Impact of PET/CT on clinical management in patients with cancer of unknown primary-a PET/CT registry study.

OBJECTIVE: To evaluate the impact of PET/CT on clinical management in patients with cancer of unknown primary (CUP). METHODS: A cohort of patients with CUP undergoing PET/CT was prospectively enrolled in a local PET/CT registry study between April 2013 and June 2018. Questionnaire data from referring physicians on intended patient management prior and after PET/CT were recorded including items on the intended treatment concept and intended additional diagnostics. Changes in management after PET/CT were recorded. Patient outcome of different cohorts was analyzed for overall survival drawn from patient records. RESULTS: One hundred fifty-five patients (53 female; 63.4 ± 12.1 years) were included. Intended therapeutic management was revised in 45.8% of patients after PET/CT, including major changes affecting the intended treatment goal in 26.5% of patients and minor changes (therapy adjustments) in 19.3% of patients. Invasive and additional diagnostic procedures were intended in 25.8% and 63.2% prior PET/CT and 13.5% and 6.5% after PET/CT. PET/CT-based curative therapy concepts were associated with significantly longer patient survival (4.7 ± 0.3 years) than palliative therapy concepts (1.8 ± 0.5 years, p = .0001). Patients with cervical CUP showed a significantly longer survival (4.3 ± 0.3 years) than patients with extracervical CUP (3.5 ± 0.5 years, p = .01). The identification of the primary did not significantly affect survival. CONCLUSION: This registry study confirms previous studies reporting that PET/CT significantly influences clinical management in patients with CUP, helping physicians to select a more individualized treatment and to avoid additional diagnostics. Furthermore, we could confirm that tumor localization and extent as shown by PET/CT have a significant impact on patient prognosis. KEY POINTS: • PET/CT significantly influences intended clinical management in patients with CUP, helping physicians to select a more individualized treatment and to avoid additional diagnostics. • Tumor localization and extent as shown by PET/CT have a significant impact on patient prognosis. • The identification of the primary tumor has no significant impact on overall patient survival.

A novel mutation in LRSAM1 causes axonal Charcot-Marie-Tooth disease with dominant inheritance.

BACKGROUND: Charcot-Marie-Tooth disease (CMT) refers to a heterogeneous group of genetic motor and sensory neuropathies. According to the primary site of damage, a distinction is made between demyelinating and axonal forms (CMT1 and 2, respectively, when inherited as an autosomal dominant trait). Leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1) is a ubiquitin-protein ligase with a role in sorting internalised cell-surface receptor proteins. So far, mutations in the LRSAM1 gene have been shown to cause axonal CMT in three different families and can confer either dominant or recessive transmission of the disease. CASE PRESENTATION: We have identified a novel mutation in LRSAM1 in a small family with dominant axonal CMT. Electrophysiological studies show evidence of a sensory axonal neuropathy and are interesting in so far as giant motor unit action potentials (MUAPs) are present on needle electromyography (EMG), while motor nerve conduction studies including compound motor action potential (CMAP) amplitudes are completely normal. The underlying mutation c.2046+1G >T results in the loss of a splice donor site and the inclusion of 63 additional base pairs of intronic DNA into the aberrantly spliced transcript. This disrupts the catalytically active RING (Really Interesting New Gene) domain of LRSAM1. CONCLUSIONS: Our findings suggest that, beyond the typical length-dependent degeneration of motor axons, damage of cell bodies in the anterior horn might play a role in LRSAM1-associated neuropathies. Moreover, in conjunction with other data in the literature, our results support a model, by which disruption of the C-terminal RING domain confers dominant negative properties to LRSAM1.

How [18F]FDG-PET/CT Affects the Management of Patients with Differentiated Thyroid Carcinoma in Clinical Routines.

