Nimotuzumab, a humanized monoclonal antibody specific for the EGFR, in combination with temozolomide and radiation therapy for newly diagnosed glioblastoma multiforme: First results in Chinese patients.

AIM: To evaluate the safety and efficacy of nimotuzumab, a humanized monoclonal antibody specific for the epidermal growth factor receptor (EGFR), in combination with temozolomide (TMZ) and radiation therapy (RT) in the treatment of newly diagnosed glioblastoma (GBM) in Chinese patients. METHODS: Twenty-six patients with newly diagnosed GBM were enrolled. All patients received standard external beam RT after surgery, with a total dose of 60 Gy in 30 fractions. During RT, concurrent TMZ was given daily at 75 mg/m(2) for 40-42 days, combined with six weekly infusions of nimotuzumab at a 200 mg dose. After a 4-week interval upon completion of RT, six cycles of adjuvant TMZ (150 to 200 mg/m(2) for 5 days in each 28-day cycle) were given. The primary end point was 6-month progression-free survival (PFS) rate. EGFR expression in tumor tissues was analyzed by immunohistochemistry. RESULTS: Treatment was well tolerated and no grade III or higher grade toxicity was observed. Median PFS and overall survival (OS) were 10.0 and 15.9 months, respectively, while the 6-month PFS and OS rates were 69.2% and 88.5%, respectively. No correlation between efficacy and EGFR expression was found. CONCLUSIONS: Combination of Nimotuzumab with RT plus concomitant and adjuvant TMZ showed favorable safety and tolerability profiles in newly diagnosed GBM in Chinese patients. The survival times were similar to those seen in historical data of standard therapy.

[Gamma knife for elderly patients with large vestibular schwannomas: 11-year follow-up].

OBJECTIVE: To evaluate the effect of Leksell Gamma Knife (LGK) on elderly patients with large vestibular schwannomas (VS) and to summarize the indications for LGK in patients with large VS. METHODS: From July 1994 to July 2000, 50 elderly patients (age range: 60.0 - 81.0 years) with large VS were treated by LGK as primary treatment modality. The maximal tumor diameter ranged from 31.0 to 61.0 mm [mean, (36.0 +/- 6.1) mm] and mean tumor volume was (14.8 +/- 8.0) cm(3) (range, 7.5 - 54.0 cm(3)). The maximal dose irradiated to tumor ranged from 22.0 to 28.0 Gy [mean: (25.0 +/- 1.6) Gy] and the mean tumor marginal dose was (12.3 +/- 0.9) Gy (range, 9.5 - 14.0 Gy). The mean follow-up duration was (86 +/- 12) months (range: 68 - 138 months). RESULTS: Of the 50 patients with follow-up data, 4 were deceased and 46 survived. Two patients with giant VS died at 6 and 9 months post-LGK respectively because of tumor swelling. Another two patients died of stroke or heart attack at 3 years and 4 years after LGK respectively, but their tumors decreased in volume. Clinical response: hearing: 14 (28%) patients preserved useful hearing as pre-LGK; 32 patients had unchanged or deteriorated hearing. Facial palsy: two patients developed mild facial palsy at 4 and 8 months respectively, one of them recovered and another improved later. Seven patients developed hydrocephalus around 6 months post-LGK and had V-P shunt. Eighteen patients had deteriorated facial numbness because of tumor swelling, 15 of them improved 3 years later. Tumor response: in 46 surviving patients, 43 tumors decreased markedly in size, 2 tumors remained stable in volume, 1 tumor progressed at five years and had second LGK. In this series tumor control rate was 94% (47/50). CONCLUSION: LGK provides an effective treatment for some selected large VS (maximal diameter

[Malignant tumor with false negative 18F-FDG PET image].

