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Purpose: To evaluate the clinical benefit of positron emission tomography (PET)/computed tomography (CT) in patients with advanced melanoma, primarily not selected for surgery based on management changes and survival data using the linked evidence approach (LEA)., Methods: A total of 201 18 F-FDG PET/CT examinations (n = 33, stage III and n = 168, stage IV) in 119 melanoma patients, primarily not scheduled for surgery, were analysed regarding their impact on clinical management. Patients were selected from a prospective oncological PET/CT registry. The three PET/CT indication groups included unclear lesions in conventional imaging (n = 8), routine follow-up after multiple surgeries (n = 115) and therapy response evaluation of systemic therapy (n = 78). PET/CT-induced management changes were categorized either as major (change from follow-up to surgical or systemic treatment or vice versa, change from surgery to systemic therapy or vice versa) or minor (modifications in systemic therapy). The expected benefit of changes was determined via the linked evidence approach (LEA) connecting registry data, outcome data including overall survival and evidence of diagnostic accuracy of PET/CT based on existing literature., Results: Related to the total study cohort, a change of management after PET/CT was observed in 48% of scans, including 10% minor and 38% major changes. Major changes involved a shift either from follow-up (33/201) or therapy pause (7/201) to systemic therapy, to surgical or other local therapy (26/201) and BSC (2/201). Nine out of 201 cases resulted in treatment pause of systemic therapy. We could confirm the prognostic value of PET/CT-based management by observing a 5-year survival rate more than roughly doubled in patients followed up after tumour exclusion or under local therapy compared with patients under systemic therapy. We could argue for a patient benefit from PET/CT-based management changes using results on accuracy and therapeutic effects from the literature., Conclusion: The use of PET/CT in advanced melanoma patients, primarily not considered for surgery, resulted in frequent changes of management associated with a relevant expected clinical benefit especially in patients classified by PET/CT as tumour-free or eligible for radical surgery.

Purpose: The purpose of this study was to evaluate the impact of PET/CT on clinical management of cancer patients based on a prospective data registry. The study was developed to inform consultations with public health insurances on PET/CT coverage., Methods: We evaluated a prospective patient cohort having a clinically indicated PET/CT at a single German University Center from April 2013 to August 2016. The registry collected questionnaire data from requesting physicians on intended patient management before and after PET/CT. A total of 4,504 patients with 5,939 PET/CT examinations were enrolled in the registry, resulting in evaluable data from 3,724 patients receiving 4,754 scans. The impact of PET/CT on patient management was assessed across 22 tumor types, for different indications (diagnosis, staging, suspected recurrence) and different categories of management including treatment (curative or palliative) and non-treatment (watchful waiting, additional imaging, invasive tests)., Results: The most frequent PET/CT indication was tumor staging (59.7%). Melanoma, lung cancer, lymphoma, neuroendocrine tumor and prostate cancer accounted for 70% of cases. Overall, the use of PET/CT resulted in a 37.1% change of clinical management (95% CI, 35.7-38.5), most frequently (30.6%) from an intended non-treatment strategy before PET/CT to active treatment after PET/CT. The frequency of changes ranged from 28.3% for head and neck cancers up to 46.0% for melanomas. The impact of PET/CT was greatest in reducing demands for additional imaging which decreased from 66.1% before PET/CT to 6.1% after PET/CT. Pre-PET/CT planned invasive tests could be avoided in 72.7% of cases. The treatment goal changed after PET/CT in 21.7% of cases, in twice as many cases from curative to palliative therapy than vice versa., Conclusions: The data of this large prospective registry confirm that physicians often change their intended management on the basis of PET/CT by initiating treatment and reducing additional imaging as well as invasive tests. This applies to various cancer types and indications.

Purpose: The aim of the study was to evaluate if 18F-FDG-PET has the potential to detect complete responders to PD1-therapy in patients with unresectable metastasized melanoma two weeks after therapy initiation., Methods: Between September 2014 and May 2016, ten patients (four females; 65 ± 12 y) received a whole-body 18F-FDG-PET/MRI examination at three time points: Before therapy start (t 0 , base-line), two weeks (t 1 , study examination) and three months after treatment initiation (t 2 , reference standard). Therapy response was assessed with PET response criteria in solid tumors (PERCIST). Time to progression and overall survival (OS) were obtained for all patients., Results: Three patients with partial metabolic response in PET at t 1 turned out to have complete response at t 2 . No tumor relapse was observed in those patients so far (observation period: 265, 511 and 728 days, respectively). At t 2 , progressive metabolic disease (PMD) was seen in six patients from whom four showed PMD and two showed stable metabolic disease (SMD) at t 1 . OS in patients with PMD at t 2 varied between 148 and 814 days. SMD at both t 1 and t 2 was seen in one patient, tumor progress was observed after 308 days., Conclusion: Our study indicates that whole-body 18F-FDG-PET might be able to reliably identify complete responders to PD1-therapy as early as two weeks after therapy initiation in stage IV melanoma patients. This might help to shorten therapy regimes and avoid unnecessary side effects in the future.

