The feasibility of dose escalation using intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) with FDG PET/CT guided in esophageal cancer.

Context: Previous studies show that dose escalation for gross tumor volume (GTV) improves local control of esophageal cancer (EC). However, optimal boosting remains uncertain. Recently, functional imaging guidance to achieve dose escalation in high-risk areas of tumors has been proposed. Aims: This study evaluated the feasibility of dose escalation in tumor regions with high fluorodeoxyglucose (FDG) uptake using intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT). Settings and Design: GTVPET was defined as a high FDG uptake region with 50% SUVmax threshold for dose escalation. IMRT and IMPT plans were generated for three boosting modes: plan 50.4 (50.4 Gy in clinical target volume, CTV), plan 63 (50.4 Gy in CTV, 63 Gy in GTV), plan 70 (50.4 Gy in CTV, 63 Gy in GTV, and 70 Gy in GTVPET). Methods and Material: Eleven patients with squamous cell carcinoma were evaluated. Dose parameters for heart, lung, and spinal cord were compared based on the dose-volume histogram (DVH). Statistical Analysis Used: Paired t-test was performed on the doses to organs-at-risk (OARs) among plan 50.4, plan 63, and plan 70 for IMRT and IMPT. Results: Dosimetric parameters for IMRT for heart, lung, and spinal cord increased significantly for plan 63 and some parameters even exceeded dose limits for OARs. Further dose escalation in GTV-PET did not increase dosimetric parameters significantly. Most dosimetric parameters of OARs in IMPT exhibited no statistical change compared with plan 50.4, and doses to OARs were far less than dose constraints. Conclusions: Dose escalation by IMRT may lead to increased risk of radiation-related injury. Further dose escalation in high FDG uptake regions did not increase doses to OARs. This dose escalation is ideal for achieving better outcomes for EC treatment.

Potential 18F-RGD PET/CT and DCE-MRI Imaging-Based Biomarkers for Postoperative Survival Prediction Among Patients With Newly Diagnosed Glioblastoma Treated With Bevacizumab and Chemoradiotherapy.

Purpose: To investigate the ability of potential imaging biomarkers based on 18F-AlF-NOTA-PRGD2 positron emission tomography/computed tomography (18F-RGD PET/CT) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) imaging to predict the response to bevacizumab combined with conventional therapy in postoperative newly diagnosed glioblastoma. Methods: Twenty patients with newly diagnosed with glioblastoma after surgery were prospectively enrolled to receive bevacizumab plus conventional concurrent radiotherapy and temozolomide (CCRT). 18F-RGD PET/CT and DCE-MRI were performed at baseline, week 3, and week 10 for each patient. Statistical methods included the analysis of variance (ANOVA), Kaplan-Meier method and Cox proportional hazard analysis. Results: All patients completed CCRT plus bevacizumab therapy without interruption. The median follow-up time was 33.9 months (95% confidence interval [CI], 28.3-39.5 months). The median progression-free survival (PFS) and overall survival (OS) was 9.66 months (95% CI, 6.20-13.12 months) and 15.89 months (95% CI, 13.89-17.78), respectively. Treatment was generally well tolerated, and there were no Treatment emergent adverse events (TEAEs) with a toxicity grade equal to or exceeding 3 or that led to termination of treatment or patient death.Over the treatment interval of bevacizumab therapy from week 3 to week 10, patients with a large decrease of SUVmean was associated with a better PFS with a hazard ratio (HR) of 6.562, 95% CI (1.318-32.667), p=0.022. According to Kaplan-Meier analysis, patients with a decrease in the SUVmean of more than 0.115 on 18F-RGD PET/CT had a longer PFS than those with a decrease in the SUVmean of 0.115 or less (12.25 months vs.7.46 months, p=0.009). For OS, only a small decrease of Ktrans was also found to have certain prognostic value (HR=0.986, 95% CI (0.975-0.998), p=0.023). Patients with a decrease in Ktrans larger than 37.03 (min-1) on DCE-MRI had worse OS than those with a decrease in Ktrans of 37.03 (min-1) or less (15.93 months vs. 26.42 months, p=0.044). Conclusion: 18F-RGD PET/CT and DCE-MRI may be valuable in evaluating the response of glioblastoma to treatment with the combination of bevacizumab and CCRT, with a greater decrease in SUVmean predicting better PFS as well as a small decrease in Ktrans predicting improved OS.