OBJECTIVE: To investigate the FDG uptake characteristics, the factors affecting 18F-FDG uptake and the extra CT diagnostic value of 18F-FDG PET/CT scan in the malignant tumor with false negative 18F-FDG PET image. METHODS: The data of PET/CT image in 17 patients with various kinds of cancers were reviewed and analyzed by visual observation and semi-quantity analysis ( SUV). The results were compared with the CT and histopathological diagnosis, respectively. RESULTS: Of 6 well-differentiated HCC patients confirmed by histopathological diagnosis, one had two lesions in the right lobe of the liver. One of these two lesions showed low FDG uptake on 18F-FDG PET scan and low density on CT scan. The other one was not shown on either 18F-FDG PET or plain CT scan. But on enhanced CT scan, these two lesions were found to be inhomogeneous with high density at arterial phase. The false negative 18F-FDG PET images of one gastric signet ring cell carcinoma in the gastric fundus with right adnexa metastasis, 3 renal cell carcinoma, one greater omentum and peritoneal metastatic adenocarcinoma and one well-differentiated prostate cancer were caused by normal physical uptake in the digestive tract or FDG retention in the urinary system due to normal excretion. The size of three metastases was smaller than or equal to 1 cm in diameter, however, two primary lesions of these metastases showed high FDG uptake and only one was negative on either 18F-FDG PET or CT scan. In this series, 68.8% of the primary tumors and 66.7% of metastases were found to show abnormal density on CT scan, and 31. 2% of the primary tumors and 33. 3% of metastases were not detectable on either PET or CT images. CONCLUSION: False negative 18F-FDG PET in malignant tumor may be correlated with the pathologic type, differentiation degree and the lesion size. Combining CT information with PET or paying attention to the scan methods during 8 F-FDG PET examination may reduce the rate of false negative 18F-FDG PET diagnosis in various kinds of malignant tumors.

[Gamma knife radiosurgery for large trigeminal schwannomas].

OBJECTIVE: To evaluate the role of gamma knife (GK) radiosurgery in controlling large trigeminal schwannoma. METHODS: The clinical data of 30 patients suffering from large trigeminal schwannoma with a maximum diameter of 39.0 mm (31.0 to 53.0 mm), who underwent GK radiosurgery, used as the primary treatment modality in 20 patients and used to cure the residuals of tumor after microsurgery in 10 patients, with the maximum irradiation dose to tumor of 25.8 Gy (20.0 to 33.0 Gy) and a tumor margin dose of 12.2 Gy (9.0 to 14.0 Gy), were analyzed respectively. RESULTS: The 30 patients had been followed up for 78 months (24 to 136 months). Twenty-nine of the 30 patients were alive, and one patient with malignant trigeminal schwannoma died of tumor progression 36 months after the GK radiosurgery. Neurological deficits were improved in 24 patients and 3 patients' condition remained stable. Two patients' symptoms worsened 5 and 30 months after the GK radiosurgery respectively because of tumor swelling and tumor cyst enlarging. Then these two patients underwent microsurgery and their tumors were subtotally removed. Disappearance of tumor occurred in 4 patients, a marked decrease in tumor volume was observed in 20 patients, three tumors kept unchanged or slightly regressed in volume, and 3 tumors, including that of the patient who died, progressed. The tumor-growth control rate was 90% (27/30). Two patients underwent craniotomy after GK radiosurgery and one of these 2 resected specimens underwent histopathological examination. The histopathological findings of this tumor resected 30 months after GK radiosurgery revealed that most of the tumor tissue necrosed and was full of microcysts, the residual tumor cells in peripheral areas underwent hyaline degeneration, and the nuclei showed pyknosis. CONCLUSION: GK may be a good alternative treatment for selective patients suffering from large trigeminal schwannoma with a maximum diameter

Long-term results of Leksell gamma knife surgery for trigeminal schwannomas.

OBJECT: The authors evaluated the long-term efficacy of gamma knife surgery (GKS) in patients with trigeminal schwannomas. METHODS: Fifty-six patients, 31 women and 25 men (mean age 42 years), underwent GKS for trigeminal schwannomas. Fourteen had previously undergone surgery, and GKS was the primary treatment in the remaining 42 patients. The mean target volume was 8.7 cm3 (range 0.8-33 cm3); the mean maximum dose was 27 Gy (range 20-40 Gy); the mean tumor margin dose was 13.3 Gy (range 10-15 Gy); and the mean follow-up period was 68 months (range 27-114 months). Disappearance of the tumor occurred in seven patients. An obvious decrease in tumor volume was observed in 41 patients, four tumors remained unchanged, and four tumors progressed at 5, 26, 30, and 60 months, respectively. One patient with disease progression died of tumor progression at 36 months after GKS. The tumor growth control rate in this group was 93% (52 of 56 cases). Mild numbness or diplopia was relieved completely in 14 patients. Improvement of other neurological deficits was demonstrated in 25 patients. Trigeminal nerve dysfunction was either unchanged or slightly worse in 13 patients after GKS. Four patients experienced mild symptom deterioration related to tumor progression. CONCLUSIONS: Radiosurgery proved to be an effective treatment for small- and medium-sized trigeminal schwannomas. Some larger tumors are also suitable for radiosurgery if there is no significant brainstem compression.

