Expert Perspectives on Controversies in Castration-Sensitive Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 1.

Purpose: Castration-sensitive prostate cancer (CSPC) is a complex and heterogeneous condition encompassing a range of clinical presentations. As new approaches have expanded management options, clinicians are left with myriad questions and controversies regarding the optimal individualized management of CSPC. Materials and Methods: The US Prostate Cancer Conference (USPCC) multidisciplinary panel was assembled to address the challenges of prostate cancer management. The first annual USPCC meeting included experts in urology, medical oncology, radiation oncology, and nuclear medicine. USPCC co-chairs and session moderators identified key areas of controversy and uncertainty in prostate cancer management and organized the sessions with multidisciplinary presentations and discussion. Throughout the meeting, experts responded to questions prepared by chairs and moderators to identify areas of agreement and controversy. Results: The USPCC panel discussion and question responses for CSPC-related topics are presented. Key advances in CSPC management endorsed by USPCC experts included the development and clinical utilization of gene expression classifiers and artificial intelligence (AI) models for risk stratification and treatment selection in specific patient populations, the use of advanced imaging modalities in patients with clinically localized unfavorable intermediate or high-risk disease and those with biochemical recurrence, recommendations of doublet or triplet therapy for metastatic CSPC (mCSPC), and consideration of prostate and/or metastasis-directed radiation therapy in select patients with mCSPC. Conclusions: CSPC is a diverse disease with many therapeutic options and the potential for adverse outcomes associated with either undertreatment or overtreatment. Future studies are needed to validate and clinically integrate novel technologies, including genomics, AI, and advanced imaging, to optimize outcomes among patients with CSPC.

Expert Perspectives on Controversies in Metastatic Castration-Resistant Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 2.

Background: Management strategies for metastatic castration-resistant prostate cancer (mCRPC) have rapidly shifted in recent years. As novel imaging and therapeutic approaches have made their way to the clinic, providers are encountering increasingly challenging clinical scenarios, with limited guidance from the current literature. Materials and Methods: The US Prostate Cancer Conference (USPCC) is a multidisciplinary meeting of prostate cancer experts intended to address the many challenges of prostate cancer management. At the first annual USPCC meeting, areas of controversy and consensus were identified during a 2-day meeting that included expert presentations, full-panel discussions, and postdiscussion responses to questions developed by the USPCC cochairs and session moderators. Results: This narrative review covers the USPCC expert discussion and perspectives relevant to mCRPC, including neuroendocrine/aggressive-variant prostate cancer (NEPC/AVPC). Areas of broad agreement identified among USPCC experts include the benefits of poly (ADP-ribose) polymerase (PARP) inhibitors for patients with BRCA1/2 mutations, the use of radioligand therapy in patients with prostate-specific membrane antigen (PSMA)-positive mCRPC, and the need for clinical trials that address real-world clinical questions, including the performance of novel therapies when compared with modern standard-of-care treatment. Ongoing areas of controversy and uncertainty included the appropriateness of PARP inhibitors in patients with non-BRCA1/2 mutations, the optimal definition of PSMA positivity, and systemic therapies for patients with NEPC/AVPC after progression on platinum-based therapies. Conclusions: The first annual USPCC meeting identified several areas of controversy in the management of mCRPC, highlighting the urgent need for clinical trials designed to facilitate treatment selection and sequencing in this heterogeneous disease state.

PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0.

Here we aim to provide updated guidance and standards for the indication, acquisition, and interpretation of PSMA PET/CT for prostate cancer imaging. Procedures and characteristics are reported for a variety of available PSMA small radioligands. Different scenarios for the clinical use of PSMA-ligand PET/CT are discussed. This document provides clinicians and technicians with the best available evidence, to support the implementation of PSMA PET/CT imaging in research and routine practice.

The Emerging Role of Next-Generation Imaging in Prostate Cancer.

