
PURPOSE: Multiparametric imaging holds great potential for characterization of disease heterogeneity. For integrated PET/MR imaging, the combination of 18F-flourodeoxyglucose (FDG) PET and diffusion weighted imaging (DWI) has been suggested for the assessment of tumor heterogeneity. However, PET image resolution is limited and DWI is prone to image distortions. The aim of this study was to assess the influence of PET point spread function (PSF) modelling and DWI distortion correction on the voxelwise correlation between FDG-PET and DWI. METHODS: Data were collected from 11 patients with head and neck cancer, each undergoing PET/MR imaging twice. PET reconstructions with and without PSF modelling and DWI with and without distortion correction were derived. Tumor SUV was compared between PET reconstructions by linear regression. Geometric distortions of DWI with and without distortion correction were quantified by voxelwise correlation coefficients to an undistorted anatomical reference. The influence of PSF modelling and DWI distortion correction on a multiparametric analysis was assessed as a change of the voxelwise correlation coefficient between FDG-PET and DWI measured in tumors. RESULTS: The inclusion of PSF modelling in the PET reconstruction affected tumor quantification by a 10-20% increase in SUV. Distortion correction reduced DWI geometric distortions significantly. The impact of PET PSF modelling on the spatial correlation with DWI was insignificant. However, distortion correction of DWI had a significant effect on the spatial correlation with PET. CONCLUSIONS: Proper preparation of the imaging modalities is important for a correct analysis and interpretation of multiparametric PET/MR imaging of head and neck cancer.
Asunto(s)
Imagen de Difusión por Resonancia Magnética , Fluorodesoxiglucosa F18 , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador , Imagen Multimodal , Tomografía de Emisión de Positrones , HumanosRESUMEN
OBJECTIVES: A previously published prognostic model in patients with head and neck squamous cell carcinoma (HNSCC) was validated in both a p16-negative and a p16-positive independent patient cohort and the performance was compared with the newly adopted 8th edition of the UICC staging system. MATERIALS AND METHODS: Consecutive patients with HNSCC treated at a single institution from 2005 to 2012 were included. The cohort was divided in three. 1.) Training cohort, patients treated from 2005 to 2009 excluding patients with p16-positive oropharyngeal squamous cell carcinomas (OPSCC); 2.) A p16-negative validation cohort and 3.) A p16-positive validation cohort. A previously published prognostic model (clinical model) with the significant covariates (smoking status, FDG uptake, and tumor volume) was refitted in the training cohort and validated in the two validation cohorts. The clinical model was used to generate four risk groups based on the predicted risk of disease recurrence after 2â¯years and the performance was compared with UICC staging 8th edition using concordance index. RESULTS: Overall 568 patients were included. Compared to UICC the clinical model had a significantly better concordance index in the p16-negative validation cohort (AUCâ¯=â¯0.63 for UICC and AUCâ¯=â¯0.73 for the clinical model; pâ¯=â¯0.003) and a borderline significantly better concordance index in the p16-positive cohort (AUCâ¯=â¯0.63 for UICC and 0.72 for the clinical model; pâ¯=â¯0.088). CONCLUSION: The validated clinical model provided a better prognostication of risk of disease recurrence than UICC stage in the p16-negative validation cohort, and similar prognostication as the newly adopted 8th edition of the UICC staging in the p16-positive patient cohort.
Asunto(s)
Genes p16 , Neoplasias de Cabeza y Cuello/patología , Estadificación de Neoplasias , Pronóstico , Neoplasias de Cabeza y Cuello/genética , HumanosRESUMEN
OBJECTIVES: The objective of this work was to develop a tool for decision support, providing simultaneous predictions of the risk of loco-regional failure (LRF) and distant metastasis (DM) after definitive treatment for head-and-neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Retrospective data for 560HNSCC patients were used to generate a multi-endpoint model, combining three cause-specific Cox models (LRF, DM and death with no evidence of disease (death NED)). The model was used to generate risk profiles of patients eligible for/included in a de-intensification study (RTOG 1016) and a dose escalation study (CONTRAST), respectively, to illustrate model predictions versus classic inclusion/exclusion criteria for clinical trials. The model is published as an on-line interactive tool (https://katrin.shinyapps.io/HNSCCmodel/). RESULTS: The final model included pre-selected clinical variables (tumor subsite, T stage, N stage, smoking status, age and performance status) and one additional variable (tumor volume). The treatment failure discrimination ability of the developed model was superior of that of UICC staging, 8th edition (AUCLRF=72.7% vs 64.2%, p<0.001 and AUCDM=70.7% vs 58.8%, p<0.001). Using the model for trial inclusion simulation, it was found that 14% of patients eligible for the de-intensification study had>20% risk of tumor relapse. Conversely, 9 of the 15 dose escalation trial participants had LRF risks<20%. CONCLUSION: A multi-endpoint model was generated and published as an on-line interactive tool. Its potential in decision support was illustrated by generating risk profiles for patients eligible for/included in clinical trials for HNSCC.
Asunto(s)
Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeza y Cuello/terapia , Selección de Paciente , Anciano , Carcinoma de Células Escamosas/patología , Sistemas de Apoyo a Decisiones Clínicas , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Riesgo , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
The purpose of this study was to investigate and assess the correlation and reproducibility of multiparametric imaging in head and neck cancer patients. METHODS: Twenty-one patients were included in this prospective scan-rescan study. All patients were scanned twice on an integrated PET and MRI scanner. Gross tumor volumes were defined on T2-weighted MR images, and volumes of interest were defined on diffusion-weighted MRI and 18F-FDG PET (VOIDWI, VOIPET). Overlap between volumes was assessed as a percentwise overlap. 18F-FDG uptake and diffusion were measured using SUV and apparent diffusion coefficient, and correlation was tested across and within patients and as a voxel-by-voxel analysis. RESULTS: Seventeen patients were available for correlation analysis, and 12 patients were available for assessment of tumor overlap. The median tumor overlap between VOIDWI and VOIPET was 82% (VOIDWI in VOIPET) and 62% (VOIPET in VOIDWI) on scan 1 and scan 2, respectively. Across patients, the correlation between SUV and apparent diffusion coefficient was weak and nonsignificant. However, in individual patients a weak but significant correlation was identified on a voxel-by-voxel basis. CONCLUSION: In multiparametric imaging with the integrated PET/MR scanner, the VOIs from DWI and 18F-FDG PET were both within the target volume for radiotherapy and overlapped substantially although not completely. No correlation between 18F-FDG uptake and DWI could be found across patients, but within individual patients a statistically significant, but weak, voxel-by-voxel correlation was found. The findings suggest that information on glucose uptake and diffusion coefficient carries complementary information of interest that may be relevant for radiotherapy treatment planning.