Induction versus no induction chemotherapy before neoadjuvant chemoradiotherapy and surgery in oesophageal adenocarcinoma: a multicentre randomised phase II trial (NCCTG N0849 [Alliance]).

AIM: report primary results from the first multicentre randomised trial evaluating induction chemotherapy prior to trimodality therapy in patients with oesophageal or gastro-oesophageal junction adenocarcinoma. Notably, recent data from a single-institution randomised trial reported that induction chemotherapy prolonged overall survival (OS) in patients with well/moderately differentiated tumours. METHODS: In this phase 2 trial (28 centres in the U.S. NCI-sponsored North Central Cancer Treatment Group [Alliance]), trimodality-eligible patients (T3-4N0, TanyN+) were randomised to receive induction (docetaxel, oxaliplatin, capecitabine; Arm A) or no induction chemotherapy (Arm B) followed by oxaliplatin/5-fluorouracil/radiation and subsequent surgery. The primary endpoint was the rate of pathologic complete response (pathCR). Secondary/exploratory endpoints were OS and disease-free survival (DFS). RESULTS: Of 55 patients evaluable for the primary endpoint, the pathCR rate was 28.6% (8/28) in A versus 40.7% (11/27) in B (P = .34). Given interim results indicating futility, accrual was terminated, but patients were followed. After a median follow-up of 60.4 months, a longer median OS in Arm A versus B was unexpectedly observed (3-year rates 57.1% versus 41.7%, respectively) driven by longer DFS after margin-free surgery. In posthoc analysis, induction (versus no induction) chemotherapy was associated with significantly longer OS and DFS among patients with well/moderately differentiated tumours, but not among patients with poorly/undifferentiated tumours (Pinteraction = 0.037). CONCLUSIONS: Adding induction chemotherapy prior to trimodality therapy did not improve the primary endpoint, pathCR. However, induction chemotherapy was associated with longer median OS, particularly among patients with well/moderately differentiated tumours. These findings may inform further development of curative-intent trials in this disease.

99mTc-Tilmanocept Versus 99mTc-Sulfur Colloid in Lymphoscintigraphy: Sentinel Lymph Node Identification and Patient-Reported Pain.

Lymphoscintigraphy plays a vital role in sentinel lymph node (SLN) identification in oncologic breast surgery. The effectiveness of SLN localization and the degree of patient pain were compared between filtered 99mTc-sulfur colloid (99mTc-SC) and 99mTc-tilmanocept. Methods: A retrospective review of patients undergoing lymphoscintigraphy for breast cancer using 99mTc-SC (June 1, 2010, to December 31, 2011) or 99mTc-tilmanocept (June 1, 2013, to January 31, 2014) was performed. SLN appearance time and uptake, SLN pathology, proportion of positive SLNs removed, and pain scores were compared for each radiopharmaceutical using the χ2 test, Fisher exact test, and unequal variance t test, as appropriate. Results: In total, 76 patients, with 86 evaluated axillae, underwent lymphoscintigraphy: 29 with 99mTc-SC and 47 with 99mTc-tilmanocept. The mean SLN appearance time was 11.0 min for 99mTc-SC and 19.3 min for 99mTc-tilmanocept (P = 0.003). There was no difference in the mean transit uptake percentage: 2.2% for 99mTc-SC and 1.9% for 99mTc-tilmanocept (P = 0.55). 99mTc-tilmanocept identified a greater proportion of intraoperative blue nodes than did 99mTc-SC (P = 0.03). There was no significant difference between 99mTc-SC and 99mTc-tilmanocept in the number of SLNs removed, number of patients with positive SLNs, or pain score. Conclusion: 99mTc-SC use in lymphoscintigraphy is an acceptable alternative to 99mTc-tilmanocept for SLN detection in breast cancer, on the basis of the similarity in intraoperative SLN identification and pain scores.

The flip-flop fungus sign: an FDG PET/CT sign of benignity.

