Correlation of tumor PD-L1 expression in different tissue types and outcome of PD-1-based immunotherapy in metastatic melanoma - analysis of the DeCOG prospective multicenter cohort study ADOREG/TRIM.

BACKGROUND: PD-1-based immune checkpoint inhibition (ICI) is the major backbone of current melanoma therapy. Tumor PD-L1 expression represents one of few biomarkers predicting ICI therapy outcome. The objective of the present study was to systematically investigate whether the type of tumor tissue examined for PD-L1 expression has an impact on the correlation with ICI therapy outcome. METHODS: Pre-treatment tumor tissue was collected within the prospective DeCOG cohort study ADOREG/TRIM (CA209-578; NCT05750511) between February 2014 and May 2020 from 448 consecutive patients who received PD-1-based ICI for non-resectable metastatic melanoma. The primary study endpoint was best overall response (BOR), secondary endpoints were progression-free (PFS) and overall survival (OS). All endpoints were correlated with tumor PD-L1 expression (quantified with clone 28-8; cutoff ≥5%) and stratified by tissue type. FINDINGS: Tumor PD-L1 was determined in 95 primary tumors (PT; 36.8% positivity), 153 skin/subcutaneous (34.0% positivity), 115 lymph node (LN; 50.4% positivity), and 85 organ (40.8% positivity) metastases. Tumor PD-L1 correlated with BOR if determined in LN (OR = 0.319; 95% CI = 0.138-0.762; P = 0.010), but not in skin/subcutaneous metastases (OR = 0.656; 95% CI = 0.311-1.341; P = 0.26). PD-L1 positivity determined on LN metastases was associated with favorable survival (PFS, HR = 0.490; 95% CI = 0.310-0.775; P = 0.002; OS, HR = 0.519; 95% CI = 0.307-0.880; P = 0.014). PD-L1 positivity determined in PT (PFS, HR = 0.757; 95% CI = 0.467-1.226; P = 0.27; OS; HR = 0.528; 95% CI = 0.305-0.913; P = 0.032) was correlated with survival to a lesser extent. No relevant survival differences were detected by PD-L1 determined in skin/subcutaneous metastases (PFS, HR = 0.825; 95% CI = 0.555-1.226; P = 0.35; OS, HR = 1.083; 95% CI = 0.698-1.681; P = 0.72). INTERPRETATION: For PD-1-based immunotherapy in melanoma, tumor PD-L1 determined in LN metastases was stronger correlated with therapy outcome than that assessed in PT or organ metastases. PD-L1 determined in skin/subcutaneous metastases showed no outcome correlation and therefore should be used with caution for clinical decision making. FUNDING: Bristol-Myers Squibb (ADOREG/TRIM, NCT05750511); German Research Foundation (DFG; Clinician Scientist Program UMEA); Else Kröner-Fresenius-Stiftung (EKFS; Medical Scientist Academy UMESciA).

Multispectral optoacoustic tomography to differentiate between lymph node metastases and coronavirus-19 vaccine-associated lymphadenopathy.

INTRODUCTION: Worldwide mass vaccination for COVID-19 started in late 2020. COVID-19 vaccines cause benign hypermetabolic lymphadenopathies. Clinical stratification between vaccine-associated benign lymphadenopathies and malignant lymphadenopathies through ultrasound, MRI or FDG PET-CT is not feasible. This leads to unnecessary lymph node biopsies, excisions and even radical lymph node dissections. Therefore, to avoid unnecessary surgeries, we assessed whether noninvasive multispectral optoacoustic tomography (MSOT) enables a better differentiation between benign and malignant lymphadenopathies. PATIENTS AND METHODS: All patients were vaccinated for COVID-19. We used MSOT to image deoxy- and oxyhaemoglobin levels in lymph nodes of tumour patients to assess metastatic status. MSOT imaging results were compared with standard ultrasound and pathological lymph node analysis. We also evaluated the influences of gender, age and time between vaccination and MSOT measurement of lymph nodes on the measured deoxy- and oxyhaemoglobin levels in patients with reactive lymph node changes. RESULTS: Multispectral optoacoustic tomography was able to identify cancer-free lymph nodes in vivo without a single false negative (33 total lymph nodes), with 100% sensitivity and 50% specificity. A statistically significant higher deoxyhaemoglobin content was detected in patients with tumour manifestations in the lymph node (p = 0.02). There was no statistically significant difference concerning oxyhaemoglobin (p = 0.65). Age, sex and time between vaccination and MSOT measurement had statistically non-significant impact on deoxy- and oxyhaemoglobin levels in patients with reactive lymph nodes. CONCLUSION: Here, we show that MSOT measurement is an advantageous clinical approach to differentiate between vaccine-associated benign lymphadenopathy and malignant lymph node metastases based on the deoxygenation level in lymph nodes.

