[share-ebook]Bone Malignancy Bone and Soft Tissue Malignancy Biochemical Studies on Angiogenesis and Metastasis in Different Types of Cancer


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Scientific Annual Report 2000-2002

8. Bone Malignancy

Chapter 8 
 

Bone and Soft Tissue Malignancy 
 
 

8.1. 131I MIBG as a Second Line Therapy in Children with Advanced Neuroblastoma

 
 

Omar M. El-Tannir, M.D.1 and Khaled El Sabban, M.D.2

1. Pediatric Oncology Unit, National Cancer institute, Cairo University, 2.Nuclear Medicine Department, School of Medicine, Cairo University, Egypt

J Egypt Nat Cancer Inst 12(1): 11-15, 2000 
 

Objectives: To evaluate the rule of 131I MIBG as a second line therapy in patients with advanced Neuroblastoma. Patients and methods: 30 children with advanced neuroblastoma who were either refractory to conventional chemotherapy or showed disease relapse after initial successful treatment received 131I MIBG as a second line therapy in a dose of 100 mci per course, at 4 weeks interval for 3-4 courses. Patients were isolated in private rooms, and given dexamethazone to guard against laryngeal edema and other radiation effects. On the 5th day post MIBG therapy, whole body scintigraphy was done to all patients. Assessment of response was done at the end of therapy by CAT scan, bone scan, 131I MIBG imaging and urinary VMA. Results: Neuroblastoma patients were 15 boys and 15 girls. All were younger than 16 years. There were 6 patients in stage III, and 24 in stage IV according to Evans stages. Three patients received 1 course of 131I MIBG, 7: 2 courses. 16:3 courses. 4: 4 courses. Three out of thirty (10%) of the children showed disease progression. 1/30 (3.3%) showed no response. The rest showed varying degrees of response from stable disease in 2/30 (6.7%). Partial response in 18/30 (60%), and complete response in 6/ 30 (20%). At 2 years. 17/30 (56.7%) are still alive and (13/30) are dead. 2 of them died of Medical causes not related to Neuroblastoma. The median performance status as measured by Karnofsky index markedly improved post MIBG therapy: 80% versus 60% pretherapy (p<0.001). The median body weight significantly increased after therapy: 34 kg versus 27 kg pretherapy (p<0.05). Conclusion: 131I MIBG therapy at a dose of 100 mci is a safe and effective line of therapy in advanced Neuroblastoma. 
 

8.2. Incidence of P53 Mutation and DNA Aneuploidy in Xeroderma Pigmentosum: A Comparative Study

 
 

*Salonas A. Marzouk and **Somaia A. El Hosseini

Departments of *Dermatology, Faculty of Medicine and Pathology **, Cancer Institute, Cairo University 
 

Background: Both P53 mutation and DNA aneuploidy develop in the sun exposed skin of xeroderma pigmentosa (XP) patients prior to malignant transformation. The finding of either of them in the normally looking sun exosed skin of this disorder, is helpful for the detection of early precutaneous changes before the incidence of nonmelanoma skin cancer. However, this abnormalities (P53 mutation and DNA aneuploidy) have not been studied in the same patient before. Aim of the work: this work was concerned with studying both P53 mutation and DNA ploidy changes in the same patients in order to find out which of these two changes occur more frequently, and thereby which of them is more reliable for the early detection of the precancerous changes in the XP. Material and Methods: Biopsies taken from the normally looking sun-exposed skin of 22 patients having XP were studied for the presence of P53 and DNA aneuoploidy using avidin-biotin peroxidase complex and image analysis respectively. Results: DNA aneuoploidy was detected in 18 patients whereas P53 mutation was found in 9 patients only. The incidence was found to be statistically much more significantly higher than that of mutant P53. Conclusion: Detection of DNA aneuoploidy by image analysis is more sensitive indicator of the precancerous changes in XP than the finding of P53 mutation.  
 

8.3. Detection of Parvovirus B19 infection in Solid Tumor Patients at Different Stages or Treatment

 
 

Randa Mohamed Aboul Fetouh, Nasr Mohamed Aly* & Abdel Hady Ali Abdel Wahab**

Clinical Pathology Dept., *Medical Oncology Dept., **Biochemistry Unit, Cancer Biology Dept., NCI, Cairo University.

Egypt. J. Lab. Med. 12(3):443-452, 2000. 
 

