Continuous Disease-free Survival Research Articles

Hypoxia-Inducible Factor-1α (HIF-1α) as a Factor to Predict the Prognosis of Spinal Chordoma.

Retrospective study. In this study, the authors explore the potential relationship between hypoxia inducible factor-1α (HIF-1α) and the prognosis of patients with spinal chordoma. Currently, prognostic factors related to the clinical course in the setting of spinal chordoma are poorly understood. Although the close relationship between HIF-1α and tumor angiogenesis, metastasis, and recurrence have been widely reported, it has not been investigated in the context of spinal chordoma. In this study, 32 samples of chordoma patients were compared with 14 nucleus pulposus tissues as controls. The specific expression of HIF-1α was detected by immunohistochemistry. Continuous disease-free survival (CDFS) was defined as the interval from tumor resection to confirmation of the first local recurrence or distant metastasis. Overall survival (OS) was defined as the interval from the date of surgery to death related to any cause. The relationship between HIF-1α expression and the clinicopathologic characteristics of patients with chordoma was analyzed using the Pearson χ 2 test. Multivariate Cox analysis was used to evaluate whether HIF-1α expression was associated with the prognosis of patients after controlling for confounders. HIF-1α was mainly expressed in the cytoplasm or nucleus in all of the chordoma samples, which showed significantly higher than that in the normal nucleus pulposus tissue ( P =0.004). Multivariate Cox regression analyses showed that high HIF-1α expression and location of HIF-1α expression were significantly associated with poor CDFS (hazard ratio (HR)=3.374; P =0.021) and OS (HR=4.511; P =0.012). In addition, we further found that high HIF-1α expression both in the cytoplasm and nucleus indicated a stronger prognostic factor for poor CDFS (HR=3.885; P =0.011) and OS (HR=4.014; P =0.011) in spinal chordoma patients. High HIF-1α expression may become a potential new biological indicator to predict a poor prognosis in patients with spinal chordoma. HIF-1α may also represent a novel therapeutic target for the treatment of spinal chordoma.

Treatment Outcomes of Langerhans Cell Histiocytosis: A Retrospective Study.

Background and Objectives: Langerhans cell histiocytosis (LCH) is a rare disease characterized by the infiltration of one or more organs by Langerhans cell-like dendritic cells. LCH often involves the bone, and its clinical evidence is limited. The purpose of this study is to report on the treatment of LCH at our institution and to add to the evidence for LCH. Materials and Methods: We reviewed six cases of LCH treated in our hospital between November 2005 and February 2016. Patient age at the first visit, sex, site of origin, symptoms, image tools used for diagnosis, biopsy site, complications, treatment, and final clinical outcome were evaluated. The median follow-up period was 41 months. Results: The median patient age at the first visit was 13.5 years. Three male and three female individuals were enrolled. Multiple lesions were observed in five cases, and a solitary lesion was observed in one case. Pain was the chief complaint in five cases. Radiography was the most commonly used imaging tool. Bone scintigraphy or magnetic resonance imaging and positron emission tomography-computed tomography were also used to diagnose systematic LCH. Biopsy of the femur was performed in two cases, and biopsy of the tibia, lumbar vertebrae, rib, and radius was performed in one case each. Regarding comorbidities, one case of hepatitis B and one case of autism were observed. Chemotherapy was initiated in two patients. The other four patients were observed naturally. Continuous disease-free survival was observed in five patients. One patient remained alive but not without disease during the final follow-up examination. Conclusion: LCH should be diagnosed as early as possible to treat it appropriately.

Cytotoxic T lymphocyte antigen-4 (CTLA-4) expression in chordoma and tumor-infiltrating lymphocytes (TILs) predicts prognosis of spinal chordoma.

