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Purpose : To investigate the prognostic value of [18F]FDG PET/CT as part of response monitoring in metastatic melanoma patients treated with immune checkpoint inhibitors (ICIs). Methods: Sixty-seven patients underwent [18F]FDG PET/CT before start of treatment (baseline PET/CT), after two cycles (interim PET/CT) and after four cycles of ICIs administration (late PET/CT). Metabolic response evaluation was based on the conventional EORTC and PERCIST criteria, as well as the newly introduced, immunotherapy-modified PERCIMT, imPERCIST5 and iPERCIST criteria. Metabolic response to immunotherapy was classified according to four response groups (complete metabolic response [CMR], partial metabolic response [PMR], stable metabolic disease [SMD], progressive metabolic disease [PMD]), and further dichotomized by response rate (responders = [CMR] + [PMR] vs. non-responders = [PMD] + [SMD]), and disease control rate (disease control = [CMR] + [PMR] + [SMD] vs. [PMD]). The spleen-to-liver SUV ratios (SLRmean, SLRmax) and bone marrow-to-liver SUV ratios (BLRmean, BLRmax) were also calculated. The results of PET/CT were correlated with patients' overall survival (OS). Results: Median patient follow up [95% CI] was 61.5 months [45.3 – 66.7 months]. On interim PET/CT, the application of the novel PERCIMT demonstrated significantly longer survival for metabolic responders, while the rest criteria revealed no significant survival differences between the different response groups. Respectively on late PET/CT, both a trend for longer OS and significantly longer OS were observed in patients responding to ICIs with metabolic response and disease control after application of various criteria, both conventional and immunotherapy-modified. Moreover, patients with lower SLRmean values demonstrated significantly longer OS. Conclusion: In patients with metastatic melanoma PET/CT-based response assessment after four ICIs cycles is significantly associated with OS after application of different metabolic criteria. The prognostic performance of the modality is also high after the first two ICIs cycles, especially with employment of novel criteria. In addition, investigation of spleen glucose metabolism may provide further prognostic information. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (mAbs) acting as immune checkpoint inhibitors (ICIs) are among the most frequently used immunotherapies in oncology. However, precision medicine approaches to adapt the treatment to the patient are still poorly exploited. Given the risk of severe adverse reactions, predicting patient eligibility for ICI therapy represents a great asset for precision medicine. Today, the extended panel of mass spectrometric approaches, accompanied by newly developed sample preparation methods is a strategy of choice for responder and non‐responder stratification on a molecular basis, and early detection of resistance. In this perspective article, we review the biodisposition of mAbs, the interest in molecular stratification of patients treated with these mAbs, and the possible analytical strategies to achieve this goal, with a major emphasis on mass spectrometric approaches. [ABSTRACT FROM AUTHOR]

Kurzzusammenfassung: Eine abnorme Aktivierung des Hedgehog-Signalwegs führt beim Basalzellkarzinom zu unkontrolliertem Tumorwachstum. Hedgehog-Signalweg-Inhibitoren sind eine wirksame Behandlungsoption für Tumoren, die durch lokale Therapien nicht mehr kontrollierbar sind. Allerdings kann die behandlungsbedingte Toxizität bei der Langzeitbehandlung zu einer Einschränkung der Lebensqualität und damit zu einer Unterbrechung oder sogar zum Abbruch der Therapie führen. Diese Übersichtsarbeit fasst wichtige und neue therapeutische Strategien für eine effektive Behandlung des lokal fortgeschrittenen Basalzellkarzinoms zusammen. Zusammenfassung: Die Erstlinientherapie für das lokal fortgeschrittene Basalzellkarzinom (laBCC) besteht aus Hedgehog-Signalweg-Inhibitoren (HHI), da sie eine gute und oft dauerhafte Wirksamkeit erzielen. Allerdings kann die Toxizität im Verlauf der Langzeitbehandlung zu einer Beeinträchtigung der Lebensqualität und in der Folge zu einer Unterbrechung oder sogar zum Abbruch der Therapie führen. Da die HHI-Therapie eine Gratwanderung zwischen Wirksamkeit, unerwünschten Ereignissen, Lebensqualität und Therapieadhärenz darstellt, haben sich zahlreiche erfolgreiche Behandlungsstrategien herausgebildet, wie z.B. Dosisreduzierung und Dosisunterbrechungen mit On-off-Behandlungsschemata oder Unterbrechungen mit Wiederaufnahme der Behandlung nach Fortschreiten der Erkrankung. Für Patienten, die eine primäre Resistenz gegen HHI aufweisen oder im Verlauf eine sekundäre Resistenz entwickeln, stehen PD-1 (Programmed Cell Death Protein 1) Inhibitoren als effektive Zweitlinienoption zur Verfügung, die mit immunbedingten Toxizitäten einhergehen können. Daher sind eine Optimierung der aktuellen Behandlungspläne, neue Wirkstoffe und Kombinationsstrategien für laBCC dringend erforderlich. In diesem Artikel wird die Behandlungssequenz für Patienten mit laBCC beschrieben und der aktuelle Stand der zugelassenen Behandlungsschemata und therapeutischen Strategien zur Optimierung der langfristigen Behandlung von laBCC zusammengefasst. [ABSTRACT FROM AUTHOR]