This study included 361 patients with different solid tumors including breast, female genital tract, GIT, head & neck, upper &c lower respiratory, urinary & male genital tract, soft tissue, bone, thyroid, neuroblastoma, osteosarcoma, Ewing sarcoma, PNET, Wilms' tumor; and Rabdomyosarcoma (RMS). Together with 300 normal healthy controls. All patients were subjected to clinical and diagnostic procedures, and were classified into 4 groups, and compared with normal control. All tested for the presence of parvovirus B19 antigen in the serum, then randomly selected 38 patients serum samples acid 30 controls serum sample which were found negative when tested for parvovirus B19 DNA using PER. Patients were classified into four groups as regards: Group I: This included 133 patients attending early screening clinic with no prior chemotherapy or blood transfusion. Parvovirus B19 was found positive in 41 out of 133 patients (30.8%). Group II: This included 36 patients with non small cell lung cancer (NSCLC) under current protocol therapy. Parvovirus B19 was found positive in 19 out of 36 patients (52.8%). Group III: This included 72 patients who finished chemotherapy courses and later they are under blood component therapy. Parvovirus B19 was found positive in 19 out of 72 patients (26.4%). Group IV: This included 120 patients who achieved complete response to chemotherapy and attending follow-up clinic. Parvovirus B19 was found positive in 17 out of 120 patients (14.2%). 
 

8.4. MRI & Contrast-Enhanced MR Angiography for Preoperative Planning and Monitoring Response to Chemotherapy of Extremity Musculoskeletal Neoplasms

 
 

Ikram H. Mahmoud MD

Radiology Department, National Cancer Institute, Cairo University.

Egypt. J Radiol & Nuc. Med. 32(1): 109-117, 2001 
 

The purpose of this study was to investigate the use of contrast-enhanced MR angiography-combined with MR imaging in evaluating vascular morphology of musculoskeletal neoplasms for preoperative planning of tumor resection and limb-salvage surgery and also to assess their use for monitoring changes in neovascularity and evaluating response to chemotherapy. Contrast-enhanced MRA were used to study patients with primary bone tumors (8 osteosarcomas, 13 soft tissue sarcomas, 2 chondrosarcomas, 1 marjolin ulcer, 1 synovial sarcoma and 1 neurofibroma). Eight patients with osteosarcomas underwent MRA following chemotherapy before limb-salvage. MRA results were compared to the digital subtraction conventional angiography and intra-operative results for those patients having limb salvage or tumor resection. MIP and 3D reconstructions of vascular structures and tumor neovascularity were displayed. The image quality was graded good in 25/26 patients and sufficient in 1/26 patients. Small vessel neovascularity, tumor feeder vessels, blush and normal vascular structures were displayed. Tumor encroachment onto (17/26) or encasement (10/26) of normal vascular structures were shown by MIP and 3D reconstructions. The eight patients with osteosarcomas who had follow up imaging showed marked neovascularity prior to chemotherapy. Three patients responded to chemotherapy. MR angiography showed marked reduction in tumor vascularity and tumor necrosis. Five patients showed intermediate response with high neovascular density. The additive effect of MR imaging and contrastenhanced MR angiography increases the diagnostic accuracy of primary musculoskeletal neoplasms, increases the diagnostic accuracy in monitoring early response to chemotherapy by combining morphologic information and changes in tumor neovascularity. MR angiography demonstrates encroachment onto and encasement of major vessels by the tumor mass and appears to be useful for assessing response to chemotherapy. It may be helpful to the surgeon in planning the surgical approach for limb-salvage, tumor resection and in identifying the need for a vascular graft and its length. 
 

8.5. Role of Tc-99m SESTAMIBI in Assessment of Treatment Response to Chemotherapy in Bone Sarcomas

 
 

Raef Ryad*, M.D.; Hosna Mustafa**, M.D.; Walid Omar*, M.D.; Ahmad Zaher*, M.D. And Emad Ebied***, M.D.

Nuclear Medicine and Pediatric Departments***, National Cancer Institute* and Kasr El-Aini Hospital**, Cairo University, Cairo, Egypt.

