A UK prospective multicentre decision impact, decision conflict and economic evaluation of the 21-gene assay in women with node+ve, hormone receptor+ve, HER2-ve breast cancer.

BACKGROUND: For a tumour profiling test to be of value, it needs to demonstrate that it is changing clinical decisions, improving clinical confidence, and of economic benefit. This trial evaluated the use of the Oncotype DX Breast Recurrence Score® assay against these criteria in 680 women with hormone receptor-positive (HR+), HER2-negative early breast cancer with 1-3 lymph nodes positive (LN+) in the UK National Health Service (NHS). METHODS: Prior to receipt of the Recurrence Score (RS) result, both the physician and the patient were asked to state their preference for or against chemotherapy and their level of confidence on a scale of 1-5. Following receipt of the RS result, the physician and patient were asked to make a final decision regarding chemotherapy and record their post-test level of confidence. RESULTS: Receipt of the RS result led to a 51.5% (95% CI, 47.2-55.8%) reduction in chemotherapy, significantly increased the relative and absolute confidence for both physicians and patients and led to an estimated saving to the NHS of £787 per patient. CONCLUSION: The use of the Oncotype DX assay fulfils the criteria of changing clinical decisions, improving confidence and saving money.

A real-world study of the first use of palbociclib for the treatment of advanced breast cancer within the UK National Health Service as part of the novel Ibrance® Patient Program.

BACKGROUND: The Ibrance® Patient Program was established to provide access to palbociclib for UK National Health Service (NHS) patients with metastatic breast cancer (MBC), pending a funding decision. METHODS: Non-interventional cohort study involving a retrospective medical record review of patients commenced on palbociclib between April and December 2017 at eight UK centres. Primary outcomes included clinicopathological characteristics, treatment patterns, clinical outcomes and selected adverse events. RESULTS: Overall, 191 patients were identified, median age of 57.0 years (range 24.3-90.9); 30% were diagnosed with de novo MBC; 72% received first-line and 10% as ≥ second-line treatment. Median progression-free survival (95% CI) was 22.8 months (16.5-not reached [NR]) in first-line; NR in patients with de novo MBC; 7.8 months (6.8-NR) in ≥ second-line (median follow-up: 24 months). Median overall survival (OS) was NR in the overall cohort; OS rate (95% CI) at 24 months was 74.2% (67.1-81.9%) in first-line; 82.1% (72.6-92.8%) in patients with de novo MBC; 55.0% (37.0-81.8%) in ≥ second-line. Forty-seven per cent of patients developed grade 3-4 neutropenia; 3% febrile neutropenia. CONCLUSION: This study supports the effectiveness of palbociclib and demonstrates the benefit to patients of early access schemes that bridge the gap between regulatory approval and NHS funding for new medicines. CLINICAL TRIAL REGISTRATION: Clinical trial: ClinicalTrial.gov:NCT03921866.

Bayesian penalized likelihood PET reconstruction impact on quantitative metrics in diffuse large B-cell lymphoma.

Evaluate the quantitative, subjective (Deauville score [DS]) and reader agreement differences between standard ordered subset expectation maximization (OSEM) and Bayesian penalized likelihood (BPL) positron emission tomography (PET) reconstruction methods. A retrospective review of 104 F-18 fluorodeoxyglucose PET/computed tomography (CT) exams among 52 patients with diffuse large B-cell lymphoma. An unblinded radiologist moderator reviewed both BPL and OSEM PET/CT exams. Four blinded radiologists then reviewed the annotated cases to provide a visual DS for each annotated lesion. Significant (P < .001) differences in BPL and OSEM PET methods were identified with greater standard uptake value (SUV) maximum and SUV mean for BPL. The DS was altered in 25% of cases when BPL and OSEM were reviewed by the same radiologist. Interobserver DS agreement was higher for OSEM (>1 cm lesion = 0.89 and ≤1 cm lesion = 0.84) compared to BPL (>1 cm lesion = 0.85 and ≤1 cm lesion = 0.81). Among the 4 readers, average intraobserver visual DS agreement between OSEM and BPL was 0.67 for lesions >1cm and 0.4 for lesions ≤1 cm. F-18 Fluorodeoxyglucose PET/CT of diffuse large B-cell lymphoma reconstructed with BPL has higher SUV values, altered DSs and reader agreement when compared to OSEM. This report finds volumetric PET measurements such as metabolic tumor volume to be similar between BPL and OSEM PET reconstructions. Efforts such as adoption of European Association Research Ltd accreditation should be made to harmonize PET data with an aim at balancing the need for harmonization and sensitivity for lesion detection.

