Dose-dense TPF induction chemotherapy for locally advanced head and neck cancer: a phase II study.

BACKGROUND: Phase 3 studies suggest that induction chemotherapy (ICT) of cisplatin and 5-fluorouracil plus docetaxel (TPF) is effective but toxic for patients with squamous-cell carcinoma of the head and neck (SCCHN). Dose-dense chemotherapy may yield favorable outcomes compared with standard-dose chemotherapy, yet the optimal induction regimen remains undefined. We assessed the efficacy and tolerability of biweekly dose-dense TPF ICT in patients with SCCHN. METHODS: In this prospective phase II study, We enrolled patients with stage III/IV (AJCC 7th edition) unresectable squamous cell carcinoma of head and neck cancer. Patients received dose-dense TPF (ddTPF) with cisplatin and docetaxel 50 mg/m2 on day 1, leucovorin 250 mg/m2 on day1, followed by 48-h continuous infusion of 2500 mg/m2 of 5-fluorouracil on day 1 and 2, every 2 weeks for 6 cycles followed by radiotherapy. The primary endpoint was the response rate (RR) after ICT. RESULTS: Fifty-eight patients were enrolled from June 2014 to September 2015. Overall RR after ICT was 89.6% [complete response (CR), 31%; partial response (PR), 58.6%]. Grade 3/4 neutropenia, mucositis, and diarrhea incidences were 25.9, 1.7, and 1.7%, respectively. 94.8% of patients completed all treatment courses of ICT without dose reduction. The 3-year overall survival (OS) was 54.3% (95%CI: 39.7 to 66.8%) and progression-free survival (PFS) was 34.3% (95%CI: 22.0 to 46.9%). Multivariate analysis showed that CR after ICT is an independent prognostic factor for OS and PFS. CONCLUSIONS: Six cycles of ddTPF is an active, well-tolerated induction regimen for patients with SCCHN. The presence of CR after ICT predicted long-term survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04397341 , May 21, 2020, retrospectively registered.

Organ Contouring for Lung Cancer Patients with a Seed Generation Scheme and Random Walks.

In this study, we proposed a semi-automated and interactive scheme for organ contouring in radiotherapy planning for patients with non-small cell lung cancers. Several organs were contoured, including the lungs, airway, heart, spinal cord, body, and gross tumor volume (GTV). We proposed some schemes to automatically generate and vanish the seeds of the random walks (RW) algorithm. We considered 25 lung cancer patients, whose computed tomography (CT) images were obtained from the China Medical University Hospital (CMUH) in Taichung, Taiwan. The manual contours made by clinical oncologists were taken as the gold standard for comparison to evaluate the performance of our proposed method. The Dice coefficient between two contours of the same organ was computed to evaluate the similarity. The average Dice coefficients for the lungs, airway, heart, spinal cord, and body and GTV segmentation were 0.92, 0.84, 0.83, 0.73, 0.85 and 0.66, respectively. The computation time was between 2 to 4 min for a whole CT sequence segmentation. The results showed that our method has the potential to assist oncologists in the process of radiotherapy treatment in the CMUH, and hopefully in other hospitals as well, by saving a tremendous amount of time in contouring.

Radiomics features analysis of PET images in oropharyngeal and hypopharyngeal cancer.

This study used radiomics image analysis to examine the differences of texture feature values extracted from oropharyngeal and hypopharyngeal cancer positron emission tomography (PET) images on various tumor segmentations, and finds the proper and stable feature groups. A total of 80 oropharyngeal and hypopharyngeal cancer cases were retrospectively recruited. Radiomics method was applied to the PET image for the 80 oropharyngeal and hypopharyngeal cancer cases to extract texture features from various defined metabolic volumes. Kruskal-Wallis one-way analysis of variance method was used to test whether feature value difference exists between groups, which were grouped by stage, response to treatment, and recurrence. If there was a significant difference, the corresponding feature cutoff value was applied to the Kaplan-Meier estimator to estimate the survival functions. For the various defined metabolic volumes, there were 16 features that had significant differences between early (T1, T2) and late tumor stages (T3, T4). Five images and 2 textural features were found to be able to predict the tumor response and recurrence, respectively, with the areas under the receiver operating characteristic curves reaching 0.7. The histogram entropy was found to be a good predictor of overall survival (OS) and primary relapse-free survival (PRFS) of oropharyngeal and hypopharyngeal cancer patients. Textural features from PET images provide predictive and prognostic information in tumor staging, tumor response, recurrence, and have the potential to be a prognosticator for OS and PRFS in oropharyngeal and hypopharyngeal cancer.