Benign granulomatous processes such as fungal infection may mimic metastatic lung cancer on FDG PET/CT. We found that these processes often have draining lymph node(s) with equal or greater FDG activity than associated lung nodule(s), a "flip-flop" of what is commonly seen in lung cancer. The aim of this study was to examine the utility of this "flip-flop fungus" (FFF) sign for diagnosing benign pulmonary disease. FDG PET/CT scans performed between 9/09-3/13 for the indications of pulmonary nodule or mass were reviewed. Scans with at least one hilar or mediastinal FDG avid draining node were included. Patients with a history of cancer, lack of pathologic confirmation, or without at least two years of imaging follow-up were excluded. A total of 209 FDG PET/CT exams were included and reviewed in a blinded fashion. A positive FFF sign had a sensitivity of 60.0% (95% CI: 47.6-71.5%) and specificity of 84.9% (95% CI: 77.8-90.4%) (P<0.0001) for benign disease. With additional strict imaging criteria applied, the FFF sign had a specificity of 98.6% (95% CI: 94.9-99.8%) (P<0.0001) and a positive predictive value of 90.0% (95% CI: 68.3-98.5%). A positive FFF sign was predominately due to granulomatous disease (91%), mostly histoplasmosis (73%). A positive FFF sign combined with positive fungal serology (n=16) had a specificity of 100% for benign disease. The FFF sign predicts benign disease in patients with a lung nodule(s) and an FDG avid draining lymph node(s) that would otherwise be considered worrisome for cancer.

Multimodality Imaging of Neurodegenerative Processes: Part 2, Atypical Dementias.

OBJECTIVE: The purpose of this article is to describe the role of multimodality imaging in the evaluation of atypical neurodegenerative conditions. An imaging approach to the more common dementia disease processes was described in part 1. This article, part 2, briefly discusses current Centers for Medicare & Medicaid Services coverage for imaging patients with dementia and illustrates the basic concepts of combining anatomic, metabolic, and amyloid imaging in the evaluation of patients with atypical neurodegenerative dementia. Although these disease processes are rare, the growing repertoire of clinically available imaging techniques necessitates an understanding of their imaging patterns. CONCLUSION: Despite the rarity of these conditions, imaging of patients with neurodegenerative disorders is on the rise, and familiarity with the imaging appearances of these atypical causes is increasingly important.

Multimodality Imaging of Neurodegenerative Processes: Part 1, The Basics and Common Dementias.

OBJECTIVE: Multimodality imaging plays an important role in the structural and functional characterization of neurodegenerative conditions. This article illustrates the basic concepts of anatomic, metabolic, and amyloid imaging and describes the application of a multimodality approach in the evaluation of patients with the more common neurodegenerative dementia processes. Proper utilization of clinically available imaging techniques allows greater insight into these common disease processes. CONCLUSION: Recognizing the strength of combined anatomic, metabolic, and amyloid imaging can allow a more complete and confident assessment of patients with common degenerative dementias. This added knowledge can improve clinical care, allow initiation of appropriate therapies and counseling, and improve prognostication.

Spectrum of Benign Articular and Periarticular Findings at FDG PET/CT.

Whole-body fluorine 18 fluorodeoxyglucose (FDG) positron-emission tomography (PET)/computed tomography (CT) is performed primarily for oncologic indications; however, FDG uptake is not specific for malignancy. Herein we focus on causes of increased FDG uptake in and around joints, as lesions in these locations are commonly benign. A combination of primary intra-articular processes and osseous processes that may occur near the joint space will be discussed. Causes of intra-articular and periarticular increased FDG activity can be broadly divided into infectious, inflammatory, degenerative, and benign neoplastic categories. A familiarity with the full range of these processes is important to avoid misinterpretation, in turn decreasing unnecessary follow-up studies, procedures, and treatments. Differentiation from malignancy is often possible on the basis of a different level of FDG activity, divergent response to therapy, or differing changes over time, in comparison with a patient's known primary cancer. Recognizing an intra-articular lesion location can also be critical, as intra-articular metastases are rare. In some cases, benign FDG-avid articular and periarticular entities have a specific appearance at FDG PET/CT and a correct diagnosis may be made without any additional workup. In most other cases, comparison with prior studies and/or additional imaging can afford an accurate diagnosis. This review is meant to introduce the reader to a spectrum of benign FDG-avid articular and periarticular processes that may be encountered at oncologic FDG PET/CT to increase confidence and diagnostic accuracy. (©)RSNA, 2016.

