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Supplementary Figure 1 Growth kinetics for all 786-0 xenografts included in the analysis from Figure 1; Supplementary Figure 2 Details of the in vitro angiogenesis assay; Supplementary Figure 3 Isolation of a sunitinib-refractory sub-line (786-0-R) from the parental 786-0 cell line; Supplementary Figure 4 Anti-angiogenic activity of sunitinib combined with trametinib within an in vitro tubule formation assay; Supplementary Figure 5 Quantification of tumor vessel density in treated tumors; Supplementary Table 1 Genotyping of the original patient sample and each generation of the PDX by STR typing

Sunitinib and pazopanib are antiangiogenic tyrosine kinase inhibitors (TKI) used to treat metastatic renal cell carcinoma (RCC). However, the ability of these drugs to extend progression-free and overall survival in this patient population is limited by drug resistance. It is possible that treatment outcomes in RCC patients could be improved by rationally combining TKIs with other agents. Here, we address whether inhibition of the Ras-Raf-MEK-ERK1/2 pathway is a rational means to improve the response to TKIs in RCC. Using a xenograft model of RCC, we found that tumors that are resistant to sunitinib have a significantly increased angiogenic response compared with tumors that are sensitive to sunitinib in vivo. We also observed significantly increased levels of phosphorylated ERK1/2 in the vasculature of resistant tumors, when compared with sensitive tumors. These data suggested that the Ras-Raf-MEK-ERK1/2 pathway, an important driver of angiogenesis in endothelial cells, remains active in the vasculature of TKI-resistant tumors. Using an in vitro angiogenesis assay, we identified that the MEK inhibitor (MEKI) trametinib has potent antiangiogenic activity. We then show that, when trametinib is combined with a TKI in vivo, more effective suppression of tumor growth and tumor angiogenesis is achieved than when either drug is utilized alone. In conclusion, we provide preclinical evidence that combining a TKI, such as sunitinib or pazopanib, with a MEKI, such as trametinib, is a rational and efficacious treatment regimen for RCC. Mol Cancer Ther; 15(1); 172–83. ©2015 AACR.

PET with targeted radiotracers has become integral to mapping the location and burden of recurrent disease in patients with biochemical recurrence (BCR) of prostate cancer (PCa). PET with 11C-choline is part of the National Comprehensive Cancer Network and European Association of Urology guidelines for evaluation of BCR. With advances in PET technology, increasing use of targeted radiotracers, and improved survival of patients with BCR because of novel therapeutics, atypical sites of metastases are being increasingly encountered, challenging the conventional view that prostate cancer rarely metastasizes beyond bones or lymph nodes. The purpose of this article is to describe such atypical metastases in the abdomen and pelvis on 11C-choline PET (including metastases to the liver, pancreas, genital tract, urinary tract, peritoneum, abdominal wall, and perineural spread) and to present multimodality imaging features and relevant imaging pitfalls. Given atypical metastases' inconsistent relationship with the serum PSA level and the nonspecific presenting symptoms, atypical metastases are often first detected on imaging. Awareness of their imaging features is important because their detection affects clinical management, patient counseling, prognosis, and clinical trial eligibility. Such awareness is particularly critical because the role of radiologists in the imaging and management of BCR will continue to increase given the expanding regulatory approvals of other targeted and theranostic radiotracers.

Supplementary Table 3. Baseline TTR and changes after SBRT predict outcomes in oligometastatic CRPC. Median event-free survival survival (in months) and hazard ratio for each outcome and group is given, stratified by baseline TTR levels (left) or change in TTR levels from baseline to day 14 post-SBRT. ns not significant; N/A not applicable

Supplementary Table 1. PSA progression by number of sites treated. 1Kaplan-Meier method; 2Cox model; 3Logrank test; 4Wald Chi-Square test.

Supplementary Figure 2. Flow cytometry gating strategies. (A) Flow cytometry gating strategies of central memory (TCM), effector memory (TEM), effector (TEF), and naïve (TN) T-cells populations. (B) Flow cytometry gating strategies of tumor reactive (TTR, CD8+CD11ahigh) T cell population analysis.

Supplementary Figure 1. PSA and distant progression by number of radiation-treated sites. (A) PSA progression by number of sites treated. (B) Distant radiographic progression by number of sites treated.

Supplementary Figure 3. Changes in CD8+CD11ahigh populations from baseline to days 1, 7, and 14.

