21 results on '"V Aedo Lopez"'
Search Results
2. 1686P Selecting patient-reported outcomes to monitor symptomatic toxicities of immune-checkpoint inhibitors: A Delphi study
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J.B.A.G. Haanen, G. Spurrier-Bernard, Alfredo Addeo, Anne Rogiers, S. Colomer-Lahiguera, Lærke Kjær Tolstrup, Olivier Michielin, V Aedo Lopez, Bart Neyns, Helle Pappot, Sandra A. Mitchell, Sandrine Aspeslagh, N-N. Mederos-Alfonso, A.M.D.S. Lopes, and Manuela Eicher
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Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Immune checkpoint inhibitors ,Delphi method ,Medicine ,Hematology ,business - Published
- 2021
3. Real life use of talimogene laherparepvec in melanoma in centers in Austria and Switzerland
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F. Weihsengruber, M. Karasek, J. Kofler, Peter Koelblinger, Christoph Hoeller, Erika Richtig, Christine Hafner, J.M. Ressler, Olivier Michielin, V Aedo Lopez, H. Kehrer, and Lukas Koch
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0301 basic medicine ,medicine.medical_specialty ,business.industry ,Melanoma ,General surgery ,Complete remission ,Hematology ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Tolerability ,Response Evaluation Criteria in Solid Tumors ,030220 oncology & carcinogenesis ,Cohort ,Medicine ,Chills ,Stage (cooking) ,medicine.symptom ,business ,Talimogene laherparepvec - Abstract
Background Talimogene Laherparepvec (TVEC), a genetically modified GM-CSF expressing HSV1 Virus that preferentially replicates in tumor cells is approved in Europe for use in melanoma patients with injectable metastatic lesions in stage III-IVM1a. Approval was based on the OPTIM study which did also include patients with distant metastases and demonstrated a ORR of 40.5% and a CR rate of 16.6%. The aim of this study was to assess the outcome of melanoma patients treated with TVEC in a real life clinical setting outside of clinical studies. Methods To this aim a retrospective chart review in 7 melanoma centers in Austria and 1 center in Switzerland was conducted and anonymized data on disease stage, treatment duration, treatment response by investigator assessment following RECIST 1.1, tolerability as well as data on follow up therapies was collected. Results A total of 62 patients received TVEC since December of 2016. The majority of patients were AJCC stage IIIB and IIIC. Two patients with stage IV M1b and M1d who had complete control of their distant metastases and a locoregional progression were treated in parallel with a PD-1 antibody in one case and in parallel with a BRAF/MEK inhibitor combination in the other. In 3 other cases TVEC was used in combination with a PD-1 inhibitor as first-line of therapy. The median number of intralesional injection cycles was 11. The ORR was 67,7%; 50% of patients achieved a complete remission. 7 of 31 patients with a CR had a subsequent progression, 4 with distant and 3 with locoregional metastases. The main side effects observed were fever and chills. Conclusions In this real life cohort treatment of TVEC shows a high overall and complete remission rate with the majority of complete responses being durable. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure C. Hoeller: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. J.M. Ressler: Speaker Bureau / Expert testimony: Amgen. H. Kehrer: Advisory / Consultancy: Amgen. P. Koelblinger: Advisory / Consultancy: Amgen. F. Weihsengruber: Advisory / Consultancy: Amgen. J. Kofler: Advisory / Consultancy: Amgen. E. Richtig: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. O.A. Michielin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. C. Hafner: Advisory / Consultancy: Amgen. All other authors have declared no conflicts of interest.
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- 2019
4. Adjuvant pertuzumab (PER) for HER2-positive early stage breast cancer (eBC): A Swiss experience
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J.P. Zurcher, Alexandre Bodmer, Athina Stravodimou, Khalil Zaman, and V. Aedo Lopez
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,medicine.disease ,Breast cancer ,Internal medicine ,medicine ,Pertuzumab ,Stage (cooking) ,business ,Adjuvant ,medicine.drug - Published
- 2018
5. A pharmacist-led interprofessional medication adherence program improved adherence to oral anticancer therapies: The OpTAT randomized controlled trial.