¹¹C-Choline PET/CT in Recurrent Prostate Cancer and Nonprostatic Neoplastic Processes.

Choline positron emission tomography (PET)/computed tomography (CT), with both carbon 11 ((11)C) choline and fluorine 18 ((18)F) choline, is an increasingly used tool in the evaluation of patients with biochemically recurrent prostate cancer. It has allowed detection and localization of locally recurrent and metastatic lesions that were difficult or impossible to identify using more conventional modalities. Many of the patients followed for their prostate cancer are elderly and have a higher rate of nonprostate cancer lesions or malignancies. As our experience with choline PET/CT has grown, it has become apparent that many of these nonprostate cancer processes, both benign and malignant, can be detected. Invasive thymoma, renal cell carcinoma, papillary thyroid carcinoma, and parathyroid adenoma are a few of the processes that have been incidentally detected with (11)C-choline PET/CT at our institution and have significantly altered subsequent clinical management of the patient. Although most of the secondary lesions are detected due to their increased (11)C-choline avidity, several have been detected due to their decreased or lack of avidity in the background of a highly avid organ. For instance, large liver masses that are relatively non-choline-avid create large activity defects in the otherwise highly active liver. Familiarity with normal (11)C-choline physiologic activity, the most common prostate metastatic patterns, and imaging characteristics of secondary lesions is essential for the detection and correct diagnosis of such lesions so that proper follow-up and management can be recommended.

ACR-ASNR Practice Parameter for Brain PET/CT Imaging Dementia.

This practice parameter is for both FDG and amyloid brain PET or PET/computed tomography (CT) for patients with cognitive decline, and has been developed collaboratively by the American College of Radiology (ACR) and the American Society for Neuroradiology (ASNR). It is estimated that the number of people with dementia, 36.5 million worldwide in 2010, will increase to 65.7 million in 2030 and to 115 million in 2050. Four primary neurodegenerative etiologies of dementia have been defined: Alzheimer disease (AD), vascular dementia, frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Alzheimer disease is the most common form of dementia, accounting for approximately 60%-80% of all cases. Indications for FDG and amyloid brain PET and qualifications for personnel are discussed in this practice parameter.

Multiple myeloma.

This article presents a review of multiple myeloma, precursor states, and related plasma cell disorders. The clinical roles of fluorodeoxyglucose PET/computed tomography (CT) and the potential to improve the management of patients with multiple myeloma are discussed. The clinical and research data supporting the utility of PET/CT use in evaluating myeloma and other plasma cell dyscrasias continues to grow.

MR imaging and PET/CT in diagnosis and management of multiple myeloma.

Multiple myeloma is a common hematologic malignancy among the elderly population. Although there have been many advances in treatment over the past few decades, the overall prognosis for the disease remains poor. Conventional radiography has long been the standard of reference for the imaging of multiple myeloma. However, 10%-20% of patients with multiple myeloma do not have evidence of disease at conventional radiography. There is a growing body of evidence supporting use of magnetic resonance (MR) imaging and 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) in diagnosis and management of multiple myeloma. MR imaging is useful in detection of bone marrow infiltration, a finding often missed at conventional radiography. FDG PET/CT is especially sensitive for the detection of extramedullary disease and can help detect the metabolically active lesions that often precede evidence of osseous destruction at conventional radiography. MR imaging and FDG PET/CT are useful tools that can provide essential information for diagnosis and management of patients with multiple myeloma. Both modalities allow accurate localization of disease after chemotherapy or autologous stem cell transplantation and can provide important prognostic information that can influence further clinical decision making regarding therapy, particularly when tumor serum markers may be a less reliable indicator of disease burden after repeated treatments.