Virtual and Augmented Reality in Cardiac Surgery

Abstract Virtual and augmented reality can be defined as a three-dimensional real-world simulation allowing the user to directly interact with it. Throughout the years, virtual reality has gained great popularity in medicine and is currently being adopted for a wide range of purposes. Due to its dynamic anatomical nature, permanent drive towards decreasing invasiveness, and strive for innovation, cardiac surgery depicts itself as a unique environment for virtual reality. Despite substantial research limitations in cardiac surgery, the current literature has shown great applicability of this technology, and promising opportunities.

Virtual and Augmented Reality in Cardiac Surgery.

Virtual and augmented reality can be defined as a three-dimensional real-world simulation allowing the user to directly interact with it. Throughout the years, virtual reality has gained great popularity in medicine and is currently being adopted for a wide range of purposes. Due to its dynamic anatomical nature, permanent drive towards decreasing invasiveness, and strive for innovation, cardiac surgery depicts itself as a unique environment for virtual reality. Despite substantial research limitations in cardiac surgery, the current literature has shown great applicability of this technology, and promising opportunities.

High-resolution three-dimensional imaging for precise staging in melanoma.

INTRODUCTION: Many cancer guidelines include sentinel lymph node (SLN) staging to identify microscopic metastatic disease. Current SLN analysis of melanoma patients is effective but has the substantial drawback that only a small representative portion of the node is sampled, whereas most of the tissue is discarded. This might explain the high clinical false-negative rate of current SLN diagnosis in melanoma. Furthermore, the quantitative assessment of metastatic load and microanatomical localisation might yield prognosis with higher precision. Thus, methods to analyse entire SLNs with cellular resolution apart from tedious sequential physical sectioning are required. PATIENTS AND METHODS: Eleven melanoma patients eligible to undergo SLN biopsy were included in this prospective study. SLNs were fixed, optically cleared, whole-mount stained and imaged using light sheet fluorescence microscopy (LSFM). Subsequently, compatible and unbiased gold standard histopathological assessment allowed regular patient staging. This enabled intrasample comparison of LSFM and histological findings. In addition, the development of an algorithm, RAYhance, enabled easy-to-handle display of LSFM data in a browsable histologic slide-like fashion. RESULTS: We comprehensively quantify total tumour volume while simultaneously visualising cellular and anatomical hallmarks of the associated SLN architecture. In a first-in-human study of 21 SLN of melanoma patients, LSFM not only confirmed all metastases identified by routine histopathological assessment but also additionally revealed metastases not detected by routine histology alone. This already led to additional therapeutic options for one patient. CONCLUSION: Our three-dimensional digital pathology approach can increase sensitivity and accuracy of SLN metastasis detection and potentially alleviate the need for conventional histopathological assessment in the future. GERMAN CLINICAL TRIALS REGISTER: (DRKS00015737).

Patient-Derived Human Basal and Cutaneous Squamous Cell Carcinoma Tissues Display Apoptosis and Immunomodulation following Gas Plasma Exposure with a Certified Argon Jet.

Reactive oxygen species (ROS) have been subject of increasing interest in the pathophysiology and therapy of cancers in recent years. In skin cancer, ROS are involved in UV-induced tumorigenesis and its targeted treatment via, e.g., photodynamic therapy. Another recent technology for topical ROS generation is cold physical plasma, a partially ionized gas expelling dozens of reactive species onto its treatment target. Gas plasma technology is accredited for its wound-healing abilities in Europe, and current clinical evidence suggests that it may have beneficial effects against actinic keratosis. Since the concept of hormesis dictates that low ROS levels perform signaling functions, while high ROS levels cause damage, we investigated herein the antitumor activity of gas plasma in non-melanoma skin cancer. In vitro, gas plasma exposure diminished the metabolic activity, preferentially in squamous cell carcinoma cell (SCC) lines compared to non-malignant HaCaT cells. In patient-derived basal cell carcinoma (BCC) and SCC samples treated with gas plasma ex vivo, increased apoptosis was found in both cancer types. Moreover, the immunomodulatory actions of gas plasma treatment were found affecting, e.g., the expression of CD86 and the number of regulatory T-cells. The supernatants of these ex vivo cultured tumors were quantitatively screened for cytokines, chemokines, and growth factors, identifying CCL5 and GM-CSF, molecules associated with skin cancer metastasis, to be markedly decreased. These findings suggest gas plasma treatment to be an interesting future technology for non-melanoma skin cancer topical therapy.