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Bandiera C, Cardoso E, Locatelli I, Zaman K, Diciolla A, Digklia A, Stravodimou A, Cristina V, Aedo-Lopez V, Dolcan A, Sarivalasis A, Bouchaab H, Pasquier J, Dotta-Celio J, Peters S, Wagner D, Csajka C, and Schneider MP
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- Humans, Female, Male, Middle Aged, Aged, Administration, Oral, Neoplasms drug therapy, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors administration & dosage, Medication Adherence, Pharmacists, Antineoplastic Agents therapeutic use, Antineoplastic Agents administration & dosage, Quality of Life
- Abstract
Background: Oral anticancer therapies such as protein kinase inhibitors (PKIs) are increasingly prescribed in cancer care. We aimed to evaluate the impact of a pharmacist-led interprofessional medication adherence program (IMAP) on patient implementation (dosing history), persistence (time until premature cessation of the treatment) and adherence to 27 PKIs prescribed for various solid cancers, as well as the impact on patients' beliefs about medicines (BAM) and quality of life (QoL)., Methods: Patients (n = 118) were randomized 1:1 into two arms. In the intervention arm, pharmacists supported patient adherence through monthly electronic and motivational feedback, including educational, behavioral and affective components, for 12 months. The control arm received standard care plus EM without intervention. All PKIs were delivered in electronic monitors (EMs). Medication implementation and adherence were compared between groups using generalized estimating equation models, in which relevant covariables were included; persistence was compared with Kaplan‒Meier curves. Information on all treatment interruptions was compiled for the analysis. Questionnaires to evaluate BAM and QoL were completed among patients who refused and those who accepted to participate at inclusion, 6 and 12 months post-inclusion or at study exit., Results: Day-by-day PKI implementation was consistently higher and statistically significant in the intervention arm (n = 58) than in the control arm (n = 60), with 98.1% and 95.0% (Δ3.1%, 95% confidence interval (CI) of the difference 2.5%; 3.7%) implementation at 6 months, respectively. The probabilities of persistence and adherence were not different between groups, and no difference was found between groups for BAM and QoL scores. No difference in BAM or QoL was found among patients who refused versus those who participated. The intervention benefited mostly men (at 6 months, Δ4.7%, 95% CI 3.4%; 6.0%), those younger than 60 years (Δ4.0%, 95% CI 3.1%; 4.9%), those who had initiated PKI more than 60 days ago before inclusion (Δ4.5%, 95% CI 3.6%; 5.4%), patients without metastasis (Δ4.5%, 95% CI 3.4%; 5.7%), those who were diagnosed with metastasis more than 2 years ago (Δ5.3%, 95% CI 4.3%; 6.4%) and those who had never used any adherence tool before inclusion (Δ3.8%, 95% CI 3.1%; 4.5%)., Conclusions: The IMAP, led by pharmacists in the context of an interprofessional collaborative practice, supported adherence, specifically implementation, to PKIs among patients with solid cancers. To manage adverse drug events, PKI transient interruptions are often mandated as part of a strategy for treatment and adherence optimization according to guidelines. Implementation of longer-term medication adherence interventions in the daily clinic may contribute to the improvement of progression-free survival., Trial Registration: ClinicalTrials.gov NCT04484064., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bandiera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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6. Testing a Model of Care for Patients on Immune Checkpoint Inhibitors Based on Electronic Patient-Reported Outcomes: Protocol for a Randomized Phase II Controlled Trial.
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da Silva Lopes AM, Colomer-Lahiguera S, Darnac C, Giacomini S, Bugeia S, Gutknecht G, Spurrier-Bernard G, Cuendet M, Muet F, Aedo-Lopez V, Mederos N, Michielin O, Addeo A, Latifyan S, and Eicher M
- Abstract
Background: Management of severe symptomatic immune-related adverse events (IrAEs) related to immune checkpoint inhibitors (ICIs) can be facilitated by timely detection. As patients face a heterogeneous set of symptoms outside the clinical setting, remotely monitoring and assessing symptoms by using patient-reported outcomes (PROs) may result in shorter delays between symptom onset and clinician detection., Objective: We assess the effect of a model of care for remote patient monitoring and symptom management based on PRO data on the time to detection of symptomatic IrAEs from symptom onset. The secondary objectives are to assess its effects on the time between symptomatic IrAE detection and intervention, IrAE grade (severity), health-related quality of life, self-efficacy, and overall survival at 6 months., Methods: For this study, 198 patients with cancer receiving systemic treatment comprising ICIs exclusively will be recruited from 2 Swiss university hospitals. Patients are randomized (1:1) to a digital model of care (intervention) or usual care (control group). Patients are enrolled for 6 months, and they use an electronic app to complete weekly Functional Assessment of Cancer Therapy-General questionnaire and PROMIS (PROs Measurement Information System) Self-Efficacy to Manage Symptoms questionnaires. The intervention patient group completes a standard set of 37 items in a weekly PROs version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaire, and active symptoms are reassessed daily for the first 3 months by using a modified 24-hour recall period. Patients can add items from the full PRO-CTCAE item library to their questionnaire. Nurses call patients in the event of new or worsening symptoms and manage them by using a standardized triage algorithm based on the United Kingdom Oncology Nursing Society 24-hour triage tool. This algorithm provides guidance on deciding if patients should receive in-person care, if monitoring should be increased, or if self-management education should be reinforced., Results: The Institut Suisse de Recherche Expérimentale sur le Cancer Foundation and Kaiku Health Ltd funded this study. Active recruitment began since November 2021 and is projected to conclude in November 2023. Trial results are expected to be published in the first quarter of 2024 and will be disseminated through publications submitted at international scientific conferences., Conclusions: This trial is among the first trials to use PRO data to directly influence routine care of patients treated with ICIs and addresses some limitations in previous studies. This trial collects a wider spectrum of self-reported symptom data daily. There are some methodological limitations brought by changes in evolving treatment standards for patients with cancer. This trial's results could entail further academic discussions on the challenges of diagnosing and managing symptoms associated with treatment remotely by providing further insights into the burden symptoms represent to patients and highlight the complexity of care procedures involved in managing symptomatic IrAEs., Trial Registration: ClinicalTrials.gov NCT05530187; https://www.clinicaltrials.gov/study/NCT05530187., International Registered Report Identifier (irrid): DERR1-10.2196/48386., (©André Manuel da Silva Lopes, Sara Colomer-Lahiguera, Célia Darnac, Stellio Giacomini, Sébastien Bugeia, Garance Gutknecht, Gilliosa Spurrier-Bernard, Michel Cuendet, Fanny Muet, Veronica Aedo-Lopez, Nuria Mederos, Olivier Michielin, Alfredo Addeo, Sofiya Latifyan, Manuela Eicher. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 18.10.2023.)
- Published
- 2023
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7. Development of an eHealth-enhanced model of care for the monitoring and management of immune-related adverse events in patients treated with immune checkpoint inhibitors.
