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Despite the improved survival rates of patients with advanced stage melanoma since the introduction of ICIs, many patients do not have (long-term) benefit from these treatments. There is evidence that the exposome, an accumulation of host-extrinsic factors including environmental influences, could impact ICI response. Recently, a survival benefit was observed in patients with BRAF wild-type melanoma living in Denmark who initiated immunotherapy in summer as compared to winter. As the Netherlands lies in close geographical proximity to Denmark and has comparable seasonal differences, a Dutch validation cohort was established using data from our nationwide melanoma registry. In this study, we did not observe a similar seasonal difference in overall survival and are therefore unable to confirm the Danish findings. Validation of either the Dutch or Danish findings in (combined) patient cohorts from other countries would be necessary to determine whether this host-extrinsic factor influences the response to ICI-treatment.

Contains fulltext : 305394.pdf (Publisher’s version ) (Open Access), Predicting who will benefit from treatment with immune checkpoint inhibition (ICI) in patients with advanced melanoma is challenging. We developed a multivariable prediction model for response to ICI, using routinely available clinical data including primary melanoma characteristics. We used a population-based cohort of 3525 patients with advanced cutaneous melanoma treated with anti-PD-1-based therapy. Our prediction model for predicting response within 6 months after ICI initiation was internally validated with bootstrap resampling. Performance evaluation included calibration, discrimination and internal-external cross-validation. Included patients received anti-PD-1 monotherapy (n = 2366) or ipilimumab plus nivolumab (n = 1159) in any treatment line. The model included serum lactate dehydrogenase, World Health Organization performance score, type and line of ICI, disease stage and time to first distant recurrence-all at start of ICI-, and location and type of primary melanoma, the presence of satellites and/or in-transit metastases at primary diagnosis and sex. The over-optimism adjusted area under the receiver operating characteristic was 0.66 (95% CI: 0.64-0.66). The range of predicted response probabilities was 7%-81%. Based on these probabilities, patients were categorized into quartiles. Compared to the lowest response quartile, patients in the highest quartile had a significantly longer median progression-free survival (20.0 vs 2.8 months; P < .001) and median overall survival (62.0 vs 8.0 months; P < .001). Our prediction model, based on routinely available clinical variables and primary melanoma characteristics, predicts response to ICI in patients with advanced melanoma and discriminates well between treated patients with a very good and very poor prognosis.

Objective: Despite lacking clinical data, the Dutch government is considering increasing the minimum annual surgical volume per center from twenty to fifty cytoreductive surgeries (CRS) for advanced-stage ovarian cancer (OC). This study aims to evaluate whether this increase is warranted. Methods: This population-based study included all CRS for FIGO-stage IIB-IVB OC registered in eighteen Dutch hospitals between 2019 and 2022. Short-term outcomes included result of CRS, length of stay, severe complications, 30-day mortality, time to adjuvant chemotherapy, and textbook outcome. Patients were stratified by annual volume: low-volume (nine hospitals, <25), medium-volume (four hospitals, 29–37), and high-volume (five hospitals, 54–84). Descriptive statistics and multilevel logistic regressions were used to assess the (case-mix adjusted) associations of surgical volume and outcomes. Results: A total of 1646 interval CRS (iCRS) and 789 primary CRS (pCRS) were included. No associations were found between surgical volume and different outcomes in the iCRS cohort. In the pCRS cohort, high-volume was associated with increased complete CRS rates (aOR 1.9, 95%-CI 1.2–3.1, p = 0.010). Furthermore, high-volume was associated with increased severe complication rates (aOR 2.3, 1.1–4.6, 95%-CI 1.3–4.2, p = 0.022) and prolonged length of stay (aOR 2.3, 95%-CI 1.3–4.2, p = 0.005). 30-day mortality, time to adjuvant chemotherapy, and textbook outcome were not associated with surgical volume in the pCRS cohort. Subgroup analyses (FIGO-stage IIIC-IVB) showed similar results. Various case-mix factors significantly impacted outcomes, warranting case-mix adjustment. Conclusions: Our analyses do not support further centralization of iCRS for advanced-stage OC. High-volume was associated with higher complete pCRS, suggesting either a more accurate selection in these hospitals or a more aggressive approach. The

Following publication of the original article [1], the authors requested to correct the word “first-line” to “second-line” in the article title. The original article has been updated.

Item does not contain fulltext, INTRODUCTION: Sentinel lymph node biopsy (SLNB) is important for staging in patients with primary cutaneous melanoma. Did having previously undergone SLNB also affect outcomes in patients once they have progressed to metastatic melanoma in the era prior to adjuvant therapy? METHODS: Data were retrieved from the Dutch Melanoma Treatment Registry, a prospectively collected, nationwide database of patients with unresectable stage IIIC or IV (advanced) melanoma between 2012 and 2018. Melanoma-specific survival (MSS) was compared between patients with advanced cutaneous melanoma, previously treated with a wide local excision (WLE) or WLE combined with SLNB as initial treatment of their primary tumor. Cox regression analyses were used to analyze the influence of different variables on MSS. RESULTS: In total, 2581 patients were included, of whom 1412 were treated with a WLE of the primary tumor alone and 1169 in whom this was combined with SLNB. At a median follow-up of 44 months from diagnosis of advanced melanoma, MSS was significantly longer in patients who had previously undergone SLNB {median 23 months (95% confidence interval [CI] 19-29) vs. 18 months (95% CI 15-20) for patients treated with WLE alone; p = 0.002}. However, multivariate Cox regression did not identify SLNB as an independent favorable prognostic factor for MSS after diagnosis of advanced melanoma. CONCLUSION: Prior to the availability of adjuvant systemic therapy, once patients have unresectable stage IIIC or IV (advanced) melanoma, there was no difference in disease outcome for patients who were or were not previously staged with SLNB.

