329 research outputs found

    Внутриартериальная химиотерапия в комбинированном лечении резектабельного рака желудка с метастазами в печень

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    В Донецком областном противоопухолевом центре разработан и внедрен способ катетеризации печеночной артерии при паллиативных операциях у больных раком желудка с метастазами в печень. По данному способу пролечено 56 больных резектабельным раком желудка с метастатическим поражением печени, что позволило увеличить продолжительность и улучшить качество жизни больных.У Донецькому обласному протипухлинному центрі розроблено та впроваджено спосіб катетеризації печінкової артерії при паліативних операціях у хворих на рак шлунку з метастазами в печінку. За цим способом проліковано 56 хворих на резектабельний рак шлунку з метастатичним ураженням печінки, що дало змогу збільшити тривалість і поліпшити якість життя хворих.A method of catheterization of hepatic artery at palliative surgery in patients with gastric cancer and metastases to the liver was worked out and introduced at Donetsk Regional Antitumor Center. This method was used in 56 patients with operable cancer of the stomach with metastases to the liver, which allowed increasing the duration and improving the quality of life of the patients

    Trends in survival and costs in metastatic melanoma in the era of novel targeted and immunotherapeutic drugs

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    BACKGROUND: The objective of this study was to evaluate trends in survival and health care costs in metastatic melanoma in the era of targeted and immunotherapeutic drugs. MATERIALS AND METHODS: Data on survival and health care resource use were retrieved from the Dutch Melanoma Treatment Registry. The Kaplan–Meier method was used to estimate overall survival. Health care costs and budget impact were computed by applying unit costs to individual patient resource use. All outcomes were stratified by year of diagnosis. RESULTS: Baseline characteristics were balanced across cohort years. The percentage of patients receiving systemic treatment increased from 73% in 2013 to 90% in 2018. Patients received on average 1.85 [standard deviation (SD): 1.14] lines of treatment and 41% of patients received at least two lines of treatment. Median survival increased from 11.8 months in 2013 [95% confidence interval (CI): 10.7-13.7 months] to 21.1 months in 2018 (95% CI: 18.2 months-not reached). Total mean costs were €100 330 (SD: €103 699); systemic treatments accounted for 84% of the total costs. Costs for patients who received systemic treatment [€118 905 (SD: €104 166)] remained reasonably stable over the years even after the introduction of additional (combination of) novel drugs. From mid-2013 to 2018, the total budget impact for all patients was €452.79 million. CONCLUSION: Our study shows a gain in survival in the era of novel targeted and immunotherapeutic drugs. These novel drugs came, however, along with substantial health care costs. Further insights into the cost-effectiveness of the novel drugs are crucial for ensuring value for money in the treatment of patients with metastatic melanoma

    Sex-Based Differences in Treatment with Immune Checkpoint Inhibition and Targeted Therapy for Advanced Melanoma:A Nationwide Cohort Study

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    SIMPLE SUMMARY: Melanoma is a malignant form of skin cancer. The overall survival of patients with advanced stages of disease were initially low. Fortunately, in recent years systemic treatment with immunotherapy has prolonged survival. We set out to answer the question whether men and women with advanced melanoma differ in prognostic factors, tumor-response to immunotherapy, and treatment-related adverse events. All patients in the Netherlands were registered between July 2013 and July 2018. We showed that although clinical and tumor characteristics differ, the safety profile of immunotherapy is comparable. Furthermore, overall, a 10% survival advantage for women was seen. Following immunotherapy there was no survival difference. ABSTRACT: Recent meta-analyses show conflicting data on sex-dependent benefit following systemic treatment for advanced melanoma patients. We examined the nationwide Dutch Melanoma Treatment Registry (July 2013–July 2018), assessing sex-dependent differences in advanced melanoma patients (stage IIIC/IV) with respect to clinical characteristics, mutational profiles, treatments initiated, grade 3–4 adverse events (AEs), treatment responses, and mortality. We included 3985 patients, 2363 men (59%) and showed that although men and women with advanced melanoma differ in clinical and tumor characteristics, the safety profile of immune checkpoint inhibition (ICI) is comparable. The data suggest a 10% survival advantage for women, mainly seen in patients ≥60 years of age and patients with BRAF V600 mutant melanoma. Following ICI there was no survival difference

    Discontinuation of anti-PD-1 monotherapy in advanced melanoma:Outcomes of daily clinical practice

