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.
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.
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.
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%.
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.
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 (Date: 31.01.2016) before initiating the study.
Cancer metabolism is characterized by an increased utilization of fermentable fuels, such as glucose and glutamine, which support cancer cell survival by increasing resistance to both oxidative ...stress and the inherent immune system in humans. Dialysis has the power to shift the patient from a state dependent on glucose and glutamine to a ketogenic condition (KC) combined with low glutamine levels—thereby forcing ATP production through the Krebs cycle. By the force of dialysis, the cancer cells will be deprived of their preferred fermentable fuels, disrupting major metabolic pathways important for the ability of the cancer cells to survive. Dialysis has the potential to reduce glucose levels below physiological levels, concurrently increase blood ketone body levels and reduce glutamine levels, which may further reinforce the impact of the KC. Importantly, ketones also induce epigenetic changes imposed by histone deacetylates (HDAC) activity (Class I and Class IIa) known to play an important role in cancer metabolism. Thus, dialysis could be an impactful and safe adjuvant treatment, sensitizing cancer cells to traditional cancer treatments (TCTs), potentially making these significantly more efficient.
Immune checkpoint inhibitors (ICPI), such as ipilimumab anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody and nivolumab or pembrolizumab anti-programmed cell death protein-1 (PD-1) antibodies, ...improve survival in several cancer types. Since inhibition of CTLA-4 or PD-1 leads to non-selective activation of the immune system, immune-related adverse events (irAEs) are frequent. Enterocolitis is a common irAE, currently managed with corticosteroids and, if necessary, anti-tumor necrosis factor-α therapy. Such a regimen carries a risk of serious side-effects including infections, and may potentially imply impaired antitumor effects. Vedolizumab is an anti-integrin α4β7 antibody with gut-specific immunosuppressive effects, approved for Crohn’s disease and ulcerative colitis. We report a case series of seven patients with metastatic melanoma or lung cancer, treated with vedolizumab off-label for ipilimumab- or nivolumab-induced enterocolitis, from June 2014 through October 2016. Clinical, laboratory, endoscopic, and histologic data were analyzed. Patients initially received corticosteroids but were steroid-dependent and/or partially refractory. One patient was administered infliximab but was refractory. The median time from onset of enterocolitis to start of vedolizumab therapy was 79 days. Following vedolizumab therapy, all patients but one experienced steroid-free enterocolitis remission, with normalized fecal calprotectin. This was achieved after a median of 56 days from vedolizumab start, without any vedolizumab-related side-effects noted. The patient in whom vedolizumab was not successful, due to active ulcerative colitis, received vedolizumab prophylactically. This is the first case series to suggest that vedolizumab is an effective and well-tolerated therapeutic for steroid-dependent or partially refractory ICPI-induced enterocolitis. A larger prospective study to evaluate vedolizumab in this indication is warranted.
•High-quality leadership and chairing skills are central components of team performance during multidisciplinary team (MDT) meetings. We applied the recently developed A Tumor Leadership Assessment ...inStrument” (ATLAS) to provide a more detailed insight into MDT chairing and leadership aspects in cancer care.•We evaluated 367 case discussions in 33 MDTs for neuro-oncology, sarcoma and hepatobiliary cancer in Swedish cancer care.•The MDTs performed well in the aspects of time management and case prioritization and showed low scores for systematic recruitment to clinical trials.•We conclude that the ATLAS instrument captures various aspects of MDT leadership performance and allows for structured feed-back to the chair and the team. The results have a potential to strengthen team communication and coordination and could contributed to more efficient MDTs.
High-quality leadership and chairing skills are central components in team performance during multidisciplinary team (MDT) meetings. We hypothesized that the recently developed A Tumor Leadership Assessment inStrument (ATLAS) could provide relevant information to support more detailed insights into MDT chairing and leadership aspects of relevance for team feedback and targeted improvements.
The observational assessment instrument ATLAS rates chairing and leadership skills during MDT meetings in 12 predefined domains that include e.g. time management, case prioritization, team involvement, discussion climate and clarity of treatment recommendations. We used ATLAS to prospectively assess 33 MDT meetings in neuro-oncology, sarcoma and hepatobiliary cancer.
The aspects time management, effective case prioritization and provision of clear treatment plans were found to be well-functioning, whereas facilitatation of case discussions, encouragment of team member contributions, keeping the meeting focused and ability to summarize case discussions showed variable and partly weak results.
We conclude that the ATLAS instrument effectively captures various aspects of MDT leadership and chairing skills. It may thereby provide relevant information to prioritize initiatives that support and develop effective teamwork and decision-making during MDT meetings.
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.
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.
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 (
< .0001). The median PFS was 7.4 months versus 3.3 months (
< .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 (
< .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.
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.