Radiomic features analysis in computed tomography images of lung nodule classification.

PURPOSE: Radiomics, which extract large amount of quantification image features from diagnostic medical images had been widely used for prognostication, treatment response prediction and cancer detection. The treatment options for lung nodules depend on their diagnosis, benign or malignant. Conventionally, lung nodule diagnosis is based on invasive biopsy. Recently, radiomics features, a non-invasive method based on clinical images, have shown high potential in lesion classification, treatment outcome prediction. METHODS: Lung nodule classification using radiomics based on Computed Tomography (CT) image data was investigated and a 4-feature signature was introduced for lung nodule classification. Retrospectively, 72 patients with 75 pulmonary nodules were collected. Radiomics feature extraction was performed on non-enhanced CT images with contours which were delineated by an experienced radiation oncologist. RESULT: Among the 750 image features in each case, 76 features were found to have significant differences between benign and malignant lesions. A radiomics signature was composed of the best 4 features which included Laws_LSL_min, Laws_SLL_energy, Laws_SSL_skewness and Laws_EEL_uniformity. The accuracy using the signature in benign or malignant classification was 84% with the sensitivity of 92.85% and the specificity of 72.73%. CONCLUSION: The classification signature based on radiomics features demonstrated very good accuracy and high potential in clinical application.

Immunohistochemical biomarkers and volumetric parameters for predicting radiotherapy-based outcomes in patients with p16-negative pharyngeal cancer.

BACKGROUND: This study determined the prognostic effects of immunohistochemical biomarkers and volumetric parameters predicting radiotherapy-based treatment in patients with p16-negative squamous cell carcinoma of the oropharynx or hypopharynx. RESULTS: VEGF immunoreactivity > 2 and GLUT1 overexpression were prognostic factors for lower cause-specific survival. Moreover, both factors were associated with lower disease-free survival. The predictors of lower primary relapse-free survival were VEGF immunoreactivity > 2 and CT-based gross tumor volume > 16 mL. MATERIALS AND METHODS: Immunohistochemical biomarkers in pretreatment biopsy specimens from 60 patients with p16-negative cancer were analyzed using tissue microarrays. Computed tomography (CT)-based and biological tumor volumes were retrieved through fluorodeoxyglucose positron emission tomography-CT. Correlations of cause-specific, disease-free, and primary relapse-free survival with volumetric parameters and the immunohistochemical biomarker score were investigated. CONCLUSIONS: For patients with p16-negative pharyngeal cancer receiving radiotherapy, treatment outcomes can be stratified by VEGF and GLUT1 expression and CT-based gross tumor volume.

The clinical outcome correlations between radiation dose and pretreatment metabolic tumor volume for radiotherapy in head and neck cancer: A retrospective analysis.

This study was to investigate the clinical outcomes between radiation dose and pretreatment metabolic tumor volume (MTV) in patients with head and neck cancer treated with definitive chemoradiotherapy.Thirty-four patients received pretreatment F-fluorodeoxyglucose (F-FDG) positron emission tomography-computed tomography (PET/CT) were recruited for this study. The CT-based volume (gross tumor volume of the primary [GTVp]) and 4 types of MTVs were measured on the basis of either a maximal standardized uptake value (SUVmax) of 2.5 (MTV2.5), 3.0 (MTV3.0), or a fixed threshold of 40% (MTV40%), 50% (MTV50%). F-FDG PET-CT images before treatment, and data including response to treatment, local recurrence, death due to the cancer, disease-free survival (DFS) and primary relapse-free survival (PRFS), were collected for analysis.The Wilcoxon rank test showed that all values determined by the different delineation techniques were significantly different from the GTVp (P < .05). Tumor volume and the homogeneity of target dose of MTV2.5, MTV3.0, MTV40%, and MTV50% were significantly different between the 2 groups of patients through treatment outcomes (P < .05).The survival curves for DFS and PRFS demonstrated that the homogeneity of the target dose in MTVs was a good indicator. The homogeneity of target dose in the tumor is a potential indicator of DSF and PRFS in patients with head and neck cancer who underwent radiotherapy.