Clinicopathologic analysis of microscopic tumor extension in glioma for external beam radiotherapy planning.

BACKGROUND: There is no consensus regarding the clinical target volume (CTV) margins in radiotherapy for glioma. In this study, we aimed to perform a complete macropathologic analysis examining microscopic tumor extension (ME) to more accurately define the CTV in glioma. METHODS: Thirty-eight supra-total resection specimens of glioma patients were examined on histologic sections. The ME distance, defined as the maximum linear distance from the tumor border to the invasive tumor cells, was measured at each section. We defined the CTV based on the relationships between ME distance and clinicopathologic features. RESULTS: Between February 2016 and July 2020, a total of 814 slides were examined, corresponding to 162 slides for low-grade glioma (LGG) and 652 slides for high-grade glioma (HGG). The ME value was 0.69 ± 0.43 cm for LGG and 1.29 ± 0.54 cm for HGG (P < 0.001). After multivariate analysis, tumor grade, O6-methylguanine-DNA-methyltransferase promoter methylated status (MGMTm), isocitrate dehydrogenase wild-type status (IDHwt), and 1p/19q non-co-deleted status (non-codel) were positively correlated with ME distance (all P < 0.05). We defined the CTV of glioma based on tumor grade. To take into account approximately 95% of the ME, a margin of 1.00 cm, 1.50 cm, and 2.00 cm were chosen for grade II, grade III, and grade IV glioma, respectively. Paired analysis of molecularly defined patients confirmed that tumors that had all three molecular alterations (i.e., MGMTm/IDHwt/non-codel) were the most aggressive subgroups (all P < 0.05). For these patients, the margin could be up to 1.50 cm, 2.00 cm, and 2.50 cm for grade II, grade III, and grade IV glioma, respectively, to cover the subclinical lesions in 95% of cases. CONCLUSIONS: The ME was different between the grades of gliomas. It may be reasonable to recommend 1.00 cm, 1.50 cm, and 2.00 cm CTV margins for grade II, grade III, and grade IV glioma, respectively. Considering the highly aggressive nature of MGMTm/IDHwt/non-codel tumors, for these patients, the margin could be further expanded by 0.5 cm. These recommendations would encompass microscopic disease extension in 95% of cases. TRIAL REGISTRATION: The trial was registered with Chinese Clinical Trial Registry ( ChiCTR2100049376 ).

Determining optimal clinical target volume margins in high-grade glioma based on microscopic tumor extension and magnetic resonance imaging.

INTRODUCTION: In this study, we performed a consecutive macropathologic analysis to assess microscopic extension (ME) in high-grade glioma (HGG) to determine appropriate clinical target volume (CTV) margins for radiotherapy. MATERIALS AND METHODS: The study included HGG patients with tumors located in non-functional areas, and supratotal resection was performed. The ME distance from the edge of the tumor to the microscopic tumor cells surrounding brain tissue was measured. Associations between the extent of ME and clinicopathological characteristics were evaluated by multivariate linear regression (MVLR) analysis. An ME predictive model was developed based on the MVLR model. RESULTS: Between June 2017 and July 2019, 652 pathologic slides obtained from 30 HGG patients were analyzed. The mean ME distance was 1.70 cm (range, 0.63 to 2.87 cm). The MVLR analysis identified that pathologic grade, subventricular zone (SVZ) contact and O6-methylguanine-DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status were independent variables predicting ME (all P < 0.05). A multivariable prediction model was developed as follows: YME = 0.672 + 0.513XGrade + 0.380XSVZ + 0.439XMGMT + 0.320XIDH + 0.333X1p/19q. The R-square value of goodness of fit was 0.780. The receiver operating characteristic curve proved that the area under the curve was 0.964 (P < 0.001). CONCLUSION: ME was heterogeneously distributed across different grades of gliomas according to the tumor location and molecular marker status, which indicated that CTV delineation should be individualized. The model could predict the ME of HGG, which may help clinicians determine the CTV for individual patients. Trial registration The trial was registered with Chinese Clinical Trial Registry (ChiCTR2100046106). Registered 4 May 2021-Retrospectively registered.