PURPOSE OF REVIEW: Prostate cancer (PCa) is the most frequently diagnosed malignancy in men in developed countries and a leading cause of cancer death worldwide. Effective methods for diagnosing and staging PCa are necessary to guide treatment options in a personalized manner. The purpose of this paper is to review recent advances in molecular imaging and therapeutics and their expanding role in imaging and treating PCa. RECENT FINDINGS: Compared with conventional imaging, PSMA PET has proven more accurate at detecting PCa in patients with newly diagnosed PCa or biochemically recurrent PCa. PSMA PET can also induce management changes in patients due to its superior accuracy in detecting metastatic disease. Further research is necessary to understand the appropriate role of PSMA PET in patients with known metastatic PCa and the impact on clinical outcomes in patients who undergo treatment planning using findings from PSMA PET. We review the role of molecular imaging in primary and biochemically recurrent PCa. We find that molecular imaging is effective in detecting PCa and may lead to management changes.

Evolving understanding and categorization of prostate cancer: preventing progression to metastatic castration-resistant prostate cancer: RADAR IV.

INTRODUCTION To interpret data and update the traditional categorization of prostate cancer in order to help treating clinicians make more informed decisions. These updates include guidance regarding how to best use next generation imaging (NGI) with the caveat that the new imaging technologies are still a work in progress. MATERIALS AND METHODS: Literature review. RESULTS: Critical goals in prostate cancer management include preventing or delaying emergence of distant metastases and progression to castration-resistant disease. Pathways for progression to metastatic castration-resistant prostate cancer (mCRPC) involve transitional states: nonmetastatic castration-resistant prostate cancer (nmCRPC), metastatic hormone-sensitive prostate cancer (mHSPC), and oligometastatic disease. Determination of clinical state depends in part on available imaging modalities. Currently, fluciclovine and gallium-68 (68Ga) prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) are the NGI approaches with the most favorable combination of availability, specificity, and sensitivity. PET imaging can be used to help guide treatment selection in most patients. NGI can help determine patients who are candidates for new treatments, most notably (next-generation androgen antagonists, eg, apalutamide, enzalutamide, darolutamide), that can delay progression to advanced disease. CONCLUSIONS: It is important to achieve a consensus on new and more easily understood terminology to clearly and effectively describe prostate cancer and its progression to health care professionals and patients. It is also important that description of disease states make clear the need to initiate appropriate treatment. This may be particularly important for disease in transition to mCRPC.

Utility of Quantitative SPECT/CT Lymphoscintigraphy in Guiding Sentinel Lymph Node Biopsy in Head and Neck Melanoma.

PURPOSE: To investigate the use of advanced SPECT/CT quantification in guiding surgical selection of positive sentinel lymph nodes (SLNs) in head and neck melanoma. METHODS: We retrospectively reviewed data from patients with cutaneous head and neck melanoma who underwent lymphoscintigraphy with SPECT/CT prior to SLN biopsy (SLNB). Quantification of radiotracer uptake from SPECT/CT data was performed using in-house segmentation software. SLNs identified using SPECT/CT were compared to SLNs identified surgically using an intraoperative γ-probe. A radioactivity count threshold using SPECT/CT for detecting a positive SLN was calculated. RESULTS: One hundred and five patients were included. Median number of SLNs detected was 3/patient with SPECT/CT and 2/patient with intraoperative γ-probe. The hottest node identified by SPECT/CT and intraoperative γ-probe were identical in 85% of patients. All 20 histologically positive SLNs were identified by SPECT/CT and γ-probe. On follow-up, all nodal recurrences occurred at lymph node levels with the hottest node identified by SPECT/CT and either the hottest or second hottest node identified by γ-probe during SLNB. Using our data, a SPECT/CT radioactivity count threshold of 20% would eliminate the unnecessary removal of 11% of SPECT/CT identified nodes and 12% of intraoperatively detected nodes. CONCLUSION: Utilizing SPECT/CT quantification, we propose that a radioactivity count threshold can be developed to help guide the selective removal of lymph nodes in head and neck SLNB. Furthermore, the nodal level containing the hottest node identified by SPECT/CT quantification must be thoroughly investigated for SLNs and undergo careful follow-up and surveillance for recurrence.