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da Silva Lopes AM, Colomer-Lahiguera S, Darnac C, Giacomini S, Bugeia S, Gutknecht G, Spurrier-Bernard G, Aedo-Lopez V, Mederos N, Latifyan S, Addedo A, Michielin O, and Eicher M
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- Humans, Immune Checkpoint Inhibitors, Medical Oncology, Patient Reported Outcome Measures, Mobile Applications, Telemedicine methods
- Abstract
Purpose: The use of electronic patient-reported outcome (ePRO) data in routine care has been tied to direct patient benefits such as improved quality of care and symptom control and even overall survival. The modes of action behind such benefits are seldom described in detail. Here, we describe the development of a model of care leveraging ePRO data to monitor and manage symptoms of patients treated with immune checkpoint inhibitors., Methods: Development was split into four stages: (1) identification of an underlying theoretical framework, (2) the selection of an ePRO measure (ePROM), (3) the adaptation of an electronic application to collect ePRO data, and (4) the description of an ePRO-oriented workflow. The model of care is currently evaluated in a bicentric longitudinal randomized controlled phase II trial, the IePRO study., Results: The IePRO model of care is grounded in the eHealth Enhanced Chronic Care Model. Patients are prompted to report symptoms using an electronic mobile application. Triage nurses are alerted, review the reported symptoms, and contact patients in case of a new or worsening symptom. Nurses use the UKONS 24-hour telephone triage tool to issue patient management recommendations to the oncology team. Adapted care coordinating procedures facilitate team collaboration and provide patients with timely feedback., Conclusion: This report clarifies how components of care are created and modified to leverage ePRO to enhance care. The model describes a workflow that enables care teams to be proactive and provide patients with timely, multidisciplinary support to manage symptoms., (© 2023. The Author(s).)
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- 2023
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8. Response and Resistance to Trametinib in MAP2K1-Mutant Triple-Negative Melanoma.
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Krebs FS, Moura B, Missiaglia E, Aedo-Lopez V, Michielin O, Tsantoulis P, Bisig B, Trimech M, Zoete V, and Homicsko K
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- Male, Humans, Pyridones therapeutic use, Pyrimidinones therapeutic use, Protein Kinase Inhibitors pharmacology, Mitogen-Activated Protein Kinase Kinases genetics, Proto-Oncogene Proteins B-raf genetics, Mutation, MAP Kinase Kinase 1 genetics, Skin Neoplasms genetics, Melanoma genetics
- Abstract
The development of targeted therapies for non- BRAF p.Val600-mutant melanomas remains a challenge. Triple wildtype (TWT) melanomas that lack mutations in BRAF , NRAS , or NF1 form 10% of human melanomas and are heterogeneous in their genomic drivers. MAP2K1 mutations are enriched in BRAF -mutant melanoma and function as an innate or adaptive resistance mechanism to BRAF inhibition. Here we report the case of a patient with TWT melanoma with a bona fide MAP2K1 mutation without any BRAF mutations. We performed a structural analysis to validate that the MEK inhibitor trametinib could block this mutation. Although the patient initially responded to trametinib, he eventually progressed. The presence of a CDKN2A deletion prompted us to combine a CDK4/6 inhibitor, palbociclib, with trametinib but without clinical benefit. Genomic analysis at progression showed multiple novel copy number alterations. Our case illustrates the challenges of combining MEK1 and CDK4/6 inhibitors in case of resistance to MEK inhibitor monotherapy.
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- 2023
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9. Adherence to the CDK 4/6 Inhibitor Palbociclib and Omission of Dose Management Supported by Pharmacometric Modelling as Part of the OpTAT Study.
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Bandiera C, Locatelli I, Courlet P, Cardoso E, Zaman K, Stravodimou A, Dolcan A, Sarivalasis A, Zurcher JP, Aedo-Lopez V, Dotta-Celio J, Peters S, Guidi M, Wagner AD, Csajka C, and Schneider MP
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The cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) palbociclib is administered orally and cyclically, causing medication adherence challenges. We evaluated components of adherence to palbociclib, its relationship with pharmacokinetics (PK), and drug-induced neutropenia. Patients with metastatic breast cancer (MBC) receiving palbociclib, delivered in electronic monitors (EM), were randomized 1:1 to an intervention and a control group. The intervention was a 12-month interprofessional medication adherence program (IMAP) along with monthly motivational interviews by a pharmacist. Implementation adherence was compared between groups using generalized estimating equation models, in which covariates were included. Model-based palbociclib PK and neutrophil profiles were simulated under real-life implementation scenarios: (1) optimal, (2) 2 doses omitted and caught up at cycle end. At 6 months, implementation was slightly higher and more stable in the intervention (n = 19) than in the control (n = 19) group, 99.2% and 97.3% (Δ1.95%, 95% CI 1.1−2.9%), respectively. The impact of the intervention was larger in patients diagnosed with MBC for >2 years (Δ3.6%, 95% CI 2.1−5.4%), patients who received >4 cycles before inclusion (Δ3.1%, 95% CI 1.7−4.8%) and patients >65 (Δ2.3%, 95% CI 0.8−3.6%). Simulations showed that 25% of patients had neutropenia grade ≥3 during the next cycle in scenario 1 versus 30% in scenario 2. Education and monitoring of patient CDK4/6i cycle management and adherence along with therapeutic drug monitoring can help clinicians improve prescription and decrease toxicity.
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- 2023
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10. Neoadjuvant Immunotherapy in Melanoma: The Paradigm Shift.
