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Predictive Value of Early Post-Treatment Diffusion-Weighted MRI for Recurrence or Tumor Progression of Head and Neck Squamous Cell Carcinoma Treated with Chemo-Radiotherapy.

ABSTRACT: AIMS:To investigate the predictive capacity of early post-treatment diffusion-weighted magnetic resonance imaging (MRI) for recurrence or tumor progression in patients with no tumor residue after chemo-radiotherapy (CRT) for head and neck squamous cell carcinoma, and, to assess the predictive capacity of pre-treatment diffusion-weighted MRI for persistent tumor residue post-CRT. MATERIALS AND METHOD:A single center cohort study was performed in one French hospital. All patients with squamous cell carcinoma receiving CRT (no surgical indication) were included. Two diffusion-weighted MRI were performed: one within 8 days before CRT and one 3 months after completing CRT with determination of median tumor apparent diffusion coefficient (ADC). MAIN OUTCOME:The primary endpoint was progression-free survival. RESULTS:59 patients were included prior to CRT and 46 (78.0%) completed CRT. A post-CRT tumor residue was found in 19/46 (41.3%) patients. In univariate analysis, initial ADC was significantly lower in patients with residue post CRT (0.56 ± 0.11 versus 0.79 ± 0.13; p < 0.001). When initial ADC was dichotomized at the median, initial ADC lower than 0.7 was significantly more frequent in patients with residue post CRT (73.7% versus 11.1%, p < 0.0001). In multivariate analysis, only initial ADC lower than 0.7 was significantly associated with tumor residue (OR = 22.6; IC [4.9-103.6], p < 0.0001). Among 26 patients without tumor residue after CRT and followed up until 12 months, 6 (23.1%) presented recurrence or progression. Only univariate analysis was performed due to a small number of events. The only factor significantly associated with disease progression or early recurrence was the delta ADC (p = 0.0009). When ADC variation was dichotomized at the median, patients with ADC variation greater than 0.7 had time of disease-free survival significantly longer than patients with ADC variation lower than 0.7 (377.5 [286-402] days versus 253 [198-370], p < 0.0001). Conclusion and relevance: Diffusion-weighted MRI could be a technique that enables differentiation of patients with high potential for early recurrence for whom intensive post-CRT monitoring is mandatory. Prospective studies with more inclusions would be necessary to validate our results.

SUBMITTER: Brenet E

PROVIDER: S-EPMC7281260 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Predictive Value of Early Post-Treatment Diffusion-Weighted MRI for Recurrence or Tumor Progression of Head and Neck Squamous Cell Carcinoma Treated with Chemo-Radiotherapy.

Brenet Esteban E Barbe Coralie C Hoeffel Christine C Dubernard Xavier X Merol Jean-Claude JC Fath Léa L Servagi-Vernat Stéphanie S Labrousse Marc M

Cancers 20200514 5

<h4>Aims</h4>To investigate the predictive capacity of early post-treatment diffusion-weighted magnetic resonance imaging (MRI) for recurrence or tumor progression in patients with no tumor residue after chemo-radiotherapy (CRT) for head and neck squamous cell carcinoma, and, to assess the predictive capacity of pre-treatment diffusion-weighted MRI for persistent tumor residue post-CRT.<h4>Materials and method</h4>A single center cohort study was performed in one French hospital. All patients wi ...[more]

PMID: 32422975

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Project description:Objectives To assess the predictive value of multiparametric MRI for treatment response evaluation of induction chemo-immunotherapy in locally advanced head and neck squamous cell carcinoma. Methods Twenty-two patients with locally advanced, histologically confirmed head and neck squamous cell carcinoma who were enrolled in the prospective multicenter phase II CheckRad-CD8 trial were included in the current analysis. In this unplanned secondary single-center analysis, all patients who received contrast-enhanced MRI at baseline and in week 4 after single-cycle induction therapy with cisplatin/docetaxel combined with the immune checkpoint inhibitors tremelimumab and durvalumab were included. In week 4, endoscopy with representative re-biopsy was performed to assess tumor response. All lesions were segmented in the baseline and restaging multiparametric MRI, including the primary tumor and lymph node metastases. The volume of interest of the respective lesions was volumetrically measured, and time-resolved mean intensities of the golden-angle radial sparse parallel-volume-interpolated gradient-echo perfusion (GRASP-VIBE) sequence were extracted. Additional quantitative parameters including the T1 ratio, short-TI inversion recovery ratio, apparent diffusion coefficient, and dynamic contrast-enhanced (DCE) values were measured. A model based on parallel random forests incorporating the MRI parameters from the baseline MRI was used to predict tumor response to therapy. Receiver operating characteristic (ROC) curves were used to evaluate the prognostic performance. Results Fifteen patients (68.2%) showed pathologic complete response in the re-biopsy, while seven patients had a residual tumor (31.8%). In all patients, the MRI-based primary tumor volume was significantly lower after treatment. The baseline DCE parameters of time to peak and wash-out were significantly different between the pathologic complete response group and the residual tumor group (p < 0.05). The developed model, based on parallel random forests and DCE parameters, was able to predict therapy response with a sensitivity of 78.7% (95% CI 71.24–84.93) and a specificity of 78.6% (95% CI 67.13–87.48). The model had an area under the ROC curve of 0.866 (95% CI 0.819–0.914). Conclusions DCE parameters indicated treatment response at follow-up, and a random forest machine learning algorithm based on DCE parameters was able to predict treatment response to induction chemo-immunotherapy.