Purpose: To evaluate the influence of 18 F-FDG-PET/CT on clinical decision making and outcome in advanced melanoma patients planned for radical metastasectomy., Methods and Materials: A cohort of 333 patients with mainly stage III/IV melanoma having a PET/CT for clinical reasons was prospectively enrolled in our oncologic PET/CT registry between 2013 and 2015. Referring physicians completed questionnaires regarding their intended management for each patient before and after PET/CT. Management changes after PET/CT were classified as major and minor changes. A subgroup of 107 patients (stage I, N = 5; stage II, N = 3; stage III, N = 42; stage IV, N = 57) was planned for complete metastasectomy initially, based on conventional imaging. Management changes and outcome were evaluated by linkage with the information obtained from patients' medical records., Results: In 28 of 107 patients (26%), the surgical treatment plan remained unchanged after PET/CT. In 24 patients (22%), minor changes were performed, such as enlargement or reduction of the surgical field. In 55 patients (51%, 95% CI 42%-61%) major changes of the intended treatment plan occurred; of those, 20 patients (19%) were classified to be tumor-free with PET/CT, 32 patients (30%) were found to have multiple previously unrecognized metastases and had to be treated by systemic therapy, three patients (3%) had to be changed to palliative radiotherapy or isolated extremity perfusion. The 1-year and 2-year overall survival (OS) in patients with complete metastasectomy (N = 52) was 90% and 79%, respectively. Systemically treated patients (N = 32) resulted in 1-year OS of 72% and 2-year OS of 61%. Eleven of 32 patients (34%) with systemic therapy experienced a complete response. Until December 2016, all 20 patients classified as tumor-free by PET/CT were alive., Conclusion: The study confirms the high impact of PET/CT on clinical management in patients with advanced melanoma planned for radical metastasectomy. PET/CT resulted in frequent management changes, preventing futile surgery in half of the patients.

Purpose: Prostate-specific membrane antigen (PSMA) is expressed ubiquitously on the membrane of most prostate tumors and its metastasis. While PET/CT using 11 C-choline was considered as the gold standard in the staging of prostate cancer, PET with radiolabelled PSMA ligands was introduced into the clinic in recent years. Our aim was to compare the PSMA ligand 68 Ga-PSMA-11 with 11 C-choline in patients with primary and recurrent prostate cancer., Methods: 123 patients underwent a whole-body PET/CT examination using 68 Ga-PSMA-11 and 11 C-choline. Suspicious lesions were evaluated visually and semiquantitatively (SUVavg). Out of these, 103 suffered from a confirmed biochemical relapse after prostatectomy and/or radiotherapy (mean PSA level of 4.5 ng/ml), while 20 patients underwent primary staging., Results: In 67 patients with biochemical relapse, we detected 458 lymph nodes suspicious for metastasis. PET using 68 Ga-PSMA-11 showed a significantly higher uptake and detection rate than 11 C-choline PET. Also 68 Ga-PSMA-11 PET identified significantly more patients with suspicious lymph nodes as well as affected lymph nodes regions especially at low PSA levels. Bone lesions suspicious for prostate cancer metastasis were revealed in 36 patients' biochemical relapse. Significantly more bone lesions were detected by 68 Ga-PSMA-11, but only 3 patients had only PSMA-positive bone lesions. Nevertheless, we detected also 29 suspicious lymph nodes and 8 bone lesions, which were only positive as per 11 C-choline PET. These findings led to crucial differences in the TNM classification and the identification of oligometastatic patients. In the patients who underwent initial staging, all primary tumors showed uptake of both tracers. Although significantly more suspicious lymph nodes and bone lesions were identified, only 2 patients presented with bone lesions only detected by 68 Ga-PSMA-11 PET., Conclusion: Thus, PET using 68 Ga-PSMA-11 showed a higher detection rate than 11 C-choline PET for lymph nodes as well as bone lesions. However, we found lymph nodes and bone lesions which were not concordant applying both tracers.