Purpose:Outcomes for resistant metastatic castration-resistant prostate cancer (CRPC) are poor. Stereotactic ablative radiotherapy (SABR) induces antitumor immunity in clinical and preclinical studies, but immunologic biomarkers are lacking.Patients and Methods:Eighty-nine patients with oligometastatic CRPC were identified by 11C-Choline-PET (Choline-PET) from August 2016 to December 2019 and treated with SABR. Prespecified coprimary endpoints were 2-year overall survival (OS) and PSA progression. Secondary endpoints included 2-year SABR-treated local failure and 6-month adverse events. Correlative studies included peripheral blood T-cell subpopulations before and after SABR.Results:128 lesions in 89 patients were included in this analysis. Median OS was 29.3 months, and 1- and 2-year OS were 96% and 80%, respectively. PSA PFS was 40% at 1 year and 21% at 2 years. Local PFS was 84.4% and 75.3% at 1 and 2 years, respectively, and no grade ≥3 AEs were observed. Baseline high levels of tumor-reactive T cells (TTR; CD8+CD11ahigh) predicted superior local, PSA, and distant PFS. Baseline high levels of effector memory T cells (TEM; CCR7−CD45RA−) were associated with improved PSA PFS. An increase in TTR at day 14 from baseline was associated with superior OS.Conclusions:This is the first comprehensive effector T-cell immunophenotype analysis in a phase II trial before and after SABR in CRPC. Results are favorable and support the incorporation of immune-based markers in the design of future randomized trials in patients with oligometastatic CRPC treated with SABR.

Supplementary Table 2. Distant radiographic progression by number of sites treated. 1Kaplan-Meier method; 2Cox model; 3Logrank test; 4Wald Chi-Square test.

OBJECTIVE. Knowledge of normal testicular 18F-FDG PET/CT (FDG PET/CT) SUVs is crucial for accurate examination interpretation. The objective of this study was to establish normal testicular SUV ranges among adult men receiving health care in North America. MATERIALS AND METHODS. A retrospective review of an institutional electronic database identified adult men undergoing pretreatment clinical FDG PET/CT examinations from March 15, 2013, through March 15, 2018. An FDG PET/CT image review of 700 testicles in 350 male patients was performed. Data collected included testicular SUVmax, SUVmean, and visual PET pattern of uptake. RESULTS. Testicular SUVmean and SUVmax values (mean ± SD) by age group were as follows: 3.1 ± 0.7 and 3.8 ± 0.9 for the age group of 18-30 years; 3.2 ± 0.6 and 4.0 ± 0.8, 31-40 years; 3.1 ± 0.4 and 3.8 ± 0.5, 41-50 years; 3.0 ± 0.5 and 3.7 ± 0.7, 51-60 years; 2.9 ± 0.5 and 3.5 ± 0.7, 61-70 years; 2.8 ± 0.5 and 3.5 ± 0.7, 71-80 years; and 2.6 ± 0.5 and 3.3 ± 0.6, more than 80 years. A statistically significant difference exists between age groups for testicular SUVmean (p ≤ .001) and SUVmax (p < .001), with SUVs peaking in the 4th decade of life and subsequently declining with age. A small but significant negative correlation exists between blood glucose level and testicular SUVmean (r = -0.12). CONCLUSION. This study reports the largest currently known cohort of SUVs in normal testicles and may guide clinical interpretation of testicular FDG activity. Discrepancies in normal SUVs may exist because of differences in patient demographics and PET technology.

Purpose The aim of this study was to examine the MRI and FDG PET/CT imaging features of pathologically proven schwannomas. Patients and methods This institutional review board-approved retrospective study examined biopsy-proven schwannomas that underwent FDG PET/CT and/or MRI at our institution between January 1, 2002, and April 1, 2018. PET/CT features analyzed included SUVmax, metabolic ratios, volumetric metabolic measures, presence of calcification, and pattern of FDG activity. MRI features included T1/T2 signal, enhancement pattern, margins, perilesional edema, presence of muscular denervation, and size. Results Ninety-five biopsy-proven schwannomas were identified (40 with both PET and MRI, 35 with PET only, and 20 with MRI only), 46 females and 49 males, average age of 57.7 ± 15.3 years. The average largest dimension was 4.6 ± 2.7 cm, the average SUVmax was 5.4 ± 2.7, and lesion SUVmax/liver SUVmean was 2.2 ± 1.2. Eleven (15%) of 75 lesions had SUVmax greater than 8.1, 26/75 (35%) had SUVmax greater than 6.1, and 14/75 (19%) had lesion SUVmax/liver SUVmean greater than 3.0. On MRI, 29/53 (55%) demonstrated internal nonenhancing areas. Twenty-eight (70%) of 40 lesions with both MRI and PET demonstrated at least 1 imaging feature concerning for malignant peripheral nerve sheath tumor (irregular margins, internal nonenhancement, perilesional edema, heterogeneous FDG uptake, or SUVmax >8.1). Lesions with heterogeneous FDG activity had higher SUVmax (6.5 ± 0.5 vs 4.7 ± 0.4, P = 0.0031) and more frequent internal nonenhancement on MRI (P = 0.0218). Conclusions Schwannomas may be large, be intensely FDG avid, and demonstrate significant heterogeneity, features typically associated with malignant peripheral nerve sheath tumors. A significant proportion exhibit FDG activity above cutoff levels previously thought useful in differentiating malignant from benign peripheral nerve sheath tumors.

