pFAK-Y397 overexpression as both a prognostic and a predictive biomarker for patients with metastatic osteosarcoma.

Focal adhesion kinase (FAK) is important for tumor cell survival and metastasis in various cancers. However, its expression and prognostic value in patients with metastatic osteosarcoma remain unknown. We investigated the expression of FAK and its phosphorylated form (pFAK-Y397) in osteosarcoma tissues from 53 patients by immunohistochemistry and evaluated their correlations with clinicopathologic characteristics and outcomes. The prognostic values were assessed using Kaplan-Meier survival and Cox regression analyses. Total FAK and pFAK-Y397 were overexpressed in 48 (90.6%) and 33 (62.3%) cases, respectively. pFAK-Y397 overexpression was correlated with poor histologic response after neoadjuvant chemotherapy in patients with osteosarcoma regardless of the presence of metastasis or not. Kaplan-Meier curve showed that patients with metastatic osteosarcoma with pFAK-Y397 overexpression had significantly worse overall survival (OS) than those with non-overexpression (P = 0.044). Multivariate Cox regression analysis confirmed pFAK-Y397 overexpression as an independent prognostic predictor for OS and post metastases OS (PMOS) (P = 0.017, P = 0.006, respectively). Age at diagnosis was also an independent indicator for PMOS (P = 0.003). However, total FAK expression was not correlated with any clinicopathologic characteristics or OS in patients with metastatic osteosarcoma. In conclusion, our findings identified FAK as a common aberrant protein overexpression in various subtypes of osteosarcoma. pFAK-Y397 overexpression can be used as a prognostic biomarker predicting poor OS for patients with metastatic osteosarcoma, and the expression of pFAK-Y397 differentiated good and poor responders to neoadjuvant chemotherapy.

Comparative outcome of Thai pediatric osteosarcoma treated with two protocols: the role of high-dose methotrexate (HDMTX) in a single institute experience.

BACKGROUND: High-dose methotrexate (HD-MTX) is recognized as an efficient component of therapy against pediatric osteosarcoma in combination with other drugs such as cisplatin (CDP), carboplatin (CBDCA), doxorubicin (ADM), etoposide (VP-16) and ifosfamide (IFO). OBJECTIVES: To demonstrate the feasibility and effectiveness of the HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)] protocol comparable to CDP/ADM/CBDCA/IFO [MTX(-)] for treating childhood osteosarcoma at Ramathibodi Hospital (1999-2014). MATERIALS AND METHODS: A retrospective analysis was conducted of osteosarcoma patients aged less than 18 years treated with two chemotherapeutic regimens between 1999 and 2014. A total of 45 patients received the MTX(-) and 21 the MTX(+) protocol. RESULTS: Overall limb-salvage and amputation rate were 12.9% and 77.7%, respectively. Kaplan- Meier analysis results for 3-year disease free survival (DFS) and overall survival (OS) regardless of treatment regimens were 43.4±6.0% and 53.2±6.1% respectively. The 3-year DFS and OS were improved significantly with the MTX(+) protocol compared to MTX(-) protocol (p=0.010 and p=0.009, log rank test) [69.8±10.5%, 79.8±9.1% for MTX(+) and 31.1±6.9%, 42.2±7.4% for MTX(-) protocol, respectively]. Patients with metastatic osteosarcoma treated with the MTX(+) protocol had statistically significant higher 3-year DFS and OS than those treated with the MTX(-) protocol (66.7±13.6% and 15.0±8.0% for 3-year DFS, p=0.010, 73.3±13.2% and 20±8.9% for 3-year OS, p=0.006, respectively). The independent risk factors for having inferior 3-year DFS and OS were poor histological response (tumor necrosis <90%) and treatment with the MTX(-) protocol. The multivariate analysis identified only the treatment with the MTX(-) protocol as an independent predictor of inferior OS with a hazard ratio (HR) of 3.53 (95% confidence interval of 1.2-10.41, p=0.022). CONCLUSIONS: Our study demonstrated the tolerability, feasibility and efficacy of the HDMTX-based regimen improving the survival rate in pediatric osteosarcoma cases, in line with reports from developed countries.

Age and survival of cervical cancer patients with bone metastasis.