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Hieken TJ, Kreidieh F, Aedo-Lopez V, Block MS, McArthur GA, and Amaria RN
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- Humans, Neoadjuvant Therapy, Immunotherapy, Melanoma, Cutaneous Malignant, Melanoma drug therapy, Skin Neoplasms
- Abstract
Clinical stage III melanoma, defined as resectable RECIST measurable nodal disease with or without in-transit metastases, represents approximately 15% of new melanoma diagnoses every year with additional cases presenting as recurrent nodal disease following previous treatment of a primary melanoma. The standard of care for patients with resectable clinical stage III melanoma is surgical resection, consisting of therapeutic lymph node dissection and/or resection of in-transit disease and consideration of adjuvant systemic therapy and occasionally adjuvant radiation. These patients have high rates of regional recurrence and progression to metastatic disease postsurgery, highlighting the need for better treatment options. With the success of immune checkpoint inhibitors in both the adjuvant and metastatic settings, the use of these agents in the neoadjuvant setting has been an emerging area of research interest. In this chapter, we will discuss the rationale for neoadjuvant immunotherapy; review impactful clinical trials; and define response monitoring, surgical considerations, emerging therapies, and unanswered questions for neoadjuvant therapy as a recent paradigm shift in the management of clinical stage III melanoma.
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- 2023
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11. Estimated Costs of the Ipilimumab-Nivolumab Therapy and Related Adverse Events in Metastatic Melanoma.
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Gautron Moura B, Gerard CL, Testart N, Caikovski M, Wicky A, Aedo-Lopez V, Berthod G, Homicsko K, Prior JO, Dromain C, Kandalaft LE, Cuendet MA, and Michielin O
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Combined ipilimumab and nivolumab significantly improve outcomes in metastatic melanoma patients but bear an important financial impact on the healthcare system. Here, we analyze the treatment costs, focusing on irAE. We conducted a retrospective analysis of 62 melanoma patients treated with ipilimumab-nivolumab at the Lausanne University Hospital between 1 June 2016 and 31 August 2019. The frequency of irAEs and outcomes were evaluated. All melanoma-specific costs were analyzed from the first ipilimumab-nivolumab dose until the therapy given subsequently or death. A total of 54/62 (87%) patients presented at least one irAE, and 31/62 (50%) presented a grade 3-4 irAE. The majority of patients who had a complete response 12/14 (86%) and 21/28 (75%) of overall responders presented a grade 3-4 toxicity, and there were no responses in patients without toxicity. Toxicity costs represented only 3% of the total expenses per patient. The most significant contributions were medication costs (44%) and disease costs (39%), mainly disease-related hospitalization costs, not toxicity-related. Patients with a complete response had the lowest global median cost per week of follow up (EUR 2425) and patients who had progressive disease (PD), the highest one (EUR 8325). Except for one patient who had a Grade 5 toxicity (EUR 6043/week), we observe that less severe toxicity grades (EUR 9383/week for Grade 1), or even the absence of toxicity (EUR 9922/week), are associated with higher median costs per week (vs. EUR 3266/week for Grade 4 and EUR 2850/week for Grade 3). The cost of toxicities was unexpectedly low compared to the total costs, especially medication costs. Patients with higher toxicity grades had better outcomes and lower total costs due to treatment discontinuation.
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- 2022
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12. Gender profile of principal investigators in a large academic clinical trials group.
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Luong VTT, Ho C, Aedo-Lopez V, and Segelov E
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Introduction: Gender equity in medicine has become a significant topic of discussion due to consistently low female representation in academia and leadership roles. Gender imbalance directly affects patient care. This study examined the gender and craft group of the Principal Investigators (PI) of clinical trials run by the Australasian Gastro-Intestinal Trials Group (AGITG)., Methods: Publicly available data was obtained from the AGITG website. Trials were divided into upper, lower gastrointestinal cancer, miscellaneous (neuroendocrine and gastrointestinal stromal tumours). Where multiple PIs were listed, all were counted. Craft group was assigned as surgical, medical, radiation oncology or other., Results: There were 69 trials with 89 PI, where 52 trials were represented exclusively by male PIs. Of all PIs, 18 were women (20.2%); all were medical oncologists. Prior to 2005, all PIs were male. The craft group distribution of PIs was: 79% medical oncologists, 12% surgical oncologists, 8% radiation oncologist, 1% nuclear medicine physicians. Regarding trials with multiple PI's, there were 19 in total. Of these, 11 had only male PIs, which included 5 surgeons. Females were more likely to be a co-PI (42%) as opposed to sole PI (18%). There was no gender policy publicly available on the AGITG website., Conclusions: There is a low percentage of female PIs in academic oncology trials in the portfolio of this large international trials group. No trial was led by a female surgical or radiation oncologist. There is a need to understand the reasons driving the disparity so that specific strategies can be put in place., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Luong, Ho, Aedo-Lopez and Segelov.)
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- 2022
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13. Adult Wilms tumour: A case report.
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Mounnarath ET, Zwieky W, Aedo-Lopez V, Fazli O, and Sheridan BJ
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The Wilms tumour is the fourth most common paediatric malignancy. On the contrary, it is extremely rare in adults as it accounts for less than 1% of all renal malignancies. This scarcity of cases placed a significant challenge in generating evidence-based treatment. Hence, treatment of adult Wilms considerably varies between centres. Standardised guidelines based on international expert consensus for adults have been introduced to help steer management. However, reporting patient outcomes remains limited. In this article, a case study will be presented. This includes modalities of treatment, side effects, tolerability, and outcome. A 40-year-old gentleman with histology consistent with the Wilms tumour received adjuvant chemotherapy according to the UMBRELLA SIOP2016 adult guidelines. Such guidelines were originally adapted from the International Society of Paediatric Oncology protocol. The patient underwent eight cycles of vincristine, actinomycin-D, and doxorubicin and concurrent radiation therapy. Use of the UMBRELLA SIOP2016 adult guideline was shown effective at treating the Wilms tumour in this adult case with minimal severe toxicity. Ongoing follow-up is still needed to determine the long-term effects and prognosis of the patient., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)
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- 2022
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14. Safety and Efficacy of Ipilimumab plus Nivolumab and Sequential Selective Internal Radiation Therapy in Hepatic and Extrahepatic Metastatic Uveal Melanoma.