Chordoma is a rare tumor of the skeletal system that is characterized by a high recurrence rate and treatment resistance. Given the common finding of immune dysregulation in chordoma, immunotherapy has emerged as potential treatment option. As an important immune checkpoint regulator, we evaluated cytotoxic T-lymphocyte antigen-4 (CTLA-4) expression and its prognostic significance for patients with chordoma of the spine. CTLA-4 expression was analyzed immunohistochemically in 32 chordoma tissues and 14 nucleus pulposus tissues to examine the specificity of CTLA-4 expression in chordoma. Univariate log-rank analysis was used to evaluate the association of CTLA-4 expression in tumor cells and tumor-infiltrating lymphocytes (TILs) with survival. Cox multivariate analysis was used to identify independent factors of survival. Positive CTLA-4 expression was observed in all of the TILs and tumor cell cytoplasm, and partial in the membrane or in both the membrane and nucleus, with a markedly higher positivity rate than that observed in normal nucleus tissues. Higher CTLA-4 expression in the tumor but not in TILs was significantly associated with shorter continuous disease-free survival (CDFS) and overall survival (OS). CTLA-4 expression in tumor cells and TILs were independent predictors for CDFS, whereas only tumor cell expression was a significant predictor of OS. Furthermore, the combination of CTLA-4 expression in the tumor and TILs had higher prognostic value. Targeting CTLA-4 may be a potential novel therapeutic strategy for chordoma patients.

PARP1 is a novel independent prognostic factor for the poor prognosis of chordoma.

To evaluate the expression of PARP1 in chordoma and analyzed its association with clinical factors and patients' prognosis. The expression of Poly (ADP-ribose) polymerase 1 (PARP1) in chordoma specimens from 74 chordoma patients (50 primary and 24 recurrent tumors of 50 patients)and 20 distant normal tissue specimens was measured by immunohistochemical staining. The association of PARP1with the clinical factors and patients' prognosis was also analyzed. Of all the chordoma samples, 78% showed high expression of PARP1, whereas, only 10% of distant normal tissues expressed a high level of PARP1 (p< 0.01). Chi-square analysis revealed that high expression of PARP1 was significantly correlated with tumor recurrence (p< 0.01) and invasion into surrounding muscle (p< 0.01), while the data did not indicate any association with patients' gender, age, tumor location and size (p> 0.05). Kaplan-Meier survival curve and log-rank test showed that continuous disease free survival time (CDFS) was significantly shorter in the PARP1-positive group than in the PARP1-negative group (P= 0.019). High expression of PARP1 is significantly associated with chordoma invasion and recurrence. PARP1 may become a potential biomarker for chordoma in predicting its recurrence and patients' prognosis.

Chemotherapy for bone sarcomas in adults: the MD anderson experience.

Increasing age is an adverse prognostic factor in the treatment of primary bone tumors. There are few published data on treatment of primary bone tumors in adults. This paper presents data from the Department of Sarcoma Medical Oncology at The University of Texas MD Anderson Cancer Center, summarizing our treatment results. To treat primary osteosarcoma, we used 90 mg/m2 of doxorubicin as a continuous intravenous infusion over 48 to 96 hours and 120 to 160 mg/m2 of cisplatin intravenously or intra-arterially. Initially, we found a marked difference in postoperative continuous disease-free survival (CDFS) between those with 90% or greater (i.e., good response) tumor necrosis and those with less than 90% (i.e., poor response) tumor necrosis. The sequential addition of high-dose methotrexate and ifosfamide to patients with poorly responding disease improved their CDFS to that of patients with good response. Older patients and those who have tumors with variant histology have inferior outcomes. Evaluation of subsequent patients revealed similar outcomes for those with good or poor response to induction therapy, supporting our practice of adaptation of postoperative chemotherapy to the results of preoperative chemotherapy. PET-CT is the best imaging modality to screen for a response with tumors inside bone. To treat Ewing sarcoma, we have employed 2 mg of vincristine, 75 to 90 mg/m2 of doxorubicin as a 72-hour infusion, and 2.5 g/m2 of ifosfamide over 3 hours daily for 4 doses (i.e., vincristine, doxorubicin, and ifosfamide [VAI]). Preliminary analysis indicates a higher CDFS when adjusted for patient age than seen with the standard alternating regimen used in pediatrics. A screening MRI of the pelvis and spine can detect subtle metastatic disease in bone or bone marrow that is missed by other imaging modalities or blind biopsy. Chondrosarcoma is treated surgically or on investigational protocols. Giant cell tumor of bone is usually managed surgically, but multiple options exist for medical treatment, and therapy is individualized with embolization, denosumab, and interferon.