The use of immune checkpoint inhibitors has been increasing rapidly. Numerous untoward immune-related adverse events due to immune checkpoint inhibitors have been reported. Acute interstitial nephritis due to immune checkpoint inhibitors is one of these immune-related adverse events. Although gold standard, it is not always straightforward to perform a kidney biopsy in oncological patients. Helpful diagnostic methods are lacking. In this case report, we discuss the potential role of positron emission tomography–computed tomography on supporting the diagnosis of acute interstitial nephritis or ruling it out in the setting of acute kidney injury following treatment with immune checkpoint inhibitors. Studies are needed to assess the possible role of positron emission tomography–computed tomography for the diagnosis of acute interstitial nephritis in these subjects.

Introduction: For a test to be of value, it needs to demonstrate that it is changing clinical decisions, improving clinical confidence and of economic benefit. This trial looked at the use of Oncotype DX Breast Recurrence Score ® (RS) assay against these criteria in 680 women with hormone receptor positive (HR+), HER2 negative early breast cancer with 1 to 3 lymph nodes positive (LN+) in the UK National Health Service (NHS) (5 teaching and 9 district general hospitals) between 2017 and 2022. Methods: Patients with LN+ early breast cancer who were willing and fit to receive chemotherapy (CT) were consented to join the trial. At the initial oncologists’ appointment, physicians were asked to state their preference for or against CT and their level of confidence in their decision on a scale of 1 to 5. Following receipt of the RS result physicians were asked to make a final decision for or against CT and similarly record their level of confidence. Descriptive analyses were used to characterize (1) patient and tumour characteristics, (2) change in treatment recommendations post-RS testing (by RS result and nodal status), and (3) change in physicians’ level of confidence post-RS testing (by RS result and nodal status). Average cost for chemotherapy and RS test price were used to estimate overall cost savings. Results: A total of 680 patients were recruited. 16 patients were excluded (5 failed samples, 5 withdrew consent, 3 HER2 positives, 2 with advanced disease, and 1 specimen delayed in transit), leaving 664 assessable patients. The median age was 58 years and 77.1% of women were post-menopausal. Most patients had a RS of 0-17 (n=400, 60.2%); while 206 (31%) had a RS of 18-30 and 58 (8.7%) had a RS of 31-100. Using post-RxPONDER cutoffs, 566 (85.2%) had an RS of 0-25; 98 (14.8%) had an RS of 26-100. Decision impact results: The decision impact results broken down by RS result and nodal status are detailed in Table 1. Of the 662 patients with complete decision impact data, in 359 (54.2%) the recommendation by the physician changed from CT+ hormone therapy (HT) to HT alone. In 286 (43.2%) cases the decision was unchanged and in 17 (2.6%) the recommendation changed from HT alone to CT+HT. Overall 342 (51.7%) cases were spared chemotherapy. Decision conflict results: The change in the physicians’ level of confidence by RS result and nodal status are detailed in Table 2. Of the 660 cases with complete decision conflict data, physicians reported an increase in confidence in their recommendations after receiving the RS in 363 (55.0%), confidence was unchanged in 219 (33.2%) and decreased confidence in 78 (11.8%) cases. Economic analysis: Using the estimates of Burdanov et al, the average costs of a course of chemotherapy in the UK is £6,000 to £7,000. An estimate of the overall cost saving of 342 courses is £2,064,00 to £2,408,000 and the overall cost of 664 RS assays at the list price of about £2580 (although an undisclosed discount applies to the NHS) is £1,713,120. This suggests that the use of RS assay represents a significant saving to the NHS. Conclusion: The use of Oncotype DX assay in node positive early breast cancer leads to about half of women being spared chemotherapy, a significant improvement in clinical confidence for oncologists and an economic saving to the health care system. Table 1 Pre- vs Post-Oncotype DX Treatment Recommendation by Physician According to Recurrence Score and Nodal Status Table 2 Change in Physicians’ Level of Confidence Post-Oncotype DX Testing According to Recurrence Score and Nodal Status Citation Format: Simon D. Holt, Priyadharshini Sai-Giridhar, Mark Verrill, Laura Pettit, Anna Rigg, Tamas Hickish, Caroline D. Archer, Anshu Wadhawan, Marianne Dillon, Jo Dent, Mark R. Nathan, Ludger Barthelmes, Shazza rehman, Paige Innis, Saira Khawaja. A UK prospective multicentre decision impact, decision conflict and economic evaluation of the use of Oncotype DX® to guide chemotherapy in 680 women with hormone receptor positive, HER2 negative breast cancer and 1 to 3 nodes involved [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-11.