Immunohistochemical overexpression of hypoxia-induced factor 1α associated with slow reduction in 18fluoro-2-deoxy-D-glucose uptake for chemoradiotherapy in patients with pharyngeal cancer.

BACKGROUND: This study examined genomic factors associated with a reduction in 18fluoro-2-deoxy-D-glucose (FDG) uptake during positron emission tomography-computed tomography (PET-CT) for definitive chemoradiotherapy (CRT) in patients with pharyngeal cancer. METHODS: The pretreatment and interim PET-CT images of 25 patients with advanced pharyngeal cancers receiving definitive CRT were prospectively evaluated. The maximum standardized uptake value (SUVmax) of the interim PET-CT and the reduction ratio of the SUVmax (SRR) between the two images were measured. Genomic data from pretreatment incisional biopsy specimens (SLC2A1, CAIX, VEGF, HIF1A, BCL2, Claudin-4, YAP1, MET, MKI67, and EGFR) were analyzed using tissue microarrays. Differences in FDG uptake and SRRs between tumors with low and high gene expression were examined using the Mann-Whitney test. Cox regression analysis was performed to examine the effects of variables on local control. RESULTS: The SRR of the primary tumors (SRR-P) was 0.59 ± 0.31, whereas the SRR of metastatic lymph nodes (SRR-N) was 0.54 ± 0.32. Overexpression of HIF1A was associated with a high iSUVmax of the primary tumor (P < 0.001) and neck lymph node (P = 0.04) and a low SRR-P (P = 0.02). Multivariate analysis revealed that patients who had tumors with low SRR-P or high HIF1A expression levels showed inferior local control. CONCLUSION: In patients with pharyngeal cancer requiring CRT, HIF1A overexpression was positively associated with high interim SUVmax or a slow reduction in FDG uptake. Prospective trials are needed to determine whether the local control rate can be stratified using the HIF1A level as a biomarker and SRR-P.

Kinetic Curve Type Assessment for Classification of Breast Lesions Using Dynamic Contrast-Enhanced MR Imaging.

OBJECTIVE: The aim of this study was to employ a kinetic model with dynamic contrast enhancement-magnetic resonance imaging to develop an approach that can efficiently distinguish malignant from benign lesions. MATERIALS AND METHODS: A total of 43 patients with 46 lesions who underwent breast dynamic contrast enhancement-magnetic resonance imaging were included in this retrospective study. The distribution of malignant to benign lesions was 31/15 based on histological results. This study integrated a single-compartment kinetic model and dynamic contrast enhancement-magnetic resonance imaging to generate a kinetic modeling curve for improving the accuracy of diagnosis of breast lesions. Kinetic modeling curves of all different lesions were analyzed by three experienced radiologists and classified into one of three given types. Receiver operating characteristic and Kappa statistics were used for the qualitative method. The findings of the three radiologists based on the time-signal intensity curve and the kinetic curve were compared. RESULTS: An average sensitivity of 82%, a specificity of 65%, an area under the receiver operating characteristic curve of 0.76, and a positive predictive value of 82% and negative predictive value of 63% was shown with the kinetic model (p = 0.017, 0.052, 0.068), as compared to an average sensitivity of 80%, a specificity of 55%, an area under the receiver operating characteristic of 0.69, and a positive predictive value of 79% and negative predictive value of 57% with the time-signal intensity curve method (p = 0.003, 0.004, 0.008). The diagnostic consistency of the three radiologists was shown by the κ-value, 0.857 (p<0.001) with the method based on the time-signal intensity curve and 0.826 (p<0.001) with the method of the kinetic model. CONCLUSIONS: According to the statistic results based on the 46 lesions, the kinetic modeling curve method showed higher sensitivity, specificity, positive and negative predictive values as compared with the time-signal intensity curve method in lesion classification.