Implementation of diffusion-weighted magnetic resonance imaging in target delineation of central lung cancer accompanied with atelectasis in precision radiotherapy.

Radiotherapy, particularly the target delineation of cancer based on scanned images, plays a key role in the planning of cancer treatment. Recently, diffusion-weighted magnetic resonance imaging (DW-MRI) has emerged as a prospective superior procedure compared with intensified computed tomography (CT) and positron emission tomography (PET) in the target delineation of cancer. However, the implication of DW-MRI in lung cancer, the leading cause of cancer-associated mortality worldwide, has not been extensively evaluated. In the present study, the gross target volumes of lung cancer masses delineated using the DW-MRI, CT and PET procedures were compared in a pairwise manner in a group of 27 lung cancer patients accompanied with atelectasis of various levels. The data showed that compared with CT and PET procedures, DW-MRI has a more precise delineation of lung cancer while exhibiting higher reproducibility. Together with the fact that it is non-invasive and cost-effective, these data demonstrate the great application potential of the DW-MRI procedure in cancer precision radiotherapy.

A comparison study between gross tumor volumes defined by preoperative magnetic resonance imaging, postoperative specimens, and tumor bed for radiotherapy after breast-conserving surgery.

BACKGROUND: The identification and contouring of target volume is important for breast-conserving therapy. The aim of the study was to compare preoperative magnetic resonance imaging (MRI), postoperative pathology, excised specimens' (ES) size, and tumor bed (TB) delineation as methods for determining the gross tumor volume (GTV) for radiotherapy after breast-conserving surgery (BCS). METHODS: Thirty-three patients with breast cancer who underwent preoperative MRI and radiotherapy after BCS were enrolled. The GTVs determined by MRI, pathology, and the ES were defined as GTVMRI, GTVPAT, and GTVES, respectively. GTVMRI+1 was defined as a 1.0-cm margin around the GTVMRI. The radiation oncologist delineated GTV of the TB (GTVTB) using planning computed tomography according to ≥5 surgical clips placed in the lumpectomy cavity (LC). RESULTS: The median GTVMRI, GTVMRI+1, GTVPAT, GTVES, and GTVTB were 0.97 cm (range, 0.01-6.88), 12.58 cm (range, 3.90-34.13), 0.97 cm (range, 0.01-6.36), 15.46 cm (range, 1.15-70.69), and 19.24 cm (range, 4.72-54.33), respectively. There were no significant differences between GTVMRI and GTVPAT, GTVMRI+1 and GTVES, GTVES and GTVTB (P = 0.188, 0.070, and 0.264, respectively). GTVMRI is positively related with GTVPAT. However, neither GTVES nor GTVTB correlated with GTVMRI (P = 0.071 and 0.378, respectively). Furthermore, neither GTVES nor GTVTB correlated with GTVMRI+1 (P = 0.068 and 0.375, respectively). CONCLUSION: When ≥5 surgical clips were placed in the LC for BCS, the volume of TB was consistent with the volume of ES. Neither the volume of TB nor the volume of ES correlated significantly with the volume of tumor defined by preoperative MRI.

Can an ¹8F-ALF-NOTA-PRGD2 PET/CT Scan Predict Treatment Sensitivity to Concurrent Chemoradiotherapy in Patients with Newly Diagnosed Glioblastoma?

