Feasibility and early clinical impact of precision medicine for late-stage cancer patients in a regional public academic hospital.

AIM: Our goal was to describe a precision medicine program in a regional academic hospital, characterize features of included patients and present early data on clinical impact. MATERIALS AND METHODS: We prospectively included 163 eligible patients with late-stage cancer of any diagnosis from June 2020 to May 2022 in the Proseq Cancer trial. Molecular profiling of new or fresh frozen tumor biopsies was done by WES and RNAseq with parallel sequencing of non-tumoral DNA as individual reference. Cases were presented at a National Molecular Tumor Board (NMTB) for discussion of targeted treatment. Subsequently, patients were followed for at least 7 months. RESULTS: 80% (N = 131) of patients had a successful analysis done, disclosing at least one pathogenic or likely pathogenic variant in 96%. A strongly or potentially druggable variant was found in 19% and 73% of patients, respectively. A germline variant was identified in 2.5%. Median time from trial inclusion to NMTB decision was one month. One third (N = 44) of patients who underwent molecularly profiling were matched with a targeted treatment, however, only 16% were either treated (N = 16) or are waiting for treatment (N = 5), deteriorating performance status being the primary cause of failure. A history of cancer among 1st degree relatives, and a diagnosis of lung or prostate cancer correlated with greater chance of targeted treatment being available. The response rate of targeted treatments was 40%, the clinical benefit rate 53%, and the median time on treatment was 3.8 months. 23% of patients presented at NMTB were recommended clinical trial participation, not dependent on biomarkers. CONCLUSIONS: Precision medicine in end-stage cancer patients is feasible in a regional academic hospital but should continue within the frame of clinical protocols as few patients benefit. Close collaboration with comprehensive cancer centers ensures expert evaluations and equality in access to early clinical trials and modern treatment.

Treatment and survival of glioblastoma patients in Denmark: The Danish Neuro-Oncology Registry 2009-2014.

BACKGROUND: As many glioblastoma patients are in a poor condition they are unable to undergo the full treatment documented in clinical trials. We aimed to examine the survival and its relationship to clinical characteristics and treatment in a nationwide population of glioblastoma patients in Denmark. METHODS: We included prospectively recorded clinical data from 1364 adult patients with histologically verified glioblastoma from the Danish Neuro-Oncology Registry, 2009-2014. RESULTS: The age standardized incidence rate was 6.3/100,000 person-years for males and 3.9 for females and the median age was 66 years. The median overall survival was 11.2 months. There was an independently significant prognostic effect of age, performance status, cognitive symptoms, tumor diameter, multifocality, crossing midline, and contrast enhancement. For partial and total resection compared to biopsy only, the adjusted risk of dying was reduced by 43% (HR [CI] 0.57 [0.48-0.68]) and 51% (0.49 [0.40-0.60]), respectively. For patients receiving a partial and full radiochemotherapy regimen compared to no postsurgical treatment, the risk reduction was 56% (HR [CI] 0.44 [0.37-0.53]) and 70% (0.30 [0.25-0.35]), respectively. The full radiochemotherapy regimen was only allocated to 50% of the patients, 29% among the oldest (70+ years) and 60% among the younger (18-69 years). CONCLUSIONS: Glioblastoma patients had a poor overall survival but with several specific independent prognostic factors. Extensive cancer treatment was associated with an increasing survival in all age groups, but only half of the patients were sufficiently fit for a full regimen of postoperative combined radiochemotherapy.

Fluorescence-guided resection of gliomas.

INTRODUCTION: Malignant gliomas remain associated with a poor prognosis despite both surgical treatment and radiochemotherapy.Previous studies have shown that complete resection of contrast-enhancing tumours is achieved in less than 20-30% of patients. 5-aminolevulinic acid (5-ALA) is a pro-drug that leads to accumulation of fluorescent protoporphyrins in malignant gliomas. The fluorescence can be visualized intraoperatively by use of a modified microscope. The Department of Neurosurgery at Aalborg Hospital has recently adopted this new technique as the first centre in Denmark. Our preliminary results are presented as a retrospective case series. MATERIAL AND METHODS: All patients who had undergone 5-ALA fluorescence-guided surgery due to suspected malignant glioma were included. Patients received a standard preoperative dose of Gliolan. All patients had a postoperative cerebral magnetic resonance imaging scan done within 72 hours to determine their postoperative resection status. RESULTS: To date, 13 patients have undergone fluorescence-guided surgery. Total resection was achieved in 54-70% of the patients depending on the inclusion criteria. Total or near total resection was achieved in 92% of patients. CONCLUSION: The small numbers in our case series do not allow for direct comparison to be made, but show that our results on postoperative resection status fall within the range reported in other studies on the efficacy of 5-ALA. The literature offers mounting evidence in support of the role of aggressive cytoreductive surgery in patients with malignant gliomas. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.