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Aedo-Lopez V, Gérard CL, Boughdad S, Gautron Moura B, Berthod G, Digklia A, Homicsko K, Schaefer N, Duran R, Cuendet MA, and Michielin O
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To assess the safety and efficacy of ipilimumab plus nivolumab around selective internal radiation therapy (SIRT) in patients with metastatic uveal melanoma (mUM). We present a retrospective, single center study of 32 patients with mUM divided into two groups based on the treatment received between April 2013 and April 2021. The SIRT_IpiNivo cohort was treated with Yttrium-90 microspheres and ipilimumab plus nivolumab before or after the SIRT ( n = 18). The SIRT cohort underwent SIRT but did not receive combined immunotherapy with ipilimumab plus nivolumab ( n = 14). Twelve patients (66.7%) of the SIRT_IpiNivo arm received SIRT as first-line treatment and six patients (33.3%) received ipilimumab plus nivolumab prior to SIRT. In the SIRT group, seven patients (50.0%) received single-agent immunotherapy. One patient treated with combined immunotherapy 68 months after the SIRT was included in this group. At the start of ipilimumab plus nivolumab, 94.4% ( n = 17) presented hepatic metastases and 72.2% ( n = 13) had extra liver disease. Eight patients (44.4%) of the SIRT_IpiNivo group experienced grade 3 or 4 immune related adverse events, mainly colitis and hepatitis. Median overall survival from the diagnosis of metastases was 49.6 months (95% confidence interval (CI); 24.1-not available (NA)) in the SIRT_IpiNivo group compared with 13.6 months (95% CI; 11.5-NA) in the SIRT group (log-rank p -value 0.027). The presence of extra liver metastases at the time of SIRT, largest liver lesion more than 8 cm (M1c) and liver tumor volume negatively impacted the survival. This real-world cohort suggests that a sequential treatment of ipilimumab plus nivolumab and SIRT is a well-tolerated therapeutic approach with promising survival rates.
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- 2022
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15. Patient-reported outcomes for monitoring symptomatic toxicities in cancer patients treated with immune-checkpoint inhibitors: A Delphi study.
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Da Silva Lopes AM, Colomer-Lahiguera S, Mederos Alfonso N, Aedo-Lopez V, Spurrier-Bernard G, Tolstrup LK, Pappot H, Aspeslagh S, Rogiers A, Neyns B, Haanen JB, Mitchell SA, Addeo A, Michielin O, and Eicher M
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- Consensus, Delphi Technique, Drug-Related Side Effects and Adverse Reactions immunology, Humans, Neoplasms immunology, Prospective Studies, Severity of Illness Index, Drug Monitoring standards, Drug-Related Side Effects and Adverse Reactions diagnosis, Immune Checkpoint Inhibitors adverse effects, Neoplasms drug therapy, Patient Reported Outcome Measures
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Background: Immune-related adverse events (IrAEs) associated with the use of immune checkpoint inhibitors (ICIs) may not be fully covered by existing measures like the PRO-CTCAE™. Selecting PRO-CTCAE™ items for monitoring symptomatic adverse events is hindered by the heterogeneity and complexity of IrAEs, and no standardised selection process exists. We aimed to reach expert consensus on the PRO-CTCAE™ symptom terms relevant for cancer patients receiving ICIs and to gather preliminary expert opinions about additional symptom terms reflecting ICI symptomatic toxicities. Additionally, we gathered expert consensus about a core set of priority symptom terms for prospective surveillance and monitoring., Design: This Delphi study involved an international panel of experts (n = 6 physicians; n = 3 nurses, n = 1 psychiatrist and n = 1 patient advocates). Experts prioritised the relevance and importance of symptom terms to monitor in patients treated with ICIs., Results: Experts reached a consensus on the relevance of all (n = 80) PRO-CTCAE™ Symptom Terms. Consensus on the importance of these symptom terms for prospective monitoring in patients receiving ICIs was reached for 81% (n = 65) of these terms. Additional symptoms terms (n = 56) were identified, with a consensus that 84% (47/56) of these additional symptom terms should also be considered when monitoring symptomatic IrAEs., Conclusion: This study identified a prioritised list of symptom terms for prospective surveillance for symptomatic IrAEs in patients receiving ICI treatment. Our results indicate the need to strengthen the validity of PRO measures used to monitor patients receiving ICIs. While these results provided some support for the content validity of the PRO CTCAE™ and resulted in a preliminary set of salient symptomatic adverse events related to the use of ICIs, broader international agreement and patient involvement are needed to further validate our initial findings., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: Da Silva Lopes reports grants from Fondation Recherche Cancer (ISREC) Foundation, during the conduct of the study; Dr. Colomer-Lahiguera reports grants from Fondation Recherche Cancer (ISREC) Foundation, during the conduct of the study; Dr. Mederos has nothing to disclose; Dr. Aedo-Lopez has nothing to disclose; Dr. Spurrier-Bernard reports grants from MSD France, grants from Novartis, personal fees from Bayer, other from MPNE, WECAN, outside the submitted work; Dr. Tolstrup has nothing to disclose; Dr. Pappot has nothing to disclose; Dr. Aspeslagh reports and has received speaker fees from Roche, BMS, Novartis, Merck and Pfizer in the last 36 months; Dr. Rogiers has nothing to disclose; Dr. Neyns reports grants and personal fees from Novartis, grants and personal fees from Pfizer, personal fees from BMS, personal fees from MSD, outside the submitted work; Dr. Haanen reports grants and other from BMS, grants and other from MSD, grants and other from Novartis, grants and other from BioNTech, other from Achilles Tx, grants and other from Amgen, other from GSK, other from Immunocore, other from Ipsen, other from Merck Serono, other from Molecular Partners, personal fees from Neogene Tx, other from Pfizer, other from Roche/Genentech, other from Sanofi, other from Seattle Genetics, other from Third Rock Ventures, other from Vaximm, outside the submitted work; Dr. Mitchell has nothing to disclose; Dr. Addeo reports personal fees from BMS, personal fees from MSD, personal fees from AstraZeneca, personal fees from Pfizer, personal fees from Roche, personal fees from Boehringer, personal fees from Ely-Lilly, outside the submitted work; Dr. Michielin reports grants and personal fees from BMS, grants and personal fees from MSD, personal fees from Roche, personal fees from Novartis, grants and personal fees from Pierre-Fabre, grants and personal fees from Amgen, personal fees from GSL, grants from Merck, outside the submitted work; Dr. Eicher reports grants from Fondation Recherche Cancer ISREC, during the conduct of the study; grants and personal fees from Roche, grants and personal fees from BMS, grants from Kaiku Health, personal fees from VIFOR, outside the submitted work., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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16. Real-life use of talimogene laherparepvec (T-VEC) in melanoma patients in centers in Austria, Switzerland and Germany.
