A Retrospective Study of Extremity Osteosarcoma Patients Who Recieved Intra-arterial Limb Infusion of Cisplatin During Neoadjuvant Chemotherapy

Between December 2009 and August 2014, 119 consecutive extremity osteosarcoma patients were initially treated in Peking University People's Hospital, which were reviewed by the investigators.

The investigators generally recommended neoadjuvant therapy followed by delayed definitive surgery and adjuvant chemotherapy after diagnosis of high-grade osteosarcoma. Patients routinely received neoadjuvant chemotherapy according to the Peking University People's Hospital-Osteosarcoma (PKUPH-OS) regimen, which began in 2008. Generally speaking,the investigators divided neoadjuvant chemotherapy protocols with IA infusion of cisplatin into three small cohorts, and all of these protocols consisted of adriamycin/doxorubicin, cisplatin, and high-dose methotrexate with or without ifosfamide with a time interval of 6-9 weeks. Doxorubicin was usually given for two courses preoperatively, and each course was given as a 3-h pump drip of 2 x 30 mg/m2/d on consecutive days (weeks 0, 6) after cisplatin infusions (weeks 0, 6), followed by two courses of high-dose methotrexate at 8-12 g/m2 with leucovorin rescue, 12 x 9 mg/m2/ i.m. per course. Ifosfamide at 5 x 2.4 g/m2 as 2-h infusions and uromitexan uroprotection was occasionally added to the protocol due to a slow response or huge tumor volume. Cisplatin was administered intravenously or intraarterially after adequate IV hydration. For IA infusion, cisplatin was given via insertion of a catheter percutaneously by using the Seldinger technique through the brachial or femoral artery under anesthesia and usually at 120 mg/m2 as a 3-h/6-h continuous infusion; while for IV administration, it was given at 100-120 mg/m2 as 6-h infusions.

Arteriograms were obtained before the administration of each dose of cisplatin. The last anteroposterior and lateral images obtained in the arteriographic sequence, which demonstrated complete contrast agent filling of the target trunk vessel (i.e., the last full column), were chosen from each arteriogram used for interpretation and comparison with future studies. Only those cases with at least two IA infusions of cisplatin could evaluate the TNV change in tumors. The volume and intensity of TNV on the baseline arteriogram were assessed and compared with those on subsequent arteriograms to assess the rate of change of TNV as an indicator of the tumor response, and only those with more than 90% disappearance of TNV were considered a good response for TNV, or else they were considered a poor response for TNV.

Definitive surgery was scheduled at least 2 weeks after the end of routine cisplatin infusion with the intention of achieving wide surgical margins. All pathology slides were reviewed by two senior pathologists (SKK and SDH). They evaluated all surgical specimens and were blinded to the clinical status. Upon histopathological examination, the tumor response was assessed on the basis of the presence and extent of necrosis, which was determined by a combination of gross and microscopic observations. Tumor necrosis was graded as per Picci et al.[26] histopathological response grading system (Huvos classification), where at least 90% necrosis was defined as a good response and less than 90% necrosis was defined as a poor response. Adjuvant chemotherapy was sequentially performed with the PKUPH-OS protocol for at least 30 weeks after surgery.

Baseline chest CT, bone scans, or positron emission tomography (PET)/CT was used to assess metastatic disease. Patients' follow-up included chest CT, local radiographs, and ultrasound/local CT scans every 3 months, as well as bone scans or PET/CT every 6 months during treatment and two years after completion of adjuvant therapy. During the third to fifth year, chest and pelvic CTs were obtained every 6 months and then yearly thereafter.