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Our purpose was to present and evaluate expert consensus on contouring primary breast tumors on magnetic resonance imaging (MRI) in the setting of neoadjuvant partial breast irradiation in trials. Expert consensus on contouring guidelines for target definition of primary breast tumors on contrast-enhanced MRI in trials was developed by an international team of experienced breast radiation oncologists and a dedicated breast radiologist during 3 meetings. At the first meeting, draft guidelines were developed through discussing and contouring 2 cases. At the second meeting 6 breast radiation oncologists delineated gross tumor volume (GTV) in 10 patients with early-stage breast cancer (cT1N0) according to draft guidelines. GTV was expanded isotropically (20 mm) to generate clinical target volume (CTV), excluding skin and chest wall. Delineations were reviewed for disagreement and guidelines were clarified accordingly. At the third meeting 5 radiation oncologists redelineated 6 cases using consensus-based guidelines. Interobserver variation of GTV and CTV was assessed using generalized conformity index (CI). CI was calculated as the sum of volumes each pair of observers agreed upon, divided by the sum of encompassing volumes for each pair of observers. For the 2 delineation sessions combined, mean GTV ranged between 0.19 and 2.44 cm3, CI for GTV ranged between 0.28 and 0.77, and CI for CTV between 0.77 and 0.94. The largest interobserver variation in GTV delineations was observed in cases with extended tumor spiculae, blood vessels near or markers within the tumor, or with increased enhancement of glandular breast tissue. Consensus-based guidelines stated to delineate all visible tumors on contrast enhanced–MRI scan 1 to 2 minutes after contrast injection and if a marker was inserted in the tumor to include this. Expert-based consensus on contouring primary breast tumors on MRI in trials has been reached. This resulted in low interobserver variation for CTV in the context of a uniform 20 mm GTV to CTV expansion margin. [ABSTRACT FROM AUTHOR]

Purpose: The dose–response relationship of the parotid gland has been described most frequently using the Lyman-Kutcher-Burman model. However, various other normal tissue complication probability (NTCP) models exist. We evaluated in a large group of patients the value of six NTCP models that describe the parotid gland dose response 1 year after radiotherapy. Methods and Materials: A total of 347 patients with head-and-neck tumors were included in this prospective parotid gland dose–response study. The patients were treated with either conventional radiotherapy or intensity-modulated radiotherapy. Dose–volume histograms for the parotid glands were derived from three-dimensional dose calculations using computed tomography scans. Stimulated salivary flow rates were measured before and 1 year after radiotherapy. A threshold of 25% of the pretreatment flow rate was used to define a complication. The evaluated models included the Lyman-Kutcher-Burman model, the mean dose model, the relative seriality model, the critical volume model, the parallel functional subunit model, and the dose–threshold model. The goodness of fit (GOF) was determined by the deviance and a Monte Carlo hypothesis test. Ranking of the models was based on Akaike''s information criterion (AIC). Results: None of the models was rejected based on the evaluation of the GOF. The mean dose model was ranked as the best model based on the AIC. The TD 50 in these models was approximately 39 Gy. Conclusions: The mean dose model was preferred for describing the dose–response relationship of the parotid gland. [Copyright &y& Elsevier]

Purpose: To evaluate the time dependency of the sensitizing effect of a large low-dose field on a small high-dose field in the rat cervical spinal cord. Methods and materials: Irradiation experiments with a relatively low dose to a large volume (bath, 2 cm, 4 Gy) were combined with high doses to a small volume (shower, 4.7 mm, 26–43 Gy) at intervals of 8 minutes and 3, 12, and 24 hours. Both a functional score defined as motor impairment and a histologic score characterized as white matter necrosis were used as end points. Results: Application of the 4-Gy bath dose resulted in a significant decrease in 50% isoeffective dose (ED50) from 48.7 Gy (small field) to 40.8 Gy. If the interval was extended, the ED50 increased to 44.4 (3 hours) and 44.8 Gy (12 hours), whereas a 24-hour interval resulted in a significant increase to 51.9 Gy. If the histologic end point was considered, the ED50 for all dose–response curves decreased slightly with 0.2 to 2.6 Gy without significantly changing the kinetics. Conclusions: The bath effect as applied in the bath-and-shower experiment lasted for at least 12 hours and disappeared in the 24-hour interval. This time scale clearly deviates from the repair kinetics in spinal cord derived from low-dose-rate and fractionated irradiations. [Copyright &y& Elsevier]