Safety and Efficacy of CT-Guided Percutaneous Biopsy of Suspicious Subcentimeter Pelvic and Retroperitoneal Lymph Nodes Detected by 11C-Choline PET in Patients With Prostate Cancer.

BACKGROUND. In patients with prostate cancer, PET using targeted radiotracers can identify increased activity in small morphologically normal lymph nodes, facilitating earlier detection of metastatic disease. OBJECTIVE. The purpose of this article was to assess the efficacy and safety of CT-guided biopsy of suspicious pelvic and retroperitoneal lymph nodes measuring smaller than 1 cm detected by 11C-choline PET in patients with prostate cancer, with comparison with nodes measuring 1 cm or larger. METHODS. This retrospective study included patients with prostate cancer who underwent CT-guided percutaneous biopsy of suspicious pelvic or retroperitoneal lymph nodes detected by 11C-choline PET/CT or PET/MRI (performed because of a rising or elevated PSA level or known recurrent or metastatic disease) between June 1, 2012, and March 20, 2020. Patient, lymph node, and procedural characteristics, as well as biopsy outcomes and complications, were recorded. Biopsies of lymph nodes measuring smaller than 1 cm and of lymph nodes measuring 1 cm and larger were compared. RESULTS. A total of 269 patients (mean age, 68.7 ± 6.8 [SD] years) were included. A total of 156 patients underwent biopsy of lymph nodes measuring smaller than 1 cm (range, 3-9 mm); 113 patients underwent biopsy of lymph nodes measuring 1 cm or larger (range, 10-35 mm). Lymph nodes smaller than 1 cm and lymph nodes 1 cm and larger showed no significant difference in diagnostic yield (89.7% vs 92.9%; p = .40). Diagnostic yield was not significantly different between nodes smaller than 1 cm and nodes 1 cm and larger for any individual anatomic location within the pelvis or retroperitoneum (all p > .05). Malignant yield was lower for nodes smaller than 1 cm than for nodes 1 cm and larger (44.9% vs 63.7%; p = .003). The single biopsied 3-mm node had a nondiagnostic specimen. Diagnostic yield and malignant yield were 100.0% and 40.0%, respectively, for 4-mm nodes, and 95.5% and 45.5%, respectively, for 5-mm nodes. Patients with nodes smaller than 1 cm and nodes 1 cm and larger showed no significant difference in minor (12.8% vs 7.1%; p = .16) or major (0.6% vs 2.7%; p = .31) complication rate. CONCLUSION. The findings support the safety and efficacy of CT-guided biopsy of suspicious subcentimeter pelvic and retroperitoneal lymph nodes detected on 11C-choline PET in patients with prostate cancer. CLINICAL IMPACT. Earlier diagnosis of metastatic lymphadenopathy will impact prognostic assessment and management decisions in patients with recurrent prostate cancer.

Atypical Metastases in the Abdomen and Pelvis From Biochemically Recurrent Prostate Cancer: 11C-Choline PET/CT With Multimodality Correlation.

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.

Phase II Evaluation of Stereotactic Ablative Radiotherapy (SABR) and Immunity in 11C-Choline-PET/CT-Identified Oligometastatic Castration-Resistant Prostate Cancer.

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.

Establishing Normal Testicular 18F-FDG PET/CT SUVs.

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.

Repeat Sentinel Lymph Node Surgery in Recurrent Breast Cancer: Peritumoral vs. Periareolar Injections.