Purpose: Outcomes for resistant metastatic castration-resistant prostate cancer (CRPC) are poor. Stereotactic ablative radiotherapy (SABR) induces antitumor immunity in clinical and preclinical studies, but immunologic biomarkers are lacking. Patients and Methods: Eighty-nine patients with oligometastatic CRPC were identified by 11C-Choline-PET (Choline-PET) from August 2016 to December 2019 and treated with SABR. Prespecified coprimary endpoints were 2-year overall survival (OS) and PSA progression. Secondary endpoints included 2-year SABR-treated local failure and 6-month adverse events. Correlative studies included peripheral blood T-cell subpopulations before and after SABR. Results: 128 lesions in 89 patients were included in this analysis. Median OS was 29.3 months, and 1- and 2-year OS were 96% and 80%, respectively. PSA PFS was 40% at 1 year and 21% at 2 years. Local PFS was 84.4% and 75.3% at 1 and 2 years, respectively, and no grade ≥3 AEs were observed. Baseline high levels of tumor-reactive T cells (TTR; CD8+CD11ahigh) predicted superior local, PSA, and distant PFS. Baseline high levels of effector memory T cells (TEM; CCR7−CD45RA−) were associated with improved PSA PFS. An increase in TTR at day 14 from baseline was associated with superior OS. Conclusions: This is the first comprehensive effector T-cell immunophenotype analysis in a phase II trial before and after SABR in CRPC. Results are favorable and support the incorporation of immune-based markers in the design of future randomized trials in patients with oligometastatic CRPC treated with SABR.

PET with targeted radiotracers has become integral to mapping the location and burden of recurrent disease in patients with biochemical recurrence (BCR) of prostate cancer (PCa). PET with

Background In the setting of recurrent cancer, there is no standard methodology regarding the technical aspects of repeat sentinel lymph node (rSLN) surgery. We analyzed our institutional experience with attempted rSLN surgery to determine the optimal injection technique. Materials and Methods Single site, retrospective review of patients with prior lumpectomy for breast cancer who presented with recurrent or new ipsilateral breast cancer and underwent attempt at rSLN surgery from 2008 to 2017. Patients with prior mastectomy or no prior ipsilateral axillary operation were excluded. Results A total of 141 patients were included; 103 (73%) underwent successful rSLN biopsy procedure. Lymphoscintigraphy showed aberrant drainage in 32 (26%). Periareolar (PA) injection resulted in failed mapping in 23/99 (23%) and aberrant drainage in 25/85 (29%). By comparison, peritumoral (PT) injection had a 14/38 (37%) incidence of failed mapping and 7/37 (19%) aberrant drainage (P = .11 and .23, respectively). Of the patients with successful sentinel lymph node (SLN) biopsy procedure via PA injection, 11/76 (14%) were positive for metastatic disease as compared with 2/24 (8%) in PT injection. Sixteen patients had lymph node metastases; 13 (81%) were SLNs, including 3 positive aberrant SLNs. Five-year regional recurrence rates were 11.4% (95% confidence interval, 0%-21.5%) and 0% for PA and PT injection techniques, respectively. Conclusion PA and PT injections had a similar incidence of SLN identification and aberrant drainage. Preoperative lymphoscintigraphy is beneficial in patients with recurrent breast cancer given the higher incidence of aberrant drainage in this population. Patients who underwent PA injections had a higher incidence of regional recurrences but this difference was not statistically significant.

Purpose Management of recurrent prostate cancer necessitates timely diagnosis and accurate localization of the sites of recurrent disease. The purpose of this study was to assess predictors of histologic outcomes after 11C-choline positron emission tomography/computed tomography (CholPET) to increase the positive predictive value and specificity of CholPET in identifying imaging predictors of malignant and benign nodal disease to better inform clinical decision making regarding local therapy planning. Materials and Methods Retrospective review of patients undergoing CholPET followed by percutaneous core needle biopsy between January 1, 2010 and January 1, 2016. A total of 153 patients were identified who underwent 166 biopsy procedures. Patient, CholPET, procedural, and pathologic characteristics were recorded. Results A total of 157 biopsies were technically successful, and 110 (70.1%; 95% confidence interval, 62.2-77.1) yielded histologic results abnormal for metastatic prostate cancer. Lesion location, lesion maximum standardized uptake value (SUVmax), SUV ratio (calculated as the ratio of SUVmax to SUV mean in the right atrium), prostate-specific antigen, lesion short axis length, total Gleason score, and castration resistance were all associated with abnormal biopsy results (P values