To evaluate models for normal-tissue–complication probability (NTCP) on describing the dose–volume effect in rat thoracolumbar spinal cord.Single-dose irradiation of four field lengths (4, 1.5, 1.0, and 0.5 cm) was evaluated by the endpoints paresis and white-matter necrosis. The resulting dose–response data were used to rank phenomenological and tissue architecture NTCP models.The 0.5-cm field length showed a steep increase in radiationtolerance. Statistical analysis of the model fits, which included evaluation of goodness of fit (GOF) and confidence intervals, resulted in the rejection of all the models considered. Excluding the smallest field length, the Schultheiss (D50 = 21.5 Gy, k = 26.5), the relative seriality (D50 = 21.4 Gy, s = 1.6, γ50 = 6.3), and the critical element (D50,FSU = 26.6 Gy, γ50,FSU = 2.3, n = 1.3) model gave the best fit.A thorough statistical analysis resulted in a serial or critical-element behavior for the field lengths of 1.0 cm and greater. Including the 0.5-cm field length, the radiation response markedly diverged from serial properties, but none of the models applied acceptably described this dose–response relationship. This study suggests that the commonly assumed serial behavior of the spinal cord might be valid for daily use in external- beam irradiation. [Copyright &y& Elsevier]

Objective: This prospective study aims to test if MRI including diffusion weighted images can replace FDG PET-CT in the diagnosis of patients with suspicion of local recurrent head and neck squamous cell carcinomas after (chemo)radiation.Methods: Seventy-five patients suspected of local recurrence underwent a MRI and a FDG PET-CT. Qualitative assessment of the images was performed. Reference standard was the results of biopsy or the absence of a recurrence during follow up.Results: Seventy patients were included. Fifty percent had local recurrence. FDG PET-CT had accuracy of 71% compared to 73% for MRI. The sensitivity and specificity were 97% compared to 69% and 46% compared to 77% for FDG PET-CT and MRI respectively.Conclusions: MRI showed similar diagnostic accuracy, superior specificity but inferior sensitivity compared to FDG PET-CT. Based on current results, we consider MRI including diffusion weighted sequences unable to replace FDG PET-CT as a single imaging modality when local recurrent disease of HNSCC after (C)RT is suspected. [ABSTRACT FROM AUTHOR]