PURPOSE: To investigate the impact of [18F]FDG-PET/CT on the management of differentiated thyroid carcinoma (DTC) in routine clinical settings. MATERIAL AND METHODS: In total, 98 patients (55 females, age 56 ± 18 years) with histologically confirmed thyroid cancer, including all types of DTC and poorly differentiated thyroid cancer (PDTC, n = 7), underwent [18F]FDG-PET/CT for staging or recurrence diagnostics performed using a state-of-the art clinical scanner (Biograph mCT, Siemens Healthineers) with a standardized examination protocol. The impact of PET/CT on clinical decision making was prospectively evaluated using standardized questionnaires completed by the referring physicians before and after PET/CT. Patient outcome was analyzed for OS drawn from patient records. RESULTS: Referring physicians were unable to establish a treatment plan for 81% of patients with thyroid cancer in the absence of PET/CT. The use of PET/CT had a notable influence on patient management, leading to the development of a well-defined treatment plan for 92% of patients. Moreover, after PET/CT a change in pre-PET/CT-intended treatments occurred in 32% of cases, and further invasive diagnostic could be waived in 7% of cases. [18F]FDG-PET/CT revealed a tumor detection rate of 68% (local tumor: 19%, lymph node metastases: 40%, distant metastases: 42%). HTg levels, when stimulated via TSH, were considerably higher in patients with metastases detected on PET/CT, compared to those without metastatic findings (p = 0.02). OS was significantly worse in patients with PDTC (p = 0.002) compared to follicular thyroid cancer (FTC) and PTC or even in patients with distant metastases at first diagnosis (p = 0.03). CONCLUSIONS: This prospective registry study confirms that [18F]FDG-PET/CT used in a routine clinical setting has a very important impact on the management of patients with thyroid cancer by initiating treatments and reducing the uses of additional imaging and invasive tests.

How [18F]-FDG-PET/CT Affects Clinical Management of Patients with Germ Cell Tumors in the Real World.

OBJECTIVE: The aim of this study was to evaluate the impact of PET/CT on clinical management of patients with germ cell tumors (GCTs) conducted in a real-world setting, including avoidance of invasive procedures, additional diagnostic imaging, and changes in treatment. METHODS: Patients with GCTs were prospectively enrolled into a PET/CT registry study between May 2013 and April 2021. Intended patient management prior and after PET/CT was documented using standardized questionnaires. Changes in oncologic staging and clinical management after PET/CT were recorded, including planned treatment and planned additional diagnostics. RESULTS: Forty-three male patients with GCTs were included consecutively in this study. After PET/CT, oncologic staging changed in 22/43 patients (51%), with upstaging in seven cases (16%), downstaging in ten cases (23%), and cancer relapse in five cases (11%). The number of patients with intended curative treatment remained stable, while a considerable change in intended therapeutic intervention was noted after PET/CT, with an increase in planned chemotherapy from three to eleven patients and a decrease in planned surgical resection from eleven to two patients. In addition, PET/CT contributed to preventing patients from intended invasive procedures including biopsy and surgery in 8/43 (19%) cases and from additional diagnostic procedures in 25 (58%) cases. CONCLUSION: With the use of FDG-PET/CT as a tool to guide patient management in GCTs, we observed a notable impact on clinical staging and a consequent reduction in the need for additional invasive and diagnostic procedures. These findings are expected to be even more consequential in the future as treatment modalities improve and the life expectancy of GCT patients further increases. KEY POINTS: PET/CT considerably influences the clinical stage of GCT patients. PET/CT has remarkable influence on the choice of therapeutic interventions and reduces additional diagnostic procedures.

Influence of [18F]FDG-PET/CT on Clinical Management Decisions in Breast Cancer Patients-A PET/CT Registry Study.

