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Immune and targeted therapies achieve long-term survival in metastatic melanoma; however, new treatment strategies are needed to improve patients' outcomes.sup.1,2. We report on the efficacy, safety and biomarker analysis from the single-arm safety run-in (part 1; n = 9) and biomarker (part 2; n = 27) cohorts of the randomized, placebo-controlled, phase 3 COMBI-i trial ((https://clinicaltrials.gov/ct2/show/NCT02967692)) of the anti-PD-1 antibody spartalizumab, in combination with the BRAF inhibitor dabrafenib and MEK inhibitor trametinib. Patients (n = 36) had previously untreated BRAF V600-mutant unresectable or metastatic melanoma. In part 1, the recommended phase 3 regimen was identified based on the incidence of dose-limiting toxicities (DLTs; primary endpoint): 400 mg of spartalizumab every 4 weeks plus 150 mg of dabrafenib twice daily plus 2 mg of trametinib once daily. Part 2 characterized changes in PD-L1 levels and CD8.sup.+ cells following treatment (primary endpoint), and analyzed additional biomarkers. Assessments of efficacy and safety were key secondary endpoints (median follow-up, 24.3 months). Spartalizumab plus dabrafenib and trametinib led to an objective response rate (ORR) of 78%, including 44% complete responses (CRs). Grade [greater than or equal to]3 treatment-related adverse events (TRAEs) were experienced by 72% of patients. All patients had temporary dose modifications, and 17% permanently discontinued all three study drugs due to TRAEs. Early progression-free survival (PFS) events were associated with low tumor mutational burden/T cell-inflamed gene expression signature (GES) or high immunosuppressive tumor microenvironment (TME) GES levels at baseline; an immunosuppressive TME may also preclude CR. Overall, the efficacy, safety and on-treatment biomarker modulations associated with spartalizumab plus dabrafenib and trametinib are promising, and biomarkers that may predict long-term benefit were identified. Clinical activity and biomarker analysis from the COMBI-i trial evaluating PD-1, BRAF and MEK inhibition in patients with metastatic melanoma demonstrate high response rates and uncover molecular correlates of long-term treatment benefit., Author(s): Reinhard Dummer [sup.1] , Celeste Lebbé [sup.2] , Victoria Atkinson [sup.3] , Mario Mandalà [sup.4] , Paul D. Nathan [sup.5] , Ana Arance [sup.6] , Erika Richtig [sup.7] , [...]

Beall's list is widely used to identify potentially predatory journals. With this study, we aim to investigate the impact of Beall's list on the perception of listed journals as well as on the publication and citation behavior of the scientific community. We performed comprehensive bibliometric analyses of data extracted from the ISSN database, PubMed, PubMed Central (PMC), Crossref, Scopus and Web of Science. Citation analysis was performed by data extracted from the Crossref Cited-by database. At the time of analysis, Beall's list consisted of 1,289 standalone journals and 1,162 publishers, which corresponds to 21,735 individual journals. Of these, 3,206 (38.8%) were located in the United States, 2,484 in India (30.0%), and 585 in United Kingdom (7.1%). The majority of journals were listed in the ISSN database (n = 8,266), Crossref (n = 5,155), PubMed (n = 1,139), Scopus (n = 570), DOAJ (n = 224), PMC (n = 135) or Web of Science (n = 50). The number of articles published by journals on Beall's list as well as on the DOAJ continuously increased from 2011 to 2017. In 2018, the number of articles published by journals on Beall's list decreased. Journals on Beall's list were more often cited when listed in Web of Science (CI 95% 5.5 to 21.5; OR = 10.7) and PMC (CI 95% 6.3 to 14.1; OR = 9.4). It seems that the importance of Beall's list for the scientific community is overestimated. In contrast, journals are more likely to be selected for publication or citation when indexed by commonly used and renowned databases. Thus, the providers of these databases must be aware of their impact and verify that good publication practice standards are being applied by the journals listed. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study evaluated the use of the intestinal microbiome as a prognostic marker that seems to modulate response to immune checkpoint inhibitor (ICI) treatment in patients with late-stage non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and metastatic melanoma. BiomeOne®, a stool microbiome-based algorithm, was able to classify patient samples according to the likeliness of achieving clinical benefit of ICI before treatment initiation by identifying an immunotherapy-favorable microbiome signature, outperforming the standard PD-L1 expression test. This study has additionally shed new light on the intestinal microbiome signature associated with the occurrence of irAEs, paving way to larger studies to validate and expand the current knowledge. Lastly, robust, easy-to-use, and non-invasive microbiome-based diagnostics hold promising potential for oncology, and further work should aim to expand these applications to other cancer types and microbiome-centered interventions, such as fecal microbiota transplantation (FMT), moving one step forward towards the era of personalized medicine. The intestinal microbiome is by now an undebatable key player in the clinical outcome of ICI therapies. However, no microbiome profiling method to aid therapy decision is yet validated. We conducted a multi-centric study in patients with stage III/IV melanoma, NSCLC, or RCC receiving ICI treatment. The stool microbiome profile of 63 patients was analyzed with BiomeOne®, a microbiome-based algorithm that anticipates whether a patient will achieve clinical benefit with ICIs prior to therapy initiation. Classification of patient samples as Rs and NRs was achieved with a sensitivity of 81% and a specificity of 50% in this validation cohort. An ICI-favorable response was characterized by an intestinal microbiome rich in bacteria such as Oscillospira sp., Clostridia UCG-014, Lachnospiraceae UCG-010 sp., Prevotella copri, and a decrease in Sutterella sp., Lactobacillales, and Streptococcus sp. Patients who developed immune-related adverse events (irAEs) had an overall increased microbial diversity and richness, and a stool microbiome depleted in Agathobacter. When compared with the programmed death-ligand 1 (PD-L1) expression test in the subcohort of NSCLC patients (n = 38), BiomeOne® exhibited a numerically higher sensitivity (78.6%) in identifying responders when compared with the PD-L1 test (67.9%). This study provides an evaluation of BiomeOne®, the first microbiome-based test for prediction of ICI response, to achieve market authorization. Validation with further indications and expansion to other microbiome-based interventions will be essential to bring microbiome-based diagnostics into standard clinical practice. [ABSTRACT FROM AUTHOR]