Multispectral optoacoustic tomography might be a helpful tool for noninvasive early diagnosis of psoriatic arthritis.

Currently used imaging methods for diagnosis of psoriatic arthritis (PsA) frequently come along with exposure to radiation and can often only show long-term effects of the disease. The aim of the study was to check the feasibility of a new optoacoustic imaging method to identify PsA. 22 psoriasis patients and 19 healthy volunteers underwent examination using multispectral optoacoustic tomography (MSOT). The presence of arthritis was assessed via quantification of optoacoustic signal intensity of the endogenous chromophores oxy- and deoxyhemoglobin. We conducted high-resolution real-time ultrasound images of the finger joints. The semi quantitative analysis of the optoacoustic signals for both hemoglobin species showed a significant higher blood content and oxygenation in PsA patients compared to healthy controls. Our results indicate that MSOT might allow detection of inflammation in an early stage. If the data is further confirmed, this technique might be a suitable tool to avoid delay of diagnosis of PsA.

Coronavirus disease 2019 vaccine mimics lymph node metastases in patients undergoing skin cancer follow-up: A monocentre study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has changed the lives of people around the world. Fortunately, sufficient vaccines are now available. Local reactions with ipsilateral lymphadenopathy are among the most common side effects. We investigated the impact of lymphadenopathy after COVID-19 vaccination on the value of ultrasound in tumour patients. PATIENTS AND METHODS: Patients with melanoma or Merkel cell carcinoma were included who underwent lymph node excision and received COVID-19 vaccination within 6 weeks before surgery. The consistency of the preoperative ultrasound findings with the histopathologic findings was investigated. RESULTS: Eight patients were included (two Merkel cell carcinoma and six melanoma patients) who underwent lymph node excision between 16th April 2021 and 19th May 2021 and had previously received COVID-19 vaccination. In three of the eight patients (one Merkel cell carcinoma and two melanoma patients), lymph node metastases were erroneously diagnosed preoperatively during tumour follow-up with physical examination, ultrasound, and or fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT). In these three patients, the suspected lymph node metastases were located in the left axilla after COVID-19 vaccination in the left upper arm, which resulted in selective lymph node removal in two patients and complete lymphadenectomy in one patient. CONCLUSION: COVID-19 vaccine-associated lymphadenopathy is expected to be observed much more frequently in the near future because of increasing vaccination rates. This cause of lymphadenopathy, which may in ultrasound as well as in FDG PET/CT resemble lymph node metastases, must be considered, especially in oncologic patients undergoing tumour follow-up. In addition, COVID-19 vaccination should be given as far away as possible from an underlying primary on the contralateral side to avoid oncologic misdiagnosis followed by malpractice.

Computed tomography-guided biopsy of radiologically unclear lesions in advanced skin cancer: A retrospective analysis of 47 cases.

BACKGROUND: Radiological imaging such as computed tomography (CT) is used frequently for disease staging and therapy monitoring in advanced skin cancer patients. Detected lesions of unclear dignity are a common challenge for treating physicians. The aim of this study was to assess the frequency and outcome of CT-guided biopsy (CTGB) of radiologically unclear, suspicious lesions and to depict its usefulness in different clinical settings. METHODS: This retrospective monocentric study included advanced skin cancer patients (melanoma, Merkel cell carcinoma, squamous cell carcinoma, angiosarcoma, cutaneous lymphoma) with radiologically unclear lesions who underwent CTGB between 2010 and 2018. RESULTS: Of 59 skin cancer patients who received CTGB, 47 received CTGB to clarify radiologically suspicious lesions of unclear dignity. 32 patients had no systemic therapy (cohort A), while 15 patients received systemic treatment at CTGB (cohort B). In both cohorts, CTGB revealed skin cancer metastasis in a large proportion of patients (37.5%, 40.0%, respectively), but benign tissue showing inflammation, fibrosis or infection in an equally large percentage (37.5%, 46.7%, respectively). Additionally, a significant number of other cancer entities was found (25.0%, 13.3%, respectively). In patients receiving BRAF/MEK inhibitors, CTGB confirmed suspicious lesions as skin cancer metastasis in 83.3%, leading to treatment change. In immune checkpoint inhibitor-treated patients, skin cancer metastasis was confirmed in 11.1% of patients only, whereas benign tissue changes (inflammation/fibrosis) were found in 77.8%. CONCLUSIONS: Our results highlight the relevance of clarifying radiologically unclear lesions by CTGB before start or change of an anti-tumour therapy to exclude benign alterations and secondary malignancies.

