Ladekarl Morten, Nøhr Anne Krogh, Sønderkær Mads, Dahl Simon Christian, Sunde Lone, Vestereghem Charles, Mapendano Christophe Kamungu, Haslund Charlotte Aaquist, Pagh Anja, Carus Andreas, Lörincz Tamás, Nowicka-Matus Kinga, Poulsen Laurids Ø, Laursen René Johannes, Dybkær Karen, Poulsen Birgitte Klindt, Frøkjær Jens Brøndum, Brügmann Anja Høegh, Ernst Anja, Wanders Alkwin, Bøgsted Martin, Pedersen Inge Søkilde
Department of Oncology and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Acta Oncol. 2023 Mar;62(3):261-271. doi: 10.1080/0284186X.2023.2185542. Epub 2023 Mar 11.
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.
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.
80% ( = 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 ( = 44) of patients who underwent molecularly profiling were matched with a targeted treatment, however, only 16% were either treated ( = 16) or are waiting for treatment ( = 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.
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.
我们的目标是描述一家地区性学术医院的精准医疗项目，刻画纳入患者的特征，并展示有关临床影响的早期数据。
在2020年6月至2022年5月的Proseq癌症试验中，我们前瞻性地纳入了163例符合条件的任何诊断的晚期癌症患者。通过全外显子测序（WES）和RNA测序对新的或新鲜冷冻的肿瘤活检组织进行分子分析，并对非肿瘤DNA进行平行测序作为个体对照。病例提交至国家分子肿瘤委员会（NMTB）讨论靶向治疗。随后，对患者进行至少7个月的随访。
80%（n = 131）的患者成功完成分析，96%的患者检测到至少一个致病或可能致病的变异。分别在19%和73%的患者中发现了强可靶向或潜在可靶向的变异。2.5%的患者鉴定出种系变异。从试验纳入到NMTB做出决定的中位时间为1个月。接受分子分析的患者中有三分之一（n = 44）匹配到了靶向治疗，但只有16%的患者接受了治疗（n = 16）或正在等待治疗（n = 5），功能状态恶化是治疗失败的主要原因。一级亲属中有癌症病史以及肺癌或前列腺癌诊断与有更多机会获得靶向治疗相关。靶向治疗的缓解率为40%，临床获益率为53%，中位治疗时间为3.8个月。在NMTB就诊的患者中有23%被推荐参加临床试验，这与生物标志物无关。
在地区性学术医院，晚期癌症患者的精准医疗是可行的，但由于受益患者较少，应在临床方案框架内继续开展。与综合癌症中心密切合作可确保专家评估以及平等参与早期临床试验和获得现代治疗的机会。