Postoperative complications such as seroma formation and wound-site infection occur following completion axillary lymph node dissection (ALND) for melanoma. We analyzed the impact of time-to-drain removal and drainage volume on seroma formation after ALND. We retrospectively analyzed data from 118 patients after completion ALND for melanoma. Primary endpoints were daily amount of drainage volume, seroma formation and time-to-drain removal. Secondary endpoints included patient-related, disease-specific and perioperative parameters as well as the number of histologically analyzed lymph nodes and surgical complications graded by the Clavien–Dindo classification (CDCL). Statistical analyses were performed using logistic regression models. Drain removal around the 8th postoperative day was statistically associated with a lower risk for the occurrence of seroma formation (p < 0.001). Patients with an increased drainage volume during the early postoperative days were more prone to develop seroma after drain removal. With 49% (CDCL I and II), most complications were managed conservatively, while only 5.9% (CDCL III) required revision surgery (CDCL overall: 55.9%). ALND is a safe procedure with a low rate of severe CDCL III type of complications. To decrease seroma evacuation, our results imply that drains should be removed around the 8th postoperative day to reduce the risk of infection, readmission or prolonged hospitalization. [ABSTRACT FROM AUTHOR]

In this group, BRAF-, MEK- or both inhibitor doses were reduced in 8, 7 and 33 cases and the proportion of patients with BRAF- or MEK-inhibitor dose reductions were 83.3% (thereof 40.0% first, 30.0% second and 30.0% third dose reduction) or 88.9% (thereof 40.0% first, 47.5% second, 12.5% third dose reduction). Although 64/88 patients took on average 2.6 additional medications and 26 patients had potential drug-drug interactions with their BRAF/MEK inhibitors, only one patient had a potential interaction with alteration of BRAF/MEK-inhibitor efficacy (assessed with eMedicInfo v0.9.15, x-tention Informationstechnologie Gmbh, Wels, Austria). [Extracted from the article]

Melanoma, although not the most common type of skin cancer in the white population, is the deadliest. However, it can be cured if detected and treated early. Screening programs are important for early detection, but should only be used in high-risk groups. Observational studies have identified various risk factors for melanoma, but the results can be contradictory. A recent study using Mendelian randomization analysis found that a history of childhood sunburn and ease of skin tanning are clear risk factors for melanoma, while there was no significant connection between melanoma risk and alcohol intake, coffee consumption, or smoking. Further research is needed to define the role of other risk factors. The study emphasizes the importance of incorporating these findings into prevention campaigns and measures. [Extracted from the article]

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Summary: Background: Anti‐programmed death 1 (PD‐1) antibodies have evolved as a new standard of care in the adjuvant treatment of completely resected melanoma. Real‐world data on treatment efficacy and safety as well as cost‐effectiveness are still limited. Patients and Methods: Treatment outcomes were retrospectively analyzed in a continuous patient cohort receiving adjuvant nivolumab (91 patients) or pembrolizumab (9 patients). Based on the obtained clinical data, a semi‐Markov model was developed to evaluate cost‐effectiveness. Results: After a median follow‐up of 11.5 months, disease recurrence was observed in 39 patients (39 %). The site of first recurrence was locoregional in 17, distant in 19, and combined locoregional and distant in three patients. Twelve‐month estimates for recurrence‐ and distant‐metastasis‐free survival were 64.8 % and 77.4 %, respectively. Sixteen patients experienced grade 3 or 4 treatment‐related adverse events, while 22 patients discontinued treatment due to adverse events. The base‐case Markov model yielded an incremental cost‐effectiveness ratio of 13,330 € per quality‐adjusted life year for adjuvant anti‐PD‐1 antibody treatment compared to a simulated observation cohort. Conclusions: Real‐world outcomes of adjuvant anti‐PD‐1 antibody therapy in completely resected melanoma appear comparable to clinical trial data. Moreover, our data suggests this treatment strategy to be cost‐effective according to Austrian health economic standards. [ABSTRACT FROM AUTHOR]

Background: Melanocytic nevi have a complex evolution influenced by several endogenous and exogenous factors and are known risk factors for malignant melanoma. Interestingly, tobacco use seems to be inversely associated with melanoma risk. However, the association between tobacco use and nevi and lentigines has not yet been evaluated. Methods: We investigated the prevalence of nevi, atypical nevi, and lentigines in relation to tobacco smoking in a cohort of 59 smokers and 60 age- and sex-matched nonsmokers, using a questionnaire and performing a total body skin examination by experts. Results: No significant differences were detected between smokers and nonsmokers in the numbers of nevi, atypical nevi, and lentigines in sun-exposed areas (p = 0.966, 0.326, and 0.241, respectively) and in non-sun-exposed areas (p = 0.095, 0.351, and 0.546, respectively). Conclusion: Our results revealed no significant differences in the prevalence of nevi, atypical nevi, and lentigines between smokers and nonsmokers in sun-exposed and non-sun-exposed areas. [ABSTRACT FROM AUTHOR]