Left ventricular ejection fraction estimation using mutual information on technetium-99m multiple-gated SPECT scans.

BACKGROUND: A new non-linear approach was applied to calculate the left ventricular ejection fraction (LVEF) using multigated acquisition (MUGA) images. METHODS: In this study, 50 patients originally for the estimation of the percentage of LVEF to monitor the effects of various cardiotoxic drugs in chemotherapy were retrospectively selected. All patients had both MUGA and echocardiography examinations (ECHO LVEF) at the same time. Mutual information (MI) theory was utilized to calculate the LVEF using MUGA imaging (MUGA MI). RESULTS: MUGA MI estimation was significantly different from MUGA LVEF and ECHO LVEF, respectively (p < 0.005). The higher repeatability for MUGA MI can be observed in the figure by the higher correlation coefficient for MUGA MI (r = 0.95) compared with that of MUGA LVEF (r = 0.80). Again, the reproducibility was better for MUGA MI (r = 0.90, 0.92) than MUGA LVEF (r = 0.77, 0.83). The higher correlation coefficients were obtained between proposed MUGA MI and ECHO LVEF compared to that between the conventional MUGA LVEF and ECHO LVEF. CONCLUSIONS: MUGA image with the aid of MI is promising to be more interchangeable LVEF to ECHO LVEF measurement as compared with the conventional approach on MUGA image.

Identification of Breast Cancer Using Integrated Information from MRI and Mammography.

OBJECTIVES: Integration of information from corresponding regions between the breast MRI and an X-ray mammogram could benefit the detection of breast cancer in clinical diagnosis. We aimed to provide a framework of registration from breast MRI to mammography and to evaluate the diagnosis using the combined information. MATERIALS AND METHODS: 43 patients with 46 lesions underwent both MRI and mammography scans, and the interval between the two examinations was around one month. The distribution of malignant to benign lesions was 31/46 based on histological results. Maximum intensity projection and thin-plate spline methods were applied for image registration for MRI to mammography. The diagnosis using integrated information was evaluated using results of histology as the reference. The assessment of annotations and statistical analysis were performed by the two radiologists. RESULTS: For the cranio-caudal view, the mean post-registration error between MRI and mammography was 2.2±1.9 mm. For the medio-lateral oblique view, the proposed approach performed even better with a mean error of 3.0±2.4 mm. In the diagnosis using MRI assessment with information of mammography, the sensitivity was 91.9±2.3% (29/31, 28/31), specificity 70.0±4.7% (11/15, 10/15), accuracy 84.8±3.1% (40/46, 38/46), positive predictive value 86.4±2.1% (29/33, 28/33) and negative predictive value 80.8±5.4% (11/13, 10/13). CONCLUSION: MRI with the aid of mammography shows potential improvements of sensitivity, specificity, accuracy, PPV and NPV in clinical breast cancer diagnosis compared to the use of MRI alone.

Fractionated changes in prostate cancer radiotherapy using cone-beam computed tomography.

The high mobility of the bladder and the rectum causes uncertainty in radiation doses prescribed to patients with prostate cancer who undergo radiotherapy (RT) multifraction treatments. The purpose of this study was to estimate the dose received by the bladder, rectum, and prostate from multifraction treatments using daily cone-beam computed tomography (CBCT). Overall, 28 patients with prostate cancer who planned to receive radiation treatments were enrolled in the study. The acquired CBCT before the treatment delivery was registered with the planning CT to map the dose distribution used in the treatment plan for estimating the received dose during clinical treatment. For all 28 patients with 112 data sets, the mean percentage differences (± standard deviation) in the volume and radiation dose were 44% (± 41) and 18% (± 17) for the bladder, 20% (± 21) and 2% (± 2) for the prostate, and 36% (± 29) and 22% (± 15) for the rectum, respectively. Substantial differences between the volumes and radiation dose and those specified in treatment plans were observed. Besides the use of image-guided RT to improve patient setup accuracy, further consideration of large changes in bladder and rectum volumes is strongly suggested when using external beam radiation for prostate cancer.

Risk stratification of metastatic neck nodes by CT and PET in patients with head and neck cancer receiving definitive radiotherapy.