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Ressler JM, Karasek M, Koch L, Silmbrod R, Mangana J, Latifyan S, Aedo-Lopez V, Kehrer H, Weihsengruber F, Koelblinger P, Posch C, Kofler J, Michielin O, Richtig E, Hafner C, and Hoeller C
- Subjects
- Adult, Aged, Aged, 80 and over, Biological Products adverse effects, Disease Progression, Europe, Female, Herpesvirus 1, Human immunology, Humans, Male, Melanoma immunology, Melanoma pathology, Middle Aged, Neoplasm Staging, Oncolytic Viruses immunology, Retrospective Studies, Skin Neoplasms immunology, Skin Neoplasms pathology, Skin Neoplasms virology, Time Factors, Treatment Outcome, Biological Products therapeutic use, Herpesvirus 1, Human pathogenicity, Melanoma therapy, Oncolytic Viruses pathogenicity, Skin Neoplasms therapy
- Abstract
Background: Talimogene laherparepvec (T-VEC) is a licensed therapy for use in melanoma patients of stage IIIB-IVM1a with injectable, unresectable metastatic lesions in Europe. Approval was based on the Oncovex Pivotal Trial in Melanoma study, which also included patients with distant metastases and demonstrated an overall response rate (ORR) of 40.5% and a complete response (CR) rate of 16.6%., Objectives: The aim of this study was to assess the outcome of melanoma patients treated with T-VEC in a real-life clinical setting., Methods: Based on data from 10 melanoma centers in Austria, Switzerland and southern Germany, we conducted a retrospective chart review, which included 88 patients (44 male, 44 female) with a median age of 72 years (range 36-95 years) treated with T-VEC during the period from May 2016 to January 2020., Results: 88 patients fulfilled the inclusion criteria for analysis. The ORR was 63.7%. 38 patients (43.2%) showed a CR, 18 (20.5%) had a partial response, 8 (9.1%) had stable disease and 24 (27.3%) patients had a progressive disease. The median treatment period was 19 weeks (range: 1-65), an average of 11 doses (range: 1-36) were applied. 39 (45.3%) patients developed adverse events, mostly mild, grade I (64.1%)., Conclusion: This real-life cohort treatment with T-VEC showed a high ORR and a large number of durable CRs., Competing Interests: Competing interests: JMR received project funding by Amgen, Speakers bureau of Amgen and Bristol Myers Squibb and travel support from Bristol Myers Squibb, Pierre Fabre outside of the submitted work. JMR has intermittent project focused consultant or advisory relationships with Merck/Pfizer, Merck Sharp & Dohme, Amgen, Novartis, Bristol Myers and Squibb and Pierre Fabre and has received travel support from Ultrasun, L’ oreal, Merck Sharp & Dohme, Bristol Myers and Squibb and Pierre Fabre outside of the submitted work. PK has received honoraria for travel/congress support and consulting/advisory roles for Roche, Bristol Myers Squibb (BMS), Merck Sharp and Dome (MSD), Novartis, Amgen, Pierre Fabre and Sanofi Aventis unrelated to the submitted work. ER Honoraria, consulting or advisory role: Amgen, Bayer, Bristol Myers Squibb, MSD, Merck, Novartis, Pierre Fabre, Roche, SanofiSpeakers'bureau: Amgen, Bristol Myers Squibb, MSD, Merck, Novartis, Pierre Fabre, SanofiResearch funding site PI: Amgen, Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, Roche Research funding steering committee: Novartistravel, accommodations, expenses: Amgen, Bristol Myers Squibb, MSD, Merck, Novartis, Pierre Fabre, Roche, Sanofi. CH is associated with consulting or advisory role for Bristol-Myers Squibb, Amgen, Merck Sharp and Dohme, Novartis, Pierre Fabre and Speaker’s bureau of Bristol-Myers Squibb, Amgen, Merck Sharp & Dohme, Pierre Fabre and received travel/accommodations/expenses from Amgen, Bristol-Myers Squibb, Merck Sharp and Dohme, Pierre Fabre.C.HO. is associated with advisory role for Advisory Boards: Amgen, Astra Zeneca, BMS, Inzyte, MSD, Novartis, Pierre Fabre, Roche and Speakers bureau of Amgen, BMS, MSD, Novartis, Roche., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2021
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17. Trametinib Induces the Stabilization of a Dual GNAQ p.Gly48Leu- and FGFR4 p.Cys172Gly-Mutated Uveal Melanoma. The Role of Molecular Modelling in Personalized Oncology.