High expression of SPHK1 in sacral chordoma and association with patients' poor prognosis.

Sacral chordoma is an aggressive bone tumor with a high local recurrence rate. Surgery remains the standard treatment because of its resistance to chemotherapy and radiotherapy. However, recurrence occurs frequently even after complete surgical resection. Great effort has been invested in discovering novel biomarkers and therapeutic targets. To date, the molecular mechanism is still unclear. In this study, we evaluated the expression of sphingosine kinase 1 (SPHK1) in 42 sacral chordoma samples and 16 distant normal tissue specimens by immunohistochemical staining. In addition, we analyzed its association with the clinical factors and patients' prognosis. Of all the chordoma samples, 69 % (29/42) showed high expression of SPHK1, whereas, only 19 % (3/16) of distant normal tissues expressed a high level of SPHK1 (p = 0.001). Chi-square analysis revealed that high expression of SPHK1 was significantly correlated with tumor recurrence (p = 0.019) and invasion into surrounding muscle (p = 0.005), while the data did not indicate any association with patients' gender, age, tumor location and size (p > 0.05). Kaplan-Meier survival curve and log-rank test showed that patients with high expression of SPHK1 possessed shorter continuous disease-free survival time. Conclusively, SPHK1 may become a potential biomarker for sacral chordoma in predicting its recurrence and patients' prognosis.

Expression of PTEN and mTOR in sacral chordoma and association with poor prognosis

Sacral chordoma is an aggressive, locally invasive neoplasm, and has a poor prognosis. However, the molecular basis for the clinical behavior remains unknown. The purpose of this study was to investigate the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and mammalian target of rapamycin (mTOR) in sacral chordoma, and explore their roles in the prognosis. PTEN and mTOR were detected immunohistochemically in 40 sacral chordoma tissues and 10 adjacent normal tissues. Correlations between PTEN and mTOR expression and clinicopathological factors were analyzed. Kaplan-Meier survival curves and log-rank test were used to analyze the continuous disease-free survival time (CDFS). The expression of PTEN in sacral chordoma was significantly lower than that in adjacent normal tissues, while the levels of mTOR expression in sacral chordoma were significantly higher than that in adjacent normal tissues (P = 0.000, P = 0.030). The positive expression of mTOR appears to correlate with the negative expression of PTEN in sacral chordoma (P = 0.021). PTEN-negative expression and mTOR-positive expression were associated with tumor invasion into the surrounding muscles (P = 0.038, P = 0.014). Log-rank test showed that PTEN-negative and mTOR-positive expressions had an important impact on the patients' CDFS (P = 0.011, P = 0.015). Our results suggest that PTEN and mTOR might play an important role in the local invasiveness of sacral chordoma. PTEN and mTOR might be recognized as important prognostic predictors of recurrence and could be used as potential therapeutic targets for the treatment for sacral chordoma.

Expression of insulin-like growth factor II mRNA-binding protein 3 (IMP3) in sacral chordoma

Sacral chordoma is a rare and aggressive tumor, with a high rate of local recurrence even when the tumor is radically resected. The fundamental knowledge of its biological behavior remains unknown. Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is one of the RNA binding proteins and is expressed during embryogenesis and in various malignant tumors. This study evaluated expression of IMP3 in sacral chordoma for association with patient's clinicopathological factors. A total of 32 patients with sacral chordoma (17 male and 15 female) and 10 samples of distant normal tissues were collected for analysis of IMP3 expression using immunohistochemistry. Association between IMP3 expression and clinicopathological factors (such as patient's age, gender, tumor location, tumor size, surrounding muscle invasion, Ki-67 expression, and tumor recurrence) were statistically analyzed. IMP3 was expressed in 20 (62.5%) patients, whereas there was no expression in the 10 distant normal tissues. IMP3 expression was associated with tumor invasion into the surrounding muscle (P = 0.028), high levels of Ki-67 expression (P = 0.009), and tumor recurrence (P = 0.012). The log-rank test revealed that patients with positive IMP3 expression had a shorter continuous disease-free survival time than those with negative IMP3 expression (P = 0.016). IMP3 expression was independent of age, gender, tumor location and tumor size. These results indicate that IMP3 was overexpressed in sacral chordoma and this expression was associated with tumor invasion and recurrence; thus, IMP3 may play an important role in tumor progression and could serve as a prognostic biomarker for sacral chordoma and IMP3 could be used as a potential therapeutic target for the treatment of sacral chordoma.