A Clinician's Guide to Next Generation Imaging in Patients With Advanced Prostate Cancer (RADAR III).

PURPOSE: The advanced prostate cancer therapeutic landscape has changed dramatically in the last several years, resulting in improved overall survival of patients with castration naïve and castration resistant disease. The evolution and development of novel next generation imaging techniques will affect diagnostic and therapeutic decision making. Clinicians must navigate when and which next generation imaging techniques to use and how to adjust treatment strategies based on the results, often in the absence of correlative therapeutic data. Therefore, guidance is needed based on best available information and current clinical experience. MATERIALS AND METHODS: The RADAR (Radiographic Assessments for Detection of Advanced Recurrence) III Group convened to offer guidance on the use of next generation imaging to stage prostate cancer based on available data and clinical experience. The group also discussed the potential impact of next generation imaging on treatment options based on earlier detection of disease. RESULTS: The group unanimously agreed that progression to metastatic disease is a seminal event for patient treatment. Next generation imaging techniques are able to detect previously undetectable metastases, which could redefine the phases of prostate cancer progression. Thus, earlier systemic or locally directed treatment may positively alter patient outcomes. CONCLUSIONS: The RADAR III Group recommends next generation imaging techniques in select patients in whom disease progression is suspected based on laboratory (biomarker) values, comorbidities and symptoms. Currently 18F-fluciclovine and 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography are the next generation imaging agents with a favorable combination of availability, specificity and sensitivity. There is ongoing research of additional next generation imaging technologies, which may offer improved diagnostic accuracy and therapeutic options. As next generation imaging techniques evolve and presumably result in improved global accessibility, clinician ability to detect micrometastases may be enhanced for decision making and patient outcomes.

Diagnostic Accuracy of F-18 FDG PET/CT for Preoperative Lymph Node Staging in Newly Diagnosed Bladder Cancer Patients: A Systematic Review and Meta-Analysis.

AIMS: We aimed to assess the diagnostic accuracy of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for preoperative lymph node (LN) staging in newly diagnosed bladder cancer (BC) patients through a systematic review and meta-analysis. PATIENTS AND METHODS: MEDLINE, Embase, and the Cochrane Library database, from the earliest available date of indexing through June 30, 2017, were searched for studies evaluating the diagnostic performance of F-18 FDG PET/CT for preoperative LN staging in newly diagnosed BC. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves. RESULTS: Across 14 studies (785 patients), the pooled sensitivity was 0.57 (95% CI: 0.49-0.64) and the pooled specificity was 0.92 (95% CI: 0.87-0.95). The LR syntheses gave an overall LR+ of 7.4 (95% CI: 4.4-12.3) and an LR- of 0.47 (95% CI: 0.39-0.56). The pooled diagnostic odds ratio was 16 (95% CI: 9-28). CONCLUSIONS: F-18 FDG PET/CT shows a low sensitivity and high specificity for the detection of metastatic LNs in patients with newly diagnosed BC.

Diagnostic accuracy of C-11 choline and C-11 acetate for lymph node staging in patients with bladder cancer: a systematic review and meta-analysis.

OBJECTIVE: We aimed to assess the diagnostic accuracy of C-11 choline and C-11 acetate positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging in bladder cancer (BC) patients through a systematic review and meta-analysis. METHODS: The MEDLINE, EMBASE, and Cochrane Library database, from the earliest available date of indexing through June 30, 2017, were searched for studies evaluating the diagnostic performance of C-11 choline and C-11 acetate PET/CT for LN staging in BC. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves. RESULTS: Across 10 studies (282 patients), the pooled sensitivity was 0.66 (95% CI 0.54-0.75) without heterogeneity (χ2 = 12.4, p = 0.19) and a pooled specificity of 0.89 (95% CI 0.76-0.95) with heterogeneity (χ2 = 29.1, p = 0.00). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 5.8 (95% CI 2.7-12.7) and negative likelihood ratio (LR-) of 0.39 (95% CI 0.28-0.53). The pooled diagnostic odds ratio (DOR) was 15 (95% CI 6-38). In meta-regression analysis, the study design (prospective vs retrospective) was the source of the study heterogeneity. CONCLUSION: C-11 choline and C-11 acetate PET/CT shows a low sensitivity and moderate specificity for the detection of metastatic LNs in patients with BC. Moreover, heterogeneity among the studies should be considered a limitation. Further large multicenter studies would be necessary to substantiate the diagnostic accuracy of C-11 choline and C-11 acetate PET/CT for this purpose.