UNLABELLED: The aim of this study was to investigate the prognostic impact of CT and (18)F-FDG PET/CT on the outcome of metastatic neck node (MNN) in patients with head and neck cancer receiving definitive radiotherapy or chemoradiotherapy. METHODS: This patient-based study included 91 patients diagnosed with pharyngeal cancers with MNN (N1, 15; N2, 70; N3, 6). All had pretreatment CT and PET/CT before definitive chemoradiotherapy/radiotherapy. Parameters of MNNs for each patient, including maximal diameter, nodal volume, radiologic central necrosis, maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis (TLG), were retrieved for the analysis. Nodal relapse-free survival (NRFS) and survivals were calculated using the Kaplan-Meier method. Independent predictors were identified using Cox regression analysis. RESULTS: After a median follow-up of 18 mo, 64 patients remained nodal relapse-free, and 27 experienced neck recurrence. Multivariate analysis showed that the application of 40% of the maximal uptake of nodal TLG (N-TLG40%) 38 g or greater (P = 0.03; hazard ratio, 2.63; 95% confidence interval, 1.10-6.30) and radiologic necrosis on CT scan (P = 0.001; hazard ratio, 10.99; 95% confidence interval, 2.56-47.62) were 2 adverse features for NRFS. Patients who had an N-TLG40% 38 g or greater and central radiologic necrosis had a significantly inferior 2-y NRFS (53% vs. 77% and 45% vs. 95%, respectively). CONCLUSION: The outcome of MNNs in patients with head and neck cancer receiving chemoradiotherapy/radiotherapy can be predicted according to radiologic necrosis and N-TLG40% value. The 2 adverse features should be validated in future trials. In this way, patients can be treated alternatively or aggressively.

Interim FDG PET/CT for predicting the outcome in patients with head and neck cancer.

OBJECTIVES/HYPOTHESIS: The study aimed to investigate the prognostic effects of interim (18) fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT) during definitive radiotherapy (RT) or chemoradiotherapy (CRT) in patients with head and neck cancer. STUDY DESIGN: This is a prospectively treatment study. METHODS: The pretreatment and interim PET/CT images of 51 patients with advanced pharyngeal cancers receiving definitive RT/CRT were evaluated prospectively. The interim PET/CT images were taken at a cumulative RT dose ranging from 41.4 to 46.8 Gy. The maximum standardized uptake value (SUVm) of the interim PET/CT and the reduction ratio of the SUVm (SRR) between the two images were measured. The differences between patients with or without local failures were examined using the Mann-Whitney test. Overall survival (OS), disease-free survival (DFS), and primary and nodal relapse-free survival rates were calculated using the Kaplan-Meier method. Independent prognosticators were identified using Cox regression analysis. RESULTS: After a median follow-up duration of 23 months, a higher interim SUVm was associated with local failures. Conducting a multivariate analysis revealed that a SUVmax reduction ratio of primary tumor (SRR-P) < 0.64 was associated with the inferior OS (hazard ratio 2.64; P =0.035) and DFS (hazard ratio 2.33; P = 0.045). Patients who had tumors with an SRR-P < 0.64 had a considerably lower 2-year OS and DFS compared with those who had SRR-P ≥ 0.64 (47% vs. 66%; 41% vs. 64%). CONCLUSION: A higher interim SUVm was associated with local recurrence. In addition, patients with a lower SRR-P should be considered to be at risk of primary failure. LEVEL OF EVIDENCE: 4.

Impact of body-mass factors on setup displacement in patients with head and neck cancer treated with radiotherapy using daily on-line image guidance.