High expression of survivin in sacral chordoma

Chordoma is a rare and invasive malignant tumor which primarily relies on surgical treatments. Anticipation of its recurrence and patient survival longevity has been a critical issue of the treatments. This retrospective study examined the survivin expression of sacral chordoma in 30 patients undergoing surgery in our hospital from January 2000 to July 2010, and compared it with chordoma recurrence. Survivin expression was 70 % positive in 30 patients. The positive expression of survivin with recurrence was significantly higher than that without recurrence (p = 0.017) and was inversely related to the continuous disease-free survival time (p < 0.001). Survivin expression was associated with recurrence. The correlation suggested that the survivin expression could be used as an independent predictor of recurrence and could be a potential bio-target gene of angiogenesis in sacral chordoma.

A Preliminary Evaluation of Limb Salvage Surgery for Osteosarcoma around Knee Joint

ObjectiveTo evaluate the effectiveness and drawbacks of diversified procedures of limb salvage surgery (LSS), providing a reference of rational surgical criterion of LSS.MethodsFifty eight patients with stage IIB extremity osteosarcoma around knee joint area between 1992 and 2002 were studied retrospectively. Among them, 43 patients were treated by LSS followed by reconstruction. Reconstruction approaches included re-implantation of irradiation-devitalized tumor bone (n = 12), autoclaving-devitalized tumor bone (n = 8), prosthetic replacement (n = 11), allograft transplantation (n = 8) and vascularized fibula autograft implantation (n = 4). Amputations were performed in 15 patients. Patients were followed up for 6–16 years.ResultsThere were no significant difference between LSS and amputation groups regarding disease free survival and local recurrence rates. The actuarial 5-year continuous disease free survival and local recurrence rate were 30.0% and 25.0% in patients of devitalized LSS group, whereas those were 56.5% and 8.7% in patients of non-devitalized reconstruction group. The complication rate was significantly higher in LSS group compared to amputation group (P = 0.003).ConclusionLSS with non-devitalized procedures is the optimal treatment for osteosarcoma around knee joint area. Prosthesis implantation is the preferred option for bone reconstruction following LSS. Prevention and treatment of post-operative complications should be paid more attention to get good long-term outcomes of surgery.

Long-term Results

A cross-sectional study. The purpose of this report is to define the role of postoperative radiotherapy in the prevention of local recurrence (LR). Sacrococcygeal chordoma is a slow growing, malignant tumor with a clinical poor outcome due to a high LR rate. Several studies emphasize that margin-free tumor resection is the most important predictor of LR. However, even after extralesional resection a high LR up to 80% remains. A retrospective series of 15 patients who underwent surgical treatment for sacrococcygeal chordoma in one center between 1981 and 2003 was reviewed. Overall survival and continuous disease-free survival rates were compared between patients with intralesional resection with standard radiotherapy and patients with extralesional resection and no standard radiotherapy. The median age at surgery was 53 years. The mean follow-up was 7 years or until death. Mean duration of preoperative complaints was 3 years. In 10 patients, an en bloc resection was (histologic resection margins were free) performed and in 5 patients, an intralesional resection was achieved. All but one patients with intralesional resection received radiotherapy (>50 Gy) and patients with extralesional resection only received radiotherapy in case of LR (6 of 10 patients). After extralesional resection (no initial radiotherapy), all 10 patients had LR of the tumor with a mean time to recurrence of 2 years. Six of these ten patients received radiotherapy after LR and had mean survival duration of 7 years. Only one (of five patients) in the group with intralesional resection and postoperative radiotherapy had LR after 11 years. The time to recurrence was significantly longer and we found a trend toward a longer overall survival in the group that received immediate radiotherapy after surgery. The results support the strategy to add radiotherapy as standard adjuvant therapy to sacrococcygeal chordoma tumor resection.