Meningiomas are the most common intracranial tumors. Diagnosis by MRI is generally straightforward, but lack of imaging specificity can present a diagnostic dilemma, particularly in patients with cancer. We report our experience with meningioma identification on Pittsburgh compound B (PiB) PET/CT. Patients who underwent PiB PET/CT from 2006 to 2015 were reviewed to identify those with intracranial tumors. Tumor types were classified by MR appearance, or by pathology when available. Maximum standardized uptake value (SUVmax) measurements of tumor PiB activity were compared across tumor types. 2472 patients underwent PiB PET/CT in the period of interest; 45 patients (1.8%) had probable or definite intracranial tumor. Tumor types were meningioma (29/45, 64%), vestibular schwannoma (7/45, 16%), pituitary macroadenoma (4/45, 9%), metastatic disease (2/45, 4%), and others (3/45, 7%). In patients with meningioma, the mean lesion SUVmax was 2.05 (SD 1.37), versus 1.00 (SD 0.42) in patients with non-meningioma tumors (p

SummaryObjective Evidence on the diagnostic performance of adrenal imaging is limited. We aimed to assess the diagnostic performance of unenhanced computed tomography (CT) and 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET)/CT imaging in a high-risk population for adrenal malignancy using an optimal reference standard. Design Retrospective cohort study. Methods Imaging studies of patients with adrenal nodules who underwent adrenal biopsy and/or adrenalectomy between 1994 and 2014 were reviewed and compared to the reference standard of histology. Eighty % of patients presented with known or suspected extra-adrenal malignancy. Results Unenhanced abdominal CT was performed in 353 patients with adrenal lesions; median size was 3 (0.7-15) cm and median radiodensity was 33 (−21-78) Hounsfield units (HU). Radiodensity of >10 HU diagnosed malignancy with a sensitivity of 100%, specificity of 33%, positive predictive value (PPV) of 72% and negative predictive value (NPV) of 100%. 18FDG-PET/CT was performed in 89 patients; median tumour size was 2.1 (0.7-9.2) cm. Maximum standardized uptake (SUV max) was higher in malignant lesions when compared to benign lesions (median=10 [2.3-29.4] vs 3.7 [1.4-24.5], respectively, P 1.8 diagnosed malignancy with a sensitivity of 87%, specificity of 84%, PPV of 85% and NPV of 86%. Conclusion Noncontract CT radiodensity of ≤10 HU excludes malignancy even in a high-risk population. For indeterminate adrenal lesions, given a superior specificity, 18FDG-PET/CT could be considered as a second stage imaging study.

Fulvestrant is a selective estrogen receptor degrader that binds, blocks and degrades the estrogen receptor (ER), leading to complete inhibition of estrogen signaling through the ER. This review article further explains the mechanism of action of the drug and goes on to review the trials carried out to optimize its dosing. Multiple trials have been undertaken to compare fulvestrant with other endocrine treatments, and results have shown it to have similar efficacy to anastrozole, tamoxifen and exemestane at 250 mg every 28 days. However, when given at 500 mg every 28 days, with an extra loading dose on day 14, it has demonstrated an improved progression-free survival (PFS) compared to anastrozole. We look at how fulvestrant has been used in combination with CDK4/6 inhibitors such as palbociclib (PALOMA-3) and ribociclib (MONALEESA-3) and drugs targeting the PI3K/AKT/mTOR pathway such as pictilisib (FERGI) and buparlisib (BELLE-2 and BELLE-3). We then go on to describe a selection of the ongoing clinical trials looking at combination therapy involving fulvestrant. Finally, we review the effect of fulvestrant in patients who have developed resistance to aromatase inhibitors via ESR1 mutation, where it has been shown to offer a PFS benefit that is further improved by the addition of the CDK4/6 inhibitor palbociclib. Whilst fulvestrant is clearly an effective drug as monotherapy, we believe that its role in the treatment of ER-positive breast cancer may be best reserved for combination therapy, and whilst there are multiple trials currently in progress, it would appear that the combination with CDK4/6 inhibitors would offer the greatest promise in terms of balancing benefit with toxicity.