J Egypt Nat Cancer Inst 13(1): 27-33, 2001 
 

The aim of this prospective study is to test the value of Tc99m MIBI scanning in assessment of response of bone sarcomas to chemotherapy. It included 28 patients with primary bone tumors patients with Ewing’s sarcoma (ES)]. Their age ranged from 8-19 years, 24 males and 4 females. All patients had pre-chemotherapy assessment with 20 mCi of Tc-99m MDP triple phase bone scan. Early dynamic and blood pool whole body scan (WBS) imaging at 2-5 mm post injection and delayed 3 hours) image were acquired to assess the primary lesion and exclude metastatic spread. Both early (20 mm) and delayed (2 hrs) WBS images with Tc-99m SestaMIBI were performed before chemotherapy and after 3-4 courses of chemotherapy to assess chemotherapy treatment response. Imaging was done on dual head gamma camera interfaced with a recent version computer system. Images were interpreted both qualitatively and quantitatively. Correlation of Tc99m MIBI scan with tumor percentage necrosis in histo-pathological examination was possible in 19 patients following salvage surgery for the involved limb. The remaining 9 patients were assessed clinically and radiologically in comparison with Tc-99m MIBI WBS. The results of the current study divided our patients according to response to therapy and scintigraphic data into 3 groups: Good responders: 12 (43%) patients with marked changes in qualitative images and marked decrease in Tc99m MIBI ratio in both early and late images. This group showed > 90% tumor necrosis. The second group included partial responders (6 patients) with some changes in the qualitative and quantitative images (mean Tc-99m MIBI uptake ratio). Percentage of tumor necrosis in this group ranged from 50-90%. The third group included patients with no response to chemotherapy with no appreciable change in qualitative images and quantitative ratio before and after treatment. This group had <50% of tumor necrosis histo-pathologically. It is concluded that Tc99m MIBI scan is a valuable diagnostic tool in assessment of response to chemotherapy in patients with bone sarcomas, its results are comparable to histopathological data. It can be safely performed during therapy to assess success of employed therapeutic strategy and guide its modulation. 
 

8.6. Prognostic Significance of P53 and CD99 Expression in Ewing's Sarcoma

 
 

Ahmed H. Fahmy, Ph.D.*; Hoda M. Ismail, Ph.D.* and Hala F. Kheidr, M.D.**

*Pathology Dep., NCI, Cairo University; **Pathology Dep., Faculty of Medicine, Cairo University

Accepted for publication in Medical J. Cairo University, December (suppl.), 2002. 
 

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    Bone Malignancy Bone and Soft Tissue Malignancy Biochemical Studies on Angiogenesis and Metastasis in Different Types of Cancer

    Scientific Annual Report 2000-2002

    8. Bone Malignancy

    Chapter 8 
     

    Bone and Soft Tissue Malignancy 
     
     

    8.1. 131I MIBG as a Second Line Therapy in Children with Advanced Neuroblastoma

     
     

    Omar M. El-Tannir, M.D.1 and Khaled El Sabban, M.D.2

    1. Pediatric Oncology Unit, National Cancer institute, Cairo University, 2.Nuclear Medicine Department, School of Medicine, Cairo University, Egypt

    J Egypt Nat Cancer Inst 12(1): 11-15, 2000 
     

    Objectives: To evaluate the rule of 131I MIBG as a second line therapy in patients with advanced Neuroblastoma. Patients and methods: 30 children with advanced neuroblastoma who were either refractory to conventional chemotherapy or showed disease relapse after initial successful treatment received 131I MIBG as a second line therapy in a dose of 100 mci per course, at 4 weeks interval for 3-4 courses. Patients were isolated in private rooms, and given dexamethazone to guard against laryngeal edema and other radiation effects. On the 5th day post MIBG therapy, whole body scintigraphy was done to all patients. Assessment of response was done at the end of therapy by CAT scan, bone scan, 131I MIBG imaging and urinary VMA. Results: Neuroblastoma patients were 15 boys and 15 girls. All were younger than 16 years. There were 6 patients in stage III, and 24 in stage IV according to Evans stages. Three patients received 1 course of 131I MIBG, 7: 2 courses. 16:3 courses. 4: 4 courses. Three out of thirty (10%) of the children showed disease progression. 1/30 (3.3%) showed no response. The rest showed varying degrees of response from stable disease in 2/30 (6.7%). Partial response in 18/30 (60%), and complete response in 6/ 30 (20%). At 2 years. 17/30 (56.7%) are still alive and (13/30) are dead. 2 of them died of Medical causes not related to Neuroblastoma. The median performance status as measured by Karnofsky index markedly improved post MIBG therapy: 80% versus 60% pretherapy (p<0.001). The median body weight significantly increased after therapy: 34 kg versus 27 kg pretherapy (p<0.05). Conclusion: 131I MIBG therapy at a dose of 100 mci is a safe and effective line of therapy in advanced Neuroblastoma. 
     