There is a lack of evidence regarding the clinical impact of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT, hereinafter referred to as PET/CT), especially regarding management changes and their link to overall survival. We analyzed 52 PET/CTs in 47 stage I-IV breast cancer patients, selected from a prospective oncological PET/CT registry. Indications for PET/CT were primary staging (n = 15), restaging (n = 17), and suspected recurrence (n = 20). PET/CT-induced management changes were categorized as major or minor. PET/CT-induced management changes in 41 of 52 scans (78.8%; 38 of 47 patients (80.9%)), of which major changes were suggested in 18 of 52 scans (34.6%, 17 of 47 patients, 36.2%). PET/CT downstaged 6 of 15 primary staging patients, excluding distant metastases. Major management changes were documented in 3 of 17 restaging exams. PET/CT ruled out clinically suspected recurrence in 6 of 20 cases and confirmed it in 11 of 20. In three cases, locoregional recurrence had already been diagnosed via biopsy. In 30 of 52 exams, additional diagnostic tests were avoided, of which 13 were invasive. PET/CT-based management changes resulted in a 5-year survival rate of 72.3% for the whole study group, 93.3% for the staging group, 53.8% for the restaging group, and 68.4% for the recurrence group. This study shows that PET/CT significantly impacts clinical management decisions in breast cancer patients in different clinical scenarios, potentially determining the patient's tumor stage as the basis for further therapy more reliably and by avoiding unnecessary diagnostic tests.

Impact of PET/CT on management of patients with esophageal cancer - results from a PET/CT registry study.

PURPOSE: To investigate the impact of positron emission tomography/computed tomography (PET/CT) on clinical management in patients with esophageal cancer and its link to overall survival (OS) in a real-world setting. METHODS: A patient cohort with advanced esophageal cancer undergoing PET/CT was prospectively enrolled in a registry study between 04/2013 and 06/2019. Intended patient management prior and after PET/CT was documented based on standardized questionnaire data. Management changes after PET/CT were recorded including major changes concerning the treatment goal (curative vs. palliative) and minor changes (therapy adjustments). OS was analyzed for subgroups with squamous cell carcinomas (SCC) or adenocarcinomas (AC) and stratified for extent of metastatic disease and treatment goals. RESULTS: 257 patients (53 female;65.5 ±â€¯10.0 yr.) were included. After PET/CT, major changes of intended therapy were observed in 34/257 patients (13.2%), from curative to palliative (8.2%), palliative to curative (1.9%) and from "not finally determined" to a curative (1.9%) or palliative (1.2%) concept. Minor changes were found in 62/257 patients (24.1%). Invasive procedures and additional imaging were intended in 70/257 (27.2%) and 94/257 (36.6%) patients before PET/CT and 20/257 (7.8%) and 8/257 (3.1%) patients after PET/CT. Curative therapy concepts based on PET/CT were associated with a longer OS (3.5 yr.[95%CI 3.1-3.8 yr.]) as compared to palliative concepts (0.9 yr.[95%CI 0.6-1.2 yr.];p < 0.0001). Patients with SCC had a worse prognosis (2.4 yr.[95%CI 2.0-2.9 yr.]) as compared to patients with AC (3.2 yr.[95%CI 2.7-3.7 yr.];p = 0.01). CONCLUSIONS: In patients with advanced esophageal cancer, PET/CT has a significant impact on clinical management by improving the selection of individualized treatment strategies and avoiding additional diagnostic procedures.

Impact of 18F-FDG-PET/CT on Clinical Management in Patients with Cholangiocellular Carcinoma.