BACKGROUND: To determine the impact of body-mass factors (BMF) before radiotherapy and changes during radiotherapy on the magnitude of setup displacement in patients with head and neck cancer (HNC). METHODS: The clinical data of 30 patients with HNC was analyzed using the alignment data from daily on-line on-board imaging from image-guided radiotherapy. BMFs included body weight, body height, and the circumference and bilateral thickness of the neck. Changes in the BMFs during treatment were retrieved from cone beam computed tomography at the 10th and 20th fractions. Setup errors for each patient were assessed by systematic error (SE) and random error (RE) through the superior-inferior (SI), anterior-posterior (AP), and medial-lateral (ML) directions, and couch rotation (CR). Using the median values of the BMFs as a cutoff, the impact of the factors on the magnitude of displacement was assessed by the Mann-Whitney U test. RESULTS: A higher body weight before radiotherapy correlated with a greater AP-SE (p = 0.045), SI-RE (p = 0.023), and CR-SE (p = 0.033). A longer body height was associated with a greater SI-RE (p = 0.002). A performance status score of 1 or 2 was related to a greater AP-SE (p = 0.043), AP-RE (p = 0.015), and SI-RE (p = 0.043). Among the ratios of the BMFs during radiotherapy, the values at the level of mastoid tip at the 20th fraction were associated with greater setup errors. CONCLUSIONS: To reduce setup errors in patients with HNC receiving RT, the use of on-line image-guided radiotherapy is recommended for patients with a large body weight or height, and a performance status score of 1-2. In addition, adaptive planning should be considered for those who have a large reduction ratio in the circumference (<1) and thickness (<0.94) over the level of the mastoid tip during the 20th fraction of treatment.

Radiotherapy for esophageal cancer using simultaneous integrated boost techniques: dosimetric comparison of helical TomoTherapy, Volumetric-modulated Arc Therapy (RapidArc) and dynamic intensity-modulated radiotherapy.

This study compared TomoTherapy (TM), with Volumetric-Modulated Arc Therapy (RapidArc, RA), and dynamic intensity-modulated radiotherapy (dIMRT) for locally advanced esophageal cancer (LAEC) with a simultaneous integrated boost (SIB) technique with regard to the target coverage and sparing of organs at risk (OARs). Twelve patients receiving four-dimensional computed tomography simulation were enrolled for dosimetric comparison. Gross tumor volume was contoured with the maximum intensity projection method. Using an SIB method, Planning target volume low (PTVL) and planning target volume high (PTVH) were prescribed as 54 Gy and 60 Gy, respectively, each administered in 30 fractions. We compared the results of statistical analysis for target coverage, homogeneity index (HI) and conformity index (CI) of PTVs, parameters of OARs and monitor unit (MU) were compared for analysis. The HI for PTVH varied significantly for the 3 techniques of TM, RA, and dIMRT (4.38 ± 0.86, 6.40 ± 0.86, and 6.11 ± 0.68, respectively; P , 0.001). The CI scores for PTVH also differed across TM, RA, and dIMRT (0.64 6 0.06, 0.53 6 0.06, and 0.59 ± 0.05, respectively; P < 0.001). The HI for PTVL showed a significant difference among TM, RA, and dIMRT (15.44 ± 0.88, 20.88 ± 1.03 and 18.65 ± 1.42, respectively; P < 0.001). The percentage of lung volume receiving 5 Gy (V5) and 20 Gy (V20) (for V5: TM 54.4 ± 8.0%; RA 67.5 ± 14.5%, P < 0.01; dIMRT 44.8 ± 8.2%; for V20: 13.6 6 3.3%, 12.2 ± 3.6%, 18.1 6 3.4%, P = 0.001, respectively). For RA, the lung V5 ≥ 65% was observed in 6 patients and the V10 ≥ 50 % in one patient. TM, RA and dIMRT provided comparable coverage of the target and sparing of OARs. TM demonstrated superior CI and HI for tumor coverage and lowered the specified dose parameters for lung. RA provided an advantage in terms of the lowest MU and V20 of the lung, but its higher lung V5 was of some concern about lung toxicity.

The clinical application of 4D 18F-FDG PET/CT on gross tumor volume delineation for radiotherapy planning in esophageal squamous cell cancer.