UNLABELLED: This study examined the value of a novel 1-step labeled integrin α(v)ß3-targeting (18)F-AlF-NOTA-PRGD2 (denoted as (18)F-RGD) scan in assessing sensitivity to concurrent chemoradiotherapy (CCRT) in patients with newly diagnosed glioblastoma multiforme (GBM). METHODS: Twenty-five patients with newly diagnosed GBM were enrolled in this study 3-5 wk after surgical resection. All participants were investigated with (18)F-RGD PET/CT on baseline (T1) and at the third week (T2) after the start of CCRT. Tumor volume, maximal and mean standardized uptake value of the tumor (SUVmax, SUVmean), and tumor-to-nontumor ratios of the tumor volume were obtained. The MRI treatment response was assessed at the 11th week (T3). The change in the lesion volume from T1 to T3 on MRI was used as an endpoint to evaluate the predictive ability of (18)F-RGD PET/CT. RESULTS: With (18)F-RGD PET/CT imaging, we successfully visualized the residual lesions of GBM. Twenty-five and 23 (18)F-RGD PET/CT scans at baseline and the third week, respectively, were available for analysis. We found that (18)F-RGD PET/CT parameters, both pretreatment SUVmax on baseline (P< 0.05) and intratreatment SUVmax at the third week (SUV(maxT2)) (P< 0.05) and tumor-to-nontumor ratios at the third week (P< 0.05), were predictive of treatment sensitivity to CCRT. Additionally, the change of volume from T1 to T2 on MRI was also predictive (P< 0.05). According to receiver-operating-characteristic curve analysis, the most significant parameter was SUV(maxT2) (area under the curve, 0.846). The threshold of SUV(maxT2) was 1.35, and its sensitivity, specificity, and accuracy were 84.6%, 90.0% and 87.0%, respectively. CONCLUSION: (18)F-RGD PET/CT allows for the noninvasive visualization of GBM lesions and the prediction of sensitivity to CCRT as early as 3 wk after treatment initiation.

[Accuracy of MRI for estimating residual tumor size after neoadjuvant chemotherapy in breast cancer with three-dimensional reconstruction technique].

OBJECTIVE: To evaluate the accuracy of MRI for estimating residual tumor size after neoadjuvant chemotherapy (NAC) with three-dimensional (3D) reconstruction technique. METHODS: This was a prospective study. The data of 61 patients with pathologically proven solitary invasive ductal carcinoma (IIA-IIIC) who had received 6 to 8 cycles of NAC from July 2010 to August 2013 was analyzed. All the patients were female, aging from 31 to 70 years with a median of 49 years. Breast specimen after surgery was prepared with part-mount sub-serial section, and residual tumors were microscopically outlined, scanned and registered by Photoshop software. The 3D model of pathological and MRI residual tumors was reconstructed with 3D-DOCTOR software. The longest diameter, maximum cross-section area and volume of the residual tumors determined using 3D MRI were compared with 3D pathological findings, and the associations between MRI and pathology were analyzed by Spearman rank correlation and Bland-Altman analysis. RESULTS: The longest diameter, maximum cross-section area and volume of the residual tumors after NAC measured by MRI and pathology was highly correlated (r=0.942, 0.941, 0.903, all P=0.00). MRI appears to underestimate pathology in the longest diameter, maximum cross-section area, but slightly overestimate in volume, and two methods had a good consistence (MD=0.3 cm, 95% CI: -1.43 to 1.9 cm; MD=1.39 cm², 95% CI: -9.55 to 12.34 cm²; MD=-0.433 cm³, 95% CI: -7.065 to 6.199 cm³). CONCLUSION: 3D MRI reconstruction after NAC could accurately detects the residual tumors after neoadjuvant chemotherapy, and contribute to select patients who received breast conserving therapy after NAC with tumor downstaging.

(18)F-Fluorothymidine PET-CT for resected malignant gliomas before radiotherapy: tumor extent according to proliferative activity compared with MRI.