The long-term results of gamma knife radiosurgery for hemangioblastomas of the brain.

OBJECT: The authors assessed the long-term result of gamma knife surgery (GKS) for hemangioblastomas of the brain (HABs) and show histopathological findings after GKS. METHODS: Thirty-five patients, 28 men and seven women, with a mean age of 36 years underwent GKS. Eighteen patients presented with multiple tumors and 17 with a solitary tumor. Twenty-one patients had von Hippel-Lindau (VHL) disease. The mean tumor diameter was 13 mm (range 5-55 mm). The mean follow up after GKS was 66 months (range 24-114 months). The mean prescription dose was 17.2 Gy (range 12-24 Gy) at the tumor margin. For tumors close to or within the brainstem a prescription dose of 12 to 13 Gy was used. At the most recent follow up, 29 patients were alive, six were dead, and satisfactory tumor control had been achieved in 29. A stable or improved neurological status was obtained in 21 patients. Eight patients underwent open surgery because of tumor-associated cyst enlargement or the development of new tumors after GKS. Seven patients developed new tumors and five of them required a second GKS. The 1-year tumor control rate was 94%; 2 years, 85%; 3 years, 82%; 4 years, 79%; and 5 years, 71%. Histopathology showed that no tumor cells were found and there was degeneration and necrosis in a tumor nodule 48 months after GKS with a prescription dose of 18 Gy. CONCLUSIONS: Gamma knife surgery was a useful choice for small- or medium-sized, solid HAB in the long term, especially when the tumor margin dose was 18 Gy. Although GKS can treat multiple tumors in a single session, for HABs associated with VHL disease, GKS faces the dual problems of tumor recurrence or development of a new tumor.

[Application of 18F-FDG PET/CT scan in following-up of nasopharyngeal carcinoma after radiotherapy].

BACKGROUND & OBJECTIVE: Local relapse,tumor residue, and whole body metastases of nasopharyngeal carcinoma (NPC) after radiotherapy were mainly confirmed by CT, MRI, SPE/CT, and PET examinations. This study was to discuss the value of F-18-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (PET/CT) in detecting suspected recurrence or tumor residue, and whole body metastases of NPC after radiotherapy. METHODS: PET/CT were performed on 38 NPC patients 3-36 months after radiotherapy. The images of PET/CT, CT, and PET were observed. PET standardized uptake value (SUV) was calculated, and SUV of > 2.5 was considered as positive. The Patients were divided into 4 groups by diagnosis: (1) no recurrence/residue, and no whole body metastases; (2) with recurrence/residue, but no whole body metastases; (3) no recurrence/residue, but with whole body metastases; (4) with both recurrence/residue and whole body metastases. Diagnoses of all patients were referred to the proved follow-up clinical information. The following-up time was 6-10 months. RESULTS: The sensitivity, and specificity of PET/CT (100%,and 89.5%) were better than that of CT alone (77.8%, and 84.2%), a litter better than that of PET alone (100%, and 80.0%). CONCLUSIONS: FDG-PET scan is a better tool than CT alone for the detection of recurrene or residue, and whole body metastases of NPC, a litter better than PET alone. PET/CT may provide valuable information for judging whether the focus is metastasis.

[Analysis of the results of gamma knife radiosurgery for hemangioblastomas of the brain and the factors related to the tumor recurrence].