Introduction: For the detection of local recurrences of head and neck squamous cell carcinomas (HNSCC) after (chemo)radiation, diagnostic imaging is generally performed. Diffusion weighted magnetic resonance imaging (DW-MRI) has been proven to be able to adequately diagnose the presence of cancer. However evaluation of DW-MR images for recurrences is difficult and could be subject to individual interpretation.Aim: To determine the interobserver agreement, intraobserver agreement and influence of experience of radiologists in the assessment of DW-MRI in patients clinically suspected of local recurrent HNSCC after (chemo)radiation.Methods: Ten experienced head and neck radiologists assessed follow-up MRI including DW-MRI series of 10 patients for the existence of local recurrence on a two point decision scale (local recurrence or local control). Patients were clinically suspected for a recurrence of laryngeal (n = 3), hypopharyngeal (n = 3) or oropharyngeal (n = 4) cancer after (chemo)radiation with curative intent. Fleiss' and Cohen's Kappa were used to determine interobserver agreement and intraobserver agreement, respectively.Results: Interobserver agreement was κ = 0.55. Intraobserver agreement was κ = 0.80. Prior experience within the field of radiology and with DW-MRI had no significant influence on the scoring.Conclusion: For the assessment of HNSCC recurrence after (chemo)radiation by DW-MRI, moderate interobserver agreement and substantial intraobserver agreement was found. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiation therapy (SBRT) is a highly effective and potentially ablative treatment for complex spinal metastases. Recent data have suggested radiobiologic effects of SBRT that expand beyond the traditional concept of DNA damage. Antitumor immunity, vascular damage leading to tumor necrosis, and increased rates of tumor apoptosis have been implied; however, in-human evidence remains scarce. The present study reports unique pathologic confirmation of SBRT-induced biological effects within spinal metastases treated with preoperative SBRT.Methods and Materials: Ten patients with spinal metastases secondary to various solid tumors were treated with preoperative single-fraction SBRT (18 Gy) to the magnetic resonance imaging-defined macroscopic metastasis, followed by spinal stabilization within 24 hours. Perioperative samples of spinal metastases were obtained, and 6 patients also had a pre-SBRT biopsy specimen available for a matched comparison. The samples were stained for tumor necrosis on routine hematoxylin-eosin-stained slices and, subsequently, immunohistochemical staining for T cells (CD3+, CD4+, CD8+), natural killer cells (CD56+), endothelium (CD31+), and apoptotic activity (caspase-3).Results: Perioperative biopsy specimens were obtained ∼6 hours (range 4.5-7.5) or 21 hours (range 18.5-22.5) after SBRT. Necrosis was observed in 83% of the 21-hour post-SBRT samples (5 of 6) compared with 0% of pre-SBRT biopsies (0 of 6) and 6-hour post-SBRT biopsies (0 of 4). Tumor cell apoptosis had increased greatly in the 21-hour post-SBRT samples compared with before and 6 hours after SBRT. The CD31+ vessel counts decreased after SBRT, as did mitotic activity. Both of the renal cell metastases displayed major decreases in vessel density. Desmoplastic reaction was visible in 67% (4 of 6) of the pre-SBRT samples compared with 100% (10 of 10) the post-SBRT samples. The T-cell and natural killer cell counts were relatively unaffected.Conclusions: High-dose single-fraction SBRT induced tumor necrosis, desmoplasia, and tumor apoptosis and decreased tumor vessel density within 24 hours, even in renal cell metastases. The role of immune cells seems limited in this early phase. These first-in-human results imply direct vascular and DNA damage mechanisms important in the clinical efficacy specific to spinal SBRT. [ABSTRACT FROM AUTHOR]

