Simultaneous Focal Boost With Stereotactic Radiation Therapy for Localized Intermediate- to High-Risk Prostate Cancer: Primary Outcomes of the SPARC Phase 2 Trial.

PURPOSE: Dose-escalated radiation therapy is associated with better biochemical control at the expense of toxicity. Stereotactic body radiation therapy (SBRT) with dose escalation to the dominant intraprostatic lesion (DIL) provides a logical approach to improve outcomes in high-risk disease while limiting toxicity. This study evaluated the toxicity and quality of life (QoL) with CyberKnife-based SBRT and simultaneous integrated boost in localized prostate cancer. METHODS AND MATERIALS: Eligible participants included newly diagnosed, biopsy-proven unfavorable intermediate- to high-risk localized prostate cancer (at least 1 of the following: Gleason ≥4+3, magnetic resonance imaging(MRI)-defined T3a N0, prostate-specific antigen ≥20) with up to 2 MRI-identified DILs. Participants received 36.25 Gy in 5 fractions on alternative days with a simultaneous boost to DIL up to 47.5 Gy as allowed by organ-at-risk constraints delivered by CyberKnife. All participants received androgen deprivation therapy. The primary outcome measure was acute grade 2+ genitourinary toxicity. Acute and late genitourinary and gastrointestinal toxicity using Radiation Therapy Oncology Group scoring, biochemical parameters, International Prostate Symptom Score, International Index of Erectile Function 5, and EQ-5D QoL outcomes were assessed. RESULTS: Between 2013 and 2023, 20 participants were enrolled with a median follow-up of 30 months. The median D95 dose to DIL was 47.43 Gy. Cumulative acute grade 2+ genitourinary and gastrointestinal toxicity were 25% and 30%, respectively. One patient developed acute grade 3 genitourinary toxicity (5%). There is no late grade 3 genitourinary or gastrointestinal toxicity to date. International Prostate Symptom Score and urinary QoL scores recovered to baseline by 6 months. Patient-reported outcomes showed no significant change in EQ-5D QoL scores at 12 weeks and 1 year. There are no cases of biochemical relapse reported to date. CONCLUSIONS: CyberKnife SBRT-delivered dose of 36.25 Gy to the prostate with a simultaneous integrated boost up to 47.5 Gy is well tolerated. Acute and late genitourinary and gastrointestinal toxicity rates are comparable to other contemporary SBRT trials and series with focal boost.

Development of Prostate Bed Delineation Consensus Guidelines for Magnetic Resonance Image-Guided Radiotherapy and Assessment of Its Effect on Interobserver Variability.

PURPOSE: The use of magnetic resonance imaging (MRI) in radiotherapy planning is becoming more widespread, particularly with the emergence of MRI-guided radiotherapy systems. Existing guidelines for defining the prostate bed clinical target volume (CTV) show considerable heterogeneity. This study aimed to establish baseline interobserver variability (IOV) for prostate bed CTV contouring on MRI, develop international consensus guidelines, and evaluate its effect on IOV. METHODS AND MATERIALS: Participants delineated the CTV on 3 MRI scans, obtained from the Elekta Unity MR-Linac, as per their normal practice. Radiation oncologist contours were visually examined for discrepancies, and interobserver comparisons were evaluated against simultaneous truth and performance level estimation (STAPLE) contours using overlap metrics (Dice similarity coefficient and Cohen's kappa), distance metrics (mean distance to agreement and Hausdorff distance), and volume measurements. A literature review of postradical prostatectomy local recurrence patterns was performed and presented alongside IOV results to the participants. Consensus guidelines were collectively constructed, and IOV assessment was repeated using these guidelines. RESULTS: Sixteen radiation oncologists' contours were included in the final analysis. Visual evaluation demonstrated significant differences in the superior, inferior, and anterior borders. Baseline IOV assessment indicated moderate agreement for the overlap metrics while volume and distance metrics demonstrated greater variability. Consensus for optimal prostate bed CTV boundaries was established during a virtual meeting. After guideline development, a decrease in IOV was observed. The maximum volume ratio decreased from 4.7 to 3.1 and volume coefficient of variation reduced from 40% to 34%. The mean Dice similarity coefficient rose from 0.72 to 0.75 and the mean distance to agreement decreased from 3.63 to 2.95 mm. CONCLUSIONS: Interobserver variability in prostate bed contouring exists among international genitourinary experts, although this is lower than previously reported. Consensus guidelines for MRI-based prostate bed contouring have been developed, and this has resulted in an improvement in contouring concordance. However, IOV persists and strategies such as an education program, development of a contouring atlas, and further refinement of the guidelines may lead to additional improvements.

The peritoneal cancer index as a predictor of complete cytoreduction at primary and interval cytoreductive surgery in advanced ovarian cancer.