Background: Choosing the adequate systemic treatment for melanoma is driven by clinical parameters and personal preferences. Objective: Evaluation of the impact of disease and treatment on the daily life of patients receiving systemic therapy for melanoma. Methods: A German‐wide, cross‐sectional comparative study was conducted at 13 specialized skin cancer centres from 08/2020 to 03/2021. A questionnaire was distributed to assess patients' perception of disease and symptoms, the impact of their current treatment on quality of life (QOL) and activities, adverse events (AEs), therapeutic visits, as well as believe in and satisfaction with their current systemic melanoma treatment. Patient‐reported outcomes (PROs) were rated on a continuous numerical rating scale or selected from a given list. Results: Four hundred and fourteen patients with systemic melanoma therapy were included. 359 (87%) received immune checkpoint inhibition (ICI) and 55 (13%) targeted therapy (TT). About 1/3 of patients were adjuvantly treated, the remaining because of unresectable/metastatic melanoma. In subgroup analyses, only in the adjuvant setting, TT patients reported a significant decrease in their treatment associated QOL compared to patients with ICI (p = 0.02). Patients with TT were 1.9 times more likely to report AEs than patients with ICI, a difference being significant just for the adjuvant setting (p = 0.01). ICI treatment intervals differed significantly between adjuvant and unresectable/metastatic setting (p = 0.04), though all patients, regardless of their specific ICI drug, evaluated their treatment frequency as adequate. TT patients with dabrafenib/trametinib (n = 37) or encorafenib/binimetinib (n = 15) did not differ regarding the strain of daily pill intake. Patients older than 63 years rated various PROs better than younger patients. Conclusions: Patients evaluated their treatment mainly positively. ICI might be preferred over TT regarding QOL and patient‐reported AEs in the adjuvant setting. Older melanoma patients appeared to be less impacted by their disease and more satisfied with their treatment. [ABSTRACT FROM AUTHOR]