The preferred treatment for oral squamous cell carcinoma is complete surgical tumour resection to achieve local-regional control. [1] Complete surgical removal requires an adequate resection margin of at least 5 mm of healthy tissue around the tumour. Unfortunately, international literature reports 30% to 85% inadequate resection margins (i.e., positive and close margins). [2] This study aims to investigate whether adequate tongue cancer resection margins can accurately be determined using ex-vivo high-field magnetic resonance imaging (MRI). This proposed technique could help improve the localisation of inadequate margins during surgery. Nine fresh resection specimens of tongue cancer patients were scanned with a small-bore 7 Tesla (7T) MRI scanner (Biospec 70/20, Bruker, Ettlingen, Germany) interfaced with a Philips console. For each resection specimen, four MRI scans were obtained: a 3D T2-weighted (T2W) Turbo Spin Echo (TSE) scan with an isotropic voxel size of 0.3 mm3 and three orthogonal multi-slice T2W TSE scans with an in-plane resolution of 0.125 mm2 and a slice thickness of 1 mm. After completion of the MR protocol, the resection specimens were processed according to routine clinical histopathological workup. The tumour was delineated by a histopathologist (HP) on the hematoxylin and eosin (HE) stained histopathological slices and by two independent radiologists (R1 and R2) on the coronal multi-slice MR scan. For each patient, a 3D representation of the resection specimen was created using the following three steps: 1) For each HE-slice, the MR-slice with the highest resemblance was found by visual inspection (Fig. 1A, 1B). 2) These corresponding slices were registered using point-based registration based on visual corresponding anatomical points (e.g., specimen contour, tumour-protrusions, mucosa) (Fig. 1C). 3) The registered HE-slices were digitally stacked to create a 3D-specimen of all HE-slices (Fig. 1D). This method to create the 3D-specimen was previously discussed and used in the work by Caldas-Magalhaes et al. [3] The delineated tumour created by the radiologists (tR1 and tR2) and histopathologist (tHP) were interpolated and mapped to the other MRI-scans (i.e., sagittal, axial, and 3D TSE scan) (Fig. 1D). The accuracy of the inadequate margin detection by R1 and R2 was determined using two different methods. First, the minimal resection margins in all five directions (anterior, posterior, craniomedial, caudolateral and central) were measured based on tR1 and tR2 and compared to the measurements reported by the HP. Second, the 95th percentile Hausdorff distance (HD95) of the overestimation (O-HD 95) and underestimation (U-HD 95) of tR1 and tR2 was calculated with respect to the ground truth (tHP) in all five directions. The relationship between the measured resection margins based on tR1, tR2 and tHP was evaluated using Pearson's correlation coefficient (PCC). Only the craniomedial, caudolateral, and central resection margins were included in the PCC analysis. [Display omitted] According to the histological report, one of the nine resection specimens was adequately resected. Based on the in-plane measurements, R1 and R2 were able to accurately determine which tumours were (in)adequately removed in 7/9 and 8/9 cases. Two of these cases were inadequate but considered adequate by the radiologists, and the other case was determined inadequate by R1 but adequate according to the HP. All these three incorrect cases had a T-stage of 1. Based on the tumour segmentation, the sensitivity and specificity of the detection of inadequate margins with respect to the final histopathological report were 77% and 50% for R1 and 65% and 57% for R2, respectively. The median U-HD95 and O-HD95 for R1 were 0.9 mm (range: 0.0-1.7 mm) and 2.5 mm (range: 0.6-11.8 mm). For R2, the median U-HD95 and O-HD95 were 0.5 mm (range: 0.3-5.3 mm) and 2.5 mm (range: 1.2-6.6 mm). [Display omitted] The PCC of the measured margins between the HP and two radiologists was 0.67 and 0.71 for R1 and R2, respectively. Between both radiologists, the PCC of the measured margins was 0.75. Figure 2 shows an example of a 3D-specimen and the corresponding MRI-slices. Ex-vivo 7T MRI enables accurate margin predictions for tongue cancer resection specimens. The radiologists' assessment of in- and adequate resections based on ex-vivo 7T MRI generally aligns with the histopathology reports. The sensitivity of both radiologists for adequate margin detection is reasonable. However, the specificity is low, which might be caused by the radiologists' overestimation of the tumour on ex-vivo 7T MRI. This study offers a proof of principle for future studies to validate and further improve the detection of inadequate margins for oral cavity resection specimens using ex-vivo 7T MRI. This technique could provide guidance for surgeons to localise inadequate margins and enable them to perform accurate re-resections during surgery. [ABSTRACT FROM AUTHOR]

Purpose: Tumor and target volume manual delineation remains a challenging task in head and neck cancer radiation therapy. The purpose of this study was to conduct a multi-institutional evaluation of manual delineations of gross tumor volume (GTV), high-risk clinical target volume (CTV), parotids, and submandibular glands on treatment simulation magnetic resonance scans of patients with oropharyngeal cancer.Methods and Materials: We retrospectively collected pretreatment T1-weighted, T1-weighted with gadolinium contrast, and T2-weighted magnetic resonance imaging scans for 4 patients with oropharyngeal cancer under an institution review board-approved protocol. We provided the scans to 26 radiation oncologists from 7 international cancer centers that participated in this delineation study. We also provide the patients' clinical history and physical examination findings, along with a medical photographic image and radiologic results. We used both the Simultaneous Truth and Performance Level Estimation algorithm and pair-wise comparisons of the contours, using overlap/distance metrics. Lastly, to assess experience and CTV delineation institutional practices, we had participants complete a brief questionnaire.Results: Large variability was measured between observers' delineations for GTVs and CTVs. The mean Dice similarity coefficient values across all physicians' delineations for GTVp, GTVn, CTVp, and CTVn were 0.77, 0.67, 0.77, and 0.69, respectively, for Simultaneous Truth and Performance Level Estimation algorithm comparison, and 0.67, 0.60, 0.67, and 0.58, respectively, for pair-wise analysis. Normal tissue contours were defined more consistently when considering overlap/distance metrics. The median radiation oncology clinical experience was 7 years. The median experience delineating on magnetic resonance imaging was 3.5 years. The GTV-to-CTV margin used was 10 mm for 6 of 7 participant institutions. One institution used 8 mm, and 3 participants (from 3 different institutions) used a margin of 5 mm.Conclusions: The data from this study suggests that appropriate guidelines, contouring quality assurance sessions, and training are still needed for the adoption of magnetic resonance-based treatment planning for head and neck cancers. Such efforts should play a critical role in reducing delineation variation and ensure standardization of target design across clinical practices. [ABSTRACT FROM AUTHOR]

