CancerCalc

Clinical tools for oncology professionals

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Pulmonary nodule malignancy risk score

1. Select model:
Brock score Estimates probability that a lung nodule will be diagnosed as cancer over a 2 to 4 year period.
Herder score Estimates probability that a lung nodule will be diagnosed as cancer.
Volume doubling time (VDT) Volume doubling time between two imaging time points can be used to predict risk of malignancy in pulmonary nodule.

Age:
years


Nodule size:
mm


Current or former smoker:


Past history of extra-thoracic cancer:


Upper lobe tumour location:


Spiculation:


FDG-PET uptake:


Age:
years


Gender:


Family history of lung cancer:


Emphysema:


Nodule size:
mm


Nodule type:


Upper lobe location:


Nodule count:


Spiculation:




Select VDT method:
Volumetric method Calculates volume doubling time using user entered nodule volume. Nodule volume should be measured by volumetry where possible.
Diameter method (XYZ plane) Estimates nodule volume using diameters in the X,Y and Z planes. This is less accurate than volumetric based method.
Spherical method Can be used to estimate nodule volume where nodule is relatively spherical in shape. This is less accurate than volumetric based method.


Time point 1:

Date:
Volume: Nodule volume should be measured using a volumetry package where possible.
mm3



Time point 2:

Date:
Volume: Nodule volume should be measured using a volumetry package where possible.
mm3
Time point 1:

Date:


Largest diameter X/Y axis:
mm


Perpendicular diameter X/Y axis:
mm


Largest diameter Z axis:
mm



Time point 2:

Date:


Largest diameter X/Y axis:
mm


Perpendicular diameter X/Y axis:
mm


Largest diameter Z axis:
mm
Time point 1:

Date:


Diameter:
mm
Volume: mm3



Time point 2:

Date:


Diameter:
mm
Volume: mm3
Score:

Pulmonary nodule malignancy risk score: Herder score, Brock score & Volume Doubling Time

Interpretation:
Pulmonary nodules identified on radiological imaging pose a diagnostic challenge. Predictive models aid decision making in managing indeterminate pulmonary nodules.

Herder score:
This model is based on an initial retrospective cohort study by Swensen et al consisting of 629 patients (320 men, 309 women) from a US population with newly diagnosed solitary pulmonary nodules on chest radiography (1). Two-thirds of the cohort (n=419) were used to develop the prediction model and the remaining patients were used as a validation data-set.

The model was extended by Herder et al to include FDG PET scanning which increased the model accuracy (2). This study included 106 patients and the combined model using predictive variables and FDG-PET scanning achieved an AUC of 0.92 (95% CI 0.87-0.97).

The original model excluded patients with history of extra-thoracic malignancy diagnosed ≤ 5 years previously. Recent validation has shown similar accuracy in patients with more recent history of extra-thoracic cancer (3). Therefore, any history of extra-thoracic cancer should be answered ‘yes’.

The model has been further validated in independent studies (3,4). Al-ameri et al found that in patients undergoing FDG-PET imaging the Herder model provided greater accuracy than the Brock model.

Brock score:
This model was developed from a population of 2537 patients enrolled in the PanCan study and a validation dataset of 1090 patients enrolled in the BCCA study. The final model showed AUC of >0.90 in the test and validation cohorts (5).

Brock and Herder scores in clinical decision making:
The BTS guidelines(7) suggest performing FDG-PET scan where the Brock model risk of malignancy is >10%.
After PET scan, the following action is suggested according to the Herder score.
  • Low risk ( <10%): Surveillance
  • Intermediate risk (10-70%): Biopsy
  • High risk (>70%): Surgery
Volume doubling time (VDT)
VDT assessment is helpful during follow up surveillance of indeterminate pulmonary nodules, in particular where initial risk assessment (using the Brock or Herder tools) estimates the risk of malignancy to be ≤10% (7).

Nodules showing VDT of <400 days or significant growth of ≥25% should be considered for further diagnostic investigation (biopsy or resection)(8).

In the Nelson trial, UK Lung Cancer Screening trial and the Danish Lung Cancer Screening trial, a VDT < 400 was used as trigger for further diagnostic investigation (9–10).

In the Nelson trial, risk of lung cancer according to VDT was as follows:
  • VDT > 600 days: 0.8% (95% CI 0·4-1·7)
  • 400-600 days: 4% (95% CI 1·8-8·3)
  • < 400 days: 9.9% (95% CI 6·9-14·1)

VDT should not be considered in isolation and management should be guided by specialist multidisciplinary review. Caveats include new solid growth in a non-solid nodule or growth in the solid component of a semi-solid nodule, irrespective of VDT.

Formulae:
The modified Schwartz formula is used to calculate VDT as follows:

VDT = (ln (T))/ ((ln(V2/V1))
Where:
Ln = Natural logarithm
T = Time in days between the two scans
V2 = Nodule volume at time point 2
V1 = Nodule volume at time point 1

For the diametric method, nodule volume is calculated as:
Nodule volume = X x Y x Z
Where:
X= Maximal diameter in X plane
Y = Diameter perpendicular to diameter X
Z = Diameter in Z axis

For the spherical method, nodule volume is calculated as:
Nodule volume = (D3 x ℼ)/6
Where D = nodule diameter

References:
  1. Swensen SJ, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES. The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules. Arch Intern Med. 1997;157(8):849-855.
  2. Herder GJ, van Tinteren H, Golding RP, et al. Clinical prediction model to characterize pulmonary nodules: validation and added value of 18F-fluorodeoxyglucose positron emission tomography. Chest. 2005;128(4):2490-2496. doi:10.1378/chest.128.4.2490
  3. Al-Ameri A, Malhotra P, Thygesen H, et al. Risk of malignancy in pulmonary nodules: A validation study of four prediction models. Lung Cancer. 2015;89(1):27-30. doi:10.1016/j.lungcan.2015.03.018
  4. Schultz EM, Sanders GD, Trotter PR, et al. Validation of two models to estimate the probability of malignancy in patients with solitary pulmonary nodules. Thorax. 2008;63(4):335-341. doi:10.1136/thx.2007.084731
  5. McWilliams A, Tammemagi MC, Mayo JR, et al. Probability of Cancer in Pulmonary Nodules Detected on First Screening CT. N Engl J Med. 2013;369(10):910-919. doi:10.1056/NEJMoa1214726
  6. Gould MK, Sanders GD, Barnett PG, et al. Cost-Effectiveness of Alternative Management Strategies for Patients with Solitary Pulmonary Nodules. Ann Intern Med. 2003;138(9):724-735. doi:10.7326/0003-4819-138-9-200305060-00009
  7. Callister MEJ, Baldwin DR, Akram AR, et al. British Thoracic Society guidelines for the investigation and management of pulmonary nodules: accredited by NICE. Thorax. 2015;70(Suppl 2):ii1 LP-ii54. doi:10.1136/thoraxjnl-2015-207168
  8. Wille MMW, Dirksen A, Ashraf H, et al. Results of the Randomized Danish Lung Cancer Screening Trial with Focus on High-Risk Profiling. Am J Respir Crit Care Med. 2016;193(5):542-551. doi:10.1164/rccm.201505-1040OC
  9. de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial. N Engl J Med. 2020;382(6):503-513. doi:10.1056/NEJMoa1911793
  10. Field JK, Vulkan D, Davies MPA, et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis. Lancet Reg Heal – Eur. 2021;10. doi:10.1016/j.lanepe.2021.100179