The Role of Therapeutic Layering in Optimizing Treatment for Patients With Castration-resistant Prostate Cancer (Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence II).

OBJECTIVE: To offer recommendations on identification of disease progression, treatment management strategies, and suggestions on timing of initiating and discontinuing specific castration-resistant prostate cancer (CRPC) treatments. MATERIALS AND METHODS: The Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence II Working Group convened to provide guidance on sequencing, combination, or layering of approved treatments for metastatic CRPC based on available data and clinical experience. RESULTS: A consensus was developed to address important questions on management of patients with metastatic CRPC. CONCLUSION: In the absence of large-scale clinical trials, the Working Group recommends that patients may best be managed with a layered approach of approved therapies with unique or complimentary mechanisms of action.

Estimation of Recurrence Risk After Normal (18)F-FDG PET/CT in Nonsmall-Cell Lung Cancer.

The authors aimed to assess the risk of recurrence in patients with nonsmall-cell lung cancer after surgery with no evidence of disease (NED) demonstrated on (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). A total of 140 subjects with adenocarcinoma or squamous cell carcinoma of the lung were included in this study. Patients had FDG PET/CT scans within a year after surgery between January 2007 and December 2014. Patients with PET/CT scans with NED were included. Following an NED PET/CT scan, recurrence or metastasis was found in 14 patients (10.0%), and deaths in 4 (2.9%) during a median follow-up of 636 days. Although the rates of recurrence or metastasis were very low, the risk for recurrence continuously increased after 600 days up to 0.03%. The risk was higher in patients with positive margin at surgery, lymphovascular invasion, N2 stage, and TNM stage III/IV. In conclusion, according to the smoothed hazard functions, there was a very low risk of recurrence until 600 days after normal (18)F-FDG PET scans. The risk was higher in patients with positive margin at surgery, lymphovascular invasion, N2 stage, and TNM stage III/IV.

Interim Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography to Predict Pathologic Response to Preoperative Chemoradiotherapy and Prognosis in Patients With Locally Advanced Rectal Cancer.

INTRODUCTION: The goal of the present study was to investigate the predictive and prognostic values of interim fluorine-18 (18F) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) parameters for the prediction of a complete pathologic response (pCR) in patients with locally advanced rectal cancer (LARC) who had received preoperative chemoradiotherapy (PCRT). PATIENTS AND METHODS: A total 103 patients with LARC were included in the present study. All the patients were evaluated by 18F FDG PET/CT before and after 45 Gy of radiotherapy with concurrent oral capecitabine chemotherapy. The quantitative, volumetric parameters and their percentage of change (Δ%) were used to predict the pCR and calculate the overall survival (OS). The predictive value for a pCR of 18F FDG PET/CT cutoff values were determined by receiver operating characteristic analysis. The prognostic significance was assessed using Kaplan-Meier analysis. RESULTS: A pCR occurred in 22 patients (21.4%). Univariate and multivariate analyses demonstrated that the post-PCRT maximum standardized uptake value (SUVmax2) and change in the SUVmax (ΔSUVmax) as significant factors for the prediction of pCR, with a sensitivity of 68.2% and specificity of 87.7% and sensitivity of 90.9% and specificity of 80.3%, respectively. Kaplan-Meier analysis showed that a low SUVmax2 (< 2.5) and high ΔSUVmax (≥ 62.2%) were potent predictors for OS. CONCLUSION: The present study has shown the capability of interim 18F FDG PET/CT parameters to predict the achievement of pCR after PCRT in patients with LARC. Of the parameters, SUVmax2 and ΔSUVmax were potent predictors for pCR and well associated with OS.