- Author
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Krebs FS, Gérard C, Wicky A, Aedo-Lopez V, Missiaglia E, Bisig B, Trimech M, Michielin O, Homicsko K, and Zoete V
- Subjects
- Amino Acid Sequence, Antineoplastic Agents therapeutic use, Female, GTP-Binding Protein alpha Subunits, Gq-G11 genetics, GTP-Binding Protein alpha Subunits, Gq-G11 metabolism, Humans, Melanoma metabolism, Melanoma pathology, Middle Aged, Models, Molecular, Mutant Proteins genetics, Mutant Proteins metabolism, Protein Conformation, Protein Stability, Receptor, Fibroblast Growth Factor, Type 4 genetics, Receptor, Fibroblast Growth Factor, Type 4 metabolism, Sequence Homology, Signal Transduction, Uveal Neoplasms metabolism, Uveal Neoplasms pathology, GTP-Binding Protein alpha Subunits, Gq-G11 chemistry, Melanoma drug therapy, Melanoma genetics, Mutant Proteins chemistry, Mutation, Pyridones therapeutic use, Pyrimidinones therapeutic use, Receptor, Fibroblast Growth Factor, Type 4 chemistry, Uveal Neoplasms drug therapy, Uveal Neoplasms genetics
- Abstract
We report a case of an uveal melanoma patient with GNAQ p.Gly48Leu who responded to MEK inhibition. At the time of the molecular analysis, the pathogenicity of the mutation was unknown. A tridimensional structural analysis showed that Gα
q can adopt active and inactive conformations that lead to substantial changes, involving three important switch regions. Our molecular modelling study predicted that GNAQ p.Gly48Leu introduces new favorable interactions in its active conformation, whereas little or no impact is expected in its inactive form. This strongly suggests that GNAQ p.Gly48Leu is a possible tumor-activating driver mutation, consequently triggering the MEK pathway. In addition, we also found an FGFR4 p.Cys172Gly mutation, which was predicted by molecular modelling analysis to lead to a gain of function by impacting the Ig-like domain 2 folding, which is involved in FGF binding and increases the stability of the homodimer. Based on these analyses, the patient received the MEK inhibitor trametinib with a lasting clinical benefit. This work highlights the importance of molecular modelling for personalized oncology.- Published
- 2020
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18. [Advances in Oncology 2019].
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Vernadou A, Ferahta N, Mederos N, Ferraro D, Dischl-Antonioni I, Diciolla A, Liapi A, Mosimann V, Latifyan S, Aedo-Lopez V, Berthold D, Digklia A, Michielin O, Montemurro M, Wagner AD, Zaman K, Peters S, Stravodimou A, and Sarivalasis A
- Subjects
- Humans, Mutation, Biomarkers, Tumor, Neoplasms diagnosis, Neoplasms therapy
- Abstract
Driven by highly specialized medicine, research and the quest for personalization of treatments, oncology witnessed substantial advances in 2019. This year numerous treatments have consolidated their importance and broadened their indications. Multiple innovative treatments, currently under study, brought hope for future advances, while biomarkers, such as PD-L1, microsatellite instability (MSI), tumor mutational burden (TMB), BRCA1/2 gene mutations, and homologous recombination deficiency (HRD) allowed better selection and customization of available treatments. This article provides an overview of this year's advances in oncology.
- Published
- 2020
19. Immunotherapy-Induced Airway Disease: A New Pattern of Lung Toxicity of Immune Checkpoint Inhibitors.
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Mitropoulou G, Daccord C, Sauty A, Pasche A, Egger B, Aedo Lopez V, Letovanec I, Beigelman-Aubry C, Nicod LP, and Lazor R
- Subjects
- Adenocarcinoma of Lung secondary, Adrenal Gland Neoplasms secondary, Adrenal Gland Neoplasms surgery, Adrenergic beta-2 Receptor Agonists therapeutic use, Aged, Bronchial Diseases drug therapy, Bronchial Diseases physiopathology, Bronchoalveolar Lavage Fluid cytology, Bronchoscopy, Dyspnea drug therapy, Dyspnea physiopathology, Female, Forced Expiratory Volume, Glucocorticoids therapeutic use, Humans, Lung Neoplasms pathology, Lymphatic Metastasis, Male, Mediastinum, Middle Aged, Nivolumab adverse effects, Pulmonary Diffusing Capacity, Respiratory Insufficiency drug therapy, Respiratory Insufficiency physiopathology, Tomography, X-Ray Computed, Adenocarcinoma of Lung drug therapy, Bronchial Diseases chemically induced, Dyspnea chemically induced, Immune Checkpoint Inhibitors adverse effects, Lung Neoplasms drug therapy, Melanoma drug therapy, Respiratory Insufficiency chemically induced, Skin Neoplasms drug therapy
- Abstract
Immune checkpoint inhibitors (ICIs) have been shown to improve overall and progression-free survival in various cancers but have been associated with various immune-related adverse events (IRAEs), including interstitial lung disease, especially organizing pneumonia. We report 2 cases of isolated severe airway disease attributable to ICIs, a rarely reported pattern of lung toxicity. The first patient received nivolumab with or without ipilimumab in a randomized double-blind trial for locoregional metastatic melanoma. The second patient was treated with nivolumab for lung adenocarcinoma. An IRAE was suspected in both cases due to a temporal relationship between ICI initiation and symptom onset. ICIs were stopped, and high-dose prednisone, inhaled corticosteroids, and bronchodilators were administered, allowing a rapid clinical and functional improvement in Patient 1. In Patient 2, despite prolonged high-dose prednisone, only a stabilization of forced expiratory volume in 1 s could be achieved, and the disease course was complicated by respiratory infections resulting in further loss of lung function. The patient died 1 year later due to progression of metastatic disease. These 2 cases suggest that pulmonary IRAEs secondary to ICIs may present as isolated bronchitis or bronchiolitis, with variable outcomes following ICI withdrawal and systemic corticosteroids., (© 2020 S. Karger AG, Basel.)
