S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" - update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Influence of 18F-FDG PET/CT on clinical management and outcome in patients with advanced melanoma not primarily selected for surgery based on a linked evidence approach.

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 18F-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.

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.

S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma - short version, part 1: diagnosis, interventions for actinic keratoses, care structures and quality-of-care indicators.

Actinic keratoses (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guideline is aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AK and cSCC. The guideline is also aimed at affected patients, their relatives, policy makers and insurance funds. In the first part, we will address aspects relating to diagnosis, interventions for AK, care structures and quality-of-care indicators.

S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma (cSCC) - short version, part 2: epidemiology, surgical and systemic treatment of cSCC, follow-up, prevention and occupational disease.

Actinic keratoses (AKs) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guidelines for actinic keratosis and cutaneous squamous cell carcinoma were developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guidelines are aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AKs and cSCC. The guidelines are also aimed at affected patients, their relatives, policy makers and insurance funds. In the second part, we will address aspects relating to epidemiology, etiology, surgical and systemic treatment of cSCC, follow-up and disease prevention, and discuss AKs and cSCC in the context of occupational disease regulations.

Practice-based evidence for the clinical benefit of PET/CT-results of the first oncologic PET/CT registry in Germany.

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.

18F-FDG-PET detects complete response to PD1-therapy in melanoma patients two weeks after therapy start.

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 (t0, base-line), two weeks (t1, study examination) and three months after treatment initiation (t2, 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 t1 turned out to have complete response at t2. No tumor relapse was observed in those patients so far (observation period: 265, 511 and 728 days, respectively). At t2, progressive metabolic disease (PMD) was seen in six patients from whom four showed PMD and two showed stable metabolic disease (SMD) at t1. OS in patients with PMD at t2 varied between 148 and 814 days. SMD at both t1 and t2 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.

Simultaneous multislice diffusion-weighted imaging in whole-body positron emission tomography/magnetic resonance imaging for multiparametric examination in oncological patients.

OBJECTIVES: The aim of this study was to compare the diagnostic performance of simultaneous multislice diffusion-weighted imaging (DWI-SMS) with that of standard DWI (DWI-STD) in whole-body 3-T PET/MRI examination protocols in oncological patients. METHODS: In a phantom study, we evaluated the apparent diffusion coefficients (ADC) from the two techniques. In ten volunteers, we assessed ADC values in different organs. In 20 oncological patients, we evaluated subjective image quality (Likert scale, 5 indicating excellent) and artefacts in different body regions. We also rated the conspicuity and acquired the ADC values of PET-positive tumorous lesions. RESULTS: The scan time for the whole-body DWI-SMS examinations was 40% shorter than the scan time for the DWI-STD examinations (84 s vs. 140 s per table position). The phantom and volunteer studies showed lower ADC values from DWI-SMS in the liver and muscle (psoas muscle 1.4 vs. 1.3). In patients, DWI-SMS provided poorer subjective image quality in the thoracoabdominal region (3.0 vs. 3.8, p = 0.02) and overall more artefacts (138 vs. 105). No significant differences regarding conspicuity and ADC values of lesions were found. CONCLUSIONS: DWI-SMS seems to provide reliable conspicuity and ADC values of tumorous lesions similar to those provided by DWI-STD. Therefore, although providing poorer image quality in certain regions, DWI-SMS can clearly reduce PET/MRI scan times in oncological patients. KEY POINTS: • DWI-SMS can reduce PET/MRI scan times in oncological patients. • DWI-SMS provides reliable ADC values and good lesion conspicuity similar to those provided by DWI-STD. • DWI-SMS may provide poorer image quality in regions with low signal.

Fast non-enhanced abdominal examination protocols in PET/MRI for patients with neuroendocrine tumors (NET): comparison to multiphase contrast-enhanced PET/CT.

PURPOSE: To evaluate fast non-enhanced protocols for abdominal PET/MRI in comparison to contrast-enhanced PET/CT with somatostatin receptor (SSR)-specific radiotracers regarding effectiveness of lesion detection in NET patients. METHODS: This was a retrospective analysis of 29 patients (12 male, 57 ± 13 years) who underwent PET/CT and subsequently PET/MRI at the same day. Two readers evaluated independently four PET/MRI setups: (I) PET + T2 Half Fourier Acquisition Single Shot Turbo Spin Echo (T2 HASTE), (II) PET + T2 HASTE + T2-weighted spin-echo sequence (T2 TSE), III) PET + T2 HASTE + Diffusion Weighted Imaging (DWI) and (IV) PET + T2 HASTE + T2 TSE + DWI. A consensus reading of PET/MRI and PET/CT including follow-up examinations served as the reference standard for lesion-based analysis. Lesion sizes were assessed. RESULTS: Setup IV provided comparable overall detection rates as PET/CT in both readers: PET/MRI 91.5%/92.9% versus 89.7% in PET/CT. In liver and bone lesions (mean diameter: 1.9 and 1.5 cm), PET/MRI was equal or superior to PET/CT: 98%/98% versus 85% in PET/CT; 100%/95% versus 100% in PET/CT, but inferior in pancreatic lesions, small bowel lesions and lymph node metastases (mean diameter: 1.3, 0.5 and 1.8 cm). CONCLUSION: A non-enhanced MR protocol comprising T2 HASTE, T2 TSE and DWI for SSR-PET/MRI seems to provide comparable effectiveness in lesions detection as multiphase contrast-enhanced PET/CT. It might, therefore, serve as valid alternative, e.g., for follow-up examinations in patients with unresectable NET and kidney failure.

