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PURPOSE: About half of patients with metastatic uveal melanoma present with isolated liver metastasis, in whom the median survival is 6-12 months. The few systemic treatment options available only moderately prolong survival. Isolated hepatic perfusion (IHP) with melphalan is a regional treatment option, but prospective efficacy and safety data are lacking. METHODS: In this multicenter, randomized, open-label, phase III trial, patients with previously untreated isolated liver metastases from uveal melanoma were randomly assigned to receive a one-time treatment with IHP with melphalan or best alternative care (control group). The primary end point was overall survival at 24 months. Here, we report the secondary outcomes of response according to RECIST 1.1 criteria, progression-free survival (PFS), hepatic PFS (hPFS), and safety. RESULTS: Ninety-three patients were randomly assigned, and 87 patients were assigned to either IHP (n = 43) or a control group receiving the investigator's choice of treatment (n = 44). In the control group, 49% received chemotherapy, 39% immune checkpoint inhibitors, and 9% locoregional treatment other than IHP. In an intention-to-treat analysis, the overall response rates (ORRs) were 40% versus 4.5% in the IHP and control groups, respectively (P < .0001). The median PFS was 7.4 months versus 3.3 months (P < .0001), with a hazard ratio of 0.21 (95% CI, 0.12 to 0.36), and the median hPFS was 9.1 months versus 3.3 months (P < .0001), both favoring the IHP arm. There were 11 treatment-related serious adverse events in the IHP group compared with seven in the control group. There was one treatment-related death in the IHP group. CONCLUSION: IHP treatment resulted in superior ORR, hPFS, and PFS compared with best alternative care in previously untreated patients with isolated liver metastases from primary uveal melanoma.

The standard treatment of glioblastoma, an aggressive brain tumour, includes radiotherapy combined with temozolomide. Based on a randomised trial, showing five months increased survival, TTF has been introduced in the management of patients with good performance status. Data from the Swedish national quality registry for CNS tumours have been analysed for TTF usage. The results demonstrate that 65 percent of the patients accepted treatment with TTF. More than half of the treated patients interrupted treatment due to low compliance or their own wish. Median treatment time was 164 days, with a range from 0 to 774 days. There was a large variation between different regions in how many patients were offered TTF treatment. A non-significant trend to better survival was seen for the group of TTF-treated patients compared to individually matched controls. In summary, TTF is a new treatment for glioblastoma, with potential to prolong survival also in real world patients. Today, the treatment is not offered equally to all patients, despite national guidelines., Publicerad på Lakartidningen.se 2023-07-03

IMPORTANCE Disulfiram has demonstrated broad antitumoral effect in several preclinical studies. One of the proposed indications is for the treatment of glioblastoma. OBJECTIVE To evaluate the efficacy and safety of disulfiram and copper as add-on to alkylating chemotherapy in patients with recurrent glioblastoma. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter, open-label, randomized phase II/III clinical trial with parallel group design. Patients were recruited at 7 study sites in Sweden and 2 sites in Norway between January 2017 and November 2020. Eligible patients were 18 years or older, had a first recurrence of glioblastoma, and indication for treatment with alkylating chemotherapy. Patients were followed up until death or a maximum of 24 months. The date of final follow-up was January 15, 2021. Data analysis was performed from February to September 2022. INTERVENTIONS Patients were randomized 1:1 to receive either standard-of-care (SOC) alkylating chemotherapy alone, or SOC with the addition of disulfiram (400 mg daily) and copper (2.5 mg daily). MAIN OUTCOMES AND MEASURES The primary end point was survival at 6 months. Secondary end points included overall survival, progression-free survival, adverse events, and patient-reported quality of life. RESULTS Among the 88 patients randomized to either SOC (n = 45) or SOC plus disulfiram and copper (n = 43), 63 (72%) were male; the mean (SD) age was 55.4 (11.5) years. There was no significant difference between the study groups (SOC vs SOC plus disulfiram and copper) in 6 months survival (62%[26 of 42] vs 44%[19 of 43]; P =.10). Median overall survival was 8.2 months (95% CI, 5.4-10.2 months) with SOC and 5.5 months (95% CI, 3.9-9.3 months) with SOC plus disulfiram and copper, and median progression-free survival was 2.6 months (95% CI, 2.4-4.6 months) vs 2.3 months (95% CI, 1.7-2.6 months), respectively. More patients in the SOC plus disulfiram and copper group had adverse events grade 3 or higher (34%[14, Funding Agencies|Swedish government [ALFGBG-716671, ALFGBG-933972]; AG foundation; Sahlgrenska Foundation; Nordic Cancer Union; Swedish Society of Medicine [SLS-681721]; Swedish Cancer Society [CAN 2018/452]; Swedish county councils concerning economic support of research and education of doctors (ALF-agreement) [ALFGBG-716671, ALFGBG-933972]