OBJECTIVE: The peritoneal cancer index quantitatively assesses cancer distribution and tumor burden in the peritoneal cavity. The aim of this study is to evaluate the association between the peritoneal cancer index and completeness of surgical cytoreduction for ovarian cancer and to identify a cut-off above which complete cytoreduction is unlikely. METHODS: This is a single-center prospective cohort observational study. A total of 100 consecutive patients who underwent ovarian cancer surgery were included. Peritoneal cancer index scores prior to and after surgery were calculated, and a cut-off value for incomplete cytoreduction was identified using a receiver operator characteristic (ROC) curve. Surgical complexity, blood loss, length of surgery, and complications were analyzed and associations with the peritoneal cancer index score were evaluated. RESULTS: The overall median peritoneal cancer index score was 9.5 (range 0-36). The median age of the patients was 61 years (range 24-85). The most common stage was III (13% stage II, 53% stage III, 34% stage IV) and the most common histologic sub-type was high-grade serous (76% high-grade serous, 8% low-grade serous, 5% clear cell, 4% serous borderline, 2% endometrioid, 2% adult granulosa cell, 2% adenocarcinoma, 1% carcinosarcoma). Complete cytoreduction was achieved in 82% of patients, with a median score of 9 (range 0-30). The remaining 18% had a median score of 28.5 (range 0-36). The best predictor of incomplete cytoreduction was the peritoneal cancer index score, with an area under the curve (AUC) of 0.928 (95% CI 0.85 to 1.00). ROC curve analysis determined a peritoneal cancer index cut-off score of 20. Major complications occurred in 15% of patients with peritoneal cancer index scores >20 and in 2.5% of patients with scores ≤20, which was statistically significant (p=0.014). CONCLUSIONS: In our study we found that a peritoneal cancer index score of ≤20 was associated with a high likelihood of complete cytoreduction. Incorporating the peritoneal cancer index into routine surgical practice and research may impact treatment plans.

Diffusion-weighted MRI to determine response and long-term clinical outcomes in muscle-invasive bladder cancer following neoadjuvant chemotherapy.

Objective: This study aims to determine local treatment response and long-term survival outcomes in patients with localised muscle-invasive bladder cancer (MIBC) patients receiving neoadjuvant chemotherapy (NAC) using diffusion-weighted MRI (DWI) and apparent diffusion coefficient (ADC) analysis. Methods: Patients with T2-T4aN0-3M0 bladder cancer suitable for NAC were recruited prospectively. DWI was performed prior to NAC and was repeated following NAC completion. Conventional response assessment was performed with cystoscopy and tumour site biopsy. Response was dichotomised into response (15.5% was associated with significant improvement in OS (HR, 0.40; 95% CI, 0.19-0.86; p=0.0179), bCSS (HR, 0.26; 95% CI, 0.08-0.82; p=0.0214), PFS (HR, 0.16; 95% CI, 0.05-0.48; p=0.0012), and time to cystectomy (HR, 0.19; 95% CI, 0.07-0.47; p=0.0004). Conclusions: Quantitative ADC analysis can successfully identify NAC response and improved long-term clinical outcomes. Multi-centre validation to assess reproducibility and repeatability is required before testing within clinical trials to inform MIBC treatment decision making. Advances in knowledge: We successfully demonstrated that measured change in DWI can successfully identify NAC response and improved long-term survival outcomes.