Objective: Tumor hypoxia results in worse local control and patient survival. We performed a digital, single-cell-based analysis to compare two biomarkers for hypoxia (hypoxia-inducible factor 1-alpha [HIF-1α] and pimonidazole [PIMO]) and their effect on outcome in laryngeal cancer patients treated with accelerated radiotherapy with or without carbogen breathing and nicotinamide (AR versus ARCON).Materials and Methods: Immunohistochemical staining was performed for HIF-1α and PIMO in consecutive sections of 44 laryngeal cancer patients randomized between AR and ARCON. HIF-1α expression and PIMO-binding were correlated using digital image analysis in QuPath. High-density areas for each biomarker were automatically annotated and staining overlap was analyzed. Kaplan-Meier survival analyses for local control, regional control and disease-free survival were performed to predict a response benefit of ARCON over AR alone for each biomarker.Results: 106 Tissue fragments of 44 patients were analyzed. A weak, significant positive correlation was observed between HIF-1α and PIMO positivity on fragment level, but not on patient level. A moderate strength correlation (r = 0.705, p < 0.001) was observed between the number of high-density staining areas for both biomarkers. Staining overlap was poor. HIF-1α expression, PIMO-binding or a combination could not predict a response benefit of ARCON over AR.Conclusion: Digital image analysis to compare positive cell fractions and staining overlap between two hypoxia biomarkers using open-source software is feasible. Our results highlight that there are distinct differences between HIF-1α and PIMO as hypoxia biomarkers and therefore suggest co-existence of different forms of hypoxia within a single tumor. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The characterization of tumor vasculature is essential in studying tumor physiology. The aim of this study was to develop a new method — based on water proton MR density measurements, in combination with ultrasmall superparamagnetic iron oxide (USPIO) administration — to measure absolute blood volume (BV) in murine colon carcinoma. Materials and Methods: MRI experiments were performed at 7 T. CPMG imaging was performed on subcutaneous murine colon carcinoma in six mice before and after administration of an USPIO blood-pool contrast agent. Density maps were obtained from the signal amplitude at TE=0 of the CPMG decay fit. Post-USPIO density maps were subtracted from pre-USPIO density maps to quantitatively yield absolute tumor BV maps. In a separate group of mice (n=6), the relative vascular area (RVA) of tumors was determined by immunohistochemistry. Results: Ultrasmall superparamagnetic iron oxide administration resulted in a small decrease in the water proton MR density. The BV averaged over the six tumors was 4.6±1.6%. The value of the RVA measured by immunohistochemical staining was equal to 3.9±2.2%. Conclusions: After administration of an USPIO blood-pool agent (T 2 relaxivity > 100 mM−1 s−1), the blood water protons become MRI invisible, and pixel-by-pixel BV map can be obtained by subtracting the calculated post-USPIO density map from the pre-USPIO density map. The value of absolute BV obtained with this novel MR approach is in good agreement with the value of the relative vascular measured by immunohistochemical staining. [Copyright &y& Elsevier]