Multidisciplinary management for esophageal and gastric cancer.

The management of esophageal and gastric cancer is complex and involves multiple specialists in an effort to optimize patient outcomes. Utilizing a multidisciplinary team approach starting from the initial staging evaluation ensures that all members are in agreement with the plan of care. Treatment selection for esophageal and gastric cancer often involves a combination of chemotherapy, radiation, surgery, and palliative interventions (endoscopic and surgical), and direct communication between specialists in these fields is needed to ensure appropriate clinical decision making. At the University of Colorado, the Esophageal and Gastric Multidisciplinary Clinic was created to bring together all experts involved in treating these diseases at a weekly conference in order to provide patients with coordinated, individualized, and patient-centered care. This review details the essential elements and benefits of building a multidisciplinary program focused on treating esophageal and gastric cancer patients.

Frequency based gating: An alternative, conformal, approach to 4D PET data utilization.

PURPOSE: Respiratory gating is a strategy for overcoming image degradation caused by patient motion in Positron Emission Tomography (PET) imaging. Traditional methods for sorting data, namely, phase-based gating or amplitude-based gating, come with an inherent trade-off between resolution improvements and added noise present in the subjugated data. If the goal of motion correction in PET is realigned from creating 4D images that attempt to mimic nongated images, towards ideal utilization of the information available, then new paths for data management emerge. In this work, the authors examine the application of a method in a new class of frequency based data subjugation algorithms, termed gating +. This strategy utilizes data driven information to locally adapt signal to its optimal segregation, thereby creating a new approach to 4D data utilization PET. METHODS: 189 (18)F-fluorodeoxyglucose (FDG) PET scans were acquired at a single bed position centered on the thorax region. 4D gated image sets were reconstructed using data driven gating. The gating+ signal optimization algorithm, previously presented in small animal PET images and simulations, was used to segregate data in frequency space to generate optimized 4D images in the population-the first application and analysis of gating+ in human PET scans. The nongated, phase gated, and gating+ representations of the data were compared using FDG uptake analysis in the identified lesions and noise measurements from background regions. RESULTS: Optimized processing required less than 1 min per scan on a standard PC (plus standard reconstruction time), and yielded entire 4D optimized volumes plus motion maps. Optimized scans had noise characteristics similar to nongated images, yet also contained much of the resolution and motion information found in the gated images. The average SUVmax increase in the lesion sample between gated/nongated and gating+/nongated (±SD in population) was 35.8% ± 34.6% and 28.6% ± 27.9%, respectively. The average percent standard deviation (%SD ± SD in population) in liver volumes of interest (VOIs) across the sample for the nongated, gated, and gating+ scans was 6.7% ± 2.4%, 13.6% ± 3.3%, and 7.1% ± 2.5%, respectively. In all cases, the noise in the gating+ liver VOIs was closer to the nongated measurements than to the gated. CONCLUSIONS: The gating+ algorithm introduces the notion of conforming 4D data segregation to the local information and statistics that support it. By segregating data in frequency space, the authors are able to generate low noise motion information rich image sets, derived solely from selective use of raw data. Their work shows that the gating+ algorithm can be robustly applied in populations, and across varying qualities of motion and scans statistics, and be integrated as part of a fully automated motion correction workflow. Furthermore, the idea of smart signal utilization underpins a new concept of low risk or even risk-free motion correction application in PET.

SPECT/CT Improves Detection of Metastatic Sentinel Lymph Nodes in Patients with Head and Neck Melanoma.