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.

FDG PET/CT and MRI Features of Pathologically Proven Schwannomas.

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.

11C-choline positron emission tomography/computed tomography for detection of disease relapse in patients with history of biochemically recurrent prostate cancer and prostate-specific antigen ≤0.1 ng/ml.

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.

Acute Lumbar Paraspinal Compartment Syndrome After Strenuous Exercise: A Case Report.

CASE: Acute lumbar paraspinal compartment syndrome (APCS) is rare. This case report describes the clinical presentation and magnetic resonance imaging (MRI) findings of APCS in a young man after strenuous weight training. The patient underwent surgical decompression of the paraspinal muscles with fasciotomy 4 days after presentation and made a complete functional recovery at the 3-month follow-up postsurgery. CONCLUSION: This case report highlights the importance of MRI in facilitating the diagnosis of APCS and demonstrates that fasciotomy, even if delayed, can result in complete functional recovery. This supports current understanding that surgical fascial decompression is the preferred treatment over conservative measures for this condition.

Percutaneous Image-Guided Nodal Biopsy After 11C-Choline PET/CT for Biochemically Recurrent Prostate Cancer: Imaging Predictors of Disease and Clinical Implications.

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 <.001, <.001, <.001, .02, .02, .02, and .015, respectively). External iliac, common iliac, and inguinal sites were associated with much lower rates of histologic positivity (mean [95% confidence interval], 51.2% [35.1-67.1], 46.2% [19.2-74.9], and 33.3% [7.5-70.1]), respectively. CONCLUSIONS: In a cohort of patients in whom core needle biopsy was performed after CholPET, characteristics of choline localization including node location, SUVmax, lesion-to-blood pool SUV ratio, prostate-specific antigen, total Gleason score, and castration resistance were significantly associated with abnormal biopsy results for metastatic disease on CholPET. Relatively high false positive rates were found in common iliac, external iliac, and inguinal lymph node locations. Histologic confirmation of these sites should be strongly considered in the appropriate clinical scenario before designing additional local therapy plans.

Multifocal Small Bowel Carcinoid: Evaluation by 68Ga-DOTATATE PET.

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.

Multimodal Imaging Aids in the Diagnosis of Perineural Spread of Prostate Cancer.

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.

The CVS Effect on American Health Insurance.

Once they have the right platforms in place, insurers can layer on predictive analytics, digital medical records, and other innovations that promise to make health care costs more manageable-and in the process make health insurers more competitive with the likes of CVS and maybe, eventually, Amazon.

Diagnostic performance of unenhanced computed tomography and 18 F-fluorodeoxyglucose positron emission tomography in indeterminate adrenal tumours.

OBJECTIVE: Evidence on the diagnostic performance of adrenal imaging is limited. We aimed to assess the diagnostic performance of unenhanced computed tomography (CT) and 18 F-fluorodeoxyglucose (18 FDG) 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%. 18 FDG-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<.0001). Similarly, median SUV max lesion to SUV max liver ratio (ALR) in malignant lesions was higher than in benign lesions (median=3 [0.74-13.4] vs 1.2 [0.5-6.6], respectively, P<.0001). 18 FDG-PET/CT ALR >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, 18 FDG-PET/CT could be considered as a second stage imaging study.

The emerging world of breast cancer immunotherapy.

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.

Pittsburgh compound B (PiB) PET imaging of meningioma and other intracranial tumors.

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 < 0.01). A receiver operating curve was created for lesion:cerebellum SUVmax ratio, with an area under the curve of 0.91 for a value of 1.68. At or above this ratio, specificity for meningioma was 100% (95% CI 79-100%) and sensitivity was 76% (95% CI 57-90%). PiB PET activity within an intracranial tumor is a highly specific and reasonably sensitive marker of meningioma. Further prospective evaluation is warranted to validate this result as well as to assess the performance of commercially available beta-amyloid radiotracers in meningioma identification.

A Review of Fulvestrant in Breast Cancer.

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.