The Value of Serial Arteriography in Osteosarcoma: Delivery of Chemotherapy, Determination of Therapy Duration, and Prediction of Necrosis

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PURPOSE

To investigate the value of serial arteriography to assess tumor response, predict necrosis, and individualize the duration of a combined intravenous (IV) and intraarterial (IA) neoadjuvant chemotherapy protocol in patients with biopsy-proven high-grade osteosarcoma or malignant fibrohistiocytoma of bone.

MATERIALS AND METHODS

Between July 1987 and March 2003, 109 patients completed a chemotherapy protocol of neoadjuvant IV doxorubicin and IA cisplatin. Patients were eligible regardless of age, disease stage, or disease site. A minimum of three IA cycles followed by definitive surgery was required for inclusion in the final analysis. IA dose and duration were increased for tumors larger than 10 cm. Initial arteriograms were scored as indicating mild, moderate, or marked tumor neovascularity (TNV). Subsequent arteriograms were prospectively compared with the baseline image for percent change in TNV. Treatment continued until a maximum of five cycles were administered or one of three criteria were met: (i) at least 90% decrease in TNV, (ii) plateau of effect, or (iii) no response.

RESULTS

Of 408 IA procedures, 42 patients underwent three cycles, 53 underwent four, and 14 required five cycles of neoadjuvant therapy. There was a 2.5% minor complication rate. Eighty-six percent of patients exhibited at least 90% decrease in TNV and 82% exhibited good histologic response (≥90% tumor necrosis). Serial arteriography predicted a good histologic response with an accuracy of 90% and a sensitivity of 97%.

CONCLUSIONS

Serial arteriography was highly sensitive and accurately predicted good responses. This individually modified, dose-intensified neoadjuvant protocol yielded an excellent histologic response rate with minimal complications. Future endeavors should involve a multiinstitutional study of this unique approach.

Section snippets

Study Design

This was a prospective, institutional review board–approved, single-arm study of newly diagnosed high-grade osteosarcoma and MFH of bone. All arteriography procedures and IA infusions were performed at a single institution (Presbyterian/St. Luke's Medical Center, Denver, CO).

To be eligible, patients were required to have biopsy-proven newly diagnosed high-grade osteosarcoma or MFH of bone. In the majority of cases, adequate biopsy tissue was obtained via core needle technique. If this sample

RESULTS

A total of 109 patients underwent 408 arteriography procedures followed by an IA infusion of cisplatin. Two hundred seventy treatments were infused over 6-hour periods and 138 were infused over 24-hour periods. Forty-two patients received the minimum three cycles, 53 required four, and 14 received five neoadjuvant cycles. Tumor neovascularity was decreased by at least 90% in 88%, 89%, and 71% of patients who received three, four, and five cycles, respectively. Fifteen patients did not exhibit a

DISCUSSION

The histologic response to neoadjuvant therapy is one of the most important prognostic factors for long-term survival in nonmetastatic osteosarcoma (11). In a multivariate analysis of 1,702 patients, Bielack et al (12) found that histologic response was the most important prognostic factor for osteosarcoma of the extremity (P <.0001). Provisor et al (13) reported 8 year event-free survival and overall survival rates of 81% and 87%, respectively, for cases with good response, versus 46% and 52%,

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    From the 2004 SIR Annual Meeting.

    None of the authors have identified a conflict of interest.

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