A combination of four-dimensional computed tomography with (18)F-fluorodeoxyglucose positron emission tomography (4D CT-FDG PET) was used to delineate gross tumor volume (GTV) in esophageal cancer (EC). Eighteen patients with EC were prospectively enrolled. Using 4D images taken during the respiratory cycle, the average CT image phase was fused with the average FDG PET phase in order to analyze the optimal standardized uptake values (SUV) or threshold. PET-based GTV (GTV(PET)) was determined with eight different threshold methods using the auto-contouring function on the PET workstation. The difference in volume ratio (VR) and conformality index (CI) between GTV(PET) and CT-based GTV (GTV(CT)) was investigated. The image sets via automatic co-registrations of 4D CT-FDG PET were available for 12 patients with 13 GTV(CT) values. The decision coefficient (R(2)) of tumor length difference at the threshold levels of SUV 2.5, SUV 20% and SUV 25% were 0.79, 0.65 and 0.54, respectively. The mean volume of GTV(CT) was 29.41 ± 19.14 ml. The mean VR ranged from 0.30 to 1.48. The optimal VR of 0.98, close to 1, was at SUV 20% or SUV 2.5. The mean CI ranged from 0.28 to 0.58. The best CI was at SUV 20% (0.58) or SUV 2.5 (0.57). The auto-contouring function of the SUV threshold has the potential to assist in contouring the GTV. The SUV threshold setting of SUV 20% or SUV 2.5 achieves the optimal correlation of tumor length, VR, and CI using 4D-PET/CT images.

Pretreatment maximal standardized uptake value of the primary tumor predicts outcome to radiotherapy in patients with pharyngeal cancer.

This study aimed to investigate whether the combination of clinical information, tumor volume and pretreatment SUVmax at the primary tumors might improve the prognostic stratification in pharyngeal cancer (PC) patients treated with radiotherapy (RT). Sixty-two patients with PC (35 oropharynx; 27 hypopharynx) treated with RT were enrolled in this retrospective analysis. All patients received pretreatment FDG- PET or PET/CT. The primary tumor relapse-free survival (PRFS) was calculated according to different variables. The median values of the SUVmax for the primary tumors (SUVp-max) and the gross tumor volume (GTVp) were used to divide patients into two groups. Independent prognosticators were identified by the Cox regression analysis. In this study, the median SUVp-max and GTVp was 11 and 15.5 ml. Patients having tumors with SUVp-max > 11 had a significantly inferior 2-year PRFS (41% vs. 75%, p = 0.003) compared with patients having lower uptake tumors. Multivariate analysis of the PRFS showed two prognostic factors: SUVp-max > 11 (p = 0.04, hazard ratio = 2.67) and GTVp > 15.5 ml (p = 0.03, hazard ratio = 2.88). For patients with a GTVp less than 15.5 ml, there was a more significant impact of SUVmax-p on their PRFS compared to that for those with large ones. We disclosed a higher pretreatment SUVp-max is a predictor for primary recurrence in PC patients treated with RT, particularly for those with smaller tumor volumes. Patients with a large tumor volume or a higher SUVp-max should be considered for requiring more aggressive treatment approaches.

Use of pretreatment metabolic tumour volumes to predict the outcome of pharyngeal cancer treated by definitive radiotherapy.

PURPOSE: The aim of the study was to investigate the predictive role of pretreatment metabolic volume (MTV) in pharyngeal cancer (PC) patients treated with definitive (chemo) radiotherapy. METHODS: This retrospective analysis enrolled 64 patients with PC treated with (chemo) radiotherapy. All patients received pretreatment fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Four PET segmentation methods were used, namely applying an isocontour at a standardized uptake value (SUV) of either 2.5 or 3.0 (MTV2.5 and MTV3.0) or using fixed thresholds of either 40 or 50 % (MTV40 %, MTV50 %) of the maximum intratumoural FDG activity. Disease-free survival (DFS) and primary relapse-free survival (PRFS) were examined according to cutoffs of the median values for each MTV and the gross tumour volume (GTVp). Independent prognosticators were identified by Cox regression analysis. RESULTS: With a median follow-up of 24 months, 19 patients died, and 26 patients experienced tumour relapse at primary sites. Multivariate analysis of the DFS showed that MTV2.5 > 13.6 ml was the only predictor of relapse [p = 0.011, hazard ratio = 2.69, 95 % confidence interval (CI) 1.25-5.76]. The independent predictor for PRFS was MTV2.5 > 13.6 ml (p = 0.003, hazard ratio = 3.76, 95 % CI 1.57-8.92), whereas GTVp > 15.5 ml had a marginal impact on PRFS (p = 0.06, hazard ratio = 3.54, 95 % CI 0.97-11.85). Patients having tumours with MTV2.5 > 13.6 ml had a significantly inferior 2-year PRFS compared with patients who had lower MTV2.5 tumours (39 vs 72 %, respectively, p = 0.001). CONCLUSION: For PC patients treated with definitive (chemo)radiotherapy, pretreatment MTV2.5 volume achieved the best predictive value for primary recurrence, and the same value was also a prognosticator for DFS.