BACKGROUND: A positive sentinel lymph node (SLN) is the most important prognostic factor for predicting survival in cutaneous melanoma. This study aimed to evaluate how the addition of single-photon emission computed tomography (SPECT) and computed tomography (CT) to planar lymphoscintigraphy (PL) alters SLN identification, yield, and localization of metastatic nodes in head and neck melanoma. METHODS: This retrospective review examined patients undergoing SLN biopsy for cutaneous melanoma of the head and neck between July 2003 and December 2015. Patient demographics and pathologic outcomes were compared for patients undergoing SPECT-CT versus PL. A multivariable logistic regression analysis was used to identify factors associated with the identification of a positive SLN. RESULTS: Among 176 patients undergoing SLN biopsy, 91 underwent PL and 85 underwent SPECT-CT and PL. The patients in the SPECT-CT group were older than the PL patients (p = 0.050) but the groups did not differ in gender (p = 0.447), Breslow thickness (p = 0.744), or total number of SLNs identified (p = 0.633). As shown by the multivariate regression analysis, only Breslow thickness [odds ratio (OR) 1.47; 95 % confidence interval (CI) 1.17-1.84] and SPECT-CT (OR 3.58; 95 % CI 1.24-10.4) were associated with a positive SLN. CONCLUSION: The use of SPECT-CT for patients with head and neck cutaneous melanoma significantly increases the likelihood of retrieving a positive SLN. Long-term follow-up evaluation is needed for further definition of the impact that SPECT-CT has on recurrence and survival.

Predictive value of repeated F-18 FDG PET/CT parameters changes during preoperative chemoradiotherapy to predict pathologic response and overall survival in locally advanced esophageal adenocarcinoma patients.

INTRODUCTION: The goal of the current study was to investigate the predictive and prognostic values of repeated F-18 FDG PET/CT parameter changes for prediction of complete pathologic response (pCR) in patients with adenocarcinoma of locally advanced esophageal cancer (LAEC) who received preoperative concurrent chemoradiotherapy (PCRT). METHODS: A total 53 patients with LAEC patients were included in the current study. All patients were evaluated by F-18 FDG PET/CT before and during chemoradiotherapy. The percent changes (∆, %) in F-18 FDG PET/CT parameters were used to predict pCR and to calculate overall survival (OS). The predictive value for pCR of F-18 FDG PET/CT cutoff values was determined by ROC analysis. The prognostic significance was assessed using Kaplan-Meier analysis. RESULTS: pCR occurred in 15 patients (28.3 %). When ΔSUVmax > 23.5 % was used as cutoff, the sensitivity and specificity of F-18 FDG PET/CT for prediction of pCR were 100 % and 52.6, respectively. The AUC was 0.750 (95 % CI; 0.612-0.859), and standard error (SE) was 0.0633 (p = 0.0002). ΔMTV resulted in 80 % sensitivity, 76.3 % specificity, and 0.731 AUC (95 % CI; 0.591-0.843, SE = 0.077, p = 0.0027) for cutoff values >25.5 %. When ΔTLG > 44.8 % was used as cutoff, the sensitivity and specificity of F-18 FDG PET/CT for prediction of pCR were 100 and 65.8 %, respectively. The AUC was 0.893 (95 % CI; 0.777-0.961), and SE was 0.0431 (p < 0.0001). Kaplan-Meier analysis showed that high ΔSUVmax, ΔMTV, and ΔTLG were associated with improved OS. CONCLUSION: In conclusion, the current study shows the capability of the changes (Δ) in repeated F-18 FDG PET/CT parameters to predict the achievement of pCR during PCRT in LAEC patients. Among the parameters, the ΔSUVmax, ΔMTV, and ΔTLG were predictors for pCR and well associated with OS.

Changes in Total Lesion Glycolysis Evaluated by Repeated F-18 FDG PET/CT as Prognostic Factor in Locally Advanced Esophageal Cancer Patients Treated with Preoperative Chemoradiotherapy.

AIMS: The present study was aimed to investigate whether volumetric parameters measured by sequential F-18 fluoro-D-glucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) could be used as prognostic factors in patients with locally advanced esophageal cancer (LAEC) who received preoperative chemoradiotherapy (CRT). METHODS: A total of 61 patients with LAEC were included in the current study. All patients were evaluated by F-18 FDG PET/CT before and after 46 Gy of radiotherapy with a concurrent cisplatin-based chemotherapy. Initial, second, and percent changes (Δ, %) of semiquantitative and volumetric parameters were used to calculate recurrence-free survival (RFS) and overall survival (OS). The median values of each parameter were used as cutoff values. The prognostic significance was assessed using univariate and multivariate Cox proportional hazard regression analyses. RESULTS: Cox proportional hazard regression analyses revealed that change in total lesion glycolysis (ΔTLG) was a potent predictor of RFS and OS. Kaplan-Meier survival curves showed better prognosis in higher ΔTLG. CONCLUSION: Our data suggest that ΔTLG measured by sequential F-18 FDG PET/CT after preoperative CRT could provide prognostic information in LAEC patients.