[Long-term healing of a therapy-refractory venous leg ulcer after crural fasciectomy and split skin graft transplantation]. / Langfristige Abheilung eines therapierefraktären Ulcus cruris venosum nach kruraler Fasziektomie und Spalthauttransplantation.

A 59-year-old obese woman had been suffering from a painful, chronic leg ulcer since 1986. We diagnosed a venous leg ulcer due to functional chronic venous insufficiency in the context of obesity per magna (dependency syndrome) and arthrogenic congestion syndrome due to immobility. Although a high ligation and stripping of the great saphenous vein and several so-called shave therapies with split skin transplantation after appropriate wound bed preparation had been previously performed, the wound persisted. In 2012, the patient wanted to amputate her leg because the course of wound healing was so refractory to therapy and she suffered from severe pain. As an alternative to amputation, we performed a crural fascietomy and, after a wound bed preparation with two cycles of negative pressure wound therapy, we covered the defect with a split skin graft using the mesh graft technique. The surgery could be performed without complications and the skin healed completely. At the current presentation 7 years after the intervention, complete healing of the previously therapy-refractory venous leg ulcer was shown despite the persistent obesity per magna and immobility. This case report shows that a crural fasciectomy should be considered, especially in the case of otherwise therapy-refractory courses of venous leg ulcers.

Salivary cortisol levels and anxiety in melanoma patients undergoing sentinel lymph node excision under local anesthesia versus general anesthesia: a prospective study.

BACKGROUND: Sentinel lymph node excision (SLNE) can be performed in tumescent local anesthesia (TLA) or general anesthesia (GA). Perioperative cortisol level changes and anxiety are common in surgical interventions and might be influenced by the type of anesthesia. In this study, we intended to determine whether the type of anesthesia impacts the patients' perioperative levels of salivary cortisol (primary outcome) and the feeling of anxiety evaluated by psychological questionnaires (secondary outcome). METHODS: All melanoma patients of age undergoing SLNE at the University Hospital Essen, Germany, could be included in the study. Exclusion criteria were patients' intake of glucocorticoids or psychotropic medication during the former 6 months, pregnancy, age under 18 years, and BMI ≥ 30 as salivary cortisol levels were reported to be significantly impacted by obesity and might confound results. RESULTS: In total, 111 melanoma patients undergoing SLNE were included in our prospective study between May 2011 and April 2017 and could choose between TLA or GA. Salivary cortisol levels were measured three times intraoperatively, twice on the third and second preoperative day and twice on the second postoperative day. To assess anxiety, patients completed questionnaires (Hospital Anxiety and Depression Scale (HADS), State-Trait Anxiety Inventory (STAI)) perioperatively. Patients of both groups exhibited comparable baseline levels of cortisol and perioperative anxiety levels. Independent of the type of anesthesia, all patients showed significantly increasing salivary cortisol level from baseline to 30 min before surgery (T3) (TLA: t = 5.07, p < 0.001; GA: t = 3.09, p = 0.006). Post hoc independent t tests showed that the TLA group exhibited significantly higher cortisol concentrations at the beginning of surgery (T4; t = 3.29, p = 0.002) as well as 20 min after incision (T5; t = 277, p = 0.008) compared to the GA group. CONCLUSIONS: The type of anesthesia chosen for SLNE surgery significantly affects intraoperative cortisol levels in melanoma patients. Further studies are mandatory to evaluate the relevance of endogenous perioperative cortisol levels on the postoperative clinical course. TRIAL REGISTRATION: German Clinical Trials Register DRKS00003076, registered 1 May 2011.

xCT (SLC7A11) expression confers intrinsic resistance to physical plasma treatment in tumor cells.