Quantitative imaging biomarkers (QIBs) derived from MRI techniques have the potential to be used for the personalised treatment of cancer patients. However, large-scale data are missing to validate their added value in clinical practice. Integrated MRI-guided radiotherapy (MRIgRT) systems, such as hybrid MRI-linear accelerators, have the unique advantage that MR images can be acquired during every treatment session. This means that high-frequency imaging of QIBs becomes feasible with reduced patient burden, logistical challenges, and costs compared to extra scan sessions. A wealth of valuable data will be collected before and during treatment, creating new opportunities to advance QIB research at large. The aim of this paper is to present a roadmap towards the clinical use of QIBs on MRIgRT systems. The most important need is to gather and understand how the QIBs collected during MRIgRT correlate with clinical outcomes. As the integrated MRI scanner differs from traditional MRI scanners, technical validation is an important aspect of this roadmap. We propose to integrate technical validation with clinical trials by the addition of a quality assurance procedure at the start of a trial, the acquisition of in vivo test-retest data to assess the repeatability, as well as a comparison between QIBs from MRIgRT systems and diagnostic MRI systems to assess the reproducibility. These data can be collected with limited extra time for the patient. With integration of technical validation in clinical trials, the results of these trials derived on MRIgRT systems will also be applicable for measurements on other MRI systems. • Daily imaging is feasible on integrated MRI-guided radiotherapy (MRIgRT) systems. • This will advance quantitative imaging biomarker (QIB) research in oncology. • QIBs have the potential to personalise radiotherapy treatment. • This paper presents a roadmap towards clinical use of QIBs on MRIgRT systems. • Technical validation should be integrated in clinical trials on MRIgRT systems. [ABSTRACT FROM AUTHOR]

Purpose: This prospective study is, to our knowledge, the first report of daily adaptive radiation therapy (ART) for head and neck cancer (HNC) using a 1.5T magnetic resonance imaging-linear accelerator (MR-linac) with particular focus on safety and feasibility and dosimetric results of an online rigid registration-based adapt to position (ATP) workflow.Methods and Materials: Ten patients with HNC received daily ART on a 1.5T/7MV MR-linac, 6 using ATP only and 4 using ATP with 1 offline adapt-to-shape replan. Setup variability with custom immobilization masks was assessed by calculating the mean systematic error (M), standard deviation of the systematic error (Σ), and standard deviation of the random error (σ) of the isocenter shifts. Quality assurance was performed with a cylindrical diode array using 3%/3 mm γ criteria. Adaptive treatment plans were summed for each patient to compare the delivered dose with the planned dose from the reference plan. The impact of dosimetric variability between adaptive fractions on the summation plan doses was assessed by tracking the number of optimization constraint violations at each individual fraction.Results: The random errors (mm) for the x, y, and z isocenter shifts, respectively, were M = -0.3, 0.7, 0.1; Σ = 3.3, 2.6, 1.4; and σ = 1.7, 2.9, 1.0. The median (range) γ pass rate was 99.9% (90.9%-100%). The differences between the reference and summation plan doses were -0.61% to 1.78% for the clinical target volume and -11.74% to 8.11% for organs at risk (OARs), although an increase greater than 2% in OAR dose only occurred in 3 cases, each for a single OAR. All cases had at least 2 fractions with 1 or more constraint violations. However, in nearly all instances, constraints were still met in the summation plan despite multiple single-fraction violations.Conclusions: Daily ART on a 1.5T MR-linac using an online ATP workflow is safe and clinically feasible for HNC and results in delivered doses consistent with planned doses. [ABSTRACT FROM AUTHOR]

Purpose: To assess the pathologic and radiologic response in patients with low-risk breast cancer treated with magnetic resonance (MR) guided neoadjuvant partial breast irradiation (NA-PBI) and to evaluate toxicity and patient-reported outcomes (PROs).Methods and Materials: For this single-arm prospective trial, women with unifocal, non-lobular tumors with a maximum diameter of 20 mm (age, 50-70 years) or 30 mm (age, ≥70 years) and tumor-negative sentinel node(s) were eligible. Patients were treated with a single ablative dose of NA-PBI followed by breast-conserving surgery after an interval of 6 to 8 months. Target volumes were defined on radiation therapy planning computed tomography scan and additional magnetic resonance imaging. Prescribed doses to gross tumor volume and clinical target volume (gross tumor volume plus 20 mm margin) were 20 Gy and 15 Gy, respectively. Primary outcome was pathologic complete response (pCR). Secondary outcomes were radiologic response (on magnetic resonance imaging), toxicity (Common Terminology Criteria for Adverse Events), PROs (European Organisation for Research and Treatment of Cancer QLQ-BR23, Hospital Anxiety and Depression Scale), and cosmesis (assessed by patient, radiation oncologist, and BCCT.core software).Results: Thirty-six patients were treated with NA-PBI, and pCR was reported in 15 patients (42%; 95% confidence interval, 26%-59%). Radiologic complete response was observed in 15 patients, 10 of whom had pCR (positive predictive value, 67%; 95% confidence interval, 39%-87%). After a median follow-up of 21 months (range, 12-41), all patients experienced grade 1 fibrosis in the treated breast volume. Transient grade 2 and 3 toxicity was observed in 31% and 3% of patients, respectively. Local recurrences were absent. No deterioration in PROs or cosmetic results was observed.Conclusions: NA-PBI has the potential to induce pCR in a substantial proportion of patients, with acceptable toxicity. This treatment seems a feasible alternative to standard postoperative irradiation and could even result in postponement or omission of surgery if pCR can be accurately predicted in selected low-risk patients. [ABSTRACT FROM AUTHOR]

