{
  "abstract": "Objectives Delays in cancer diagnosis for patients with non-specific symptoms (NSSs) lead to poorer outcomes. Rapid Diagnostic Clinics (RDCs) expedite care, but most NSS patients do not have cancer, highlighting the need for better risk stratification. This study aimed to develop biomarker-based clinical prediction scores to differentiate high-risk and low-risk NSS patients, enabling more targeted diagnostics.Design Retrospective and prospective cohort study.Setting Secondary care RDC in London.Participants Adult patients attending an RDC between December 2016 and September 2023 were included. External validation used data from another RDC.Outcome measures The primary outcome was a cancer diagnosis. Biomarker-based risk scores were developed using Latent Class Analysis (LCA) and Least Absolute Shrinkage and Selection Operator (LASSO). Model performance was assessed using logistic regression, receiver operating characteristic curves (AUROC) and decision curve analysis.Results Among 5821 RDC patients, LCA identified high white cell count, low haemoglobin, low albumin, high serum lambda light chain, high neutrophil-to-lymphocyte ratio, high serum kappa light chain (SKLC), high erythrocyte sedimentation rate (ESR), high C-reactive protein (CRP) and high neutrophils as cancer risk markers. LASSO selected high platelets, ESR, CRP, SKLC, alkaline phosphatase and lactate dehydrogenase. Each one-point increase in score predicted higher odds of cancer (LCA: AOR 1.19, 95% CI 1.16 to 1.23; LASSO: AOR 1.29, 95% CI 1.25 to 1.34). Scores ≥2 predicted significantly higher cancer odds (LCA: AOR 3.79, 95% CI 2.91 to 4.95; LASSO: AOR 3.44, 95% CI 2.66 to 4.44). Discrimination was good (AUROC: LCA 0.74; LASSO 0.73). External validation in 573 patients confirmed predicted increases in cancer risk per one-point LASSO score rise (AOR 1.28, 95% CI 1.15 to 1.42), with a borderline increase for LCA (AOR 1.16, 95% CI 1.06 to 1.27).Conclusion Biomarker-based scores effectively identified NSS patients at higher cancer risk. LCA captured a broader biomarker range, offering higher sensitivity, while LASSO achieved higher specificity with fewer markers. These scores may also help detect severe benign conditions, improving RDC triage. Further validation is needed before broader clinical implementation.",
  "authors": [
    {
      "affiliations": [
        "Transforming Cancer Research Outcomes Through Research (TOUR), King’s College London, London, UK"
      ],
      "name": "Maria Jose Monroy-Iglesias"
    },
    {
      "affiliations": [
        "Transforming Cancer Research Outcomes Through Research (TOUR), King’s College London, London, UK"
      ],
      "name": "Aida Santaolalla"
    },
    {
      "affiliations": [
        "Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London, England, UK"
      ],
      "name": "Sabine Martin"
    },
    {
      "affiliations": [
        "Cancer Prevention Trials Unit, Cancer Prevention Group, King’s College London, London, UK"
      ],
      "name": "Bernard North"
    },
    {
      "affiliations": [
        "Transforming Cancer Research Outcomes Through Research (TOUR), King’s College London, London, UK"
      ],
      "name": "Charlotte Moss"
    },
    {
      "affiliations": [
        "South East London Cancer Alliance, London, England, UK"
      ],
      "name": "Kate Haire"
    },
    {
      "affiliations": [
        "South East London Cancer Alliance, London, England, UK"
      ],
      "name": "Geraint Jones"
    },
    {
      "affiliations": [
        "Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London, England, UK"
      ],
      "name": "Lindsay Steward"
    },
    {
      "affiliations": [
        "Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London, England, UK"
      ],
      "name": "Carlos Cargaleiro"
    },
    {
      "affiliations": [
        "Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London, England, UK"
      ],
      "name": "Flaminia Bruno"
    },
    {
      "affiliations": [
        "Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London, England, UK"
      ],
      "name": "Juliet Millwaters"
    },
    {
      "affiliations": [
        "Specialist Medicine, Queen Elizabeth Hospital, Lewisham & Greenwich NHS Trust, London, England, UK"
      ],
      "name": "Chandra Basyal"
    },
    {
      "affiliations": [
        "Specialist Medicine, Queen Elizabeth Hospital, Lewisham & Greenwich NHS Trust, London, England, UK"
      ],
      "name": "Sarah Weild"
    },
    {
      "affiliations": [
        "Transforming Cancer Research Outcomes Through Research (TOUR), King’s College London, London, UK"
      ],
      "name": "Beth Russell"
    },
    {
      "affiliations": [
        "Transforming Cancer Research Outcomes Through Research (TOUR), King’s College London, London, UK"
      ],
      "name": "Mieke Van Hemelrijck"
    },
    {
      "affiliations": [
        "Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London, England, UK"
      ],
      "name": "Saoirse Dolly"
    }
  ],
  "title": "Exploring a panel of serum biomarkers for cancer risk in patients with non-specific symptoms: a comparative analysis of feature selection methods",
  "uid": "cf4b1eee-4c9b-52e7-bfc6-aafc3edd8470"
}