The solitary pulmonary nodule: Assessing the success of predicting malignancy Poster No.: C-0829 Congress: ECR 2010 Type: Scientific Exhibit Topic: Chest Authors: R. W. K. Lindsay, J. Foster, K. McManus; Belfast/UK Keywords: Lung cancer, Differential Diagnosis, Solitary Pulmonary Nodule DOI: 10.1594/ecr2010/C-0829 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 14
Purpose A solitary pulmonary nodule (SPN) can defined as a single discrete pulmonary opacity that is surrounded by normal lung tissue and is not associated with adenopathy or atelectasis. The solitary pulmonary nodule remains a diagnostic problem. lthe initial workup of these lesions includes clinical history, CT chest, PET/CT scan, bronchoscopy, biopsy and surgical resection. A number of articles have reported the significance of various CT features in determining risk of malignancy. (1, 2, 3) Spiculation is the most significant positive finding and should be recorded if present (OR 5.8) Site, size and cavitation are all relevant. Calcification is a significant negative indicator of malignancy. Solitary pulmonary nodule (SPN) calculators exist (eg. www.chestx-ray.com/spn/spnprob) which can help rate the risk of a SPN being malignant. The advent of PET has increased the sensitivity and specificity of imaging in differentiating between benign and malignant nodules. Shim et al. (6) and Herder et al. (7) found that PET/CT increased the sensitivity, specificity and accuracy of detection of malignant nodules as compared to CT alone. Brant and Cerfolio (8) highlighted that a number of malignancies are commonly PET negative, limiting the specificity of PET. lwww.chestx-ray.com/spn/spnprob uses a figure of 2.5 as the level above which the risk of malignancy rises, but literature indicates that SUV levels are more dynamic The aim of this project was to follow-up all patients referred as suspected T1 N0 M0 lung cancers to regional MDT, to define the natural history of radiologically suspicious nodules in our population. We also aimed to assess the value of each step in the investigative process in predicting or excluding malignancy, and the success of SPN calculators in predicting malignancy. We also aim to define the success of the regional MDT in differentiating benign lesions from malignant. Page 2 of 14
Images for this section: Fig. 1: Example of a solitary pulmonary nodule on CT. Page 3 of 14
Methods and Materials All patients referred to the Lung Cancer multi-disciplinary team (MDT) in the Northern Ireland Cancer Centre (NICC) as suspected T1 N0 M0 lung cancers were included in the review. The Lung MDT notes were reviewed to obtain the relevant clinical details (eg. age, smoking, pack years, haemoptysis etc.) Imaging (CT and PET/CT) for all these patients was reviewed. Surgical details of all patients referred to the thoracic surgery service were obtained The labs system was reviewed for each patient to check for pathology. Patients with a history of known metastatic malignancy were excluded. Patients whose imaging features were not consistent with T1 N0 M0 were excluded. Patients who had no pathological confirmation obtained were reviewed using serial CT. If a lesion remained stable, or resolved over the course of 24 months it was declared benign for the purposes of this review. Patients who did not have a >24 month period of follow-up were excluded. Using the solitary pulmonary nodule calculator (www.chestx-ray.com/spn/spnprob ) the risk for each nodule was calculated before and after PET results to allow the effect of PET to be assessed. Accuracy of CT was calculated. Receiver operator curves for CT risk (as per calculator), CT and PET risk, SUVmax were calculated. Images for this section: Page 4 of 14
Fig. 1: Example of a spiculated nodule Page 5 of 14
Fig. 2: Example of a nodule with a lobulated margin. Page 6 of 14
Fig. 3: Positive lesion on PET/CT Page 7 of 14
Results 76 patients were referred to the Lung MDT with suspected T1 N0 M0 lung cancer during the 30 month period of the review. 7 patients were excluded due to a previous history of metastatic malignancy (in four cases this was the cause of the nodule). Of 69 patients remaining one patient discharged himself from further follow up, 10 were discharged with a diagnosis of probable malignancy but unfit for treatment. Palliative care was to be arranged if when required. 3 patients were referred for radical radiotherapy - no tissue diagnosis was available to confirm the diagnosis of malignancy 3 patients are undergoing follow-up, but have not been monitored for more than 24 months. 50 patients were included in the group with either tissue diagnosis or with follow up of an unchanged or resolving lesion for greater than 24 months. 50% were male. 41.3 average pack years. Only 4 patients reported haemoptysis - possibly due to the small size of the lesions. 