Correlation between early 18F-FDG PET/CT response to BRAF and MEK inhibition and survival in patients with BRAF-mutant metastatic melanoma.

PURPOSE: Metabolic response to treatment measured by fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET has prognostic implications in many cancers. This study investigated the association between survival and early changes on (18)F-FDG PET/computed tomography (CT) for patients with BRAF-mutant melanoma receiving combined BRAF and MEK inhibition therapy. MATERIALS AND METHODS: Overall, 24 patients with advanced BRAF-mutant melanoma were included. Patients were treated with a BRAF inhibitor (vemurafenib or dabrafenib) and a MEK inhibitor (cobimetinib or trametinib), and were imaged at baseline and shortly thereafter with (18)F-FDG PET/CT. Each scan yielded two values of maximum standardized uptake value (SUVmax): one for the most metabolically active focus and one for the least responsive focus. Short-term treatment response was assessed by evaluating the target lesions using the EROTC criteria. A Cox proportional hazards model was used to examine associations between overall survival (OS) and progression-free survival (PFS) and changes in SUVmax. RESULTS: The mean time to follow-up (18)F-FDG PET/CT was 26 days. At follow-up, two patients achieved a complete response. For the most metabolically active focus, 22 patients showed a partial response. For the least responsive focus, 18 patients showed a partial response, two had stable disease, and two had progressive disease.A total of 16 patients were alive at the end of the study. For the most metabolically active tumor, no association was observed between changes in SUVmax and OS (P=0.73) or PFS (P=0.17). For the least responsive tumor, change in SUVmax was associated with PFS [hazard ratio (HR)=1.34, 95% confidence interval (CI): 1.06-1.71, P=0.01], but not OS (P=0.52). The ECOG score was associated with OS (HR=11.81, 95% CI: 1.42-97.60, P=0.02) and PFS (HR=24.72, 95% CI: 3.23-189.42, P=0.002). CONCLUSION: Change in SUVmax for the least responsive tumor and baseline functional performance may be useful prognostic indicators for PFS in patients with BRAF-mutant melanoma.

Cognitive-Motor Related Brain Activity During Walking: Differences Between Men and Women With Multiple Sclerosis.

OBJECTIVE: To determine if sex differences in glucose uptake, a marker of brain activity, are present in brain regions that facilitate walking performance in persons with multiple sclerosis (MS). DESIGN: Cross-sectional, observational pilot. SETTING: University laboratory. PARTICIPANTS: Positron emission tomography with fluorine-18-labeled deoxyglucose (FDG) was performed on persons with MS and healthy controls (4 men and 4 women per group; N=16) after a 15-minute walking test. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Brain activity was quantified as the mean standardized uptake value (SUV). RESULTS: The mean SUV was significantly lower in the thalamus (P=.029) and cerebellum (P=.029) for men with MS compared with women with MS, but not for the prefrontal (P=.057) or frontal (P=.057) cortices. Similar nonsignificant trends were found for healthy controls. No mean SUV group × sex interaction effects were found between the MS and healthy control groups (all P>.05). CONCLUSIONS: To our knowledge, this is the first study of brain activity sex differences based on FDG uptake in persons with MS during walking. Significantly less FDG uptake in the thalamus and cerebellum brain regions important for walking performance was found in men with MS compared with women with MS; however, these comparisons were not significantly different in the healthy control group. No differences in FDG uptake were found between the MS and healthy control groups in any of the brain regions examined. Results from this study provide pilot data for larger studies aimed at identifying underlying mechanisms responsible for accelerated disability in men with MS.