Item does not contain fulltext, Since the introduction of BRAF(/MEK) inhibition and immune checkpoint inhibition (ICI), the prognosis of advanced melanoma has greatly improved. Melanoma is known for its remarkably long time to first distant recurrence (TFDR), which can be decades in some patients and is partly attributed to immune-surveillance. We investigated the relationship between TFDR and patient outcomes after systemic treatment for advanced melanoma. We selected patients undergoing first-line systemic therapy for advanced melanoma from the nationwide Dutch Melanoma Treatment Registry. The association between TFDR and progression-free survival (PFS) and overall survival (OS) was assessed by Cox proportional hazard regression models. The TFDR was modeled categorically, linearly, and flexibly using restricted cubic splines. Patients received anti-PD-1-based treatment (n = 1844) or BRAF(/MEK) inhibition (n = 1618). For ICI-treated patients with a TFDR <2 years, median OS was 25.0 months, compared to 37.3 months for a TFDR >5 years (P = .014). Patients treated with BRAF(/MEK) inhibition with a longer TFDR also had a significantly longer median OS (8.6 months for TFDR <2 years compared to 11.1 months for >5 years, P = .004). The hazard of dying rapidly decreased with increasing TFDR until approximately 5 years (HR 0.87), after which the hazard of dying further decreased with increasing TFDR, but less strongly (HR 0.82 for a TFDR of 10 years and HR 0.79 for a TFDR of 15 years). Results were similar when stratifying for type of treatment. Advanced melanoma patients with longer TFDR have a prolonged PFS and OS, irrespective of being treated with first-line ICI or targeted therapy.

Item does not contain fulltext, PURPOSE: The use of Patient-Reported Outcome Measures (PROMs) for individual patient management within clinical practice is becoming increasingly important. New evidence about graphic visualization formats for PROMs scores has become available. This systematic literature review evaluated evidence for graphic visualization formats of PROMs data in clinical practice for patients and clinicians, for both individual and group level PROMs data. METHODS: Studies published between 2000 and 2020 were extracted from CINAHL, PubMed, PsychInfo, and Medline. Studies included patients ≥ 18 years old in daily clinical practice. Papers not available in English, without full-text access, or that did not specifically describe visualization of PROMs data were excluded. Outcomes were: visualization preferences; interpretation accuracy; guidance for clinical interpretation. RESULTS: Twenty-five out of 789 papers were included for final analysis. Most frequently studied formats were: bar charts, line graphs, and pie charts. Patients preferred bar charts and line graphs as these were easy and quick for retrieving information about their PROMs scores over time. Clinicians' interpretation accuracy and preferences were similar among graphic visualization formats. Scores were most often compared with patients' own previous scores; to further guide clinical interpretation, scores were compared to norm population scores. Different 'add-ons' improved interpretability for patients and clinicians, e.g. using colors, descriptions of measurement scale directionality, descriptive labels, and brief definitions. CONCLUSION: There was no predominant graphical visualization format approach in terms of preferences or interpretation accuracy for both patients and clinicians. Detailed clarification of graph content is essential. Patient-Reported Outcome Measures (PROMs) capture patients' self-reported health through the use of questionnaires. PROMs measure health related quality of life, daily functioning

Contains fulltext : 244556.pdf (Publisher’s version ) (Open Access), The COVID-19 pandemic had a severe impact on medical care. Our study aims to investigate the impact of COVID-19 on advanced melanoma care in the Netherlands. We selected patients diagnosed with irresectable stage IIIc and IV melanoma during the first and second COVID-19 wave and compared them with patients diagnosed within the same time frame in 2018 and 2019. Patients were divided into three geographical regions. We investigated baseline characteristics, time from diagnosis until start of systemic therapy and postponement of anti-PD-1 courses. During both waves, fewer patients were diagnosed compared to the control groups. During the first wave, time between diagnosis and start of treatment was significantly longer in the southern region compared to other regions (33 vs 9 and 15 days, P-value <.05). Anti-PD-1 courses were postponed in 20.0% vs 3.0% of patients in the first wave compared to the control period. Significantly more patients had courses postponed in the south during the first wave compared to other regions (34.8% vs 11.5% vs 22.3%, P-value <.001). Significantly more patients diagnosed during the second wave had brain metastases and worse performance status compared to the control period. In conclusion, advanced melanoma care in the Netherlands was severely affected by the COVID-19 pandemic. In the south, the start of systemic treatment for advanced melanoma was more often delayed, and treatment courses were more frequently postponed. During the second wave, patients were diagnosed with poorer patient and tumor characteristics. Longer follow-up is needed to establish the impact on patient outcomes.