Comparison of 68Ga-labelled PSMA-11 and 11C-choline in the detection of prostate cancer metastases by PET/CT.

PURPOSE: Prostate-specific membrane antigen (PSMA) is expressed ubiquitously on the membrane of most prostate tumors and its metastasis. While PET/CT using 11C-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 68Ga-PSMA-11 with 11C-choline in patients with primary and recurrent prostate cancer. METHODS: 123 patients underwent a whole-body PET/CT examination using 68Ga-PSMA-11 and 11C-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 68Ga-PSMA-11 showed a significantly higher uptake and detection rate than 11C-choline PET. Also 68Ga-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 68Ga-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 11C-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 68Ga-PSMA-11 PET. CONCLUSION: Thus, PET using 68Ga-PSMA-11 showed a higher detection rate than 11C-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.

Impact of 18F-FDG-PET/CT on surgical management in patients with advanced melanoma: an outcome based analysis.

PURPOSE: To evaluate the influence of 18F-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.

Imaging of gastrointestinal melanoma metastases: Correlation with surgery and histopathology of resected specimen.

OBJECTIVE: To assess the appearance of gastrointestinal melanoma metastases on CT and PET/CT and evaluate the diagnostic value of CT and PET/CT compared with surgery and histopathology. METHODS: We retrospectively included 41 consecutive patients (aged 56.1 ± 13.5 years) with gastrointestinal melanoma metastases who underwent preoperative imaging (CT: all, PET/CT: n = 24) and metastasectomy. Two blinded radiologists assessed CT and PET/CT for gastrointestinal metastases and complications. Diagnostic accuracy and differences regarding lesion detectability and complications were assessed, using surgical findings and histopathology as standard of reference. RESULTS: Fifty-three gastrointestinal melanoma metastases (5.0 ± 3.8 cm) were confirmed by surgery and histopathology. Lesions were located in the small bowel (81.1 %), colon (15.1 %) and stomach (3.8 %), and described as infiltrating (30.2 %), polypoid (28.3 %), cavitary (24.5 %) and exoenteric (17.0 %). Fifteen patients (37 %) had gastrointestinal complications. Higher complication rates were associated with large and polypoid lesions (p ≤ .012). Diagnostic accuracy was high for CT and PET/CT (AUC ≥ .802). For reader B (less experienced), CT yielded lower diagnostic accuracy than PET/CT (p = .044). CONCLUSION: Most gastrointestinal melanoma metastases were located in the small bowel. Large and polypoid metastases were associated with higher complication rates. PET/CT was superior for detection of gastrointestinal melanoma metastases and should be considered in patients with limited disease undergoing surgery. KEY POINTS: • Gastrointestinal melanoma metastases (GI-MM) are rare but often cause serious gastrointestinal complications. • Early detection of GI-MM is important to prevent complications and guide surgery. • PET/CT is superior to CT for detection of GI-MMs. • PET/CT should be considered for patients with limited disease before surgical resection.

Overlap of highly FDG-avid and FMISO hypoxic tumor subvolumes in patients with head and neck cancer.

BACKGROUND: PET imaging may be used to personalize radiotherapy (RT) by identifying radioresistant tumor subvolumes for RT dose escalation. Using the tracers [18F]-fluorodeoxyglucose (FDG) and [18F]-fluoromisonidazole (FMISO), different aspects of tumor biology can be visualized. FDG depicts various biological aspects, e.g., proliferation, glycolysis and hypoxia, while FMISO is more hypoxia specific. In this study, we analyzed size and overlap of volumes based on the two markers for head-and-neck cancer patients (HNSCC). MATERIAL AND METHODS: Twenty five HNSCC patients underwent a CT scan, as well as FDG and dynamic FMISO PET/CT prior to definitive radio-chemotherapy in a prospective FMISO dose escalation study. Three PET-based subvolumes of the primary tumor (GTVprim) were segmented: a highly FDG-avid volume VFDG, a hypoxic volume on the static FMISO image acquired four hours post tracer injection (VH) and a retention/perfusion volume (VM) using pharmacokinetic modeling of dynamic FMISO data. Absolute volumes, overlaps and distances to agreement (DTA) were evaluated. RESULTS: Sizes of PET-based volumes and the GTVprim are significantly different (GTVprim>VFDG>VH >VM; p < .05). VH is covered by VFDG or DTAs are small (mean coverage 74.4%, mean DTA 1.4 mm). Coverage of VM is less pronounced. With respect to VFDG and VH, the mean coverage is 48.7% and 43.1% and the mean DTA is 5.3 mm and 6.3 mm, respectively. For two patients, DTAs were larger than 2 cm. CONCLUSIONS: Hypoxic subvolumes from static PET imaging are typically covered by or in close proximity to highly FDG-avid subvolumes. Therefore, dose escalation to FDG positive subvolumes should cover the static hypoxic subvolumes in most patients, with the disadvantage of larger volumes, resulting in a higher risk of dose-limiting toxicity. Coverage of subvolumes from dynamic FMISO PET is less pronounced. Further studies are needed to explore the relevance of mismatches in functional imaging.