Cold physical plasma is a partially ionized gas investigated as a new anticancer tool in selectively targeting cancer cells in monotherapy or in combination with therapeutic agents. Here, we investigated the intrinsic resistance mechanisms of tumor cells towards physical plasma treatment. When analyzing the dose-response relationship to cold plasma-derived oxidants in 11 human cancer cell lines, we identified four 'resistant' and seven 'sensitive' cell lines. We observed stable intracellular glutathione levels following plasma treatment only in the 'resistant' cell lines indicative of altered antioxidant mechanisms. Assessment of proteins involved in GSH metabolism revealed cystine-glutamate antiporter xCT (SLC7A11) to be significantly more abundant in the 'resistant' cell lines as compared to 'sensitive' cell lines. This decisive role of xCT was confirmed by pharmacological and genetic inhibition, followed by cold physical plasma treatment. Finally, microscopy analysis of ex vivo plasma-treated human melanoma punch biopsies suggested a correlation between apoptosis and basal xCT protein abundance. Taken together, our results demonstrate that xCT holds the potential as a biomarker predicting the sensitivity of tumor cells towards plasma treatment.

Assessment of Nonradioactive Multispectral Optoacoustic Tomographic Imaging With Conventional Lymphoscintigraphic Imaging for Sentinel Lymph Node Biopsy in Melanoma.

Importance: The metastatic status of sentinel lymph nodes (SLNs) is the most relevant prognostic factor in breast cancer, melanoma, and other tumors. The conventional standard to label SLNs is lymphoscintigraphy with technetium Tc 99m. A worldwide shortage and known disadvantages of Tc 99m have intensified efforts to establish alternative, nonradioactive imaging techniques. Objective: To assess a new nonradioactive method using multispectral optoacoustic tomographic (MSOT) imaging in comparison with conventional lymphoscintigraphic imaging for SLN biopsy (SLNB) in melanoma. Design, Setting, and Participants: Analysis of a cross-sectional study was conducted at the University Hospital-Essen, Skin Cancer Center, Essen, Germany. Between June 2, 2014, and February 22, 2019, 83 patients underwent SLNB with an additional preoperative indocyanine green (ICG) application. Sentinel lymph node basins were preoperatively identified by MSOT imaging, and ICG-labeled SLNs were intraoperatively detected using a near-infrared camera. The surgeons were blinded to the lymphoscintigraphic imaging results in the beginning of the SLNB. Use of a γ probe was restricted until the SLNB procedure was attempted by the nonradioactive method. Main Outcomes and Measures: Concordance of SLN basins and SLNs identified by MSOT imaging plus near-infrared camera vs lymphoscintigraphic imaging plus single-photon emission computed tomographic or computed tomographic imaging was assessed. Results: Of the 83 patients (mean [SD] age, 54.61 [17.53] years), 47 (56.6%) were men. In 83 surgical procedures, 165 SLNs were excised. The concordance rate of ICG-labeled and Tc 99m-marked detected SLN basins was 94.6% (n = 106 of 112). Intraoperatively, 159 SLNs were detected using a near-infrared camera and 165 were detected by a γ probe, resulting in a concordance rate of 96.4%. Multispectral optoacoustic tomographic imaging visualized SLNs in all anatomic regions with high penetration depth (5 cm). Conclusions and Relevance: The findings of this study suggest that nonradioactive SLN detection via MSOT imaging allows identification of SLNs at a frequency equivalent to that of the current radiotracer conventional standard. Multispectral optoacoustic tomographic imaging appears to be a viable nonradioactive alternative to detect SLNs in malignant tumors.

Frequent Occurrence of NRAS and BRAF Mutations in Human Acral Naevi.

Acral naevi are benign melanocytic tumors occurring at acral sites. Occasionally they can progress to become malignant tumors (melanomas). The genetics of acral naevi have not been assessed in larger studies. In our study, a large cohort of 130 acral naevi was screened for gene mutations known to be important in other naevi and melanoma subtypes by targeted next-generation sequencing. Mutation status was correlated with clinicopathological parameters. Frequent mutations in genes activating the MAP kinase pathway were identified, including n = 87 (67%) BRAF, n = 24 (18%) NRAS, and one (1%) MAP2K1 mutations. BRAF mutations were almost exclusively V600E (n = 86, 99%) and primarily found in junctional and compound naevi. NRAS mutations were either Q61K or Q61R and frequently identified in dermal naevi. Recurrent non-V600E BRAF, KIT, NF1, and TERT promoter mutations, present in acral melanoma, were not identified. Our study identifies BRAF and NRAS mutations as the primary pathogenic event in acral naevi, however, distributed differently to those in non-acral naevi. The mutational profile of acral naevi is distinct from acral melanoma, which may be of diagnostic value in distinguishing these entities.