Observation versus screening spinal MRI and pre-emptive treatment for spinal cord compression in patients with castration-resistant prostate cancer and spinal metastases in the UK (PROMPTS): an open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Early diagnosis of malignant spinal cord compression (SCC) is crucial because pretreatment neurological status is the major determinant of outcome. In metastatic castration-resistant prostate cancer, SCC is a clinically significant cause of disease-related morbidity and mortality. We investigated whether screening for SCC with spinal MRI, and pre-emptive treatment if radiological SCC (rSCC) was detected, reduced the incidence of clinical SCC (cSCC) in asymptomatic patients with metastatic castration-resistant prostate cancer and spinal metastasis. METHODS: We did a parallel-group, open-label, randomised, controlled, phase 3, superiority trial. Patients with metastatic castration-resistant prostate cancer were recruited from 45 National Health Service hospitals in the UK. Eligible patients were aged at least 18 years, with an Eastern Co-operative Oncology Group performance status of 0-2, asymptomatic spinal metastasis, no previous SCC, and no spinal MRI in the past 12 months. Participants were randomly assigned (1:1), using a minimisation algorithm with a random element (balancing factors were treatment centre, alkaline phosphatase [normal vs raised, with the upper limit of normal being defined at each participating laboratory], number of previous systemic treatments [first-line vs second-line or later], previous spinal treatment, and imaging of thorax and abdomen), to no MRI (control group) or screening spinal MRI (intervention group). Serious adverse events were monitored in the 24 h after screening MRI in the intervention group. Participants with screen-detected rSCC were offered pre-emptive treatment (radiotherapy or surgical decompression was recommended per treating physician's recommendation) and 6-monthly spinal MRI. All patients were followed up every 3 months, and then at month 30 and 36. The primary endpoint was time to and incidence of confirmed cSCC in the intention-to-treat population (defined as all patients randomly assigned), with the primary timepoint of interest being 1 year after randomisation. The study is registered with ISRCTN, ISRCTN74112318, and is now complete. FINDINGS: Between Feb 26, 2013, and April 25, 2017, 420 patients were randomly assigned to the control (n=210) or screening MRI (n=210) groups. Median age was 74 years (IQR 68 to 79), 222 (53%) of 420 patients had normal alkaline phosphatase, and median prostate-specific antigen concentration was 48 ng/mL (IQR 17 to 162). Screening MRI detected rSCC in 61 (31%) of 200 patients with assessable scans in the intervention group. As of data cutoff (April 23, 2020), at a median follow-up of 22 months (IQR 13 to 31), time to cSCC was not significantly improved with screening (hazard ratio 0·64 [95% CI 0·37 to 1·11]; Gray's test p=0·12). 1-year cSCC rates were 6·7% (95% CI 3·8-10·6; 14 of 210 patients) for the control group and 4·3% (2·1-7·7; nine of 210 patients) for the intervention group (difference -2·4% [95% CI -4·2 to 0·1]). Median time to cSCC was not reached in either group. No serious adverse events were reported within 24 h of screening. INTERPRETATION: Despite the substantial incidence of rSCC detected in the intervention group, the rate of cSCC in both groups was low at a median of 22 months of follow-up. Routine use of screening MRI and pre-emptive treatment to prevent cSCC is not warranted in patients with asymptomatic castration-resistant prostate cancer with spinal metastasis. FUNDING: Cancer Research UK.

Diagnostic Accuracy of FEC-PET/CT, FDG-PET/CT, and Diffusion-Weighted MRI in Detection of Nodal Metastases in Surgically Treated Endometrial and Cervical Carcinoma.

PURPOSE: Preoperative nodal staging is important for planning treatment in cervical cancer and endometrial cancer, but remains challenging. We compare nodal staging accuracy of 18F-ethyl-choline-(FEC)-PET/CT, 18F-fluoro-deoxy-glucose-(FDG)-PET/CT, and diffusion-weighted-MRI (DW-MRI) with conventional morphologic MRI. EXPERIMENTAL DESIGN: A prospective, multicenter observational study of diagnostic accuracy for nodal metastases was undertaken in 5 gyne-oncology centers. FEC-PET/CT, FDG-PET/CT, and DW-MRI were compared with nodal size and morphology on MRI. Reference standard was strictly correlated nodal histology. Eligibility included operable cervical cancer stage ≥ 1B1 or endometrial cancer (grade 3 any stage with myometrial invasion or grade 1-2 stage ≥ II). RESULTS: Among 162 consenting participants, 136 underwent study DW-MRI and FDG-PET/CT and 60 underwent FEC-PET/CT. In 118 patients, 267 nodal regions were strictly correlated at histology (nodal positivity rate, 25%). Sensitivity per patient (n = 118) for nodal size, morphology, DW-MRI, FDG- and FEC-PET/CT was 40%*, 53%, 53%, 63%*, and 67% for all cases (*, P = 0.016); 10%, 10%, 20%, 30%, and 25% in cervical cancer (n = 40); 65%, 75%, 70%, 80% and 88% in endometrial cancer (n = 78). FDG-PET/CT outperformed nodal size (P = 0.006) and size ratio (P = 0.04) for per-region sensitivity. False positive rates were all <10%. CONCLUSIONS: All imaging techniques had low sensitivity for detection of nodal metastases and cannot replace surgical nodal staging. The performance of FEC-PET/CT was not statistically different from other techniques that are more widely available. FDG-PET/CT had higher sensitivity than size in detecting nodal metastases. False positive rates were low across all methods. The low false positive rate demonstrated by FDG-PET/CT may be helpful in arbitration of challenging surgical planning decisions.

CT-Based Pelvic T1-Weighted MR Image Synthesis Using UNet, UNet++ and Cycle-Consistent Generative Adversarial Network (Cycle-GAN).