Project description:BackgroundTo determine the usefulness of Diffusion Weighted Imaging (DWI) derived from PET/MRI in discriminating normal from metastatic lymph nodes and the correlation between the metastatic lymph nodes with the grade and the localization of the primary tumor.MethodsRetrospective study of 90 lymph nodes from 90 subjects; 65 patients who had proven histopathological metastatic lymph nodes from (HNSCC) who had undergone 18F- PET/MRI for clinical staging and assessment and twenty-five lymph nodes were chosen from 25 healthy subjects. Apparent Diffusion Coefficient (ADC) map was generated from DWI with b values (0 and 800 s/mm2). ADC values of the metastatic lymph nodes were calculated and compared to the normal lymph nodes ADC values, ROC was used to determine the best cut-off values to differentiate between the two group. Metastatic lymph nodes ADC mean values were compared to primary tumor grade and localization.ResultsADCmean value of the metastatic lymph nodes in the overall sample (0.899 ± 0.98*10- 3 mm2/sec) was significantly lower than the normal lymph nodes' ADCmean value (1.267 ± 0.88*10- 3 mm2/sec); (P = 0.001). The area under the curve (AUC) was 98.3%, sensitivity and specificity were 92.3 and 98.6%, respectively, when using a threshold value of (1.138 ± 0.75*10- 3 mm2/sec) to differentiate between both groups. Significant difference was found between metastatic lymph nodes (short-axis diameter < 10 mm), ADCmean (0.898 ± 0.72*10- 3 mm2/sec), and the benign lymph nodes ADCmean, (P = 0.001). No significant difference was found between ADCmean of the metastatic lymph nodes < 10 mm and the metastatic lymph nodes > 10 mm, ADCmean (0.899 ± 0.89*10- 3 mm2/sec), (P = 0.967). No significant differences were found between metastatic lymph nodes ADCmean values and different primary tumor grades or different primary tumor localization, (P > 0.05).ConclusionDWI-ADC is an effective and efficient imaging technique in differentiating between normal and malignant lymph nodes, and might be helpful to discriminate sub-centimeters lymph nodes.Trial registrationThe trial is registered in clinical trials under ID: NCT04360993 , registration date: 17/04/2020.

Project description:PurposePatients with cancers of oropharynx have a favorable prognosis and are an ideal candidate for adaptive therapy. A replan to improve coverage or escalate/de-escalate dose based on morphological information alone may not be adequate as the grossly involved lymph nodes (LNs) of a subset of these patients tend to become cystic and often do not regress. Functional adaptation may be a better approach when considering replanning for these patients. The purpose of this study was to evaluate the weekly trends in treatment related morphological and physiological changes for these LNs using diffusion-weighted MRI (DW-MRI) and evaluate its implications for adaptive replanning.MethodsTen patients with histologically proven oropharynx HNSCC undergoing concurrent chemoradiation were analyzed in this study. MR imaging protocol included axial T1w, T2w, and DW-MRI using a 3 T Philips MR scanner. The patients were scanned weekly in radiation treatment planning position using a 16 element phased-array anterior coil and a 44 element posterior coil. A total of 65 DWI and T2w scans were analyzed. DWI was performed using an optimized single-shot echo planar imaging sequence (TR/TE = 5000/65 ms, slice thickness = 5 mm; slices = 28; b values = 0 and 800 s/mm(2)). Quantification of the DW-MRI images was performed by calculating the apparent diffusion coefficient (ADC). T2w and DWI scans were imported into the Eclipse treatment planning system and gross tumor volumes (GTVs) corresponding to grossly involved LNs were contoured on each axial slice by physician experts. An attempt was made to remove any cystic or necrotic components so that the ADC analysis was of viable tumor only. A pixel-by-pixel fit of signal intensities within the GTVs was performed assuming monoexponential behavior. From each GTV histogram mean, median, standard deviation, skewness, and kurtosis were calculated. Absolute and percent change in weekly ADC histogram parameters and percent change in T2w GTV were also calculated.ResultsFor all nodes, an immediate change in ADC was observed during first 2-3 weeks after which ADC values either continued to increase or plateaued. A few nodal volumes had a slightly decreased ADC value during later weeks. Percent increase in median ADC from weeks 1 to 6 with respect to baseline was 14%, 25%, 41%, 42%, 45%, and 58%. The corresponding change in median T2 volumes was 8%, 10%, 16%, 22%, 40%, and 42%, respectively. The ADC distribution of the viable tumors was initially highly kurtotic; however, the kurtosis decreased as treatment progressed. The ADC distribution also showed a higher degree of skewness in the first 2 weeks, progressively becoming less skewed as treatment progressed so as to slowly approach a more symmetric distribution.ConclusionsPhysiological changes in LNs represented by changes in ADC evaluated using DW-MRI are evident sooner than the morphological changes calculated from T2w MRI. The decisions for adaptive replanning may need to be individualized and should be based primarily on tumor functional information. The authors' data also suggest that for many patients, week 3 maybe the optimal time to intervene and replan. Larger studies are needed to confirm their findings.