Objectives: Diffusion weighted imaging (DWI) is a frequently performed MRI sequence in cancer patients. While previous studies have shown the clinical value of the apparent diffusion coefficient (ADC) for response prediction and response monitoring, less is known about the biological background of ADC. In the tumor microenvironment, hypoxia and increased proliferation of tumor cells contribute to resistance to (radio-)therapy, while high T-cell influx is related to better prognosis. We investigated the correlation between these three tissue characteristics and ADC in 20 oropharyngeal squamous cell carcinoma patients.Materials and Methods: 20 patients with oropharyngeal squamous cell carcinoma (OPSCC) who underwent 1.5 T MRI, including DWI were included in this pilot study. Corresponding formalin-fixed paraffin-embedded tumor tissues were immunohistochemically analyzed for protein expression of hypoxia-inducible factor 1a (HIF-1a), Ki-67 and CD3. Expression of these markers was correlated with ADC.Results: ADC negatively correlated with Ki-67 expression (p = .024) in tumor cells. There was a significant negative correlation between ADC and CD3-positive cell count (p = .009). No correlation was observed between HIF-1a expression and ADC.Conclusion: This study suggests that ADC reflects characteristics of tumor cells as well as the surrounding microenvironment. Interestingly, high tumor proliferation (a negative prognostic factor) and high T-cell influx (a beneficial prognostic factor) are both associated with a lower ADC. Further studies should be performed to correlate ADC to these histological characteristics in relation to previously known factors that affect ADC, to gain further knowledge on the role of DW-MRI in diagnostics and personalized medicine. [ABSTRACT FROM AUTHOR]

Purpose To explore and evaluate the potential value of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for the prediction of pathologic response to neoadjuvant chemoradiotherapy (nCRT) in oesophageal cancer. Material and methods Twenty-six patients underwent DCE-MRI before, during (week 2–3) and after nCRT, but before surgery (pre/per/post, respectively). Histopathologic tumour regression grade (TRG) was assessed after oesophagectomy. Tumour area-under-the-concentration time curve (AUC), time-to-peak (TTP) and slope were calculated. The ability of these DCE-parameters to distinguish good responders (GR, TRG 1–2) from poor responders (noGR, TRG ⩾ 3), and pathologic complete responders (pCR) from no-pCR was assessed. Results Twelve patients (48%) showed GR of which 8 patients (32%) pCR. Analysis of AUC change throughout treatment, AUC per-pre , was most predictive for GR, at a threshold of 22.7% resulting in a sensitivity of 92%, specificity of 77%, PPV of 79%, and a NPV of 91%. AUC post-pre was most predictive for pCR, at a threshold of −24.6% resulting in a sensitivity of 83%, specificity of 88%, PPV of 71%, and a NPV of 93%. TTP and slope were not associated with pathologic response. Conclusions This study demonstrates that changes in AUC throughout treatment are promising for prediction of histopathologic response to nCRT for oesophageal cancer. [ABSTRACT FROM AUTHOR]