Future of thoracic PET scanning.

The advances in PET scanning for thoracic diseases that are deemed most likely to have clinical impact in the near-term future are highlighted in this article. We predict that the current practice of medicine will continue to embrace the power of molecular imaging and specifically PET scanning. 18F-fluorodeoxyglucose-PET scanning will continue to evolve and will expand into imaging of inflammatory disorders. New clinically available PET scan radiotracers, such as PET scan versions of octreotide and amyloid imaging agents, will expand PET imaging into different disease processes. Major improvements in thoracic PET/CT imaging technology will become available, including fully digital silicone photomultipliers and Bayesian penalized likelihood image reconstruction. These will result in significant improvements in image quality, improving the evaluation of smaller lung nodules and metastases and allowing better prediction of prognosis. The birth of clinical PET/MRI scan will add new imaging opportunities, such as better PET imaging of pleural diseases currently obscured by complex patient motion.

Diagnostic imaging in paraneoplastic autoimmune multiorgan syndrome: retrospective single site study and literature review of 225 patients.

BACKGROUND: The utility of diagnostic imaging in paraneoplastic autoimmune multiorgan syndrome (PAMS) is unknown. METHODS: We examined the role of diagnostic imaging in patients with PAMS evaluated at our tertiary referral center (at Mayo Clinic, Rochester, MN, USA) and in the English literature between January 1, 1996, and August 31, 2012. RESULTS: We included 17 patients from our institution and 208 patients from the literature review. Of these 225 patients, 113 (50.2%) were not known to have a malignancy diagnosis at the time of PAMS diagnosis. Of the 123 patients from our institution and from the literature reported to undergo imaging studies, conventional computed tomography (CT) was the predominant imaging modality (n = 110; 89.4%); 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT was also used, albeit infrequently (n = 12; 9.8%). When CT was included in imaging to identify or confirm the presence of a malignancy, imaging was successful in all patients who ultimately were diagnosed with an associated malignancy. At our institution, a relatively high percentage (n = 7; 41%) of patients had 18F-FDG PET/CT, which not only identified all tumors found on CT but also facilitated staging of lymphoma and guided biopsy procedures. CONCLUSION: Diagnostic imaging is frequently utilized in PAMS with unknown malignancy. Both conventional CT and 18F-FDG PET/CT are likely to detect the typical underlying neoplasms. Relative to conventional CT, 18F-FDG PET/CT may provide additional useful information regarding prognosis for the likely underlying malignancies, although there is a paucity of reports describing the use of this modality for this purpose.

A phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: NCCTG N057K.

BACKGROUND: The mammalian target of rapamycin (mTOR) functions within the phosphatidylinositol-3 kinase (PI3K)/Akt pathway as a critical modulator of cell survival. This clinical trial evaluated the combination of the mTOR inhibitor everolimus with conventional temozolomide (TMZ)-based chemoradiotherapy. METHODS: Newly diagnosed patients with glioblastoma multiforme were eligible for this single arm, phase II study. Everolimus (70 mg/wk) was started 1 week prior to radiation and TMZ, followed by adjuvant TMZ, and continued until disease progression. The primary endpoint was overall survival at 12 months, and secondary endpoints were toxicity and time to progression. Eleven patients were imaged with 3'-deoxy-3'-(18)F-fluorothymidine ((18)FLT)-PET/CT before and after the initial 2 doses of everolimus before initiating radiation/TMZ. Imaged patients with sufficient tumor samples also underwent immunohistochemical and focused exon sequencing analysis. RESULTS: This study accrued 100 evaluable patients. Fourteen percent of patients had grade 4 hematologic toxicities. Twelve percent had at least one grade 4 nonhematologic toxicity, and there was one treatment-related death. Overall survival at 12 months was 64% and median time to progression was 6.4 months. Of the patients who had (18)FLT-PET data, 4/9 had a partial response after 2 doses of everolimus. Focused exon sequencing demonstrated that (18)FLT-PET responders were less likely to have alterations within the PI3K/Akt/mTOR or tuberous sclerosis complex/neurofibromatosis type 1 pathway compared with nonresponders. CONCLUSION: Combining everolimus with conventional chemoradiation had moderate toxicity. (18)FLT-PET studies suggested an initial antiproliferative effect in a genetically distinct subset of tumors, but this did not translate into an appreciable survival benefit compared with historical controls treated with conventional therapy.