Purpose: To evaluate the influence of (18)F-FDG PET/CT in comparison to CT alone on treatment decisions in patients with advanced melanoma and to analyse the 5-year survival data in comparison to literature data., Methods: Therapy management in 64 consecutive patients (primary staging n = 52; surveillance n = 12) with stage III/IV melanoma who underwent (18)F-FDG PET/CT between 2004 and 2005 in our department was retrospectively analysed. Treatment decisions were made by two dermatooncologists for each patient twice, first based on the CT results and then based on the PET/CT results. Therapy changes based on the PET/CT results were classified as "major" (e.g. change from metastasectomy to systemic therapy) or "minor" (e.g. change from first to second line chemotherapy). The 5-year survival data of different patient cohorts were calculated., Results: In the 52 patients in the primary staging group, the results of (18)F-FDG PET/CT led to therapy change in 59% and a major therapy change in 52%. (18)F-FDG PET/CT led to the avoidance of futile operations in 13 patients with suspicious lesions on CT that were deemed nontumorous on PET/CT. In the 12 patients in the surveillance group, the results of (18)F-FDG PET/CT led to therapy change in 33% and a major change in 17%. The 5-year survival rates were 30% in the entire cohort, 34% in the primary staging group, and 17% in the surveillance group. A significant overall survival benefit was observed in patients in whom (18)F-FDG PET/CT excluded metastases or in whom metastases could be completely removed compared with patients who were not eligible for surgery (41% vs. 10%)., Conclusion: Primary staging of patients with stage III/IV melanoma should be performed with (18)F-FDG PET/CT, leading to higher diagnostic accuracy and enabling individualized therapeutic management, especially optimal patient selection for metastasectomy. This strategy may extend long-term survival even in patients with advanced disease.

Purpose: The purpose was to investigate the diagnostic performance of different combinations of anatomical and functional imaging techniques in PET/MRI and PET/CT for the evaluation of metastatic colorectal cancer lesions., Methods: Image data of 15 colorectal cancer patients (FDG-PET/CT and subsequent FDG-PET/MRI) were retrospectively evaluated by two readers in five reading sessions: MRI (morphology) alone, MRI/diffusion-weighted MRI (DWI), MRI/PET, MRI/DWI/PET; and PET/CT. Diagnostic performance of lesion detection with each combination was assessed in general and organ-based. The reference standard was given by histology and/or follow-up imaging. Separate analysis of mucinous tumours was performed., Results: One hundred and eighty lesions (110 malignant) were evaluated (intestine n = 6, liver n = 37, lymph nodes n = 55, lung n = 4, and peritoneal n = 74). The overall lesion-based diagnostic accuracy was 0.46 for MRI, 0.47 for MRI/DWI, 0.57 for MRI/PET, 0.69 for MRI/DWI/PET and 0.66 for PET/CT. In the organ-based assessment, MRI/DWI/PET showed the highest accuracy for liver metastases (0.74), a comparable accuracy to PET/CT in peritoneal lesions (0.55), and in lymph node metastases (0.84). The accuracy in mucinous tumour lesions was limited in all modalities (MRI/DWI/PET = 0.52)., Conclusions: PET/MRI including DWI is comparable to PET/CT in the evaluation of colorectal cancer metastases, with a markedly higher accuracy when using combined imaging data than the modalities separately. Further improvement is needed in the imaging of peritoneal carcinomatosis and mucinous tumours.

Non-small-cell lung cancer is the most common type of lung cancer and one of the leading causes of cancer-related death worldwide. For this reason, advances in diagnosis and treatment are urgently needed. With the introduction of new, highly innovative hybrid imaging technologies such as PET/CT, staging and therapy response monitoring in lung cancer patients have substantially evolved. In this review, we discuss the role of FDG PET/CT in the management of lung cancer patients and the importance of new emerging imaging technologies and radiotracer developments on the path to personalized medicine.

Purpose: The aim of this study was to investigate correlations between glucose metabolism as determined by [(18)F]FDG PET/CT and tumour perfusion as quantified by volume perfusion CT in primary tumours and mediastinal lymph nodes (MLN) of patients with non-small-cell lung cancer (NSCLC)., Methods: Enrolled in the study were 17 patients with NSCLC. [(18)F]FDG uptake was quantified in terms of SUVmax and SUVavg. Blood flow (BF), blood volume (BV) and flow extraction product (K(trans)) were determined as perfusion parameters. The correlations between the perfusion parameters and [(18)F]FDG uptake values were subsequently evaluated., Results: For the primary tumours, no correlations were found between perfusion parameters and [(18)F]FDG uptake. In MLN, there were negative correlations between BF and SUVavg (r = -0.383), BV and SUVavg (r = -0.406), and BV and SUVmax (r = -0.377), but not between BF and SUVmax, K(trans) and SUVavg, or K(trans) and SUVmax. Additionally, in MLN with SUVmax >2.5 there were negative correlations between BF and SUVavg (r = -0.510), BV and SUVavg (r = -0.390), BF and SUVmax (r = -0.536), as well as BV and SUVmax (r = -0.346)., Conclusion: Perfusion and glucose metabolism seemed to be uncoupled in large primary tumours, but an inverse correlation was observed in MLN. This information may help improve therapy planning and response evaluation.