Introduction For patients with esophageal cancer undergoing neoadjuvant chemoradiation (CRT) followed by surgical resection, complete histopathologic response (pCR) is associated with favorable overall survival (OS). The aim of this study was to evaluate the correlation between 18 F-fluorodeoxyglucose positron emission tomography (FDG PET) response to neoadjuvant CRT and pCR. Methods Maximum standardized uptake values and standardized uptake ratios (SURs) were measured before and after CRT. SUR was normalized to liver uptake and mediastinal blood pool uptake. FDG PET complete response was defined as metabolic activity normalization to hepatic and blood pool activity. The correlation between FDG PET parameters and pCR was examined through logistic regression analyses. Results In total, 193 patients were monitored for a median of 3.6 years after initiation of CRT. Most tumors were adenocarcinoma (85%) and stage T3 (75%). Complete FDG PET response and pCR occurred in 27% and 34% of patients, respectively. Histologic findings, chemotherapy type, tumor stage, and radiation dose were not significantly associated with complete radiographic response. The rates of pCR in patients with and without radiographic complete response were 42% and 31% ( p = 0.17), respectively. No predictive correlation was found between pCR and change in maximum standardized uptake value ( p = 0.25), in SUR normalized to blood pool uptake ( p = 0.20), or in SUR normalized to liver uptake ( p = 0.15). The 5-year OS rate was 46% for patients with a complete FDG PET response versus 44% without a complete response ( p = 0.78). The 5-year OS rate of patients who achieved pCR was 49% versus 43% for patients with residual tumor ( p = 0.04). Conclusion For patients with esophageal cancer who received neoadjuvant chemoradiation, pretreatment and posttreatment FDG PET parameters did not correlate with pCR or OS.

Carcinoid is a subtype of neuroendocrine tumor, a rare group of tumors that are known to express somatostatin receptor 2. Ga-DOTATATE is a somatostatin analog that is specific for somatostatin receptor 2 and therefore allows visualization of neuroendocrine tumors. We present 2 cases of primary multifocal small bowel carcinoid evaluated using Ga-DOTATATE PET/CT, along with contrast-enhanced CT corollary findings. Given the increased sensitivity of Ga-DOTATATE PET/CT compared with CT and In-octreotide scintigraphy, we expect multifocal carcinoid to become increasingly recognized.

Objectives The objective was to evaluate the diagnostic performance of surveillance11 C-choline positron emission tomography/computed tomography (PET/CT) for the detection of disease relapse in patients with a history of biochemically recurrent (BCR) prostate cancer (PCa) and prostate-specific antigen (PSA) ≤0.1 ng/ml. Materials and methods We included patients who had been treated for BCR PCa and had a surveillance11 C-choline PET/CT at serum PSA ≤0.1 ng/ml. Positive surveillance PET/CT was defined as a study that identified a new tracer-avid lesion or new tracer uptake in a previously treated lesion or both. Findings were confirmed against a composite radiologic-pathologic gold standard. Time to recurrence association analyses were performed for disease relapse risk with the use of Cox proportional hazards regression. Results In total, 13 (12.1%) of the 107 patients had positive surveillance PET/CT scans, confirmed on pathologic assessment (n = 5) and subsequent imaging (n = 8). Among these 13 patients, ten had distant metastases, two had local recurrence, and one had both. Nine of the ten patients with metastases had oligometastatic disease defined as the presence of ≤3 metastases. Serum PSA became detectable again in only seven patients with positive surveillance PET/CT, after a mean interval from surveillance PET/CT of 292 days (range: 105-543 days). We identified an association of N stage with increased risk of recurrence (hazard ratio = 3.85; P = 0.036) although this was not significant after accounting for multiple testing. Conclusions Surveillance11 C-choline PET/CT can detect early disease relapse at serum PSA ≤0.1 ng/ml in patients with a history of BCR PCa.

OBJECTIVE The role of percutaneous adrenal biopsy in a high-risk population for adrenal malignancy has not been fully investigated. Our aim was to describe the clinical presentation leading to the adrenal biopsy and evaluate the diagnostic performance, complications and non diagnostic rate of adrenal biopsy. DESIGN Single-centre, retrospective cohort study. PATIENTS AND MEASUREMENTS Medical records of patients who underwent adrenal biopsy between 1994 and 2014 were reviewed. Adrenal biopsy outcome was compared to a predefined reference standard. RESULTS Biopsy was performed in 418 patients [62% men, median age 69 years (range, 15-91)] on 419 adrenal lesions, median size 3·1 cm (range, 0·6-24). The main indication for adrenal mass biopsy was (349/419, 83%) suspected adrenal metastasis from a known or suspected extra-adrenal primary source. Only 116 of 419, 28% of cases had prebiopsy biochemical testing for pheochromocytoma. Biopsy-related complications occurred in 4% of the patients. Histology revealed a metastasis in 231 of 419 (55%), benign adrenal tissue in 137 of 419 (33%), adrenocortical carcinoma in eight of 419 (2%), other lesions in 23 of 419 (5%) including seven cases of pheochromocytoma and six cases of infectious process. Biopsy was nondiagnostic in 20 of 419 (5%). All adrenal masses with unenhanced radiodensity ≤10 HU (42/137, 31%) proved to be benign adrenal adenomas. Adrenal biopsy diagnosed malignancy with a sensitivity of 88·5%, specificity of 91·5%, positive predictive value of 93·4% and negative predictive value of 85·5%. CONCLUSION When used in the appropriate clinical setting, adrenal biopsy is a powerful tool in the diagnostic algorithm of the evaluation of adrenal masses with features suspicious for malignancy. Efforts to increase awareness to perform biochemical testing for pheochromocytoma prior to adrenal biopsy are needed.