Malignant involvement of the peripheral nervous system in patients with cancer: multimodality imaging and pathologic correlation.

The clinical and imaging evaluation of peripheral neuropathies in patients with cancer is challenging. It is critically important to differentiate malignant invasion of the peripheral nervous system from nonmalignant causes, such as radiation-induced neuritis, neuropathy associated with chemotherapy, and inflammatory neuropathies. Contrast material-enhanced magnetic resonance (MR) imaging is the initial noninvasive test of choice; however, interpretation can be challenging when the anatomic features are distorted by prior surgery, radiation, or both. Fluorine 18 ((18)F)-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is an imaging adjunct to MR imaging that is particularly helpful for evaluating peripheral nerves because the metabolic activity depicted with (18)F-FDG PET/CT helps differentiate malignant from benign disease and assists in making certain management decisions. For example, sites of high (18)F-FDG activity in a peripheral nerve can be targeted to increase the diagnostic yield of a biopsy because malignant involvement of peripheral nerves can be patchy. Of note, (18)F-FDG PET/CT can show clinically unsuspected metastases elsewhere in the body. If cancer is found, (18)F-FDG PET/CT allows excellent assessment of treatment response. (18)F-FDG PET/CT is also useful in evaluating primary nerve sheath tumors in that such tumors with low metabolic activity on FDG PET/CT images are unlikely to be malignant, although the specificity is limited. It is essential to have a good understanding of the imaging characteristics of benign and malignant causes of peripheral neuropathy if (18)F-FDG PET/CT is to be used effectively for accurate diagnosis.

Structural and functional imaging in parkinsonian syndromes.

Movement disorders with parkinsonian features are common, and in recent years imaging has assumed a greater role in diagnosis and management. Thus, it is important that radiologists become familiar with the most common imaging patterns of parkinsonism, especially given the significant clinical overlap and diagnostic difficulty associated with these disorders. The authors review the most common magnetic resonance (MR) and molecular imaging patterns of idiopathic Parkinson disease and atypical parkinsonian syndromes. They also discuss the interpretation of clinically available molecular imaging studies, including assessment of cerebral metabolism with 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET), cortical amyloid deposition with carbon 11 ((11)C) Pittsburgh compound B and fluorine 18 ((18)F) florbetapir PET, and dopaminergic activity with iodine 123 ((123)I) ioflupane single photon emission computed tomography (SPECT). Although no single imaging test is diagnostic, a combination of tests may help narrow the differential diagnosis. Findings at (123)I ioflupane SPECT can confirm the loss of dopaminergic neurons in patients with parkinsonism and help distinguish these syndromes from treatable conditions, including essential tremor and drug-induced parkinsonism. FDG PET uptake can demonstrate patterns of neuronal dysfunction that are specific to a particular parkinsonian syndrome. Although MR imaging findings are typically nonspecific in parkinsonian syndromes, classic patterns of T2 signal change can be seen in multiple system atrophy and progressive supranuclear palsy. Finally, positive amyloid-binding PET findings can support the diagnosis of dementia with Lewy bodies. Combined with a thorough clinical evaluation, multimodality imaging information can afford accurate diagnosis, allow selection of appropriate therapy, and provide important prognostic information.

Role of positron emission tomography/computed tomography in bone malignancies.

This article presents an overview of positron emission tomography combined with computed tomography (PET/CT) imaging of bone tumors for the practicing radiologist. The clinical roles and utility of (18)F-labeled fluorodeoxyglucose PET/CT in patients with primary bone tumors, osseous metastases, and multiple myeloma are reviewed. The clinical and research data supporting the utility of PET/CT in the evaluation of skeletal malignancies continues to grow.