OBJECTIVE: To compare the presence of post-operative residual disease by magnetic resonance imaging (MRI) and [18F]fluorothymidine (FLT)-positron emission tomography (PET)-computer tomography (CT) in patients with malignant glioma and to estimate the impact of 18F-FLT PET on the delineation of post-operative target volumes for radiotherapy (RT) planning. METHODS: Nineteen patients with post-operative residual malignant gliomas were enrolled in this study. For each patient, 18F- FLT PET-CT and MRI were acquired in the same week, within 4 weeks after surgery but before the initiation of RT. The PET-CT and MRI data were co-registered based on mutual information. The residual tumor volume defined on the 18F-FLT PET (Vol-PET) was compared with that of gadolinium [Gd] enhancement on T1-weighted MRI (Vol-T1) and areas of hyperintensity on T2-weighted MRI (Vol-T2). RESULTS: The mean Vol-PET (14.61 cm3) and Vol-T1 (13.60 cm3) were comparable and smaller than the mean Vol-T2 (32.93 cm3). The regions of 18F-FLT uptake exceeded the contrast enhancement and the hyperintense area on the MRI in 14 (73.68%) and 8 patients (42.11%), respectively. In 5 (26.32%) of the 19 patients, Vol-PET extended beyond 25 mm from the margin of Vol-T1; in 2 (10.53%) patients, Vol-PET extended 20 mm from the margin of Vol-T2. Vol-PET was detected up to 35 mm away from the edge of Vol-T1 and 24 mm away from the edge of Vol-T2. In 16 (84.21%) of the 19 patients, the Vol-T1 extended beyond the Vol-PET. In all of the patients, at least some of the Vol-T2 was located outside of the Vol-PET. CONCLUSIONS: The volumes of post-operative residual tumor in patients with malignant glioma defined by 18F-FLT uptake on PET are not always consistent with the abnormalities shown on post-operative MRI. Incorporation of 18F-FLT-PET in tumor delineation may have the potential to improve the definition of target volume in post-operative radiotherapy.

Diffusion-weighted imaging in assessing pathological response of tumor in breast cancer subtype to neoadjuvant chemotherapy.

PURPOSE: To investigate the efficacy of diffusion-weighted imaging (DWI) for reflecting and predicting pathological tumor response in breast cancer subtype to neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: The retrospective study included 176 patients with breast cancer who underwent magnetic resonance imaging (MRI) examinations before and after NAC prior to surgery. The pre- and post-NAC apparent diffusion coefficient (ADC) values of tumor were measured respectively on DWI. The pathological response was classified into either a complete response (pCR) or as a noncomplete response (pNCR) to NAC with the Miller & Payne system. The relationship between the ADC value and the pathological response was assessed according to intrinsic subtypes (Luminal A, Luminal B, HER2-enriched, and triple negative) defined by immunohistochemical features. RESULTS: Multiple comparisons respectively showed that pre-NAC and post-NAC ADC were significantly different among four subtypes (P < 0.001). After the comparison between two different subtypes, the pre-NAC ADC value of the triple-negative and HER2-enriched subtypes were significantly higher than Luminal A (P < 0.001 and P < 0.001) and Luminal B subtype (P < 0.001 and P = 0.009), and the post-NAC ADC of triple-negative subtype was significantly higher than the others (P < 0.001). The pre-NAC ADC of pCRs was significantly lower than that of pNCRs only in the triple-negative subtype among four subtypes (P < 0.001), and the post-NAC ADC of pCRs was significantly higher than that of pNCRs in each subtype (P < 0.001). CONCLUSION: DWI appears to be a promising tool to determine the association of pathological response to NAC in breast cancer subtypes.

[Correlations between MRI apparent diffusion coefficient and histological grade and molecular biology of breast invasive ductal carcinoma].

OBJECTIVE: To study the correlation between the MRI apparent diffusion coefficient (ADC) value and histological grade and molecular biology of breast invasive ductal carcinoma (IDC). METHODS: This retrospective study included 125 patients with IDC verified by pathology from February 2010 to February 2013. Conventional MRI and diffusion-weighted imaging (DWI) examination were performed using a 3.0T scanner with diffusion factor of 0 and 800 s/mm(2). The region of interest (ROI) was drawn on the largest lesion and/or its two adjacent slices. The ADC value of the whole tumor was calculated as the mean ADC value. The correlation between mean ADCs and histological grade and biological factors was analyzed. RESULTS: The mean ADC of pathological grade I, II and III IDC was (1.152 ± 0.072)×10(-3) mm(2)/s, (1.102 ± 0.101)×10(-3) mm(2)/s, and (1.035 ± 0.107)×10(-3) mm(2)/s, respectively. There was a statistically significant difference among them (P = 0.003). Statistically a significant difference was observed between grade III and I (P = 0.034), grade III and II (P = 0.006), but not between grade I and II (P = 0.741). A significant correlation was observed between ADC value and pathological grade (r = -0.342, P < 0.001). The median ADC values were significantly higher in the ER-negative than in the ER-positive cases [(1.130 ± 0.115)×10(-3) mm(2)/s vs. (1.060 ± 0.089) ×10(-3) mm(2)/s, P < 0.001)], in PR-negative than in PR-positive cases [(1.121 ± 0.106)×10(-3) mm(2)/s vs. (1.055 ± 0.096) ×10(-3) mm(2)/s, P < 0.001)], and in Ki-67-negative than in Ki-67-positive cases [(1.153 ± 0.090)×10(-3) mm(2)/s vs. (1.063 ± 0.101) ×10(-3) mm(2)/s, P < 0.001]. A statistically significant correlation was observed between ADC value and expressions of ER, PR, and Ki-67 (r = -0.311, r = -0.317, r = -0.414, P < 0.001). CONCLUSION: ADC value of breast invasive ductal carcinoma is correlated with histological grade, and expression of ER, PR and Ki-67.