BACKGROUND: To determine survival times of cervical cancer patients with bone metastasis related to the effect of age at the time of cervical cancer diagnosis, we performed the retrospectively analytical study. METHODS: A total of 68 cervical cancer patients with bone metastasis were treated at a single hospital, during January 1998 to December 2010. Fifty-two medical records were identified and collected, the remaining sixteen medical records were not found. Main outcome measures were patient characteristics, clinical information, duration from cervical cancer diagnosis to bone metastasis diagnosis, survival time after bone metastasis and overall survival time. RESULTS: Among fifty-two cervical cancer patients with bone metastasis, there were 13 patients who were less than 45 years old, and 39 patients were 45 years old or more at the time of cervical cancer diagnosis. The younger group had less median overall survival than the older group, with a statistically significant difference (21 months, 95% CI 19.93-22.06; 34 months, 95% CI 23.27-44.72, p = 0.021). However, they were comparable in the duration from cervical cancer diagnosis to bone metastasis diagnosis and the survival time after bone metastasis. CONCLUSION: Young patients with bone metastasis aged less than 45 years old at the time of cervical cancer diagnosis have a poorer prognosis than the elderly patients. IMPACT: To improve survival and quality of life, more intensive and novel multimodal treatments at the time of cervical cancer diagnosis should be considered in patients less than forty-five years, who can tolerate the side effects better.

Parosteal ossifying lipoma of the fibula: a case report with contrast-enhanced MR study and a review of the literature.

This report describes a rare case of parosteal ossifying lipoma of the fibula. Very few reports have described the magnetic resonance (MR) imaging features with gadolinium enhancement of this neoplasm. In this case, low-signal-intensity strands within the lipomatous mass on T1-weighted image with varying degrees of enhancement were detected. Thus, parosteal ossifying lipoma should be included within the group of gadolinium-enhanced benign lipomatous tumours that may mimic liposarcoma on MR imaging. However, the characteristic radiographic appearance, together with computed tomography or MR imaging features, should aid in the correct diagnosis of this condition.

Emergency ultrasonography in patients with clinically suspected soft tissue infection of the legs.

INTRODUCTION: We aimed to retrospectively review the ultrasonography (US) findings of patients with clinically suspected soft tissue infection of the legs and to determine whether there is a correlation between US diagnosis and further clinical management. METHODS: We reviewed the US findings of consecutive patients with clinically suspected soft tissue infection of the legs who were referred for emergency US during a consecutive two-year period. The indications for US were recorded and the findings evaluated. The effect of the US findings on further clinical management (medication alone versus medication with surgical intervention [SI]) was reviewed. RESULTS: A total of 51 legs from 38 patients were enrolled in the study. The most common indication for US was to rule out necrotising fasciitis (35.3%). The most frequent US diagnosis was isolated cellulitis (21.6%). Both groups of patients (with and without abscess) were treated with medication with or without SI. There was no statistically significant correlation between the presence or absence of abscess and further clinical management (p = 0.216), between the size (length and thickness) of the abscess and the type of SI (p = 0.687 and 0.243, respectively) CONCLUSION: In our study, the most frequent US diagnosis was isolated cellulitis, and we found no significant correlation between US findings and clinical management (medication or SI). Our results should encourage sonologists to evaluate in detail patients with clinically suspected soft tissue infection of the legs and to provide information regarding each layer of tissue studied.

Dynamic contrasted MR imaging in differentiation of recurrent malignant soft tissue tumor from posttreatment changes.