28 (56%) patients were diagnosed with malignancy. 22 were primary lung carcinoma, 21 non-small lung cancer and 1 small-call lung cancer. 5 patients had T2 lung cancer at resection. In two of these patients the tumours had increased in size during follow-up to T2 size. 3 patients had invasion of visceral pleura on histology, not evident on imaging (see image) 4 patients had nodal disease - this was detected in 50% on the PET scan. CT Overall accuracy of 56%. Given nature of the study group the sensitivity was 100%, but specificity is only 44%. Risk calculator tends to sacrifice specificity for sensitivity. PET/CT Adding PET result to the SPN calculator does improve sensitivity and specificity, but negates significance of SUVmax. Using the SPN calculator also excludes the interpretation of a nuclear medicine radiologist. Page 8 of 14
Using SUVmax alone obviously risks missing PET negative lesions. It also has a poor sensitivity and specificity when used in isolation from other imaging findings. For example an SUVmax of 5 has sens 72% and spec 73%, whilst SUV max of 4 has sens 81% and spec 66%. MDT - referrals for resection Given the limited specificity of diagnostic modalities there is an inevitable false positive rate amongst surgical candidates 25 patients underwent surgery on basis of imaging findings. 20 (80%) had malignancy found at pathology. 2 (8%) were found to be metastases from occult primaries. In the five patients with benign lesions resected only one patient had a calculated risk of greater than 80% 2 patients had calculated risk of under 20%. This implies a tendancy for over-referring to thoracic surgery. However, both cases of resected metastases had calculated risks of <20%. Of 27 patients with pathologically proven malignancy, 25 were referred to thoracic surgery. Other two had occult metastases picked up on subsequent imaging, not apparent on initial CT. Overall the sensitivity of the MDT decisions with respect to the ability to direct patients with malignancy for surgery over a 30 month period was 95% and specificity was 81% (PPV 95%;NPV 84%). This is more sensitive and specific than any of the methodologies alone. Images for this section: Page 9 of 14
Fig. 1: ROC curve for calculated risk as per SPN calculator for CT alone. Fig. 2: Tabulated results as demonstrated in above ROC graph for CT findings alone. Page 10 of 14
Fig. 3: ROC for calculated risk as per SPN calculator incorporating PET results along with CT findings. Fig. 4: Tabulated results as demonstrated in above graph for PET/CT findings. Page 11 of 14
Fig. 5: ROC curve showing value of SUV max alone in predicting malignancy in SPN. Page 12 of 14
Conclusion Why is MDT better? This format allows for an accurate clinical history to be provided by the referring clinician, as this is not invariably present on the form. It also allows for the interpretation of Imaging by specialists to encourage discussion and consensus opinions. Finally the most important factor is time. The MDT format allows for inconclusive nodules to be followed up to allow diagnosis to become apparent. Of the NSCLC group the average SUVmax was 7.32 (max 13.7, min 3.4). No lung cancer patients were PET negative. Two patients with metastases (cervical and breast) had SUVmax less than 2.5 Of the benign group average SUVmax was 3 (max 7.1, min 0) (Note the SPN calculator uses the level of 2.5 used to discriminate between benign and malignant). The risk of malignancy in a SPN deemed to be radiologically suspicious is 56%. This patient group is biased toward malignancy given that only radiologically suspicious nodules were referred to the MDT. The final study group is further biased as only patients suitable for treatment were followed up to diagnosis. CT alone is a sensitive modality for detection of lung malignancy, but it is not specific. Using a SPN calculator does improve sens. and spec. PET/CT incorporated into a SPN calculator has the most significant effect in increasing sensitivity and specificity using a risk of 90%. However the sensitivity and specificity of the Lung MDT decisions regarding need for surgery was 95% and 81% respectively. Thus the MDT forum for discussing potential lung carcinoma is the single most successful method of reducing unnecessary surgery and missing lung cancer. References Page 13 of 14
1) Swensen SJ, Silverstein MD, Ilstrup DM, Scleck CD, Edell, ES. The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminant nodules. Archives of Internal Medicine. 157 (8):849-55, 1997. 2) Gurney JW. Determining the likelihood of malignancy in solitary pulmonary nodules with Bayesian analysis. Part 1. Theory. Radiology. 186: 405-413, 1993 3) Gurney JW. Determining the likelihood of malignancy in solitary pulmonary nodules with Bayesian analysis. Part 2. Application. Radiology. 186: 415-422, 1993 Personal Information Page 14 of 14