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    There is no consensus on the optimal treatment duration of anti-PD-1 for advanced melanoma. The aim of our study was to gain insight into the outcomes of anti-PD-1 discontinuation, the association of treatment duration with progression and anti-PD-1 re-treatment in relapsing patients. Analyses were performed on advanced melanoma patients in the Netherlands who discontinued first-line anti-PD-1 monotherapy in the absence of progressive disease (n = 324). Survival was estimated after anti-PD-1 discontinuation and with a Cox model the association of treatment duration with progression was assessed. At the time of anti-PD-1 discontinuation, 90 (28%) patients had a complete response (CR), 190 (59%) a partial response (PR) and 44 (14%) stable disease (SD). Median treatment duration for patients with CR, PR and SD was 11.2, 11.5 and 7.2 months, respectively. The 24-month progression-free survival and overall survival probabilities for patients with a CR, PR and SD were, respectively, 64% and 88%, 53% and 82%, 31% and 64%. Survival outcomes of patients with a PR and CR were similar when anti-PD-1 discontinuation was not due to adverse events. Having a PR at anti-PD-1 discontinuation and longer time to first response were associated with progression [hazard ratio (HR) = 1.81 (95% confidence interval, CI = 1.11-2.97) and HR = 1.10 (95% CI = 1.02-1.19; per month increase)]. In 17 of the 27 anti-PD-1 re-treated patients (63%), a response was observed. Advanced melanoma patients can have durable remissions after (elective) anti-PD-1 discontinuation

    A prospective study on rapid exome sequencing as a diagnostic test for multiple congenital anomalies on fetal ultrasound

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    Objective: Conventional genetic tests (quantitative fluorescent-PCR [QF-PCR] and single nucleotide polymorphism-array) only diagnose ~40% of fetuses showing ultrasound abnormalities. Rapid exome sequencing (rES) may improve this diagnostic yield, but includes challenges such as uncertainties in fetal phenotyping, variant interpretation, incidental unsolicited findings, and rapid turnaround times. In this study, we implemented rES in prenatal care to increase diagnostic yield. Methods: We prospectively studied 55 fetuses. Inclusion criteria were: (a) two or more independent major fetal anomalies, (b) hydrops fetalis or bilateral renal cysts alone, or (c) one major fetal anomaly and a first-degree relative with the same anomaly. In addition to conventional genetic tests, we performed trio rES analysis using a custom virtual gene panel of ~3850 Online Mendelian Inheritance in Man (OMIM) genes. Results: We established a genetic rES-based diagnosis in 8 out of 23 fetuses (35%) without QF-PCR or array abnormalities. Diagnoses included MIRAGE (SAMD9), Zellweger (PEX1), Walker-Warburg (POMGNT1), Noonan (PTNP11), Kabuki (KMT2D), and CHARGE (CHD7) syndrome and two cases of Osteogenesis Imperfecta type 2 (COL1A1). In six cases, rES diagnosis aided perinatal management. The median turnaround time was 14 (range 8-20) days. Conclusion: Implementing rES as a routine test in the prenatal setting is challenging but technically feasible, with a promising diagnostic yield and significant clinical relevance

    Clinical outcome of patients with metastatic melanoma of unknown primary in the era of novel therapy

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    Melanoma of unknown primary (MUP) is considered different from melanoma of known primary (MKP), and it is unclear whether these patients benefit equally from novel therapies. In the current study, characteristics and overall survival (OS) of patients with advanced and metastatic MUP and MKP were compared in the era of novel therapy. Patients were selected from the prospective nation-wide Dutch Melanoma Treatment Registry (DMTR). The following criteria were applied: diagnosis of stage IIIc unresectable or IV cutaneous MKP (cMKP) or MUP between July 2012 and July 2017 and treatment with immune checkpoint inhibition and/or targeted therapy. OS was estimated using the Kaplan-Meier method. The stratified multivariable Cox regression model was used for adjusted analysis. A total of 2706 patients were eligible including 2321 (85.8%) patients with cMKP and 385 (14.2%) with MUP. In comparative analysis, MUP patients more often presented with advanced and metastatic disease at primary diagnosis with poorer performance status, higher LDH, and central nervous system metastases. In crude analysis, median OS of cMKP or MUP patients was 12 months (interquartile range [IQR] 5 - 44) and 14 months (IQR 5 - not reached), respectively (P = 0.278). In adjusted analysis, OS in MUP patients was superior (hazard rate 0.70, 95% confidence interval 0.58-0.85; P < 0.001). As compared to patients with advanced and metastatic cMKP, MUP patients have superior survival in adjusted analysis, but usually present with poorer prognostic characteristics. In crude analysis, OS was comparable indicating that patients with MUP benefit at least equally from treatment with novel therapies

    Response to immune checkpoint inhibitors in acral melanoma:A nationwide cohort study

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    Background: Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM). Methods: We included patients with advanced AM and CM treated with first-line anti-programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry. Objective response rates, progression-free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS. Results: In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8–5.6) than patients with CM (10.1 months; 95%CI: 8.5–12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26–2.11; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15–2.06; P = 0.004) than CM. Conclusions: This study shows lower effectiveness of anti-PD -1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies

    Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients

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    BACKGROUND: Checkpoint inhibitor-induced hepatitis is an immune-related adverse event of programmed cell death protein 1 (PD-1) inhibition, cytotoxic T-lymphocyte associated 4 (CTLA-4) inhibition or the combination of both. Aim of this study was to assess whether checkpoint inhibitor-induced hepatitis is related to liver metastasis and outcome in a real-world nationwide cohort. METHODS: Data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR) was used to analyze incidence, risk factors of checkpoint inhibitor-induced grade 3–4 hepatitis and outcome. RESULTS: 2561 advanced cutaneous melanoma patients received 3111 treatments with checkpoint inhibitors between May 2012 and January 2019. Severe hepatitis occurred in 30/1620 (1.8%) patients treated with PD-1 inhibitors, in 29/1105 (2.6%) patients treated with ipilimumab and in 80/386 (20.7%) patients treated with combination therapy. Patients with hepatitis had a similar prevalence of liver metastasis compared to patients without hepatitis (32% vs. 27%; p = 0.58 for PD-1 inhibitors; 42% vs. 29%; p = 0.16 for ipilimumab; 38% vs. 43%; p = 0.50 for combination therapy). There was no difference in median progression free and overall survival between patients with and without hepatitis (6.0 months vs. 5.4 months progression-free survival; p = 0.61; 17.0 vs. 16.2 months overall survival; p = 0.44). CONCLUSION: Incidence of hepatitis in a real-world cohort is 1.8% for PD-1 inhibitor, 2.6% for ipilimumab and 20.7% for combination therapy. Checkpoint inhibitor-induced hepatitis had no relation with liver metastasis and had no negative effect on the outcome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12072-021-10151-4

    The unfavorable effects of COVID-19 on Dutch advanced melanoma care

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    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

    Safety and Efficacy of Checkpoint Inhibition in Patients With Melanoma and Preexisting Autoimmune Disease:A Cohort Study

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    BACKGROUND: Because immune checkpoint inhibition (ICI) can cause immune-related adverse events (irAEs) mimicking immunologic diseases, patients with preexisting autoimmune disease (AID) have been excluded from clinical trials. OBJECTIVE: To evaluate the safety and efficacy of ICI in patients with advanced melanoma with and without AID. DESIGN: Nationwide cohort study. SETTING: The Netherlands. PATIENTS: 4367 patients with advanced melanoma enrolled in the Dutch Melanoma Treatment Registry (DMTR) between July 2013 and July 2018 and followed through February 2019. MEASUREMENTS: Patient, clinical, and treatment characteristics; irAEs of grade 3 or higher; treatment response; and survival. RESULTS: A total of 415 patients (9.5%) had AID, categorized as rheumatologic AID (n = 227), endocrine AID (n = 143), inflammatory bowel disease (IBD) (n = 55), or "other" (n = 8). Of these, 228 patients (55%) were treated with ICI (vs. 2546 [58%] without AID); 87 were treated with anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), 187 with anti-programmed cell death 1 (PD-1), and 34 with the combination. The incidences of irAEs of grade 3 or higher in patients with AID were 30% (95% CI, 21% to 41%) with anti-CTLA-4, 17% (CI, 12% to 23%) with anti-PD-1, and 44% (CI, 27% to 62%) with combination therapy; for patients without AID, the incidences were 30% (CI, 27% to 33%) (n = 916), 13% (CI, 12% to 15%) (n = 1540), and 48% (CI, 43% to 53%) (n = 388), respectively. Patients with AID more often discontinued anti-PD-1 treatment because of toxicity than patients without AID (17% [CI, 12% to 23%] vs. 9% [CI, 8% to 11%]). Patients with IBD were more prone to anti-PD-1-induced colitis (6 / 31 = 19% [CI, 7% to 37%]) than patients with other AIDs (3% [CI, 0% to 6%]) and patients without AID (2% [CI, 2% to 3%]). The objective response rate was similar in patients with versus without AID who were treated with anti-CTLA-4 (10% [CI, 5% to 19%] vs. 16% [CI, 14% to 19%]), anti-PD-1 (40% [CI, 33% to 47%] vs. 44% [CI, 41% to 46%]), or the combination (39% [CI, 20% to 59%] vs. 43% [CI, 38% to 49%]). Survival did not differ between patients with and those without AID (median, 13 months [CI, 10 to 16 months] vs. 14 months [CI, 13 to 15 months]). LIMITATION: Information was limited on AID severity and immunosuppressive treatment. CONCLUSION: Response to ICI with anti-CTLA-4, anti-PD-1, or their combination for advanced melanoma and overall incidence of any irAEs of grade 3 or higher were similar in patients with and without preexisting AID. However, severe colitis and toxicity requiring early discontinuation of treatment occurred more frequently among patients with preexisting IBD, warranting close follow-up. PRIMARY FUNDING SOURCE: The Netherlands Organization for Health Research and Development
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