PURPOSE About half of patients with metastatic uveal melanoma present with isolated liver metastasis, in whom the median survival is 6-12 months. The few systemic treatment options available only moderately prolong survival. Isolated hepatic perfusion (IHP) with melphalan is a regional treatment option, but prospective efficacy and safety data are lacking. METHODS In this multicenter, randomized, open-label, phase III trial, patients with previously untreated isolated liver metastases from uveal melanoma were randomly assigned to receive a one-time treatment with IHP with melphalan or best alternative care (control group). The primary end point was overall survival at 24 months. Here, we report the secondary outcomes of response according to RECIST 1.1 criteria, progression-free survival (PFS), hepatic PFS (hPFS), and safety. RESULTS Ninety-three patients were randomly assigned, and 87 patients were assigned to either IHP (n = 43) or a control group receiving the investigator's choice of treatment (n = 44). In the control group, 49% received chemotherapy, 39% immune checkpoint inhibitors, and 9% locoregional treatment other than IHP. In an intention-to-treat analysis, the overall response rates (ORRs) were 40% versus 4.5% in the IHP and control groups, respectively (P < .0001). The median PFS was 7.4 months versus 3.3 months (P < .0001), with a hazard ratio of 0.21 (95% CI, 0.12 to 0.36), and the median hPFS was 9.1 months versus 3.3 months (P < .0001), both favoring the IHP arm. There were 11 treatment-related serious adverse events in the IHP group compared with seven in the control group. There was one treatment-related death in the IHP group. CONCLUSION IHP treatment resulted in superior ORR, hPFS, and PFS compared with best alternative care in previously untreated patients with isolated liver metastases from primary uveal melanoma., PURPOSEAbout half of patients with metastatic uveal melanoma present with isolated liver metastasis, in whom the median survival is 6-12 months. The few systemic treatment options available only moderately prolong survival. Isolated hepatic perfusion (IHP) with melphalan is a regional treatment option, but prospective efficacy and safety data are lacking.METHODSIn this multicenter, randomized, open-label, phase III trial, patients with previously untreated isolated liver metastases from uveal melanoma were randomly assigned to receive a one-time treatment with IHP with melphalan or best alternative care (control group). The primary end point was overall survival at 24 months. Here, we report the secondary outcomes of response according to RECIST 1.1 criteria, progression-free survival (PFS), hepatic PFS (hPFS), and safety.RESULTSNinety-three patients were randomly assigned, and 87 patients were assigned to either IHP (n = 43) or a control group receiving the investigator's choice of treatment (n = 44). In the control group, 49% received chemotherapy, 39% immune checkpoint inhibitors, and 9% locoregional treatment other than IHP. In an intention-to-treat analysis, the overall response rates (ORRs) were 40% versus 4.5% in the IHP and control groups, respectively (P <.0001). The median PFS was 7.4 months versus 3.3 months (P <.0001), with a hazard ratio of 0.21 (95% CI, 0.12 to 0.36), and the median hPFS was 9.1 months versus 3.3 months (P <.0001), both favoring the IHP arm. There were 11 treatment-related serious adverse events in the IHP group compared with seven in the control group. There was one treatment-related death in the IHP group.CONCLUSIONIHP treatment resulted in superior ORR, hPFS, and PFS compared with best alternative care in previously untreated patients with isolated liver metastases from primary uveal melanoma.

