FDG-PET/CT Limited to the Thorax and Upper Abdomen for Staging and Management of Lung Cancer.

Purpose This study evaluates the diagnostic accuracy of [F-18]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) of the chest/upper abdomen compared to the generally performed scan from head to upper thighs, for staging and management of (suspected) lung cancer in patients with no history of malignancy or complaints outside the thorax.Methods FDG-PET/CT scans of 1059 patients with suspected or recently proven lung cancer, with no history of malignancy or complaints outside the thorax, were analysed in a retrospective multi-centre trial. Suspect FDG-avid lesions in the chest and upper abdomen, the head and neck area above the shoulder line and in the abdomen and pelvis below the caudal tip of the liver were noted. The impact of lesions detected in the head and neck area and abdomen and pelvis on additional diagnostic procedures, staging and treatment decisions was evaluated.Results The head and neck area revealed additional suspect lesions in 7.2%, and the abdomen and pelvis in 15.8% of patients. Imaging of the head and neck area and the abdomen and pelvic area showed additional lesions in 19.5%, inducing additional diagnostic procedures in 7.8%. This resulted in discovery of additional lesions considered malignant in 10.7%, changing patient management for lung cancer in 1.2%. In (suspected) lung cancer, PET/CT limited to the chest and upper abdomen resulted in correct staging in 98.7% of patients, which led to the identical management as full field of view PET in 98.8% of patients.Conclusion High value of FDG-PET/CT for staging and correct patient management is already achieved with chest and upper abdomen. Findings in head and neck area and abdomen and pelvis generally induce investigations with limited or no impact on staging and treatment of NSCLC, and can be interpreted accordingly

Managing Nonmetastatic Castration-resistant Prostate Cancer.

CONTEXT:Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) have rising prostate-specific antigen (PSA) and castrate testosterone levels, with no radiological findings of metastatic disease on computed tomography and bone scan. Given recent drug approvals for nmCRPC, with many other therapeutics and imaging modalities being developed, management of nmCRPC is a rapidly evolving field that merits detailed investigation. OBJECTIVE:To review current nmCRPC management practices and identify opportunities for improving care of nmCRPC patients. EVIDENCE ACQUISITION:A literature search up to July 2018 was conducted, including clinical trials and clinical practice guidelines (National Comprehensive Cancer Network, European Society for Medical Oncology, European Association of Urology, Prostate Cancer Clinical Trials Working Group, Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence). Keywords included prostate cancer, nonmetastatic, castration resistance, rising PSA, and biochemical relapse. EVIDENCE SYNTHESIS:Recommendations regarding indications for, and frequency of, imaging and PSA testing, as well as for initiating systemic therapy in nmCRPC are based on PSA rise kinetics and symptoms. Both enzalutamide and apalutamide have been shown to significantly increase metastasis-free survival in phase III placebo-controlled randomised trials in nmCRPC patients with PSA doubling time (DT) ≤10 mo. The expected impact of new imaging techniques in the assessment of nmCRPC is also reviewed. CONCLUSIONS:nmCRPC is a heterogeneous disease; while observation may be an option for some patients, enzalutamide and apalutamide may be appropriate to treat nmCRPC patients with PSA-DT ≤10 mo. The emergence of more accurate imaging modalities as well as circulating tumour biomarker assays will likely redefine the assessment of nmCRPC in the near future. PATIENT SUMMARY:Herein, we review key literature and clinical practice guidelines to summarise the optimal management of patients with prostate cancer and rising prostate-specific antigen despite castrate testosterone levels, but with no evidence of distant metastasis on traditional imaging. New drugs are being developed for this disease setting; novel imaging and tumour biomarker blood tests are likely to define this disease state more accurately

HER3-Mediated Resistance to Hsp90 Inhibition Detected in Breast Cancer Xenografts by Affibody-Based PET Imaging.

Purpose: Recent studies have highlighted a role of HER3 in HER2-driven cancers (e.g., breast cancer), implicating the upregulation of the receptor in resistance to HER-targeted therapies and Hsp90 inhibitors (e.g., AUY922). Therefore, we have developed an affibody-based PET radioconjugate that quantitatively assesses HER3 changes induced by Hsp90 inhibition in vivoExperimental Design: ZHER3:8698 affibody molecules were conjugated via the C-terminus cysteine to DFO-maleimide for 89Zr radiolabeling. The probe was characterized in vitro and in vivo in a panel of human breast cell lines and xenograft models with varying HER3 receptor levels. In addition, the radioconjugate was investigated as a tool to monitor the outcome of AUY922, an Hsp90 inhibitor, in an MCF-7 xenograft model.Results: We demonstrated that 89Zr-DFO-ZHER3:8698 can track changes in receptor expression in HER3-positive xenograft models and monitor the outcome of AUY922 treatment. Our in vitro findings showed that MCF-7 cells, which are phenotypically different from BT474, develop resistance to treatment with AUY922 through HER3/IGF-1Rβ-mediated signaling. Of note, the lack of response in vitro due to HER3 recovery was confirmed in vivo using 89Zr-DFO-ZHER3:8698-based imaging. Upon AUY922 treatment, higher radioconjugate uptake was detected in treated MCF-7 xenografts, correlating with an AUY922-induced HER3 upregulation concomitant with an increase in IGF-1Rβ expression.Conclusions: These data underline the potential of HER3-based PET imaging to noninvasively provide information about HER3 expression and to identify patients not responding to targeted therapies due to HER3 recovery. Clin Cancer Res; 24(8); 1853-65. ©2018 AACR

Performance of automatic image segmentation algorithms for calculating total lesion glycolysis for early response monitoring in non-small cell lung cancer patients during concomitant chemoradiotherapy.

Background and purpose This study evaluated the use of total lesion glycolysis (TLG) determined by different automatic segmentation algorithms, for early response monitoring in non-small cell lung cancer (NSCLC) patients during concomitant chemoradiotherapy.Materials and methods Twenty-seven patients with locally advanced NSCLC treated with concomitant chemoradiotherapy underwent (18)F-fluorodeoxyglucose (FDG) PET/CT imaging before and in the second week of treatment. Segmentation of the primary tumours and lymph nodes was performed using fixed threshold segmentation at (i) 40% SUVmax (T40), (ii) 50% SUVmax (T50), (iii) relative-threshold-level (RTL), (iv) signal-to-background ratio (SBR), and (v) fuzzy locally adaptive Bayesian (FLAB) segmentation. Association of primary tumour TLG (TLGT), lymph node TLG (TLGLN), summed TLG (TLGS=TLGT+TLGLN), and relative TLG decrease (ΔTLG) with overall-survival (OS) and progression-free survival (PFS) was determined using univariate Cox regression models.Results Pretreatment TLGT was predictive for PFS and OS, irrespective of the segmentation method used. Inclusion of TLGLN improved disease and early response assessment, with pretreatment TLGS more strongly associated with PFS and OS than TLGT for all segmentation algorithms. This was also the case for ΔTLGS, which was significantly associated with PFS and OS, with the exception of RTL and T40.Conclusions ΔTLGS was significantly associated with PFS and OS, except for RTL and T40. Inclusion of TLGLN improves early treatment response monitoring during concomitant chemoradiotherapy with FDG-PET