BACKGROUND: Computed tomography (CT) and magnetic resonance imaging (MRI) are the mainstay imaging modalities in radiotherapy planning. In MR-Linac treatment, manual annotation of organs-at-risk (OARs) and clinical volumes requires a significant clinician interaction and is a major challenge. Currently, there is a lack of available pre-annotated MRI data for training supervised segmentation algorithms. This study aimed to develop a deep learning (DL)-based framework to synthesize pelvic T1-weighted MRI from a pre-existing repository of clinical planning CTs. METHODS: MRI synthesis was performed using UNet++ and cycle-consistent generative adversarial network (Cycle-GAN), and the predictions were compared qualitatively and quantitatively against a baseline UNet model using pixel-wise and perceptual loss functions. Additionally, the Cycle-GAN predictions were evaluated through qualitative expert testing (4 radiologists), and a pelvic bone segmentation routine based on a UNet architecture was trained on synthetic MRI using CT-propagated contours and subsequently tested on real pelvic T1 weighted MRI scans. RESULTS: In our experiments, Cycle-GAN generated sharp images for all pelvic slices whilst UNet and UNet++ predictions suffered from poorer spatial resolution within deformable soft-tissues (e.g. bladder, bowel). Qualitative radiologist assessment showed inter-expert variabilities in the test scores; each of the four radiologists correctly identified images as acquired/synthetic with 67%, 100%, 86% and 94% accuracy. Unsupervised segmentation of pelvic bone on T1-weighted images was successful in a number of test cases. CONCLUSION: Pelvic MRI synthesis is a challenging task due to the absence of soft-tissue contrast on CT. Our study showed the potential of deep learning models for synthesizing realistic MR images from CT, and transferring cross-domain knowledge which may help to expand training datasets for 21 development of MR-only segmentation models.

Laparoscopic assessment improves case selection for exenterative surgery in recurrent cervical and endometrial cancer.

The objective of this study is to evaluate the role of laparoscopy in the case selection of patients for pelvic exenteration to treat recurrent cervical or endometrial cancer. Pelvic exenteration is a rare surgical procedure performed by specialised multidisciplinary surgical teams. We performed a review of 55 consecutive laparoscopies for patients being evaluated for possible exenterative surgery for recurrent cervical or endometrial cancer at a single centre in the UK with a significant exenterative surgical practice. All patients had no evidence of metastatic disease on imaging prior to the laparoscopy. Despite thorough radiological assessment laparoscopy detected peritoneal, nodal or extrapelvic metastases in 20.8% of cases. 5.6% of the patients who underwent exenterative surgery were found to have unresectable pelvic disease intraoperatively. In these cases, the extent of disease was not determined radiologically or during the initial exploratory laparotomy. In our view, laparoscopic assessment is an essential component of the pre-operative work up of patients with recurrent cervical or endometrial cancer being considered for exenterative surgery.Impact statementWhat is already known on this subject? Pelvic exenteration is potentially curative in cases of recurrent pelvic malignancy. Case selection is essential to determine those patients without metastases and with resectable pelvic disease - this will improve patient outcomes, avoid the unnecessary morbidity of major surgery, as well as the psychological consequences of abandoned procedures. The only two previous studies, published in 1998 (Plante and Roy 1998) and 2002 (Köhler et al. 2002) have shown laparoscopic assessment to be safe and improve case selection.What do the results of this study add? This study provides evidence that in the context of modern imaging modalities, including PET-CT scans, laparoscopic assessment continues to improve case selection for exenterative surgery.What are the implications of these findings for clinical practice and/or further research? This study provides further evidence of the benefit of laparoscopy in the assessment of patients being considered for exenterative surgery for recurrent pelvic cancer. Routine laparoscopy improves case selection and will enhance patient experiences and outcomes.

Stereotactic radiotherapy with focal boost for intermediate and high-risk prostate cancer: Initial results of the SPARC trial.

INTRODUCTION: Dose escalation to dominant intraprostatic lesions (DILs) is a novel method to increase the therapeutic ratio in localised prostate cancer. The Stereotactic Prostate Augmented Radiotherapy with Cyberknife (SPARC) trial was designed to determine the feasibility of a focal boost defined with multiparametric magnetic resonance imaging (mpMRI) using stereotactic ablative body radiotherapy (SABR). MATERIALS AND METHODS: Patients were included with newly diagnosed intermediate to high risk prostate cancer with at least one of: Gleason score 4 + 3, stage T3a, or PSA > 20 ng/ml. Visible disease on mpMRI was mandatory and up to 2 separate nodules were allowed. All patients received androgen deprivation. Patients received 36.25 Gy in 5 fractions using CyberKnife® and the DIL received a simultaneous boost to a maximum of 47.5 Gy, as allowed by OAR constraints. Genitourinary (GU) and gastrointestinal (GI) toxicity was reported using the RTOG scoring criteria. International Index of Erectile Function (IIEF) and EQ-5D global health scores were regularly captured. RESULTS: An interim safety analysis was performed on the first 8 patients, recruited between July 2013 and December 2015. Median follow up was 56 months (range 50-74). Median D95 values for the prostate PTV and boost volume were 36.55 Gy (range 35.87-36.99) and 46.62 Gy (range 44.85-48.25) respectively. Of the dose constraints, 10/80 were not achieved but all were minor dose variations. Grade 2+ acute GU and GI toxicities were 37.5% respectively while grade 2+ late GU and GI toxicities were 12.5% and 0% respectively. IIEF and quality of life scores recovered over time and all patients remain in biochemical remission. CONCLUSION: The first patients have been successfully treated with prostate SABR and focal boost on the SPARC trial, with excellent adherence to the planning protocol. Toxicity and efficacy results are promising and further recruitment is underway.