3.0T MR-CAD: Clinical Value in Diagnosis of Breast Tumor Compared with Conventional MRI.

PURPOSE: to explore the clinical value of 3.0T magnetic resonance (MR) imaging compared with computer-aided MR diagnosis (MR-CAD) in differential diagnosis of benign and malignant breast tumors. MATERIALS AND METHODS: MRI method and MR-CAD method was used in the diagnosis of a total of 93 breast lesions of 78 patients, based on the morphological and time-intensity-curve (TIC) analysis. The accuracy of the two modalities in differentiating malignant and benign breast tumor was compared. RESULTS: MR-CAD method yielded a statistically better accuracy than MRI method. For 51 mass-like lesions, MRI and MR-CAD had no difference in diagnosing accuracy, but MR-CAD had better accuracy in 42 non-mass-like lesions. CONCLUSION: MR-CAD had a notable advantage over MRI in differential diagnosis of benign and malignant breast tumors, especially non-mass-like tumor.

Prognostic value of 3'-deoxy-3'-18F-fluorothymidine ([(18)F] FLT PET) in patients with recurrent malignant gliomas.

INTRODUCTION: 3'-deoxy-3'-18F-fluorothymidine ([(18)F] FLT) PET has been proven to be of value in diagnosis and assessment of glioma grading, in differentiating tumor recurrence from necrosis, in response assessment and in predicting overall survival (OS) in the primary high grade glioma. In this study, we evaluated the value of [(18)F] FLT PET-CT in predicting the OS of patients with recurrent malignant glioma. METHODS: Fifty-six patients with recurrent malignant glioma were enrolled in this prospective study. The PET-CT and contrast-enhanced MRI scans were performed in all patients. Tumor volume was determined from both PET image (proliferative volume, PV) and MRI image (Vol-MRI). Patients were followed up clinically until death. The likelihood of using PET-derived parameters of SUVmax, tumor-to-normal (T/N) ratio, and PV to predict the OS of patients were assessed in comparison with Vol-MRI and other clinical parameters. RESULT: The follow up periods for all patients ranged from 1.5 to 35.6 months with median of 9.8 months. Univariate analysis showed that the following parameters were significantly correlated with OS: grade of primary tumor (p=0.042), Karnofsky performance score (KPS) (p=0.041), T/N ratio (p<0.01), Vol-MRI (p=0.041), and PV (p<0.001). However, multivariate Cox regression showed that only the PV (p<0.001) and T/N ratio (p=0.001) were independent predictors. The thresholds to predict OS were 16.88 cm(3) for PV and 10.94 for T/N ratio. Kaplan-Meier analyses using these thresholds showed a significant discrimination between short and long OS groups (p<0.001). CONCLUSION: The PV and T/N ratio of tumor on [(18)F] FLT PET-CT are independent predictors of survival in patients with recurrent malignant glioma. The PV on [(18)F] FLT PET seems to be more predictive than tumor volume on T1-weighted MRI for OS.

[Development and applications of the extracorporeal control point module on multi-mode medical images].

This paper introduces a display module which can be used on multi-mode medical images. The module has a small size and can be easily used for point-selecting puncture diagnosis and treatment, and registration for image fusion control points.