1. Nick Wegner 4/22/10 The Use of CT in Diagnosing Pulmonary Metastases in Osteosarcoma

2. JN 15 y/o male with no sig PMH that initially presented to PCP in Tacoma with 4 x 4 cm LLE proximal tibial swelling. X-rays showed proximal tibia soft tissue swelling and calcifications. MRI at OSH significant for enhancing, lobulated mass involving the medial aspect of the proximal left tibial metaphysis, with associated soft tissue component. PMH: Learning difficulties PSH: none Meds: None All: chlorhexidine, reglan, vancomycin ROS: 1.5 year hx of recurrent flu-like episodes with fatigue and wt loss. CBC: Hct 44.5, Plts 209, WBC 6.9, ANC 4023 Imaging:

3.  Tibial X-ray JN

6. JN Clinical Course 10/09: – Biopsy of Mass: Chondroblastic Osteosarcoma – CT Chest: No mets – PET scan: No mets 11/09 – Started on Neoadjuvant chemo: High dose Methotrexate, Cisplatin/Doxorubicin 1/10 – Limb sparing resection of osteosarcoma with osteocondral graft reconstruction.

7. JN Clinical Course 1/10 – Restarted on Chemo regimen post-op: High dose Methotrexate, Cisplatin/Doxorubicin 3/10 – Admitted for enterococcus line infection – CVC replaced with Hickman catheter

8. JN Clinical Course  4/10 Restaging CT Chest Multiple new ill-defined nodules within the left lower lobe superior segment General Surgery Consulted for evaluation of possible biopsy

9. CT Chest

11. Clinical Questions  Focus Why is a presence of a pulmonary metastsis important in this patients prognosis Accuracy of CT scanning in diagnosing pulmonary metastases CT features that make a pulmonary nodule more/less likely metastatic

12. Survival according to presence of metastatic disease at time of diagnosis  Retrospective study  Osteosarcoma patients (1977-1997) with pulmonary nodules on chest CT 32 of 215 pt diagnosed with metastatic osteosarcoma (15%) 31 with lung mets only, 1 with bone mets  Pulmonary Metastases Parenchymal nodules Subpleural opacities  Thoracotomy: persistent pulmonary nodules at wk 9 of chemo nodules increasing in size/number of nodules Kaste et al. Cancer 1999;86: 1602-1608

13. Survival according to presence of metastatic disease at time of diagnosis Findings: 5 yr survival in metastatic group = 29 +/- 8%. 5 yr survival in nonmetastatic group = 69 +/- 4%  4 of 28 patients with mets had calcifications seen on CT  5% of patients underwent negative thoracotomy (1/23)

14. Overall Survival according to presence of metastatic disease at time of diagnosis Kaste et al. Cancer 1999;86: 1602-1608

15. Overall Survival according to presence of metastatic disease at time of diagnosis  Factors affecting Prognosis Multiple lesions Multiple lobe involvement Kaste et al. Cancer 1999;86: 1602-1608 Factors affecting Overall Survival

16. How accurate are CT scans in pulmonary Staging of Osteosarcoma?  51 consecutive patients with lung nodules on initial CT chest had lung surgery with histological diagnosis of lesions CT reviewed by radiologists from 2 sarcoma groups  Pre-op CT found 143 and 146 nodules in the 51 patients  Total of 204 nodules discovered on thoracotomy.  109 of 204 nodules excised during surgery were metastatic Positive Predictive value of 53% of nodules  Metastases in 29 of 51 patients Positive Predictive value of 57% of patients  22 patients (43%) biopsied had no metastases (59 negative biopsies) Picci et al. Annels of Oncology 2001;12: 1601-1604

17. Factors linked to metastatic nodules  Factors related to false positive nodules (benign) Number of nodules unchanged during pre-op chemo 46 patients with multiple CTs Initial size of nodules <5mm* No change in size of nodules during pre-op chemo*  Factors related to true positive lesions (mets) Increase or decrease in number of nodules* Increase or decrease in size of nodules* *not statistically significant Picci et al. Annels of Oncology 2001;12: 1601-1604

18. Important Results  CT scan does not recognize many pulmonary nodules seen on subsequent thoracotomy.  Little predictive information can be gain from the appearance of the nodule on CT scan.