The standard treatment of glioblastoma, an aggressive brain tumour, includes radiotherapy combined with temozolomide. Based on a randomised trial, showing five months increased survival, TTF has been introduced in the management of patients with good performance status. Data from the Swedish national quality registry for CNS tumours have been analysed for TTF usage. The results demonstrate that 65 percent of the patients accepted treatment with TTF. More than half of the treated patients interrupted treatment due to low compliance or their own wish. Median treatment time was 164 days, with a range from 0 to 774 days. There was a large variation between different regions in how many patients were offered TTF treatment. A non-significant trend to better survival was seen for the group of TTF-treated patients compared to individually matched controls. In summary, TTF is a new treatment for glioblastoma, with potential to prolong survival also in real world patients. Today, the treatment is not offered equally to all patients, despite national guidelines., TTF (tumour treating fields) är en ny, nationellt godkänd utrustning, som inducerar alternerande elektriska fält och används vid behandling av hjärntumören glioblastom. Behandlingen kan vara inskränkande i vardagen, och data från det nationella registret för CNS-tumörer visar att mer än hälften av patienterna avbryter TTF på grund av dålig användningsgrad eller egen önskan. Genomsnittlig behandlingstid enligt registret är 164 dagar. Jämfört med matchade kontroller visar data från registret en trend med längre överlevnad för patienter som behandlas med TTF; dock är skillnaden inte statistiskt signifikant. Det finns en stor regional variation i andelen patienter som erbjudits behandlingen.

Background: There is an urgent need for effective treatments against glioblastoma (GBM). In this trial, we investigated the efficacy and safety of an adoptive cell-based immunotherapy. Methods: Patients with newly diagnosed GBM were recruited at 4 study sites in Sweden. The patients were randomized 1:2 to receive either radiotherapy (RT), 60 Gy/30 fractions, with concomitant and adjuvant temozolomide (TMZ) only, or RT and TMZ with the addition of Autologous Lymphoid Effector Cells Specific Against Tumor (ALECSAT) in an open-label phase II trial. The primary endpoint was investigator-assessed progression-free survival (PFS). The secondary endpoints were survival and safety of ALECSAT. Results: Sixty-two patients were randomized to either standard of care (SOC) with RT and TMZ alone (n = 22) or SOC with ALECSAT (n = 40). Median age was 57 years (range 38-69), 95% of the patients were in good performance status (WHO 0-1). There was no significant difference between the study arms (SOC vs ALECSAT + SOC) in PFS (7.9 vs 7.8 months; hazard ratio [HR] 1.28; 95% confidence interval [CI] 0.70-2.36; P = .42) or in median overall survival (OS) (18.3 vs 19.2 months; HR 1.16, 95% CI 0.58-2.31; P = .67). The treatment groups were balanced in terms of serious adverse events (52.4% vs 52.5%), but adverse events ≥grade 3 were more common in the experimental arm (81.0% vs 92.5%). Conclusion: Addition of ALECSAT immunotherapy to standard treatment with radiochemotherapy was well tolerated but did not improve PFS or OS for patients with newly diagnosed GBM.

Purpose: Multidisciplinary team (MDT) meetings integrate complex information and base recommendations for clinical management on interdisciplinary and multiprofessional deci-sion-making. To support high-quality decision-making and define key performance indica-tors, we aimed to determine completeness of case information and contributions to MDT case discussions in cancer care. Methods: In a prospective observational study design, based on three MDTs, we applied the Metric for Observation of Decision-Making (MODe) tool to assess the quality of case presentation and team members’ contributions to case discussions. The MDTs handled patients with brain tumors, soft tissue sarcomas and hepatobiliary cancers. The results were correlated to patient and team characteristics and to MDT leadership skills. Results: Data were collected from 349 case discussions during 32 MDT meetings. Information on radiology received the highest scores, followed by case history and information on histopathology. Patient-related information was less frequently mentioned and gen-erally received low scores. Contributions to the case discussions were predominantly by the chair, surgeons, and oncologists with limited contributions from nurses. Leadership skills showed a positive correlation with case presentations scores and failure to reach a treatment recommendation correlated with lower case discussion scores. Conclusion: Considerable resources are spent on MDT meetings in cancer care, which motivate initiatives to ensure high-quality and efficient decision-making processes. We identify unbalanced contributions from team members during MDT meetings, demonstrate limited provision of patient-related information and show that leadership skills may posi-tively influence the quality of the case presentations. We suggest that MDTs should consider and develop these aspects to ensure high-quality MDT-based case management and decision-making.

Background: Multidisciplinary team (MDT) meetings provide treatment recommendations based on available information and collective decision-making in teams with complementary professions, disciplines and skills. We aimed to map ancillary medical and nonmedical patient information during case presentations and case discussions in MDT meetings in cancer care. Methods: Through a nonparticipant, observational approach, we mapped verbal information on medical, nonmedical and patient-related characteristics and classified these based on content. Data were collected from 336 case discussions in three MDTs for neuro-oncology, sarcoma and hepato-biliary cancer. Results: Information on physical status was presented in 48.2% of the case discussions, psychological status in 8.9% and comorbidity in 48.5% of the cases. Nonmedical factors, such as family relations, occupation, country of origin and abode were referred to in 3.6–7.7% of the cases, and patient preferences were reported in 4.2%. Conclusions: Provision of information on comorbidities in half of the cases and on patient characteristics and treatment preferences in <10% of case discussions suggest a need to define data elements and develop reporting standards to support robust MDT decision-making.