Clinical implications of the tumor volume reduction rate in head-and-neck cancer during definitive intensity-modulated radiotherapy for organ preservation.

PURPOSE: To investigate the prognostic value of the volume reduction rate (VRR) in patients with head-and-neck cancer treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Seventy-six patients with oropharyngeal cancer (OPC) and another 76 with hypopharyngeal cancer (HPC) were enrolled in volumetric analysis. All patients received allocated radiotherapy courses. Adaptive computed tomography was done 4 to 5 weeks after the start of IMRT. Primary tumor volume measurement was derived using separate images for the pretreatment gross tumor volume (pGTV) and the interval gross tumor volume. RESULTS: In the OPC group, the pGTV ranged from 6.6 to 242.6 mL (mean, 49.9 mL), whereas the value of the VRR ranged from 0.014 to 0.74 (mean, 0.43). In HPC patients, the pGTV ranged from 4.1 to 152.4 mL (mean, 35.6 mL), whereas the VRR ranged from -1.15 to 0.79 (mean, 0.33). Multivariate analysis of the primary tumor relapse-free survival for OPC revealed three prognostic factors: T4 tumor (p = 0.0001, hazard ratio 7.38), pGTV ≥20 mL (p = 0.01, hazard ratio 10.61), and VRR <0.5 (p = 0.001, hazard ratio 6.49). Multivariate analysis of the primary tumor relapse-free survival for HPC showed two prognostic factors: pGTV ≥30 mL (p = 0.001, hazard ratio 2.87) and VRR <0.5 (p = 0.03, hazard ratio 2.25). CONCLUSION: The VRR is an outcome predictor for local control in OPC and HPC patients treated with IMRT. Those with large tumor volumes or a VRR <0.5 should be considered for a salvage operation or a dose-escalation scheme.

18F-FDG PET/CT-based gross tumor volume definition for radiotherapy in head and neck cancer: a correlation study between suitable uptake value threshold and tumor parameters.

BACKGROUND: To define a suitable threshold setting for gross tumor volume (GTV) when using 18Fluoro-deoxyglucose positron emission tomography and computed tomogram (PET/CT) for radiotherapy planning in head and neck cancer (HNC). METHODS: Fifteen HNC patients prospectively received PET/CT simulation for their radiation treatment planning. Biological target volume (BTV) was derived from PET/CT-based GTV of the primary tumor. The BTVs were defined as the isodensity volumes when adjusting different percentage of the maximal standardized uptake value (SUVmax), excluding any artifact from surrounding normal tissues. CT-based primary GTV (C-pGTV) that had been previously defined by radiation oncologists was compared with the BTV. Suitable threshold level (sTL) could be determined when BTV value and its morphology using a certain threshold level was observed to be the best fitness of the C-pGTV. Suitable standardized uptake value (sSUV) was calculated as the sTL multiplied by the SUVmax. RESULTS: Our result demonstrated no single sTL or sSUV method could achieve an optimized volumetric match with the C-pGTV. The sTL was 13% to 27% (mean, 19%), whereas the sSUV was 1.64 to 3.98 (mean, 2.46). The sTL was inversely correlated with the SUVmax [sTL = -0.1004 Ln (SUVmax) + 0.4464; R2 = 0.81]. The sSUV showed a linear correlation with the SUVmax (sSUV = 0.0842 SUVmax + 1.248; R2 = 0.89). The sTL was not associated with the value of C-pGTVs. CONCLUSION: In PET/CT-based BTV for HNC, a suitable threshold or SUV level can be established by correlating with SUVmax rather than using a fixed threshold.