OBJECTIVE: To determine the impact of 18F-FDG-PET/CT on clinical management of patients with cholangiocellular carcinoma (CCA). METHODS: Patients with CCA undergoing clinically indicated 18F-FDG-PET/CT between 04/2013 and 08/2018 were prospectively included in a local PET/CT registry study. Intended clinical management ("non-treatment" such as watchful-waiting or additional diagnostic tests, and "palliative" or "curative treatment") was recorded before and after PET/CT. Changes in intended management after PET/CT were analyzed. RESULTS: 27 patients (mean age: 60 years, IQR: 51.5-67.5 years, 56% males) with 43 PET/CT examinations were included. Intended management changed in 35/43 cases (81.4%) following PET/CT. Major changes (i.e., between "non-treatment" and "treatment" strategies or between a "curative" and "palliative" treatment goal) occurred in 27/43 (62.8%) cases. Before PET/CT, additional imaging and/or biopsy were intended in 21/43 (48.8%) and 9/43 (20.9%) cases, respectively. After PET/CT, further imaging was carried out in one case and imaging-targeted biopsy in eight cases. Although the absolute number of biopsies after PET/CT did not decrease, in only one of these eight cases biopsy had already been planned before PET/CT, whereas in the other eight cases, the originally planned biopsies were dispensable after PET/CT. CONCLUSIONS: 18F-FDG-PET/CT significantly impacts clinical management of patients with CCA. It guides decisions on treatment strategy (especially curative vs palliative treatment goal) and on additional tests, particularly by helping referring clinicians to avoid unnecessary imaging and by guiding targeted biopsy. ADVANCES IN KNOWLEDGE: Systematic implementation of 18F-FDG-PET/CT may enable a more appropriate and tailored treatment of patients with CCA, especially in cases of suspected recurrence.

Clinical and prognostic value of tumor volumetric parameters in melanoma patients undergoing 18F-FDG-PET/CT: a comparison with serologic markers of tumor burden and inflammation.

BACKGROUND: To investigate the association of tumor volumetric parameters in melanoma patients undergoing 18F-FDG-PET/CT with serologic tumor markers and inflammatory markers and the role as imaging predictors for overall survival. METHODS: A patient cohort with advanced melanoma undergoing 18F-FDG-PET/CT for planning metastasectomy between 04/2013 and 01/2015 was retrospectively included. The volumetric PET parameters whole-body MTV and whole-body TLG as well as the standard uptake value (SUV) peak were quantified using 50%-isocontour volumes of interests (VOIs) and then correlated with the serologic parameters lactate dehydrogenase (LDH), S-100 protein, c-reactive protein (CRP) and alkaline phosphatase (AP). PET parameters were dichotomized by their respective medians and correlated with overall survival (OS) after PET/CT. OS was compared between patients with or without metastases and increased or not-increased serologic parameters. RESULTS: One hundred seven patients (52 female; 65 ± 13.1yr.) were included. LDH was strongly associated with MTV (rP = 0.73, p <  0.001) and TLG (rP = 0.62, p <  0.001), and moderately associated with SUVpeak (rP = 0.55, p <  0.001). S-100 protein showed a moderate association with MTV (rP = 0.54, p <  0.001) and TLG (rP = 0.48, p <  0.001) and a weak association with SUVpeak (rP = 0.42, p <  0.001). A strong association was observed between CRP and MTV (rP = 0.66, p <  0.001) and a moderate to weak association between CRP and TLG (rP = 0.53, p <  0.001) and CRP and SUVpeak (rP = 0.45, p <  0.001). For differentiation between patients with or without metastases, receiver operating characteristic (ROC) analysis revealed a cut-off value of 198 U/l for serum LDH (AUC 0.81, sensitivity 0.80, specificity 0.72). Multivariate analysis for OS revealed that both MTV and TLG were strong independent prognostic factors. TLG, MTV and SUVpeak above patient median were accompanied with significantly reduced estimated OS compared to the PET parameters below patient median (e.g. TLG: 37.1 ± 3.2 months vs. 55.9 ± 2.5 months, p <  0.001). Correspondingly, both elevated serum LDH and S-100 protein were accompanied with significantly reduced OS (36.5 ± 4.9 months and 37.9 ± 4.4 months) compared to normal serum LDH (49.2 ± 2.4 months, p = 0.01) and normal S-100 protein (49.0 ± 2.5 months, p = 0.01). CONCLUSIONS: Tumor volumetric parameters in 18F-FDG-PET/CT serve as prognostic imaging biomarkers in patients with advanced melanoma which are associated with established serologic tumor markers and inflammatory markers.