Aim: The recent introduction of long axial field-of-view (LAFOV) PET/CT scanners has yielded very promising results regarding image quality and sensitivity in oncological patients. We, herein, aim to determine an appropriate acquisition time range for the new long axial field of view Biograph Vision Quadra PET/CT (Siemens Healthcare) using low dose [18F]FDG activity in a group of melanoma patients. Methodology: Forty-nine melanoma patients were enrolled in the study. All patients underwent total body PET/CT from the top of the head through the feet in two bed positions (field-of-view 106 cm) after i.v. injection of 2.0 MBq/kg [18F]FDG. The PET images of the first bed position (head to upper thigh; PET-10) were reconstructed and further split into 8-min (PET-8), 6-min (PET-6), 5-min (PET-5), 4-min (PET-4), and 2-min (PET-2) duration groups. Comparisons were performed between the different reconstructed scan times with regard to the visual evaluation of the PET/CT scans using the PET-10 images as reference and by calculating the 95%-CI for the differences between different time acquisitions. Moreover, objective evaluation of PET/CT image quality was performed based on SUV calculations of tumor lesions and background, leading to calculation of liver signal-to-noise ratio (SNR), and tumor-to-background ratio (TBR). Results: A total of 60 scans were evaluated. Concerning visual analysis, 49/60 (81.7%) PET-10 scans were pathological, while the respective frequencies were 49/60 (81.7%) for PET-8 (95%-CI: − 0.0602–0.0602), 49/60 (81.7%) for PET-6 (95%-CI: − 0.0602–0.0602), 48/60 (80%) for PET-5 (95%-CI: − 0.0445–0.0886), 46/60 (76.7%) for PET-4 (95%-CI: − 0.0132–0.1370), and 45/60 (75%) for PET-2 (95%-CI: 0.0025–0.1593). In 18 PET-10 scans, the extent of metastatic involvement was very large, rendering the accurate calculation of [18F]FDG-avid tumor lesions very complicated. In the remaining 42 PET-10 scans, for which the exact calculation of tumor lesions was feasible, a total of 119 tumor lesions were counted, and the respective lesion detection rates for shorter acquisitions were as follows: 97.5% (116/119) for PET-8 (95%-CI: 0–1), 95.0% (113/119) for PET-6 (95%-CI: 0–1), 89.9% (107/119) for PET-5 (95%-CI: 0–2), 83.2% (99/119) for PET-4 (95%-CI: 1–2), and 73.9% (88/119) for PET-2 (95%-CI: 2–4). With regard to objective image quality evaluations, as a general trend, the reduction of acquisition time was associated with a decrease of liver SNR and a decrease of TBR, although in lesion-based analysis the change in TBR and tumor SUVmean values was non-significant up to 6 and 5 min acquisitions, respectively. Conclusions: In melanoma, low-dose LAFOV PET/CT imaging is feasible and can reduce the total scan time from head to upper thigh up to 5 min providing comparable diagnostic data to standard lengths of acquisition. This may have significant implications for the diagnostic work-up of patients with melanoma, given the need for true whole-body imaging in this type of cancer. [ABSTRACT FROM AUTHOR]

Objectives: Rheumatic immune-related adverse events (irAE) such as (poly)arthritis in patients undergoing immune checkpoint inhibitor (ICI) treatment pose a major clinical challenge. ICI therapy improves CD8+ T cell (CD8) function, but CD8 contributes to chronic inflammation in autoimmune arthritis (AA). Thus, we investigated whether immune functional and metabolic changes in CD8 explain the development of musculoskeletal irAE in ICI-treated patients.Methods: Peripheral CD8 obtained from ICI-treated patients with and without arthritis irAEs and from AA patients with and without a history of malignancy were stimulated in media containing 13C-labelled glucose with and without tofacitinib or infliximab. Changes in metabolism, immune-mediator release, expression of effector cell-surface molecules and inhibition of tumour cell growth were quantified.Results: CD8 from patients with irAE showed significantly lower frequency and expression of cell-surface molecule characteristic for activation, effector-functions, homing, exhaustion and apoptosis and reduced release of cytotoxic and proinflammatory immune mediators compared with CD8 from ICI patients who did not develop irAE. This was accompanied by a higher glycolytic rate and ATP production. Gene-expression analysis of pre-ICI-treated CD8 revealed several differentially expressed transcripts in patients who later developed arthritis irAEs. In vitro tofacitinib or infliximab treatment did not significantly change the immune-metabolic profile nor the capacity to release cytolytic mediators that inhibit the growth of the human lung cancer cell line H838.Conclusions: Our study shows that CD8 from ICI-treated patients who develop a musculoskeletal irAE has a distinct immune-effector and metabolic profile from those that remain irAE free. This specific irAE profile overlaps with the one observed in CD8 from AA patients and may prove useful for novel therapeutic strategies to manage ICI-induced irAEs. [ABSTRACT FROM AUTHOR]

A study was conducted to evaluate the efficacy and safety of ipilimumab as a form of treatment and survival in the case of patients with metastatic melanoma. Results indicated that ipilimumab improved the overall survival rate in the case of such patients.