We compared signal change on magnetic resonance imaging (MRI) with fat suppression and bone scan activity of lumbar facet joints to determine if these two imaging findings are correlated.We retrospectively identified all patients who underwent imaging of the lumbar spine for pain evaluation using both technetium-99m methylene disphosphonate single-photon emission computed tomography/computed tomography (99mTc-MDP SPECT/CT) and MRI with at least one fat-suppressed T2- or T1-weighted sequence with gadolinium enhancement within a 180-day interval, at our institution between 1 January 2008 and 19 February 2013. Facet joint activity on 99mTc-MDP SPECT/CT and peri-facet signal change on MRI were rated as normal or increased. Agreement between the two examination types were determined with the κ and prevalence-adjusted bias-adjusted κ (PABAK) statistics.This study included 60 patients (28 male, 47%), with a mean age of 49±19.7 years (range, 12-93 years). The κ value indicated no agreement between 99mTc-MDP SPECT/CT and MRI (κ=-0.026; 95% confidence interval: -0.051, 0.000). The PABAK values were fair to high at each spinal level, which suggests that relatively low disease prevalence lowered the κ values. Together, the κ and PABAK values indicate that there is some degree of intermodality agreement, but that it is not consistent.Overall, facet joint signal change on fat-suppressed MRI did not always correlate with increased 99mTc-MDP SPECT/CT activity. MRI and 99mTc-MDP SPECT/CT for facet joint evaluation should not be considered interchangeable examinations in clinical practice or research.

Background The perineural spread of prostate cancer into pelvic peripheral nerves is a rare, but increasingly recognized, entity. This form of metastasis invades the lumbosacral plexus via the splanchnic nerves innervating the prostate. The prevalence of perineural spread is likely underappreciated, and further imaging-based studies are needed to elucidate its true frequency. Methods A retrospective review was performed using an institutional radiology database. Medical reports from patients with prostate cancer who had undergone positron emission tomography (PET) imaging were queried for terms suggestive of perineural spread. PET and magnetic resonance imaging (MRI) from the identified patients were blindly reviewed for peripheral nerve involvement by 2 nuclear medicine and 2 musculoskeletal radiologists. Results A total of 22 patients were identified. After review by the radiologists, 16 patients had positive findings of perineural spread found on PET and 15 had abnormalities found on MRI involving lumbosacral plexus neural elements. All patients with biopsy-proven neoplastic perineural spread (including 1 patient with malignant peripheral nerve sheath tumor) had positive findings on both PET and MRI. All patients with biopsy-proven inflammatory lesions had negative PET and variable MRI findings. Conclusions The perineural spread of prostate cancer might be more common than previously thought. The use of multimodal imaging for patients suspected of having perineural spread should be a part of the treatment algorithm. Targeted fascicular biopsy might be indicated for patients with progressive neurological deficit and an unclear diagnosis.

BRAF inhibitors vemurafenib and dabrafenib have become the standard of care for treatment of stage IV metastatic melanoma harboring a BRAF mutation. Panniculitis is a rare but known adverse side effect of these agents and presents with tender erythematous nodules. These nodules may demonstrate uptake on F-FDG PET/CT, which may mimic metastatic disease in patients undergoing treatment. We present a case of BRAF inhibitor-induced panniculitis in a patient with stage IV metastatic melanoma and discuss the imaging findings on F-FDG PET/CT.

Evidence on the diagnostic performance of adrenal imaging is limited. We aimed to assess the diagnostic performance of unenhanced computed tomography (CT) andRetrospective cohort study.Imaging studies of patients with adrenal nodules who underwent adrenal biopsy and/or adrenalectomy between 1994 and 2014 were reviewed and compared to the reference standard of histology. Eighty % of patients presented with known or suspected extra-adrenal malignancy.Unenhanced abdominal CT was performed in 353 patients with adrenal lesions; median size was 3 (0.7-15) cm and median radiodensity was 33 (-21-78) Hounsfield units (HU). Radiodensity of10 HU diagnosed malignancy with a sensitivity of 100%, specificity of 33%, positive predictive value (PPV) of 72% and negative predictive value (NPV) of 100%.Noncontract CT radiodensity of ≤10 HU excludes malignancy even in a high-risk population. For indeterminate adrenal lesions, given a superior specificity