19. How accurate are CT scans in Pulmonary Staging of Osteosarcoma ?  Retrospective Study of 54 thoracotomies on 28 patients for pulmonary nodules on CT CT scans reviewed by 2 pediatric radiologist blinded to path results  183 lung nodules on pre-op CT scans 329 lung nodules resected, with 209 metastatic nodules Kayton et al. Journal of Pediatric Surgery 2006;41: 200-206

20. How do CT scan and Thoracotomy Results Correlate Correlation  CT underestimated number of mets in 19/54 thoracotomies (35%)  Exact concordance in 15/54 thoracotomies (28%)  Overestimated number of mets in 20/54 thoracotomies (37%) Overall correlation coefficient of.45  8 thoracotomies with no nodules on pre-op CT ○ 4/8 with metastases  7 negative thoracotomies (15% neg. thoracotomy rate) Kayton et al. Journal of Pediatric Surgery 2006;41: 200-206

21. CT Scan vs. Thoracotomy results Kayton et al. Journal of Pediatric Surgery 2006;41: 200-206

22. Important Findings  Poor correlation in number of nodules seen on CT scan compared with those palpated on thoracotomy  Negative thoracotomy rate of 15% using bilateral staged thoracotomy for resection.  CT scans to not provide and adequate pre- operative depictions of all nodules.

23. Can CT scan differentiate between benign and malignant pulmonary nodules?  Retrospective study of 41 pediatric patients with primary malignant solid tumors  81 total lung nodules biopsied within 3 weeks of obtaining CT scans  24/41 had metastatic disease (58%) 15 patients had multiple biopsies 4/15 had both benign and malignant nodules  17/21 had only benign nodules (42%) McCarville et al. Radiology 2006 239: 514-520

24. Can CT scan differentiate between benign and malignant pulmonary nodules?  3 Reviewers viewed pre-op CT scans  Classified lesions as: 1. Benign 2. Intermediate 3. Malignant  Criteria used to classify Number of nodules Size Nodule Margin Pattern of Calcification Calcification Growth Associated adenopathy New Nodules at follow-up Hilar/Mediastinal Adenopathy

25. Can CT scan differentiate between benign and malignant pulmonary nodules?  Reviewer 1: 65% of nodules ID correctly ○ Malignant pred value: 0.93 ○ Benign Pred value: 0.74  Reviewer 2: 57% of nodules ID correctly ○ Malignant Pred value: 0.57  Reviewer 3: 67% of nodules ID correctly ○ Malignant Pred value: 0.73, ○ Benign Pred value 0.74  Interreviewer agreement was low (<0.43) between all three reviewers.  Maximum of 65/81 nodules were recognized on CT scan McCarville et al. Radiology 2006 239: 514-520

26. CT findings associated with correctly diagnosis of malignant lesions McCarville et al. Radiology 2006 239: 514-520 Distinct nodule margins (P < 0.03) Development of new nodules (P < 0.03) Bilateral nodules* Large number of nodules* * not statistically significant

27. Overall Important Findings  CT scan consistently misses nodules found on palpation at thoracotomy  Difficult to assess whether nodules seen on CT scan are malignant vs. benign  Malignant Findings in Kids ○ Distinct Margin ○ Development of new nodules ○ Small size (<5 mm) just as likely to be malignant as larger nodules

28. Future Recommendations  New research in imaging modalities needed to evaluate pulmonary mets Consider PET/CT scans to evaluate metabolic level of lesions to see if correlates with metastases

29. Works Cited 1. Kaste et al. Metastases Detected at the Time of Diagnosis of Primary Pediatric Extremity Osteosarcoma at Diagnosis: Imaging Features. Cancer 1999;86: 1602-1608 2. McCarville et al. Distinguishing Benign form Malignant Pulmonary Nodules with Helical Chest CT in Children with Malignant Solid Tumors Radiology 2006 239: 514-520 3. Picci et al. Computed tomography of pulmonary metastases from osteosarcoma: The less poor technique. A study of 51 patients with histological correlation. Annels of Oncology 2001;12: 1601-1604 4. Kayton et. al. Computed tomographic scan of the chest underestimates the number of metastatic lesion in osteosarcoma. Journal of Pediatric Surgery 2006;41: 200-206. 5. Absalon et. al. Pulmonary Nodules Discovered During the Initial Evaluation of Pediatric Patients with Bone and Soft-Tissue Sarcoma. Pediatric Blood Cancer 2008;50: 1147-1153.