The prognostic value of sentinel lymph nodes on distant metastasis-free survival in patients with high-risk squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common cutaneous cancer worldwide. Several tumour characteristics are considered to pose an elevated risk for systemic spread of carcinoma cells ('high-risk' features). Early detection of subclinical metastases could permit early treatment and improve overall survival. To detect occult metastases and evaluate risk of future distant metastases, diagnostic extirpation of the sentinel lymph node (SLNE) is routinely performed in cutaneous melanoma and can be offered in high-risk cutaneous squamous cell carcinoma (hrcSCC). However, the clinical utility of SLNE in patients with hrcSCC remains unknown. MATERIAL AND METHODS: An ambidirectional cohort study with prospective patient recruitment was performed. Between July 2008 and April 2017, of 139 eligible patients, SLNE was performed in 114 cases (25 patients refused). Median follow-up was 23.7 months. RESULTS: We analysed the characteristics of 114 patients with hrcSCC who underwent SLNE. Eighty-nine patients (78.1%) were men, and 25 patients (21.9%) were women (median age 72.2 years). In multivariable analyses, histopathological detection of ulceration (hazard ratio, HR 2.9 [95% confidence interval, CI 0.7-12.2]), perineural growth (HR 3.0 [95% CI 0.6-14.6]) and clinically occult SLN metastases (HR 10.7 [95% CI 1.9-60.6]) were strongly associated with future occurrence of distant metastases. A positive predictive value of 50% was noted for patients where SLN metastasis was detected to develop distant metastases. However, distant metastases also occurred in seven patients when histopathological SLN evaluation had shown no evidence of metastases. CONCLUSIONS: Our data suggest SLNE is not a reliable diagnostic approach to evaluate the risk of future systemic carcinoma spread and development of distant metastases in patients with hrcSCC.

Sentinel lymph node excision with or without preoperative hybrid single-photon emission computed tomography/computed tomography (SPECT/CT) in melanoma: study protocol for a multicentric randomized controlled trial.

BACKGROUND: Melanoma has become a growing interdisciplinary problem in public health worldwide. According to the World Health Organization, the incidence of melanoma is increasing faster than any other cancer in the world. Because melanoma metastasizes early into the regional lymph nodes, sentinel lymph node excision (SLNE) is included in the current American Joint Committee of Cancer guidelines. However SLNE of melanoma has a high false-negative rate of up to 44%. METHODS: The gold standard for detection and extirpation of the sentinel lymph node is preoperative lymphoscintigraphy. SPECT/CT provides complementary information: the advantages include accurate anatomical localization, identification of false positives, reduction in the number of false negatives, and alteration of the surgical approach. Therefore, sentinel lymph node-SPECT/CT provides valuable information before sentinel lymph node excision and advocates its use in melanoma. We present a multicenter, unblinded superiority randomized controlled trial to compare SPECT/CT-aided SLNE versus standard SLNE in melanoma patients. DISCUSSION: The primary efficacy endpoint is distant metastasis-free survival. Secondary endpoints comprise overall survival, disease-free survival, rate of local relapses within the follow-up period (false-negative rate of sentinel lymph node), number of positive sentinel lymph nodes (sensitivity, false-positive rate), complication rate, quality of life, quality-adjusted life years, inpatient days, and overall costs during hospital stays. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03683550 . Registered on 20 September 2018.

Can integrated 18F-FDG PET/MR replace sentinel lymph node resection in malignant melanoma?