Jessica Wihl,1– 3 Linn Rosell,1,2 Kirsten Frederiksen,4 Sara Kinhult,1,3 Gert Lindell,5 Mef Nilbert1,4,6 1Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden; 2Regional Cancer Centre South, Region Skåne, Lund, Sweden; 3Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden; 4Danish Cancer Society Research Centre, Copenhagen, Denmark; 5Department of Surgery, Skåne University Hospital, Lund, Sweden; 6Clinical Research Centre, Hvidovre University Hospital and Copenhagen University, Copenhagen, DenmarkCorrespondence: Jessica WihlDepartment of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Scheelev. 2, Lund, 223 63, SwedenEmail jessica.wihl@med.lu.sePurpose: Multidisciplinary team (MDT) meetings integrate complex information and base recommendations for clinical management on interdisciplinary and multiprofessional decision-making. To support high-quality decision-making and define key performance indicators, we aimed to determine completeness of case information and contributions to MDT case discussions in cancer care.Methods: In a prospective observational study design, based on three MDTs, we applied the Metric for Observation of Decision-Making (MODe) tool to assess the quality of case presentation and team members’ contributions to case discussions. The MDTs handled patients with brain tumors, soft tissue sarcomas and hepatobiliary cancers. The results were correlated to patient and team characteristics and to MDT leadership skills.Results: Data were collected from 349 case discussions during 32 MDT meetings. Information on radiology received the highest scores, followed by case history and information on histopathology. Patient-related information was less frequently mentioned and generally received low scores. Contributions to the case discussions were predominantly by the chair, surgeons, and oncologists with limited contributions fr

Background: Disulfiram (DSF) is a well-tolerated, inexpensive, generic drug that has been in use to treat alcoholism since the 1950s. There is now independent preclinical data that supports DSF as an anticancer agent, and experimental data suggest that copper may increase its anti-neoplastic properties. There is also some clinical evidence that DSF is a promising anticancer agent in extracranial cancers. In glioblastoma, DSF induced O 6-methylguanine methyltransferase (MGMT) inhibition may increase response to alkylating chemotherapy. A recent phase I study demonstrated the safety of DSF in glioblastoma patients when DSF was administered at doses below 500 mg/day together with chemotherapy. We plan to assess the effects of DSF combined with nutritional copper supplement (DSF-Cu) as an adjuvant to alkylating chemotherapy in glioblastoma treatment. Methods: In an academic, industry independent, multicenter, open label randomized controlled phase II/III trial with parallel group design (1:1) we will assess the efficacy and safety of DSF-Cu in glioblastoma treatment. The study will include 142 patients at the time of first recurrence of glioblastoma where salvage therapy with alkylating chemotherapy is planned. Patients will be randomized to treatment with or without DSF-Cu. Primary end-point is survival at 6 months. Secondary end-points are overall survival, progression free survival, quality of life, contrast enhancing tumor volume and safety. Discussion: There is a need to improve the treatment of recurrent glioblastoma. Results from this randomized controlled trial with DSF-Cu in glioblastoma will serve as preliminary evidence of the future role of DSF-Cu in glioblastoma treatment and a basis for design and power estimations of future studies. In this publication we provide rationale for our choices and discuss methodological issues. Trial registration: The study underwent registration in EudraCT 2016-000167-16 (Date: 30.03.2016,) and Clinicaltrials.gov NCT02678975

The management of patients with brain metastases has become a major issue due to the increasing frequency and complexity of the diagnostic and therapeutic approaches. In 2014, the European Association of Neuro-Oncology (EANO) created a multidisciplinary Task Force to draw evidence-based guidelines for patients with brain metastases from solid tumors. Here, we present these guidelines, which provide a consensus review of evidence and recommendations for diagnosis by neuroimaging and neuropathology, staging, prognostic factors, and different treatment options. Specifically, we addressed options such as surgery, stereotactic radiosurgery/stereotactic fractionated radiotherapy, whole-brain radiotherapy, chemotherapy and targeted therapy (with particular attention to brain metastases from non-small cell lung cancer, melanoma and breast and renal cancer), and supportive care.