    8.2. Incidence of P53 Mutation and DNA Aneuploidy in Xeroderma Pigmentosum: A Comparative Study

     
     

    *Salonas A. Marzouk and **Somaia A. El Hosseini

    Departments of *Dermatology, Faculty of Medicine and Pathology **, Cancer Institute, Cairo University 
     

    Background: Both P53 mutation and DNA aneuploidy develop in the sun exposed skin of xeroderma pigmentosa (XP) patients prior to malignant transformation. The finding of either of them in the normally looking sun exosed skin of this disorder, is helpful for the detection of early precutaneous changes before the incidence of nonmelanoma skin cancer. However, this abnormalities (P53 mutation and DNA aneuploidy) have not been studied in the same patient before. Aim of the work: this work was concerned with studying both P53 mutation and DNA ploidy changes in the same patients in order to find out which of these two changes occur more frequently, and thereby which of them is more reliable for the early detection of the precancerous changes in the XP. Material and Methods: Biopsies taken from the normally looking sun-exposed skin of 22 patients having XP were studied for the presence of P53 and DNA aneuoploidy using avidin-biotin peroxidase complex and image analysis respectively. Results: DNA aneuoploidy was detected in 18 patients whereas P53 mutation was found in 9 patients only. The incidence was found to be statistically much more significantly higher than that of mutant P53. Conclusion: Detection of DNA aneuoploidy by image analysis is more sensitive indicator of the precancerous changes in XP than the finding of P53 mutation.  
     

    8.3. Detection of Parvovirus B19 infection in Solid Tumor Patients at Different Stages or Treatment

     
     

    Randa Mohamed Aboul Fetouh, Nasr Mohamed Aly* & Abdel Hady Ali Abdel Wahab**

    Clinical Pathology Dept., *Medical Oncology Dept., **Biochemistry Unit, Cancer Biology Dept., NCI, Cairo University.

    Egypt. J. Lab. Med. 12(3):443-452, 2000. 
     

    This study included 361 patients with different solid tumors including breast, female genital tract, GIT, head & neck, upper &c lower respiratory, urinary & male genital tract, soft tissue, bone, thyroid, neuroblastoma, osteosarcoma, Ewing sarcoma, PNET, Wilms' tumor; and Rabdomyosarcoma (RMS). Together with 300 normal healthy controls. All patients were subjected to clinical and diagnostic procedures, and were classified into 4 groups, and compared with normal control. All tested for the presence of parvovirus B19 antigen in the serum, then randomly selected 38 patients serum samples acid 30 controls serum sample which were found negative when tested for parvovirus B19 DNA using PER. Patients were classified into four groups as regards: Group I: This included 133 patients attending early screening clinic with no prior chemotherapy or blood transfusion. Parvovirus B19 was found positive in 41 out of 133 patients (30.8%). Group II: This included 36 patients with non small cell lung cancer (NSCLC) under current protocol therapy. Parvovirus B19 was found positive in 19 out of 36 patients (52.8%). Group III: This included 72 patients who finished chemotherapy courses and later they are under blood component therapy. Parvovirus B19 was found positive in 19 out of 72 patients (26.4%). Group IV: This included 120 patients who achieved complete response to chemotherapy and attending follow-up clinic. Parvovirus B19 was found positive in 17 out of 120 patients (14.2%). 
     

    8.4. MRI & Contrast-Enhanced MR Angiography for Preoperative Planning and Monitoring Response to Chemotherapy of Extremity Musculoskeletal Neoplasms

     
     

    Ikram H. Mahmoud MD

    Radiology Department, National Cancer Institute, Cairo University.