PURPOSE: To compare the sensitivity and specificity of 18F-fluordesoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), 18F-FDG PET/magnetic resonance (18F-FDG PET/MR) and 18F-FDG PET/MR including diffusion weighted imaging (DWI) in the detection of sentinel lymph node metastases in patients suffering from malignant melanoma. MATERIAL & METHODS: Fifty-two patients with malignant melanoma (female: n = 30, male: n = 22, mean age 50.5 ± 16.0 years, mean tumor thickness 2.28 ± 1.97 mm) who underwent 18F-FDG PET/CT and subsequent PET/MR & DWI for distant metastasis staging were included in this retrospective study. After hybrid imaging, lymphoscintigraphy including single photon emission computed tomography/CT (SPECT/CT) was performed to identify the sentinel lymph node prior to sentinel lymph node biopsy (SLNB). In a total of 87 sentinel lymph nodes in 64 lymph node basins visible on SPECT/CT, 17 lymph node metastases were detected by histopathology. In separate sessions PET/CT, PET/MR, and PET/MR & DWI were assessed for sentinel lymph node metastases by two independent readers. Discrepant results were resolved in a consensus reading. Sensitivities, specificities, positive predictive values and negative predictive values were calculated with histopathology following SPECT/CT guided SLNB as a reference standard. RESULTS: Compared with histopathology, lymph nodes were true positive in three cases, true negative in 65 cases, false positive in three cases and false negative in 14 cases in PET/CT. PET/MR was true positive in four cases, true negative in 63 cases, false positive in two cases and false negative in 13 cases. Hence, we observed a sensitivity, specificity, positive predictive value and negative predictive value of 17.7, 95.6, 50.0 and 82.3% for PET/CT and 23.5, 96.9, 66.7 and 82.3% for PET/MR. In DWI, 56 sentinel lymph node basins could be analyzed. Here, the additional analysis of DWI led to two additional false positive findings, while the number of true positive findings could not be increased. CONCLUSION: In conclusion, integrated 18F-FDG PET/MR does not reliably differentiate N-positive from N-negative melanoma patients. Additional DWI does not increase the sensitivity of 18F-FDG PET/MR. Hence, sentinel lymph node biopsy cannot be replaced by 18F-FDG-PE/MR or 18F-FDG-PET/CT.

A Skin Cancer Prevention Facial-Aging Mobile App for Secondary Schools in Brazil: Appearance-Focused Interventional Study.

BACKGROUND: The incidence of melanoma is increasing faster than any other major cancer both in Brazil and worldwide. Southeast Brazil has especially high incidences of melanoma, and early detection is low. Exposure to ultraviolet (UV) radiation is a primary risk factor for developing melanoma. Increasing attractiveness is a major motivation among adolescents for tanning. A medical student-delivered intervention that takes advantage of the broad availability of mobile phones and adolescents' interest in their appearance indicated effectiveness in a recent study from Germany. However, the effect in a high-UV index country with a high melanoma prevalence and the capability of medical students to implement such an intervention remain unknown. OBJECTIVE: In this pilot study, our objective was to investigate the preliminary success and implementability of a photoaging intervention to prevent skin cancer in Brazilian adolescents. METHODS: We implemented a free photoaging mobile phone app (Sunface) in 15 secondary school classes in southeast Brazil. Medical students "mirrored" the pupils' altered 3-dimensional (3D) selfies reacting to touch on tablets via a projector in front of their whole grade accompanied by a brief discussion of means of UV protection. An anonymous questionnaire capturing sociodemographic data and risk factors for melanoma measured the perceptions of the intervention on 5-point Likert scales among 356 pupils of both sexes (13-19 years old; median age 16 years) in grades 8 to 12 of 2 secondary schools in Brazil. RESULTS: We measured more than 90% agreement in both items that measured motivation to reduce UV exposure and only 5.6% disagreement: 322 (90.5%) agreed or strongly agreed that their 3D selfie motivated them to avoid using a tanning bed, and 321 (90.2%) that it motivated them to improve their sun protection; 20 pupils (5.6%) disagreed with both items. The perceived effect on motivation was higher in female pupils in both tanning bed avoidance (n=198, 92.6% agreement in females vs n=123, 87.2% agreement in males) and increased use of sun protection (n=197, 92.1% agreement in females vs n=123, 87.2% agreement in males) and independent of age or skin type. All medical students involved filled in a process evaluation revealing that they all perceived the intervention as effective and unproblematic, and that all pupils tried the app in their presence. CONCLUSIONS: The photoaging intervention was effective in changing behavioral predictors for UV protection in Brazilian adolescents. The predictors measured indicated an even higher prospective effectiveness in southeast Brazil than in Germany (>90% agreement in Brazil vs >60% agreement in Germany to both items that measured motivation to reduce UV exposure) in accordance with the theory of planned behavior. Medical students are capable of complete implementation. A randomized controlled trial measuring prospective effects in Brazil is planned as a result of this study.