Metastatic Soft Tissue Tumors

Between 1998 and 2007, we treated 157 patients with malignant soft tissue tumors. Patients with obvious lymph node metastasis, metastasis from bone or soft tissue sarcoma, and with obvious advanced stage disease which had multiple metastases were excluded from the present analysis. Finally, sixteen of the 157 patients were diagnosed to have soft tissue metastasis from carcinomas or hematopoietic malignancies. There were 10 males and 6 females with an average age of 65 (range, 50 - 83) years. Four lesions were located in the abdomen and back, 3 in the thigh, 2 in the chest, and 1 lesion each in the upper arm, lower leg and buttock. There were 9 intramuscular and 7 subcutaneous metastases. The average tumor size was 6 cm (range 2 - 17 cm). The initial diagnoses were a primary soft tissue tumor in 8 cases, primary soft tissue tumor or metastatic soft tissue tumor in 6, and inflammatory lesions in 2. Four of the 6 cases were suspected to be a metastatic soft tissue tumor in the initial diagnosis based on a past history of malignancy. There were no characteristic findings of metastatic soft tissue tumors in the imaging studies. The primary origins were lung cancer in 6 cases, malignant lymphoma in 5, gastric cancer in 2, and esophageal cancer, pancreatic cancer and uterine cancer in 1 patient each. Treatments were administered to all cases, including radiotherapy and chemotherapy in 11, chemotherapy in 2, wide resection and chemotherapy in 1, radiotherapy in 1 and palliative therapy in 1. The final oncological status was continuous disease free survival in 1 patient, no evidence of disease in 1, alive with disease in 7, and dead of disease in 7 patients. The estimated one-year survival was 47% and the two-year survival was 0%.

Development of Conventional Osteosarcoma after 13 Years Continuous Disease-free Survival of Periosteal Osteosarcoma

Periosteal osteosarcoma is a rare variant of osteosarcoma and has represented 1-2% of all osteosarcomas. Most local recurrences or progression to metastatic disease occurred within the first 3 years after presentation and lung metastasis is more common than bony metastasis. We describe a periosteal osteosarcoma of tibia patient who developed conventional osteosarcoma of proximal humerus after 13 years from the completion of treatment.

Expression of vascular endothelial growth factor and matrix metalloproteinase-9 in sacral chordoma

Sacral chordoma is a vessel-rich and infiltrative tumor, but the fundamental knowledge of its biological behavior remains unknown. This study was designed to investigate the expression levels and contributions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in the angiogenesis and recurrence of sacral chordoma and their correlations. An immunohistochemical method was used to investigate the expression of VEGF, MMP-9, and microvascular density (MVD) in 36 patients with sacral chordoma. Their differences in expressions were statistically analyzed and their correlations with angiogenesis and recurrence were evaluated. The mean MVD of sacral chordomas was significantly higher than that of the adjacent normal tissues (P = 0.033). Immunoreactivity for VEGF and MMP-9 was significantly higher in sacral chordoma tissues than in adjacent normal tissues (P = 0.008, P = 0.005). The mean MVD of VEGF and MMP-9 were statistically higher in positive group than in negative group (P = 0.015, P = 0.004), respectively . Moreover, a significant correlation was found between the VEGF and MMP-9 (P = 0.002). The log-rank test revealed that continuous disease-free survival time (CDFS) was significantly shorter in the MMP-9-positive group than in the MMP-9-negative group (P = 0.019), but the difference in the VEGF-positive group and the VEGF-negative group was not statistically significant (P = 0.938). Our data suggest that VEGF and MMP-9 might act with a synergistic effect and can positively regulate the angiogenesis in sacral chordoma. Positive expression of MMP-9 might indicate the local recurrence of sacral chordoma. The result suggests that some specific drugs which inhibit VEGF, MMP-9, or their receptors may have a good therapeutic effect for sacral chordoma.