OBJECTIVE: To investigate dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in term of differentiation recurrent malignant soft tissue tumor (MSTT) from post-treatment changes. MATERIAL AND METHOD: DCE-MRI was performed in consecutive patients in two-year periods to differentiate recurrent MSTT from post-treatment (surgery radiotherapy chemotherapy) changes. The steepest slope (SS) ratio between the artery and the lesion, sensitivity, and specificity were calculated. RESULTS: Thirty-five DCE-MRI studies were performed in 30 patients, which included 14 males and 16 females with an age range from 12 to 71 years (median 45.81 year). Thirteen were with recurrence and 22 were with post-treatment changes. The SS ratios were ranged from 0.66 to 29.15. The lesions with the SS ratio > 9.28 were all benign at follow up of at least two months, whereas those with SS ratio < 1.05 were all recurrent tumors proven by biopsy or surgery. Overlapping occurred when the SS ratios > 1.05 but < 9.28 in which the recurrence was 42.31%. The chance of having recurrence rather than post-treatment changes was approximately two andfive times in patients with the ratio of 5. 07 and 1.55, with the specificity of 54.55% and 90.91%, respectively CONCLUSION: The SS ratio between the artery and the lesion has limitations to differentiate recurrent MSTT from posttreatment changes. It is useful when the ratio is less than 1.05 (malignant) or more than 9.28 (benign). The chance of having recurrence rather than post-treatment changes was approximately two and five times in patients with the ratio of 5.07 and 1.55, respectively The less value the ratio is, the more possibility to be recurrent tumor.

Comparison of outcomes for patients with cervical cancer who developed bone metastasis after the primary treatment with concurrent chemoradiation versus radiation therapy alone.

OBJECTIVES: The aims of this study were to retrospectively compare outcomes for patients with cervical cancer who developed bone metastasis later after the primary treatment at the time of diagnosis of cervical cancer with concurrent chemoradiation (CCRT) to radiation therapy alone (RT). METHODS: We retrospectively analyzed the patients with cervical cancer during the period from January 1998 to December 2007. Of these, 11 patients who received CCRT and 24 patients who received RT went on to develop bone metastasis. RESULTS: Among 4620 patients with cervical cancer, 51 patients had bone metastases. Sixteen patients were excluded including 10 patients with unavailable records and 6 patients who did not receive CCRT or RT at the time of diagnosis of cervical cancer. Thirty-five patients who had bone metastasis received primary treatment with CCRT or RT. The 2 groups of patients (CCRT vs RT) were similar in age, histologic cell type, and the International Federation of Gynecology and Obstetrics stages. The characteristics of bone metastasis in both groups were also not significantly different. The patients who received CCRT did not have a better overall survival than the patients who received RT (median, 19 vs 22 months; 95% confidence interval [CI], 14.68-23.32 vs 8.56-35.44). They were comparable in the interval from cervical cancer diagnoses to diagnoses of bone metastasis (CCRT group: median, 14 months; 95% CI, 9.14-18.86; RT group: median; 15 months; 95% CI, 10.20-19.80) and the survival after diagnosis of bone metastasis between both groups (CCRT group: median, 4 months; 95% CI, 0.76-7.24; RT group: median, 7 months; 95% CI, 4.70-9.30). CONCLUSIONS: Our retrospective analysis showed that there were no differences in survival benefits observed between the patients with cervical cancer who developed bone metastases later after the primary treatment with CCRT and RT.

Bone metastasis in cervical cancer patients over a 10-year period.

INTRODUCTION: Cervical cancer is the major cancer burden in developing countries. Bone is the third most common site of distant metastasis after the lungs and liver. Therefore, the aims of this study were to find the incidence and clinical characteristics of bone metastasis in our hospital. PATIENTS AND METHODS: Fifty-one cervical cancer patients with bone metastasis during the period from January 1998 to December 2007 were recruited. All patients' medical records were reviewed and analyzed. RESULTS: Among 4620 cervical cancer patients, there were 51 patients (1.1%) who had bone metastases. Ten patients' medical records were not found; thus, 41 patients were available for evaluation. The median age of the patients was 49 years. International Federation of Gynecology and Obstetrics stage IIB was the most common stage (43.9%). Most patients had squamous cell carcinoma (80.48%) and received radiation therapy alone as their primary treatment (58.53%). The most common presenting symptom was pain (78.04%). Most of the patients had multiple bone lesions and extrapelvic bone metastases. The lumbar spine was the most common site (36.36%). Sixteen patients (39.02%) were treated by palliative radiation therapy. The median overall survival was 23 months. CONCLUSIONS: Bone metastases could be found at all stages. Common sites were the bone beyond the radiation field of their primary treatment. It was found at a median of 16 months after cervical cancer diagnosis. Currently, there are many varieties of treatment that result only in palliation. This group of patients has a poor prognosis.