Application of the National Institute on Aging-Alzheimer's Association AD criteria to ADNI.

OBJECTIVE: We describe the operationalization of the National Institute on Aging-Alzheimer's Association (NIA-AA) workgroup diagnostic guidelines pertaining to Alzheimer disease (AD) dementia in a large multicenter group of subjects with AD dementia. METHODS: Subjects with AD dementia from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with at least 1 amyloid biomarker (n = 211) were included in this report. Biomarker data from CSF Aß42, amyloid PET, fluorodeoxyglucose-PET, and MRI were examined. The biomarker results were assessed on a per-patient basis and the subject categorization as defined in the NIA-AA workgroup guidelines was determined. RESULTS: When using a requirement that subjects have a positive amyloid biomarker and single neuronal injury marker having an AD pattern, 87% (48% for both neuronal injury biomarkers) of the subjects could be categorized as "high probability" for AD. Amyloid status of the combined Pittsburgh compound B-PET and CSF results showed an amyloid-negative rate of 10% in the AD group. In the ADNI AD group, 5 of 92 subjects fit the category "dementia unlikely due to AD" when at least one neuronal injury marker was negative. CONCLUSIONS: A large proportion of subjects with AD dementia in ADNI may be categorized more definitively as high-probability AD using the proposed biomarker scheme in the NIA-AA criteria. A minority of subjects may be excluded from the diagnosis of AD by using biomarkers in clinically categorized AD subjects. In a well-defined AD dementia population, significant biomarker inconsistency can be seen on a per-patient basis.

Semiquantitative analysis of brain metabolism in patients with paraneoplastic neurologic syndromes.

PURPOSE: The objective of this study was to evaluate brain metabolism with F-FDG-PET in patients with definite or possible paraneoplastic neurologic syndromes (PNS) using qualitative assessment and semiquantitative measurements with subsequent correlation with MRI. METHODS: The institutional review board approved this Health Insurance Portability and Accountability Act-compliant study. A prospective PET database of patients referred for PNS between 2001 and 2010 was queried retrospectively and identified 102 patients who met the diagnostic criteria for PNS, had PET brain imaging, and lacked clinical or MRI evidence of an alternative diagnosis.Qualitative and semiquantitative evaluation of brain metabolism was obtained by 3-dimensional stereotactic surface projection and region-based analysis. Qualitative and semiquantitative assessment was performed blinded to clinical data. RESULTS: PET/CT demonstrated that 67 patients had abnormal brain glucose metabolism. Six categories of brain hypometabolism were identified: diffuse (36/67), cerebellar (10/67), basal ganglia (10/67), frontal (9/67), temporal (1/67), and occipital (1/67). The mean Z score of the cerebral cortex in diffuse hypometabolism was 1.65 (range, 0.25-3.46). For cerebellar hypometabolism, the mean Z score of the cerebellum was 2.31 (range, 0.52-4.54). In basal ganglia hypometabolism, the mean Z score was 2.53 (range, 1.78-3.89), and in frontal lobe hypometabolism, the mean Z score was 2.11 (range, 1.39-4.45). The majority (39/67, 62.9%) with abnormal glucose metabolism on PET had a normal MR. CONCLUSIONS: Patients with PNS frequently have abnormal brain metabolism on semiquantitative PET/CT. With semiquantitative analysis, we defined 6 common patterns of abnormalities, which often correlated with clinical symptoms. Both qualitative and semiquantitative analyses of brain glucose metabolism may be helpful in evaluating PNS, especially in patients with a normal MRI.

Dopamine Transporter SPECT Imaging in Parkinson Disease and Dementia.

The clinical diagnosis of Parkinson disease (PD) is difficult, as several other neurodegenerative and basal ganglia disorders have similar clinical presentations. Dopamine transporter single-photon emission computed tomography has been proposed as possible diagnostic tool to help differentiate idiopathic PD from essential tremor and other disorders that present with parkinsonian symptoms. In addition, it is valuable in the diagnosis of dementia with Lewy bodies, differentiating it from other causes of dementia such as Alzheimer disease.