Geometric analysis of loco-regional recurrences in relation to pre-treatment hypoxia in patients with head and neck cancer.

INTRODUCTION: A previous pattern-of-failure study has suggested that up to 50% of the loco-regional failures (LRF) in head and neck squamous cell carcinoma (HNSCC) occur outside the initial hypoxic volume determined by [18F]-fluoromisonidazole-PET ([18F]-FMISO-PET). The aim of the present analysis was to correlate spatial patterns of failure with respect to the pretherapeutic dynamic [18F]-FMISO-PET/CT in HNSCC after radiochemotherapy (RCT). MATERIAL AND METHODS: Within a running phase 2 trial using [18F]-FMISO-PET imaging prior to RCT in HNSCC patients (n = 54), we have observed so far 11 LRF with a minimum follow-up of 12 months. For nine patients, LRF imaging (CT or [18F]-FDG-PET/CT) for pattern-of-failure analysis was available. Analysis included the static 4-h hypoxic subvolume (VH) as well as a M-parameter volume (VM), which is derived from modeling of dynamic PET. Deformable image registration of the CT scan with the recurrent tumor to the pre-treatment [18F]-FMISO-PET/CT and the planning CT was done to quantify the hypoxic subvolumes compared to the recurrent tumor volume. Moreover, a point-of-origin analysis was performed. RESULTS: A total of five local, two regional and two loco-regional recurrences were detected. After deformable image registration of the CT scan with the recurrent tumor to the pre-treatment [18F]-FMISO-PET/CT and the planning CT, a significant overlap of the recurrence volume with [18F]-FMISO-positive subvolumes in the initial gross tumor volume (GTV) was observed. Median overlap of 40.2%, range 9.4-100.0%, for VH and 49.0%, range 4.4-96.4%, for VM was calculated. The point-of-origin analysis showed median distances of 0.0 mm, range 0.0-11.3 mm to VH and 8.6 mm, range 0.0-15.5 mm to VM, respectively. CONCLUSIONS: Our data suggest that loco-regional recurrences after RCT originate from the initial GTV (primary tumor and/or lymph node metastases) containing hypoxic subvolumes, which supports the concept of hypoxia imaging-based dose escalation.

Influence of (18)F-FDG PET/CT on therapy management in patients with stage III/IV malignant melanoma.

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.

Image-derived biomarkers and multimodal imaging strategies for lung cancer management.

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.

Robustness of quantitative hypoxia PET image analysis for predicting local tumor control.

BACKGROUND: Previous studies suggested the maximum tumor to background ratio (TBRmax) in FMISO PET images as a potentially predictive parameter for local control after radio-chemotherapy (CRT) in head and neck squamous cell carcinomas (HNSCC). However, different TBRmax thresholds for stratification were reported, implying that a common threshold cannot readily be used among different institutions without the risk of reducing prediction accuracy. Therefore, this study investigated the robustness of using a common pre-defined TBRmax, simulating a multicenter clinical trial. MATERIAL AND METHODS: FMISO PET/CT was performed four hours post-injection in 22 patients with advanced HNSCC in a phase II FMISO dose escalation study. PET background regions of interest (ROIs) were manually defined in deep neck muscles. TBRmax was calculated as the mean of the highest-valued voxels within the high risk RT planning target volume. Its predictive power with respect to local control was tested, classifying patients using median TBRmax as threshold. The influence of systematically varying quantification between institutions was studied in silico by applying offsets of ± 10% and ± 20% to the TBRmax of all patients, while the threshold remained constant. The effect was analyzed using a receiver operating characteristic (ROC). True positive and false positive rates (TPR/FPR) as well as positive and negative predictive values (PPV/NPV) were evaluated. RESULTS: For the reference condition without an offset the median TBRmax was 2.0 (1.4-3.5). Patients were classified using this threshold and TPR = 0.7, FPR = 0.4, PPV = 0.5 and NPV = 0.8 were observed. Accuracy declined with increasing offsets. Negative offsets of -10% and -20% resulted in TPR = 0.43 and 0.14, FPR = 0.20 and 0.13, PPV = 0.50 and 0.33 and NPV = 0.75 and 0.68, respectively. Positive offsets of + 10% and + 20% resulted in TPR = 1.00 and 1.00, FPR = 0.53 and 0.67, PPV = 0.47 and 0.41 and NPV = 1.00 and 1.00, respectively. CONCLUSIONS: Using a common pre-defined TBRmax threshold in multicenter trials requires careful standardization and harmonization of all steps from patient preparation to image analysis. Our results indicate that TBRmax should deviate less than 10% from reference conditions (absolute value in this dataset ± 0.2). This conclusion likely applies to all low contrast nitroimidazole hypoxia PET tracers.