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- 2020
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20. The combination of stereotactic radiosurgery with immune checkpoint inhibition or targeted therapy in melanoma patients with brain metastases: a retrospective study.
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Martins F, Schiappacasse L, Levivier M, Tuleasca C, Cuendet MA, Aedo-Lopez V, Gautron Moura B, Homicsko K, Bettini A, Berthod G, Gérard CL, Wicky A, Bourhis J, and Michielin O
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Immunological therapeutic use, Brain Neoplasms immunology, Brain Neoplasms metabolism, Brain Neoplasms pathology, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Male, Melanoma immunology, Melanoma metabolism, Melanoma pathology, Middle Aged, Prognosis, Retrospective Studies, Survival Rate, Brain Neoplasms therapy, Immunotherapy mortality, Ipilimumab therapeutic use, Melanoma therapy, Molecular Targeted Therapy mortality, Protein Kinase Inhibitors therapeutic use, Radiosurgery mortality
- Abstract
Background: Evidence pointing to a synergistic effect of stereotactic radiosurgery (SRS) with concurrent immunotherapy or targeted therapy in patients with melanoma brain metastases (BM) is increasing. We aimed to analyze the effect on overall survival (OS) of immune checkpoint inhibitors (ICI) or BRAF/MEK inhibitors initiated during the 9 weeks before or after SRS. We also evaluated the prognostic value of patients' and disease characteristics as predictors of OS in patients treated with SRS., Methods: We identified patients with BM from cutaneous or unknown primary origin melanoma treated with SRS between 2011 and 2018., Results: We included 84 patients. The median OS was 12 months (95% CI 9-20 months). The median follow-up was 30 months (95% CI 28-49). Twenty-eight patients with newly diagnosed BM initiated anti-PD-1 +/-CTLA-4 therapy (n = 18), ipilimumab monotherapy (n = 10) or BRAF+/- MEK inhibitors (n = 11), during the 9 weeks before or after SRS. Patients who received anti-PD-1 +/-CTLA-4 mAb showed an improved survival in comparison to ipilimumab monotherapy (OS 24 vs. 7.5 months; HR 0.32, 95% 0.12-0.83, p = 0.02) and BRAF +/-MEK inhibitors (OS 24 vs. 7 months, respectively; HR 0.11, 95% 0.04-0.34, p = 0.0001). This benefit remained significant when compared to the subgroup of patients treated with dual BRAF/MEK inhibition (BMi) (n = 5). In a multivariate Cox regression analysis an age > 65, synchronous BM, > 2 metastatic sites, > 4 BM, and an ECOG > 1 were correlated with poorer prognosis. A treatment with anti-PD-1+/-CTLA-4 mAbs within 9 weeks of SRS was associated with better outcomes. The presence of serum lactate dehydrogenase (LDH) levels ≥ 2xULN at BM diagnosis was associated with lower OS (HR 1.60, 95% CI 1.03-2.50; p = 0.04)., Conclusions: The concurrent administration of anti-PD-1+/-CTLA-4 mAbs with SRS was associated with improved survival in melanoma patients with newly diagnosed BM. In addition to CNS tumor burden, the extension of systemic disease retains its prognostic value in patients treated with SRS. Elevated serum LDH levels are predictors of poor outcome in these patients.
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- 2020
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21. Multiple nivolumab-induced CNS demyelination with spontaneous resolution in an asymptomatic metastatic melanoma patient.
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Pillonel V, Dunet V, Hottinger AF, Berthod G, Schiappacasse L, Peters S, Michielin O, and Aedo-Lopez V
- Subjects
- Adult, Antineoplastic Agents, Immunological administration & dosage, Asymptomatic Diseases, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Melanoma diagnosis, Melanoma drug therapy, Nivolumab administration & dosage, Remission, Spontaneous, Antineoplastic Agents, Immunological adverse effects, Demyelinating Diseases diagnosis, Demyelinating Diseases etiology, Melanoma complications, Nivolumab adverse effects
- Abstract
Background: Immune checkpoint inhibitors (ICPis) have revolutionised the treatment of melanoma by significantly increasing survival rates and disease control. However, ICPis can have specific immune-related adverse events, including rare but severe neurological toxicity., Case Presentation: We report a 44-year-old man diagnosed with stage IIIB melanoma who developed metastatic disease (pulmonary and brain metastases) and was treated with stereotactic radiosurgery and nivolumab immunotherapy. He developed asymptomatic multifocal diffuse white matter lesions consistent with active central nervous system demyelination seen on brain MRI. One month after cessation of the immunotherapy, spontaneous regression of the demyelinating lesions was observed, suggesting a nivolumab-related toxicity., Conclusion: We report the first case of a melanoma patient with an asymptomatic and spontaneously reversible central nervous system demyelination following nivolumab immunotherapy. This case highlights the need for better recognition of such atypical and rare neurological toxicities which could be mistaken for progressive brain metastases. Early recognition and appropriate management are crucial to reduce severity and duration of these toxicities, especially for patients with less favourable evolution.
- Published
- 2019
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