UKCGG Consensus Group guidelines for the management of patients with constitutional TP53 pathogenic variants.

Constitutional pathogenic variants in TP53 are associated with Li-Fraumeni syndrome or the more recently described heritable TP53-related cancer syndrome and are associated with increased lifetime risks of a wide spectrum of cancers. Due to the broad tumour spectrum, surveillance for this patient group has been limited. To date, the only recommendation in the UK has been for annual breast MRI in women; however, more recently, a more intensive surveillance protocol including whole-body MRI (WB-MRI) has been recommended by International Expert Groups. To address the gap in surveillance for this patient group in the UK, the UK Cancer Genetics Group facilitated a 1-day consensus meeting to discuss a protocol for the UK. Using a preworkshop survey followed by structured discussion on the day, we achieved consensus for a UK surveillance protocol for TP53 carriers to be adopted by UK Clinical Genetics services. The key recommendations are for annual WB-MRI and dedicated brain MRI from birth, annual breast MRI from 20 years in women and three-four monthly abdominal ultrasound in children along with review in a dedicated clinic.

Standard and Hypofractionated Dose Escalation to Intraprostatic Tumor Nodules in Localized Prostate Cancer: Efficacy and Toxicity in the DELINEATE Trial.

PURPOSE: To report a planned analysis of the efficacy and toxicity of dose escalation to the intraprostatic dominant nodule identified on multiparametric magnetic resonance imaging using standard and hypofractionated external beam radiation therapy. METHODS AND MATERIALS: DELINEATE is a single centre prospective phase 2 multicohort study including standard (cohort A: 74 Gy in 37 fractions) and moderately hypofractionated (cohort B: 60 Gy in 20 fractions) prostate image guided intensity modulated radiation therapy in patients with National Comprehensive Cancer Network intermediate- and high-risk disease. Patients received an integrated boost of 82 Gy (cohort A) and 67 Gy (cohort B) to lesions visible on multiparametric magnetic resonance imaging. Fifty-five patients were treated in cohort A, and 158 patients were treated in cohort B; the first 50 sequentially treated patients in cohort B were included in this planned analysis. The primary endpoint was late Radiation Therapy Oncology Group rectal toxicity at 1 year. Secondary endpoints included acute and late toxicity measured with clinician- and patient-reported outcomes at other time points and biochemical relapse-free survival for cohort A. Median follow-up was 74.5 months for cohort A and 52.0 months for cohort B. RESULTS: In cohorts A and B, 27% and 40% of patients, respectively, were classified as having National Comprehensive Cancer Network high-risk disease. The cumulative 1-year incidence of Radiation Therapy Oncology Group grade 2 or worse rectal and urinary toxicity was 3.6% and 0% in cohort A and 8% and 10% in cohort B, respectively. There was no reported late grade 3 rectal toxicity in either cohort. Within cohort A, 4 of 55 (7%) patients had biochemical relapse. CONCLUSIONS: Delivery of a simultaneous integrated boost to intraprostatic dominant nodules is feasible in prostate radiation therapy using standard and moderately hypofractionated regimens, with rectal and genitourinary toxicity comparable to contemporary series without an intraprostatic boost.

Realizing the potential of magnetic resonance image guided radiotherapy in gynaecological and rectal cancer.

CT-based radiotherapy workflow is limited by poor soft tissue definition in the pelvis and reliance on rigid registration methods. Current image-guided radiotherapy and adaptive radiotherapy models therefore have limited ability to improve clinical outcomes. The advent of MRI-guided radiotherapy solutions provides the opportunity to overcome these limitations with the potential to deliver online real-time MRI-based plan adaptation on a daily basis, a true "plan of the day." This review describes the application of MRI guided radiotherapy in two pelvic tumour sites likely to benefit from this approach.

Contrast-Enhanced CT Density Predicts Response to Sunitinib Therapy in Metastatic Renal Cell Carcinoma Patients.