Project description:INTRODUCTION:In this study, we investigate the role of radiomics for prediction of overall survival (OS), locoregional recurrence (LRR) and distant metastases (DM) in stage III and IV HNSCC patients treated by chemoradiotherapy. We hypothesize that radiomic analysis of (peri-)tumoral tissue may detect invasion of surrounding tissues indicating a higher chance of locoregional recurrence and distant metastasis. METHODS:Two comprehensive data sources were used: the Dutch Cancer Society Database (Alp 7072, DESIGN) and "Big Data To Decide" (BD2Decide). The gross tumor volumes (GTV) were delineated on contrast-enhanced CT. Radiomic features were extracted using the RadiomiX Discovery Toolbox (OncoRadiomics, Liege, Belgium). Clinical patient features such as age, gender, performance status etc. were collected. Two machine learning methods were chosen for their ability to handle censored data: Cox proportional hazards regression and random survival forest (RSF). Multivariable clinical and radiomic Cox/ RSF models were generated based on significance in univariable cox regression/ RSF analyses on the held out data in the training dataset. Features were selected according to a decreasing hazard ratio for Cox and relative importance for RSF. RESULTS:A total of 444 patients with radiotherapy planning CT-scans were included in this study: 301 head and neck squamous cell carcinoma (HNSCC) patients in the training cohort (DESIGN) and 143 patients in the validation cohort (BD2DECIDE). We found that the highest performing model was a clinical model that was able to predict distant metastasis in oropharyngeal cancer cases with an external validation C-index of 0.74 and 0.65 with the RSF and Cox models respectively. Peritumoral radiomics based prediction models performed poorly in the external validation, with C-index values ranging from 0.32 to 0.61 utilizing both feature selection and model generation methods. CONCLUSION:Our results suggest that radiomic features from the peritumoral regions are not useful for the prediction of time to OS, LR and DM.

Project description:Head and neck cancer is a highly genetic and metabolic heterogeneous collection of malignancies of the lip, oral cavity, salivary glands, pharynx, esophagus, paranasal sinuses, and larynx with five-year survival rates ranging from 12% to 93%. Patients with head and neck cancer typically present with advanced stage III, IVa, or IVb disease and are treated with comprehensive modality including chemotherapy, radiotherapy, and surgery. Despite advancements in treatment modality and technique, noisome recurrence, invasiveness, and resistance as well as posttreatment complications severely influence survival rate and quality of life. Thus, new therapeutic strategies are urgently needed that offer enhanced efficacy with less toxicity. ROS in cancer cells plays a vital role in regulating cell death, DNA repair, stemness maintenance, metabolic reprogramming, and tumor microenvironment, all of which have been implicated in resistance to chemo-/radiotherapy of head and neck cancer. Adjusting ROS generation and elimination to reverse the resistance of cancer cells without impairing normal cells show great hope in improving the therapeutic efficacy of chemo-/radiotherapy of head and neck cancer. In the current review, we discuss the pivotal and targetable redox-regulating system including superoxide dismutases (SODs), tripeptide glutathione (GSH), thioredoxin (Trxs), peroxiredoxins (PRXs), nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/keap1), and mitochondria electron transporter chain (ETC) complexes and their roles in regulating ROS levels and their clinical significance implicated in chemo-/radiotherapy of head and neck cancer. We also summarize several old drugs (referred to as the non-anti-cancer drugs used in other diseases for a long time) and small molecular compounds as well as natural herbs which effectively modulate cellular ROS of head and neck cancer to synergize the efficacy of conventional chemo-/radiotherapy. Emerging interdisciplinary techniques including photodynamic, nanoparticle system, and Bio-Electro-Magnetic-Energy-Regulation (BEMER) therapy are promising measures to broaden the potency of ROS modulation for the benefit of chemo-/radiotherapy in head and neck cancer.

Dataset Information

Predictive Value of Early Post-Treatment Diffusion-Weighted MRI for Recurrence or Tumor Progression of Head and Neck Squamous Cell Carcinoma Treated with Chemo-Radiotherapy.

Publications

Predictive Value of Early Post-Treatment Diffusion-Weighted MRI for Recurrence or Tumor Progression of Head and Neck Squamous Cell Carcinoma Treated with Chemo-Radiotherapy.

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