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© 2003 American Society for Clinical Oncology
Prognostic Value of Timing of Pulmonary Metastases Identification in Osteosarcoma PatientsGeneral Surgery, Rizzoli Orthopaedic Institute, Bologna, Italy To the Editor:We read with great interest the recent article by Hiroyuki Tsuchiya1 about the prognostic value of timing of pulmonary metastases identification in osteosarcoma patients. On the basis of our personal experience of 281 consecutive pulmonary metastasectomies in osteosarcoma patients from June 1980 to June 2002,2,3 we agree with the Authors’ conclusion. Moreover, the patients we treated who were metastatic at presentation had a 5-year event-free survival of 23% and an overall survival of 27%. Furthermore, we would like to underline that, regarding lung metastases, the second relapse-free interval does not have as strong a prognostic role as the first. In fact, analyzing the data of a series of 65 patients operated on for repeated pulmonary localizations from 1980 to 1996, the most statistically important factors were age, the relapse-free interval after the first metastasectomy, the number of metastases, the presence of a local recurrence of the primary tumor, and the uni- or bilateral side of lesions. Applying a logistic regression model to our data to elaborate them contemporarily, we obtained a good sensitivity (0.833) and specificity (0.6) model, which demonstrated that prognosis is principally because of age (P = .04) and number of metastases (P = .03). On the contrary, the data concerning the side is not significant. In particular, the death probability is increased by a factor of 0.91 each year of age, 0.97 each month of relapse-free interval, 1.6 for each metastasis, and 2.48 in case of local recurrence. References
1. Tsuchiya H, Kanazawa Y, Abdel-Wanis ME, et al: Effect of timing of pulmonary metastases identification on prognosis of patients with osteosarcoma: The Japanese Muscoloskeletal Oncology Group Study. J Clin Oncol 20:3470–3477, 2002 2. Longhi A, Fabbri N, Donati D, et al: Neoadjuvant chemotherapy for patients with synchronous multifocal osteosarcoma: Results in eleven cases. J Chemother 13:324–330, 2001[Medline] 3. Bacci G, Briccoli A, Ferrari S, et al: Neoadjuvant chemotherapy for osteosarcoma of the extremity: Long-term results of the Rizzoli’s 4th protocol. Eur J Cancer 37:2030–2039, 2001[CrossRef][Medline]
In Reply:Department of Orthopaedic Surgery, School of Medicine, Kanazawa University, Kanazawa, Japan In our article, we investigated the clinical course of patients with osteosarcoma after the patients develop lung metastasis, dividing the patients into four groups, depending on timing of identification of lung metastases.1 Few data exist on the literature about the effect of relapse of pulmonary metastatic disease from osteosarcoma on patient survival.2 Unfortunately, Professor Briccoli did not report the total survival of the 65 patients of recurrent pulmonary metastases reported in his letter. However, the data supplied by Professor Briccoli would be complementary to our data and an addition toward better understanding of the factors affecting the survival of osteosarcoma patients with pulmonary metastases at different stages of their disease. This might help to detect patients who are good candidates for metastasectomy. Unfortunately, our article is a multicenter study, and the questionnaire did not include sufficient data about the relapse of lung metastases, so we could not confirm the reproducibility of results obtained by Professor Briccoli on patients of our study. To answer his comments, timing of local recurrence of the primary tumor should also be considered.
We tested the prognostic importance of age and local recurrence of the primary tumor on the survival of all osteosarcoma patients with lung metastases that we reported in our article. With regard to age, patients were divided into six groups (<10, 10 to < 15, 15 to < 20, 20 to < 30, 30 to < 40, and In our patients, local recurrence of the primary tumor was reported in a total of 48 patients (17.1%). There was no significant difference in survival curves between these 48 patients and other patients (P = .1394). When the comparison was performed in each group (between the survival of patients who had local recurrence and those who did not), no significant difference could be detected (P = 0.2387 in group 1, 0.7067 in group 2, 0.7698 in group 3, and 0.5912 in group 4, and hazard ratio was 1.299 [P = .1380; 95% CI, 0.919 to 1.837]). However, patients who did not receive surgical excision for local recurrence (n = 15) had a definitely shorter survival (hazard ratio 3.069; P = .0001; 95% CI, 1.721 to 5.475). Local recurrence of the primary lesion might not be the major factor on prognosis in patients who already have pulmonary metastases. Therefore, it is very important to know which is first—local tumor recurrence or lung metastasis—and which patients have both local tumor recurrence and lung metastases simultaneously. Our results seem to agree with the results obtained by Tabone et al,4 who reported on 42 cases of recurrence that occurred in initially nonmetastatic osteosarcoma. The survival rate was better in patients with a local or a pulmonary first recurrence than in patients who had local recurrence to bone, soft tissues, or multiple sites. The most important prognostic indicator at first recurrence was the possibility of complete resection of the disease. In their study, patients not amenable to surgery had a poor prognosis. The reported data in our article, together with this letter, further ensure the need for development of novel therapeutic modalities for treatment of pulmonary metastases from osteosarcoma, other than metastasectomy, to be used in patients who have well-recognized bad prognostic factors. References
1. Tsuchyia H, Kanazawa Y, Abdel-Wanis ME, et al: Effect of timing of pulmonary metastases identification on prognosis of patients with osteosarcoma: The Japanese Musculoskeletal Oncology Group Study. J Clin Oncol 20:3470–3477, 2002
2. Kandioler D, Kromer E, Tuchler H, et al: Long-term results after repeated surgical removal of pulmonary metastases. Ann Thorac Surg 65:909–912, 1998
3. Meyers PA, Heller G, Healey JH, et al: Osteogenic sarcoma with clinically detectable metastasis at initial presentation. J Clin Oncol 11:449–453, 1993
4. Tabone MD, Kalifa C, Rodary C, et al: Osteosarcoma recurrences in pediatric patients previously treated with intensive chemotherapy. J Clin Oncol 12:2614–2620, 1994 This article has been cited by other articles:
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Copyright © 2003 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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40 years of age). No difference in survival curve in the six groups could be detected (P = .6964). Hazard ratio was 0.989 (P = .135; 95% confidence interval [CI], 0.974 to 1.004). Although the difference between groups was not statistically significant, the death probability decreased 0.011 (1 to 0.989) each year of age. Meyers et al