Analysis of risk factors for recurrence after the resection of sacral chordoma combined with embolization

Background context Although several authors have already reported on the high local recurrence rate of sacral chordomas after surgical resection, there are no reports on the risk factors for recurrence after resection when combined with preoperative tumor-related blood vessel embolism by digital subtraction angiography (DSA) technique. Purpose To investigate the factors related to the continuous disease-free survival time (CDFS) after the resection of sacral chordomas combined with embolization. Study design/setting Retrospective review of the signs, images, and immunohistochemical data of patients with sacral chordomas treated with an initial operation combined with transcatheter arterial embolization. Patient sample Twenty-two patients with sacral chordomas received initial resection combined with transcatheter arterial embolization. Outcome measures Recurrence, proliferating cell nuclear antigen (PCNA) expression, basic fibroblast growth factor (bFGF) expression, CDFS. Methods All cases were selected and followed for an average of 39.2 months. The roles of gender, age, tumor size, tumor location, surgical method, radiation therapy, PCNA expression, and bFGF expression in local recurrence were analyzed using the log-rank test. Results Sacral chordomas recurred in eight of 22 cases. The CDFS was significantly greater in tumors located below S3 as compared with those above S3. When evaluating PCNA and bFGF expression levels, the CDFS was greater in low expressions rather than high expressions. It was determined that the surgical method used was of prognostic significance to the CDFS. Conclusions Higher tumor location and higher expressions of PCNA and bFGF will lead to a shorter CDFS. Resecting the tumor as completely as possible will decrease the chances of local recurrence of sacral chordomas.

Prognostic factors of sacral chordoma after surgical therapy: a study of 36 patients

Retrospective study. To investigate prognostic factors of sacral chordomas and provide theoretical foundation for an improvement of continuous disease-free survival (CDFS). Thirty-six patients underwent initial operation for sacral chordoma between 1992 and 2007. Data regarding age, gender, tumor size, tumor location, and type of surgery, surgical margins, surrounding muscle invasion, radiation therapy, and recurrences were reviewed and analyzed statistically. The average duration of follow-up was 74.4 months (range, 16-182 months). Sixteen patients developed local recurrences at the time of final follow-up. The average recurrence time was 30 months (range, 3-84 months). The 5-year and 10-year actuarial CDFS were 59.5 and 42%, respectively. CDFS was found statistically longer in patients whose tumor highest level at or below S3 compared with above S3 (P=0.047). Patients who had invasion into the surrounding muscle had a shorter CDFS than those without surrounding muscle invasion (P=0.014). Statistic analysis showed that the type of surgery was the most valuable indicator of CDFS (P=0.001). The local recurrence rate was statistically higher when an inadequate margin has been achieved (P=0.021). The Cox multivariate regression analysis showed that surrounding muscle invasion (P=0.024) was an independent adverse prognostic factor for CDFS, whereas incomplete excision (P=0.056) achieved borderline significance. The higher level of tumor involvement, invasion into the surrounding muscle, incomplete excision, and inadequate surgical margins are poor prognostic factors. Resecting the tumor completely with wide surgical margins may provide a better prognosis for these patients.

Effect of a local surgical procedure on the incidence of metastases following neoadjuvant chemotherapy of osteosarcoma

Following preoperative chemotherapy of 9-18 weeks duration limb salvage procedures were performed instead of ablative surgery in about 1/2 of the patients (pts). Overall continuous disease-free survival rate is 69% (80/115) at 37 (21-51) months. 5 pts died from therapy related complications, 4 developed a local failure (2 following amputation and 2 following limb salvage each) and 26 pts developed pulmonary metastases. The incidence of pulmonary metastases after en bloc resection, but not after shank rotation plasty, was found to be significantly increased over that after ablative surgery (83% vs 60% metastases free survival (MFS) at 40 months, p less than 0.05). The outcome was most unfavourable following en bloc resection of large tumors (36% MFS) and of tumors poorly responding to preoperative chemotherapy. Delaying surgery for preoperative chemotherapy in itself did not influence MFS-rate but it enabled a thorough planing and preparation of surgical procedures. Chemotherapy has very much improved the prognosis of osteosarcoma, trials on limb salvage surgery are indicated therefore. However, these procedures appear to be hazardous by increasing the rate of pulmonary metastases. Until the underlying mechanisms are not uncovered and preventive strategies worked out, limb salvage surgery in osteosarcoma has to be regarded and handled as an experimental procedure.