Cardiotoxicity is a serious side effect of cancer treatment with the commonly used drug 5-fluorouracil (5-FU). The pathophysiology of this is unclear. Experimental studies show a thrombogenic effect ...of 5-FU, secondary to a direct toxic effect on the endothelium, possibly mediated by radical generation. Probucol is a lipid-lowering drug with strong antioxidant properties. The aim of this study was to evaluate the possibility of using probucol treatment to protect against the toxicity of 5-FU on vascular endothelium of the central artery in the ears of rabbits. Five groups of rabbits were treated with 1) 5-FU, 2) saline, 3) probucol high-dose and saline, 4) probucol high-dose and 5-FU, 5) probucol low-dose and 5-FU. Damage to the arterial endothelium was evaluated by scanning electron microscopy. Damage to the endothelium in 5-FU+probucol-treated animals was minimal and comparable to that of the control group. Intima disruption or thrombus formation was seen with 5-FU only. The results of the study indicate that treatment with probucol prevents 5-FU-induced endothelial injury.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
9532 Background: Uveal melanoma is a rare subtype of melanoma characterized by frequent metastases to the liver. The median survival for patients with liver metastases is less than one year, and ...there are few systemic treatment options available, providing only small survival benefits. Patients with liver metastases of uveal melanoma were in the SCANDIUM trial randomized to a one-time treatment with isolated hepatic perfusion (IHP) with high dose melphalan and investigator´s choice. We have previously reported that IHP gave significantly superior response rates and progression-free survival compared to best alternative care Furthermore, the primary endpoint, overall survival (OS) rate at 24 months was numerically higher for the IHP treated group (46.5% vs 29.5%), but the difference was not statistically significant. Here we present extended OS follow-up. Methods: In this randomized, controlled, phase III trial, treatment naïve Swedish patients with isolated liver metastases from uveal melanoma were between 2013 and 2021 randomly assigned in a 1:1 ratio to receive a one-time treatment with IHP or best alternative care (control group). No crossover from the control group to the IHP group was allowed. Results: A total of 87 patients were randomized and assigned to either IHP (43 patients) or control (44 patients). In the IHP group, 41 (89%) patients received IHP. In the control group, the first-line treatment was chemotherapy (49%), immunotherapy (39%) or localized treatment interventions (9%). The overall response rate was 40% in the IHP group, with a median duration of response of 13.7 months (95% CI, 11.6-18.3, n=17). At a minimum follow-up of 36 months, the 3-year OS rate was 18.6% (95% CI, 10.0-34.8%) in the IHP group compared to 9.1% (95% CI, 3.6-23.1%) in the control group (p=0.23, fisher exact test), and the 5-year OS rate was 16.3% (95% CI, 8.3-32.1%) compared to 6.8% (95% CI, 2.3-20.3%). The median OS in the IHP group was 21.4 months (95% CI, 19.0-30.4 months) compared to 17.3 months (95% CI, 13.8-22.3 months) in the control group (p=0.11, log-rank test). Conclusions: This extended analysis from the SCANDIUM trial supports long-term efficacy of a one-time treatment with IHP compared to best alternative care in patients with isolated liver metastases of uveal melanoma. Clinical trial information: NCT01785316 .
LBA9512
Background: Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in ...approximately 50% of the patients, with the liver being the most common site. The median survival for patients with liver metastases is about 6-12 months, and there are only few systemic treatment options available providing only small survival benefits. The SCANDIUM trial previously demonstrated significantly superior response rate (40% vs 4.5%) and progression free survival (7.4 vs 3.3 months), compared to best alternative care, in patients with liver metastases of uveal melanoma receiving first-line treatment with isolated hepatic perfusion (IHP). Here we present the primary endpoint, overall survival (OS) rate at 24 months. Methods: In this multicenter randomized, controlled, phase III trial, adult patients with a performance status ECOG 0-1, and with previously untreated isolated liver metastasis from uveal melanoma, were randomized 1:1 between 2013 and 2021 to receive a one-time treatment with IHP or best alternative care (control group). No crossover from the control group to the IHP group was allowed. The primary endpoint was OS rate at 24 months, with the hypothesis of a treatment effect leading to a 50% OS rate in the IHP group compared to 20% in the control group. Results: A total of 93 patients were randomized, with three patients in each group being excluded due to either withdrawal of consent or inappropriate enrollment, and a total of 87 patients were assigned to either IHP group (43 patients) or control group (44 patients). In the IHP group, 41 (89%) patients received IHP. In the control group, the first-line of treatment was chemotherapy (49%), immunotherapy (39%) or localized treatment interventions (9%). In the intention-to-treat (ITT) population, the OS rate at 24 months in the IHP group was 46.5% (95% CI, 31.2-60.4%) compared to 29.5% (95% CI, 17.0-43.2%) in the control group (p = 0.12, Fisher’s exact test). The median OS in the IHP group was 21.7 months (95% CI, 19.1-NA months) compared to 17.6 months (95% CI, 13.5-21.4 months) in the control group (p = 0.10, log-rank test), with a hazard ratio of 0.64 (95% CI 0.37-1.10) in favor of the IHP group. Conclusions: In the SCANDIUM trial, patients with metastatic uveal melanoma receiving IHP experienced a significantly improved PFS. At two years, OS was longer in patients receiving IHP, but the difference was not statistically significant. This could in part be attributed to the control group performing better than expected, potentially due to the introduction of immunotherapy during the study period. Prolonged follow-up of the cohorts will further elucidate how IHP affects OS in patients with uveal melanoma. Clinical trial information: NCT01785316 .
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