The first-line therapy in metastatic renal cell carcinoma (mRCC), sunitinib, exhibits an objective response rate of approximately 30%. Therapeutic alternatives such as other tyrosine kinase inhibitors, VEGF inhibitors, or mTOR inhibitors emphasize the clinical need to predict the patient's response to sunitinib therapy before treatment initiation. In this study, we evaluated the prognostic value of pretreatment portal venous phase contrast-enhanced computed tomography (CECT) mean tumor density on overall survival (OS), progression-free survival (PFS), and tumor growth in 63 sunitinib-treated mRCC patients. Higher pretreatment CECT tumor density was associated with longer PFS and OS [hazard ratio (HR)=0.968, P=.002, and HR=0.956, P=.001, respectively], and CECT density was inversely correlated with tumor growth (P=.010). Receiver operating characteristic analysis identified two CECT density cut-off values (63.67 HU, sensitivity 0.704, specificity 0.694; and 68.67 HU, sensitivity 0.593, specificity 0.806) which yielded subpopulations with significantly different PFS and OS (P<.001). Pretreatment CECT is therefore a promising noninvasive strategy for response prediction in sunitinib-treated mRCC patients, identifying patients who will derive maximum therapeutic benefit.

Slice Encoding for Metal Artefact Correction in magnetic resonance imaging examinations for radiotherapy planning.

BACKGROUND AND PURPOSE: Magnetic resonance (MR) and computed tomography (CT) images are degraded in the presence of metallic implants. We investigate whether SEMAC (Slice Encoding for Metal Artifact Correction) MR is advantageous for radiotherapy (RT) planning. METHODS: Conventional and SEMAC MR protocols were compared (1.5T). A spine fixation device suspended in gelatine, two patients with spine fixation devices and six patients with bilateral hip replacements were scanned with both conventional and SEMAC protocols. In spine patients the visibility of the spinal canal and spinal cord was assessed; in prostate patients, the visibility of the prostate, pelvic structures and the pelvic girdle. RESULTS: The signal loss volume surrounding the spine fixation device was reduced by approximately 20% when the SEMAC protocol was employed, and registration errors were reduced. For spine patients, the spinal canal was completely visible only using the SEMAC protocol. In hip replacement patients, metal artifacts were local; the signal loss extended to the internal surface of the acetabulum in eight implants with conventional protocols, but only in four using SEMAC. CONCLUSIONS: SEMAC MR contributes towards correct co-registration of MR and CT images for RT planning, and is particularly relevant when the TV or OARs are close to implants.

What Burden of Prostate Cancer Can Radiologists Rule Out on Multiparametric Magnetic Resonance Imaging? A Sensitivity Analysis Based on Varying the Target Condition in Template Prostate Mapping Biopsies.

OBJECTIVE: To evaluate the minimum disease burden of prostate cancer at which multiparametric magnetic resonance imaging (MRI) optimally performs. METHODS: Between 2006 and 2008, 64 men underwent multiparametric MRI imaging (index test) followed by template prostate mapping biopsy (reference test). Three radiologists independently reported each quadrant of every prostate on a scale of 1 to 5: highly likely benign, likely benign, equivocal, likely malignant, highly likely malignant (≥3 or ≥4 was considered positive). There were 256 prostate sectors; bootstrapping adjustment was used to account for nonindependence. The target condition indicating cancer on biopsies was varied by changing the maximum cancer core length (MCCL) and total cancer core length (TCCL) within each sector from 1 mm to 10 mm. The sensitivity, specificity, and positive (PPVs) and negative predictive values (PPVs) were calculated for each MCCL and TCCL. Gleason ≤3+3 and Gleason ≥3+4 cancers were analyzed separately. RESULTS: Mean age was 62 years (range, 40-76 years), and mean prostate-specific antigen level was 8.2 µg/L (range, 2.1-43 µg/L). Fifty percent of quadrants (127 of 256) had prostate cancer, of which 65% (83 of 127) were Gleason ≤3+3. For Gleason ≤3+3, multiparametric MRI had an NPV of ≥95% at an MCCL of ≥5 mm and at a TCCL of ≥7 mm (MRI score ≥3). For Gleason ≥3+4, an NPV of ≥95% was seen at an MCCL of ≥5 mm (MRI score ≥3) and TCCL ≥6 mm. CONCLUSION: Multiparametric MRI may allow areas of the prostate which test negative to avoid biopsy. Whether multiparametric MRI can be used as a "triage" test before the first biopsy requires results from ongoing prospective validating cohort studies.

Consensus Guidelines and Contouring Atlas for Pelvic Node Delineation in Prostate and Pelvic Node Intensity Modulated Radiation Therapy.