Over the last few years, the developments around cancer immunotherapy (CIT) have led to a paradigm shift in the treatment of many different cancers, in particular melanoma, renal, bladder and lung cancers with a remarkable impact on response rate and, most importantly, overall survival. Breast cancer is most commonly considered to be a 'non-inflamed' cancer and so this shift has been less marked within its treatment. However, some subsets of breast cancer, most notably triple negative breast cancer, are deemed to be more 'inflamed' and therefore may prove to be an appropriate cohort for CIT. This review looks back at the theory of the cancer immunity cycle and mechanism of action behind immune checkpoint inhibitors and goes on to explore their role within the various subtypes of breast cancer. It looks at the first trials performed using CIT monotherapy which demonstrated that breast cancer could respond to CIT with a small population reaping considerable benefit. It then examines the continuing body of work being undertaken to explore CIT in combination with chemotherapy to try to increase the proportion of patients who might reap the considerable rewards on offer.

The aim of this study was to compare 11C-choline PET/CT with pelvic multiparametric MR imaging for detection of recurrent prostate carcinoma in patients with suspected recurrence after radical prostatectomy and to identify an optimal imaging method to restage these patients. Methods: This was a retrospective, single-institution study of 115 prostatectomy patients with suspected tumor recurrence who underwent both 11C-choline PET/CT and multiparametric MR imaging with endorectal coil. The reference standard included histopathology, treatment change, and imaging follow-up for determination of locally recurrent tumor, lymph node (LN) metastases, and skeletal metastases. Two nuclear medicine and 2 genitourinary radiologists independently and in a masked manner reviewed PET/CT and multiparametric MR imaging, respectively. The reviewers assessed for local recurrence in the prostatectomy bed as well as LN and bone metastases, rating their diagnostic confidence with a 5-point scoring system for each location. Receiver-operating-characteristic analysis was used to compare the 2 modalities. Results: The standard of reference (either positive or negative) for the diagnosis of local recurrence and pelvic LN and bone metastases was met in 87, 70, and 95 patients, respectively. Documented local recurrence and pelvic LN and bone metastases was present in 61 of 87 (70.1%), 50 of 70 (71.4%), and 16 of 95 (16.8%) patients, respectively. Patient-based area under the receiver-operating-characteristic curves of multiparametric MR imaging versus PET/CT for the diagnosis of local recurrence and pelvic LN and bone metastases were 0.909 versus 0.761 (P = 0.0079), 0.812 versus 0.952 (P = 0.0064), and 0.927 versus 0.898 (P = 0.69), respectively. Among 61 patients with local recurrence, 32 patients (52.4%) were correctly diagnosed as having local recurrence by both multiparametric MR imaging and PET/CT, 22 (36.1%) were correctly diagnosed by multiparametric MR imaging only, 6 (9.8%) could not be diagnosed by either modality, and 1 (1.6%) was correctly diagnosed by PET/CT only. The patient-based sensitivity, specificity, and accuracy of multiparametric MR imaging for diagnosing local recurrence were 88.5% (54/61), 84.6% (22/26), and 87.4% (76/87) whereas those of PET/CT for detecting body LN or bone metastases were 92.3% (72/78), 100% (18/18), and 93.8% (90/96), respectively. Conclusion: Multiparametric MR imaging with endorectal coil is superior for the detection of local recurrence, PET/CT is superior for pelvic LN metastasis, and both were equally excellent for pelvic bone metastasis. 11C-choline PET/CT and pelvic multiparametric MR imaging are complementary for restaging prostatectomy patients with suspected recurrent disease.

Prostate cancer is the most common non-cutaneous malignancy among men in the Western world, and continues to be a major health problem. Imaging has recently become more important in the clinical management of prostate cancer patients, including diagnosis, staging, choice of optimal treatment strategy, treatment follow up and restaging. Positron emission tomography, a functional and molecular imaging technique, has opened a new field in clinical oncological imaging. The most common positron emission tomography radiotracer, 18F-fluorodeoxyglucose, has been limited in imaging of prostate cancer. Recently, however, other positron emission tomography tracers, such as 11C-acetate and 11C- or 18F-choline, have shown promising results. In the present review article, we overview the potential and current use of positron emission tomography or positron emission tomography/computed tomography imaging employing the four most commonly used positron emission tomography radiotracers, 18F-fluorodeoxyglucose, 11C-acetate and 11C- or 18F-choline, for imaging evaluation of prostate cancer.

In this report we present a patient with a recent diagnosis of cervical adenocarcinoma with progressive left lower extremity pain and weakness. MR imaging of the pelvis and subsequent FDG CT/PET were complementary in demonstrating abnormalities worrisome for perineural spread of malignancy, which was confirmed with an open fascicular biopsy of the sciatic nerve. We review the imaging and propose a mechanism of perineural spread to the sciatic nerve, which we believe is supported by the imaging in this case.