Background While surgery remains the cornerstone of rectal cancer treatment, organ-preservation is upcoming. Therefore, neo-adjuvant treatment should be optimized. By escalating doses, response can be increased. To limit toxicity of boost, accurate gross tumor volume (GTV) definition is required. MRI, especially undeformed fast spin echo diffusion-weighted MRI (DWI), looks promising for delineation. However, inconsistencies between observers should be quantified before clinical implementation. We aim to find which MRI sequence (T2w, DWI or combination) is optimal and clinically useful for GTV definition by evaluating inter-observer agreement. Methods Locally advanced rectal cancer patients (tumors <10 cm from anal verge) were scanned on 3T MRI transverse T2w and DWI ( b = 800 s/mm 2 ). Three independent observers delineated T2w, DWI and combination (Combi) after training-set. Volumes, conformity index (CI), and maximum Hausdorff distance (HD) were calculated between any observer-pair per patient per modality. Results Twenty-four consecutive patients were included. One patient had cT2 (4.2%), 19 cT3 (79.1%) and 4 cT4 (16.7%), with 2 clinical node negative (8.3%), 4 cN1 (16.7%), and 18 cN2 (75.0%) on MRI. From 24 patients, 70 sequences were available (24x T2, 23x DWI, and 23x Combi). Between observers, no significant volume differences were observed per modality. T2 showed significantly largest volumes compared to DWI (mean difference 19.85 ml, SD 17.42, p < 0.0001) and Combi (mean difference 7.16 ml, SD 11.58, p < 0.0001). Mean CI was 0.70, 0.71 and 0.69 for T2, DWI and Combi respectively ( p > 0.61). Average HD was largest on T2 (18.60 mm, max 31.40 mm, min 9.20 mm). Discussion Delineation on DWI resulted in delineation of the smallest volumes with similar consistency and mean distances, but with slightly lower Hausdorff distances compared to T2 and Combi. However, with lack of a gold standard it remains difficult to establish if delineations also represent true tumor. Study strengths were DWI adaptation to exclude geometrical distortions and training-set. DWI shows great potential for delineation purposes as long as sufficient experience exists and geometrical distortions are eliminated. [ABSTRACT FROM AUTHOR]

Purpose To derive and validate a statistical model of motion and deformation for the clinical target volume (CTV) of early-stage rectal cancer patients. Methods and Materials For 16 patients, 4 to 5 magnetic resonance images (MRI) were acquired before each fraction was administered. The CTV was delineated on each MRI. Using a leave-one-out methodology, we constructed a population-based principal component analysis (PCA) model of the CTV motion and deformation of 15 patients, and we tested the model on the left-out patient. The modeling error was calculated as the amount of the CTV motion-deformation of the left-out-patient that could not be explained by the PCA model. Next, the PCA model was used to construct a PCA target volume (PCA-TV) by accumulating motion-deformations simulated by the model. A PCA planning target volume (PTV) was generated by expanding the PCA-TV by uniform margins. The PCA-PTV was compared with uniform and nonuniform CTV-to-PTV margins. To allow comparison, geometric margins were determined to ensure adequate coverage, and the volume difference between the PTV and the daily CTV (CTV-to-PTV volume) was calculated. Results The modeling error ranged from 0.9 ± 0.5 to 2.9 ± 2.1 mm, corresponding to a reduction of the CTV motion-deformation between 6% and 60% (average, 23% ± 11%). The reduction correlated with the magnitude of the CTV motion-deformation ( P <.001, R=0.66). The PCA-TV and the CTV required 2-mm and 7-mm uniform margins, respectively. The nonuniform CTV-to-PTV margins were 4 mm in the left, right, inferior, superior, and posterior directions and 8 mm in the anterior direction. Compared to uniform and nonuniform CTV-to-PTV margins, the PCA-based PTV significantly decreased ( P <.001) the average CTV-to-PTV volume by 128 ± 20 mL (49% ± 4%) and by 35 ± 6 mL (20% ± 3.5%), respectively. Conclusions The CTV motion-deformation of a new patient can be explained by a population-based PCA model. A PCA model-generated PTV significantly improved sparing of organs at risk compared to uniform and nonuniform CTV-to-PTV margins. [ABSTRACT FROM AUTHOR]