PURPOSE: The purpose of this study was to establish reproducible guidelines for delineating the clinical target volume (CTV) of the pelvic lymph nodes (LN) by combining the freehand Royal Marsden Hospital (RMH) and Radiation Therapy Oncology Group (RTOG) vascular expansion techniques. METHODS AND MATERIALS: Seven patients with prostate cancer underwent standard planning computed tomography scanning. Four different CTVs (RMH, RTOG, modified RTOG, and Prostate and pelvIs Versus prOsTate Alone treatment for Locally advanced prostate cancer [PIVOTAL] trial) were created for each patient, and 6 different bowel expansion margins (BEM) were created to assess bowel avoidance by the CTV. The resulting CTVs were compared visually and by using Jaccard conformity indices. The volume of overlap between bowel and planning target volume (PTV) was measured to aid selection of an appropriate BEM to enable maximal LN yet minimal normal tissue coverage. RESULTS: In total, 84 nodal contours were evaluated. LN coverage was similar in all groups, with all of the vascular-expansion techniques (RTOG, modified RTOG, and PIVOTAL), resulting in larger CTVs than that of the RMH technique (mean volumes: 287.3 cm(3), 326.7 cm(3), 310.3 cm(3), and 256.7 cm(3), respectively). Mean volumes of bowel within the modified RTOG PTV were 19.5 cm(3) (with 0 mm BEM), 17.4 cm(3) (1-mm BEM), 10.8 cm(3) (2-mm BEM), 6.9 cm(3) (3-mm BEM), 5.0 cm(3) (4-mm BEM), and 1.4 cm(3) (5-mm BEM) in comparison with an overlap of 9.2 cm(3) seen using the RMH technique. Evaluation of conformity between LN-CTVs from each technique revealed similar volumes and coverage. CONCLUSIONS: Vascular expansion techniques result in larger LN-CTVs than the freehand RMH technique. Because the RMH technique is supported by phase 1 and 2 trial safety data, we proposed modifications to the RTOG technique, including the addition of a 3-mm BEM, which resulted in LN-CTV coverage similar to that of the RMH technique, with reduction in bowel and planning target volume overlap. On the basis of these findings, recommended guidelines including a detailed pelvic LN contouring atlas have been produced and implemented in the PIVOTAL trial.

Diffusion-weighted MR neurography for the assessment of brachial plexopathy in oncological practice.

BACKGROUND: To evaluate diffusion-weighted MR neurography (DW-MRN) for visualizing the brachial plexus and for the assessment of brachial plexopathy. METHODS: 40 oncological patients with symptoms of brachial plexopathy underwent 1.5 T MRI using conventional MR sequences and unidirectional DW-MRN. The images were independently reviewed by two radiologists. Anatomic visualization of the brachial plexus was scored using a 5 point scale on conventional MR sequences and then combined with DW-MRN. A brachial plexus abnormality was also scored using a 5 point scale and inter-observer agreement determined by kappa statistics. Diagnostic accuracy for brachial plexopathy assessed by conventional MRI alone versus conventional MRI combined with DW-MRN was compared by ROC analysis using reference standards. RESULTS: DW-MRN significantly improved visualization of the brachial plexus compared with conventional MRI alone (P<0.001). When assessing brachial plexopathy, inter-observer agreement was moderate for conventional MRI (kappa=0.48) but good for conventional MRI with DW-MRN (kappa=0.62). DW-MRN combined with conventional MRI significantly improved diagnostic accuracy in one observer (P<0.05) but was similar in the other observer. CONCLUSION: DW-MRN improved visualization of the brachial plexus. Combining DW-MRN with conventional MRI can improve inter-observer agreement and detection of brachial plexopathy in symptomatic oncological patients.

The role of 18F-FDG PET/CT in the management of testicular cancers.

OBJECTIVES: The aim of this study was to determine the utility of fluorine-18 fluorodeoxyglucose PET/computed tomography ((18)F-FDG PET/CT) in managing testicular cancer. PATIENTS AND METHODS: Sixty-two patients (29 seminoma, 28 nonseminoma and five mixed) underwent 75 (18)F-FDG PET/CT scans (16 scans for primary staging, 44 for residual masses and 15 for rising tumour markers). Follow-up histology, clinical scans and tumour marker results were included for retrospective analysis. RESULTS: (i) Primary staging: eight of 11 patients with equivocal CT scans had true-negative (18)F-FDG PET/CT scans. Five high-risk patients with normal stage 1 CT scans had negative (18)F-FDG PET/CT scans, but two subsequently relapsed. (ii) Residual masses: of the 20 scans interpreted as showing viable disease, five were false positive. Nineteen scans were negative (18 true negative and one false negative). (iii) Rising tumour markers: of the 15 scans, two were false negative and 13 were true positive. CONCLUSION: (18)F-FDG PET/CT is helpful when primary staging CT scans are equivocal but insufficiently sensitive to predict relapse in high-risk patients with normal CT scans. With residual masses, a negative scan is rarely associated with relapse. (18)F-FDG PET/CT is helpful in defining recurrent disease in the majority of patients with rising tumour markers and negative CT scans.

Utility of preoperative ferumoxtran-10 MRI to evaluate retroperitoneal lymph node metastasis in advanced cervical cancer: Results of ACRIN 6671/GOG 0233.