Mesenchymal Chondrosarcoma Treated With Total En Bloc Spondylectomy for 2 Consecutive Lumbar Vertebrae Resulted in Continuous Disease-Free Survival for More Than 5 Years

A case report of an extremely rare malignant spinal tumor successfully treated with total en bloc spondylectomy and chemotherapy. To describe points for consideration when an osteogenic lesion in the spine is diagnosed and treated. Primary mesenchymal chondrosarcoma in the spine is extremely rare. There were no reports of this tumor being treated with spondylectomy to achieve total surgical resection with a wide margin followed by chemotherapy. A 44-year-old female presented with low back pain and left flank pain. Magnetic resonance imaging and computerized tomography showed an osteosclerotic tumor of the lumbar vertebrae. Tc-99m HMDP bone scintigraphy was positive, but thallium-201 scintigraphy and gallium scintigraphy were negative. The patient was diagnosed as having chondrosarcoma based on biopsy findings. To resect the tumor completely, total en bloc spondylectomy for 2 consecutive lumbar vertebrae was performed. However, the postoperative pathologic diagnosis was extremely difficult because the patient was initially suspected to have osteosarcoma, but the final diagnosis was mesenchymal chondrosarcoma. Five years after surgery, there have not been any signs of local recurrence or distant metastasis, and the patient has remained continuously disease free. To our knowledge, we reported the first case of mesenchymal chondrosarcoma occurring from the lumbar spine treated with total en bloc spondylectomy and chemotherapy. Successful radical resection of the tumor could be accomplished. Although the effect of chemotherapy on the final results could not be clearly determined, considering that at least continuous disease-free survival was achieved, it is highly likely that chemotherapy contributed to the favorable results.

The expression and prognostic significance of bone morphogenetic protein-2 in patients with malignant fibrous histiocytoma

We investigated the rates of expression of bone morphogenetic protein-2 (BMP-2) in 29 adult patients with high-grade malignant fibrous histiocytoma of soft tissue, using the BMP-2-specific monoclonal antibody, AbH3b2/17, and found that they ranged from 1.9% to 78.9%. The survival at five years of the groups expressing high (> or = 30%) and low (< 30%) levels of BMP-2 was 85.7% and 36.3%, respectively. Multivariable analysis showed that only BMP-2 had prognostic significance for continuous disease-free survival and for overall survival (p < 0.05). Our findings indicate that over-expression of BMP-2 in malignant fibrous histiocytoma of soft tissue is the most reliable prognostic indicator of the parameters assessed.

Relationship between dose-intensity of treatment and outcome for patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy.

One hundred and forty-four patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy at the authors' institution between 1986 and 1989 were retrospectively analyzed to evaluate the relationship between the dose-intensity of chemotherapy actually received (RDI) and the prognosis. Preoperative chemotherapy consisted of high-dose methotrexate i.v., cisplatin i.a., and doxorubicin i.v. After surgery "good responder" patients (90% or more tumor necrosis) had a 31-weeks of chemotherapy with the same drugs, while "poor responder" patients (less than 90% tumor necrosis) received a 40 weeks treatment with ifosfamide and etoposide added to the three drugs used preoperatively. Due to delays and dose-reductions, only 17 patients (12%) received the treatment exactly as scheduled by the protocol, 66 (46%) received a dose-intensity between 90 and 99%, and 61 (42%) a dose-intensity between 63 and 89%. At a follow-up ranging between 10 and 13 years, 97 patients (67%) remained continuously free of disease, 45 relapsed, and two died of doxorubicin-induced cardiopathy. The continuous disease-free survival (CDFS) was not related to patients' gender and age, tumor histology, site and size, serum value of alkaline phosphatase, type of surgery and histologic response to chemotherapy. According to the RDI, CDFS resulted significantly higher for those 81 patients who received 90% or more of the scheduled dose-intensity than for those 61 who had less than 90% of the scheduled dose-intensity (76.5% v.s. 57.3%; p<0.02). These results seem to suggest that in neoadjuvant treatment of osteosarcoma the dose-intensity of chemotherapy is crucial for outcome, therefore every effort should be made to avoid reductions of doses and/or delays in performing the cycles of chemotherapy.