Purpose: State-of-the-art positron emission tomography/computed tomography (PET/CT) systems incorporate multislice CT technology, thus facilitating the acquisition of multiphase, contrast-enhanced CT data as part of integrated PET/CT imaging protocols. We assess the influence of a highly concentrated iodinated contrast medium (CM) on quantification and image quality following CT-based attenuation correction (CT-AC) in PET/CT., Methods: Twenty-eight patients with suspected malignant liver lesions were enrolled prospectively. PET/CT was performed 60 min after injection of 400 MBq of (18)F-fluorodeoxyglucose (FDG) and following the biphasic administration of an intravenous CM (400 mg iodine/ml, Iomeron 400). PET images were reconstructed with CT-AC using any of four acquired CT image sets: non-enhanced, pre-contrast (n-PET), arterial phase (art-PET), portal venous phase (pv-PET) and late phase (late-PET). Normal tissue activity and liver lesions were assessed visually and quantitatively on each PET/CT image set., Results: Visual assessment of PET following CT-AC revealed no noticeable difference in image appearance or quality when using any of the four CT data sets for CT-AC. A total of 44 PET-positive liver lesions was identified in 21 of 28 patients. There were no false-negative or false-positive lesions on PET. Mean standardized uptake values (SUV) in 36 evaluable lesions were: 5.5 (n-PET), 5.8 (art-PET), 5.8 (pv-PET) and 5.8 (late-PET), with the highest mean increase in mean SUV of 6%. Mean SUV changes in liver background increased by up to 10% from n-PET to pv-PET., Conclusion: Multiphase CT data acquired with the use of highly concentrated CM can be used for qualitative assessment of liver lesions in torso FDG PET/CT. The influence on quantification of FDG uptake is small and negligible for most clinical applications.

Immunoscintigraphy with technetium-99m labelled anti-granulocyte antibodies (AGA) is an equivalent technique to imaging with in vitro-labelled leucocytes, which is now considered state of the art in the diagnostic work-up of patients with suspected post-traumatic chronic osteomyelitis. In this study, we evaluated the use of a combined single-photon emission tomography/computed tomography (SPET/CT) device to improve detection and anatomical definition of inflammatory bone lesions. Twenty-seven patients with 29 sites of suspected bone infection underwent immunoscintigraphy with 750 MBq 99mTc-labelled AGA. Planar scans were acquired immediately, 4 h and 24 h after injection, and combined SPET/CT was performed using a dual-head multifunctional gamma camera equipped with a low-power X-ray system. Accumulation of AGA in inflammatory lesions was quantitated, comparing uptake at 4 and 24 h after injection. The validation was based on culture data derived from surgical or biopsy samples (20 lesions in 18 patients) or clinical follow-up without further therapy for more than 6 months (nine lesions). On a lesion-by-lesion basis 19 true positive, one false positive and nine true negative findings were obtained. SPET/CT correctly identified the location of all positive foci in the appendicular skeleton and that of a cold lesion in the axial skeleton. It also enabled differentiation between soft tissue infection, septic arthritis and osteomyelitis, as well as between cortical, corticomedullary and subperiosteal foci. Sensitivity was identical for SPET and SPET/CT (100%), whereas specificity was improved from 78% to 89% by the use of SPET/CT. Combined SPET/CT improves the accuracy of immunoscintigraphy by allowing correct differentiation between soft tissue infection and bone involvement. This technique may gain clinical relevance in the selection of patients for surgical therapy.

The purpose of this study was to evaluate the use of combined transmission and emission tomography (TET) for correct localisation of heterotopic splenic tissue and differentiation of splenosis from other masses. The TET technique comprises the fusion of SPET and CT data obtained using the same imaging device to allow perfect overlap of anatomical and functional images. TET was performed in seven patients who either had haematological disorders and relapsing anaemia or thrombocytopenia after splenectomy or were under immunosuppression for different reasons. These patients presented 20 equivocal lesions on CT or MRI. Presence of splenic tissue was investigated using technetium-99m labelled colloids or heat-damaged red blood cells. Findings of spleen scintigraphy, TET and CT or MRI were compared with respect to localisation of splenosis and correct classification of lesions by CT or MRI. Histological validation was achieved by surgery or biopsy in all cases. All 20 lesions demonstrated by CT or MRI were correctly classified by TET as splenosis. Three additional lesions initially overlooked by CT or MRI could be detected. Diagnostic relevance was highest for intrahepatic, intrapulmonary or pleural splenic implants. It is concluded that TET allows exact localisation of heterotopic splenic tissue in patients with suspected splenosis.