RATIONALE AND OBJECTIVES: To assess if ferumoxtran-10 (f-10) improves accuracy of MRI to detect lymph node (LN) metastasis in advanced cervical cancer. MATERIALS AND METHODS: F-10 MRI component of an IRB approved HIPAA compliant ACRIN/GOG trial was analyzed. Patients underwent f-10 MRI followed by extra-peritoneal or laparoscopic pelvic and abdominal lymphadenectomy. F-10-sensitive sequences were T2* GRE sequences with TE of 12 and 21. Seven independent blinded readers reviewed f-10-insensitive sequences and all sequences in different sessions. Region correlations were performed between pathology and MRI for eight abdomen and pelvis regions. Sensitivity and specificity were calculated at participant level. Reference standard is based on pathology result of surgically removed LNs. RESULTS: Among 43 women enrolled in the trial between September 2007 and November 2009, 33 women (mean age 49 ±11 years old) with advanced cervical cancer (12 IB2, 3 IIA, 15 IIB and 3 IIIB, 29 squamous cell carcinomas, 32 grade 2 or 3) were evaluable. Based on histopathology, LN metastasis was 39% in abdomen and 70% in pelvis. Sensitivity of all sequence review in pelvis, abdomen, and combined were 83%, 60%, and 86%, compared with 78%, 54%, and 80% for f-10 insensitive sequences (P: 0.24, 0.44 and 0.14, respectively). Mean diameter of the largest positive focus on histopathology was 13.7 mm in abdomen and 18.8 mm in pelvis (P = 0.018). Specificities of all sequence review in pelvis, abdomen, and combined were 48%, 75%, and 43%, compared with 75%, 83%, and 73% (P: 0.003, 0.14, 0.002 respectively) for f-10 insensitive sequences. CONCLUSION: Addition of f-10 increased MRI sensitivity to detect LN metastasis in advanced cervical cancer. Increased sensitivity did not reach statistical significance and was at the expense of lower specificity.

Revised Choi imaging criteria correlate with clinical outcomes in patients with metastatic renal cell carcinoma treated with sunitinib.

PURPOSE: To compare revised Choi criteria that incorporate concurrent size and attenuation changes at early follow-up imaging with Response Evaluation Criteria in Solid Tumors ( RECIST Response Evaluation Criteria in Solid Tumors ) 1.1 and original Choi criteria in stratification of clinical outcomes in patients with metastatic renal cell carcinoma ( mRCC metastatic renal cell carcinoma ) treated with sunitinib. MATERIALS AND METHODS: Institutional review board approved this retrospective study and waived informed consent. Baseline and first follow-up computed tomographic scans in 69 patients (50 men, 19 women; mean age, 60.3 years; range, 19-83 years) with mRCC metastatic renal cell carcinoma treated with sunitinib from October 1, 2008, to March 1, 2013, were evaluated for tumor response by using RECIST Response Evaluation Criteria in Solid Tumors 1.1, original Choi criteria, and revised Choi criteria. Correlations with overall survival ( OS overall survival ) and progression-free survival ( PFS progression-free survival ) were compared and stratified according to each radiologic criteria with Kaplan-Meier and multivariate Cox regression analysis. RESULTS: Median follow-up time was 29.7 months (95% confidence interval [ CI confidence interval ]: 18.9, 45.9). Response according to revised Choi criteria was independently correlated with OS overall survival (hazard ratio, 0.47 [95% CI confidence interval : 0.23, 0.99]; P = .046) and PFS progression-free survival (hazard ratio, 0.53 [95% CI confidence interval : 0.29, 0.99]; P = .047). Response according to RECIST Response Evaluation Criteria in Solid Tumors was not significantly correlated with OS overall survival (hazard ratio, 0.65 [95% CI confidence interval : 0.27, 1.58]; P = .344) or PFS progression-free survival (hazard ratio, 0.89 [95% CI confidence interval : 0.42, 1.91]; P = .768). Response according to original Choi criteria was not significantly correlated with OS overall survival (hazard ratio, 0.60 [95% CI confidence interval : 0.32, 1.11]; P = .106) or PFS progression-free survival (hazard ratio, 0.59 [95% CI confidence interval : 0.34, 1.02]; P = .060). Median OS overall survival and PFS progression-free survival in responders according to revised Choi criteria was 39.4 months (95% CI confidence interval : 9.1, upper limit not estimated) and 13.7 months (95% CI confidence interval : 6.4, 24.6), respectively, compared with 12.8 months (95% CI confidence interval : 8.7, 18.0) and 5.3 months (95% CI confidence interval : 3.9, 8.4), respectively, in nonresponders. CONCLUSION: Contemporaneous reduction in tumor size and attenuation were correlated with favorable clinical outcomes. Response according to revised Choi criteria showed better correlation with clinical outcomes compared with that according to RECIST Response Evaluation Criteria in Solid Tumors or original Choi criteria in patients with mRCC metastatic renal cell carcinoma treated with sunitinib.