    Egypt. J Radiol & Nuc. Med. 32(1): 109-117, 2001 
     

    The purpose of this study was to investigate the use of contrast-enhanced MR angiography-combined with MR imaging in evaluating vascular morphology of musculoskeletal neoplasms for preoperative planning of tumor resection and limb-salvage surgery and also to assess their use for monitoring changes in neovascularity and evaluating response to chemotherapy. Contrast-enhanced MRA were used to study patients with primary bone tumors (8 osteosarcomas, 13 soft tissue sarcomas, 2 chondrosarcomas, 1 marjolin ulcer, 1 synovial sarcoma and 1 neurofibroma). Eight patients with osteosarcomas underwent MRA following chemotherapy before limb-salvage. MRA results were compared to the digital subtraction conventional angiography and intra-operative results for those patients having limb salvage or tumor resection. MIP and 3D reconstructions of vascular structures and tumor neovascularity were displayed. The image quality was graded good in 25/26 patients and sufficient in 1/26 patients. Small vessel neovascularity, tumor feeder vessels, blush and normal vascular structures were displayed. Tumor encroachment onto (17/26) or encasement (10/26) of normal vascular structures were shown by MIP and 3D reconstructions. The eight patients with osteosarcomas who had follow up imaging showed marked neovascularity prior to chemotherapy. Three patients responded to chemotherapy. MR angiography showed marked reduction in tumor vascularity and tumor necrosis. Five patients showed intermediate response with high neovascular density. The additive effect of MR imaging and contrastenhanced MR angiography increases the diagnostic accuracy of primary musculoskeletal neoplasms, increases the diagnostic accuracy in monitoring early response to chemotherapy by combining morphologic information and changes in tumor neovascularity. MR angiography demonstrates encroachment onto and encasement of major vessels by the tumor mass and appears to be useful for assessing response to chemotherapy. It may be helpful to the surgeon in planning the surgical approach for limb-salvage, tumor resection and in identifying the need for a vascular graft and its length. 
     

    8.5. Role of Tc-99m SESTAMIBI in Assessment of Treatment Response to Chemotherapy in Bone Sarcomas

     
     

    Raef Ryad*, M.D.; Hosna Mustafa**, M.D.; Walid Omar*, M.D.; Ahmad Zaher*, M.D. And Emad Ebied***, M.D.

    Nuclear Medicine and Pediatric Departments***, National Cancer Institute* and Kasr El-Aini Hospital**, Cairo University, Cairo, Egypt.

    J Egypt Nat Cancer Inst 13(1): 27-33, 2001 
     

    The aim of this prospective study is to test the value of Tc99m MIBI scanning in assessment of response of bone sarcomas to chemotherapy. It included 28 patients with primary bone tumors patients with Ewing’s sarcoma (ES)]. Their age ranged from 8-19 years, 24 males and 4 females. All patients had pre-chemotherapy assessment with 20 mCi of Tc-99m MDP triple phase bone scan. Early dynamic and blood pool whole body scan (WBS) imaging at 2-5 mm post injection and delayed 3 hours) image were acquired to assess the primary lesion and exclude metastatic spread. Both early (20 mm) and delayed (2 hrs) WBS images with Tc-99m SestaMIBI were performed before chemotherapy and after 3-4 courses of chemotherapy to assess chemotherapy treatment response. Imaging was done on dual head gamma camera interfaced with a recent version computer system. Images were interpreted both qualitatively and quantitatively. Correlation of Tc99m MIBI scan with tumor percentage necrosis in histo-pathological examination was possible in 19 patients following salvage surgery for the involved limb. The remaining 9 patients were assessed clinically and radiologically in comparison with Tc-99m MIBI WBS. The results of the current study divided our patients according to response to therapy and scintigraphic data into 3 groups: Good responders: 12 (43%) patients with marked changes in qualitative images and marked decrease in Tc99m MIBI ratio in both early and late images. This group showed > 90% tumor necrosis. The second group included partial responders (6 patients) with some changes in the qualitative and quantitative images (mean Tc-99m MIBI uptake ratio). Percentage of tumor necrosis in this group ranged from 50-90%. The third group included patients with no response to chemotherapy with no appreciable change in qualitative images and quantitative ratio before and after treatment. This group had <50% of tumor necrosis histo-pathologically. It is concluded that Tc99m MIBI scan is a valuable diagnostic tool in assessment of response to chemotherapy in patients with bone sarcomas, its results are comparable to histopathological data. It can be safely performed during therapy to assess success of employed therapeutic strategy and guide its modulation. 
     

    8.6. Prognostic Significance of P53 and CD99 Expression in Ewing's Sarcoma

     
     

    Ahmed H. Fahmy, Ph.D.*; Hoda M. Ismail, Ph.D.* and Hala F. Kheidr, M.D.**

    *Pathology Dep., NCI, Cairo University; **Pathology Dep., Faculty of Medicine, Cairo University

    Accepted for publication in Medical J. Cairo University, December (suppl.), 2002.