OBJECTIVE: To assess the 5-year-result of leksell gamma knife (LGK) in controlling hemangioblastomas of the brain (HB) and to analyze the factors related to tumor recurrence or development of new tumors. METHODS: From November 1993 to September 2001, 35 patients, 28 males and 7 females, aged 36 (16 approximately 61), 18 with multiple tumors and 17 with solitary tumor, the number of tumors being 93 in total, were treated by LGK. Twenty-one patients with HBs were associated with von Hippel-Lindau disease (VHLD). The tumor size ranged 5 approximately 55 mm with a mean size of 13 mm. The mean maximum irradiation dose was 35.6 Gy (20.0 approximately 50.0 Gy) at tumor center and the mean minimum dose was 17.2 Gy (12.0 approximately 24.0 Gy) at tumor periphery. Fisher exact test, independent T test and Wilcoxon rank sum W test were used to analyze the results of LGK on solitary and multiple HBs, the recurrent time of the HBs, and the relation between minimum irradiation dose and tumor control. RESULTS: 35 patients had been followed for 24 - 114 months with a mean value of 66 months. 29 patients were alive and 6 died. Of the 29 patients 21 achieved satisfying tumor control, and 8 patients underwent open surgery because of tumor-associated cysts enlarging or development of new tumors after LGK. 21 patients had improvement or remained stable in neurological status. Of the 8 reopened patients, 2 had deteriorated symptoms and the other 6 remained neurologically stable. Of the 35 patients, 7 developed new tumor during the follow-up period, and 5 had second LGK. Tumor control: Of the 29 cases, solitary or multiple tumors in 23 patients decreased in volume or remained the same, although two developed new tumors. The result of LGK in controlling HBs showed no significant difference between the solitary and multiple HBs (P > 0.05), but the dose of long-term tumor control was significantly higher than that of uncontrolled tumors (W = 98, P < 0.01). The tumor control rate was 94% 1 year after; 85% 2 years after; 82% 3 years after; 79% 4 years after; and 71% 5 years after. For the patients with solitary tumor, the mean time of development of new tumor was 63 months, but for the patients with multiple HBs, the time was 25 months. There was a significant difference between the two groups (t = 3.987, P < 0.001). With margin dose of 18 Gy, histopathology showed that no tumor cell was found and there were coagulation necrosis, hyaline degeneration and fibrosis tissues in the tumor nodule 48 months after LGK. CONCLUSION: LGK is a good choice for small- or medium-sized, solid HB in long term, especially when tumor margin dose is 16 - 20 Gy. Although LGK can treat multiple tumors in one single treatment session, for HB in patients associated with VHLD, LGK faces the problem of tumor recurrence or development of new tumor.

[Gamma knife radiosurgery for trigeminal schwannomas].

OBJECTIVE: To evaluate the role of gamma knife (GK) in the treatment of trigeminal schwannomas. METHODS: From June 1994 to June 2000, 38 patients with trigeminal schwannoma treated with GK radiosurgery were reviewed. GK was the primary treatment modality in 30 cases and followed microsurgery in 8 cases. Of the 38 tumors, 12 had small cysts within the tumors, the rest were solid. The mean diameter of the 38 tumors was 32 mm (range: 16 approximately 48 mm) and the tumors ranged in volume from 2 to 33 cm(3) (with a mean mean volume of 9 cm(3)). The maximum dose irradiated to tumor was 20 to 33 Gy (mean: 26 Gy), the tumor margin dose ranged from 11 to 15 Gy (mean: 13 Gy). RESULTS: 35 patients had been followed for 26 to 98 months (mean: 65 months). 20 had been followed more than 60 months. Mild numbness or diplopia relieved completely in 12 patients after GK treatment. Improvement of neurological deficits was seen in 11, unchanged dysfunction or slightly worsening of trigeminal nerve deficits in 9. Three patients had mild worsened symptoms at different time because of tumor progression. Tumor growth control: tumor disappeared after GK treatment was observed in 5 cases from 18 to 36 months after, a marked decrease in volume was observed in 24 cases, unchange in 2 cases and increase in 3 cases at 5, 26, and 60 months after respectively. One patient with resolved symptom refused to have MRI examination for more than 6 years. Of the three increased tumors, one recurrent malignant schwannoma elapsed 26 months after GK treatment. The second was a small tumor and started to progress 5 years after, but after second GK treatment, the tumor decreased again. The third was large tumor and was subtotally removed through surgery because of tumor swelling 5 months after. At last follow-up, the residual tumor remained stable. The control rate of the 35 tumors was 91% (32/35). CONCLUSION: Small and middle-size trigeminal schwannomas are the best candidates for GK radiosurgery. The control dose is 13 to 14 Gy.

[Gamma knife radiosurgery for hemangioblastomas: clinical results and pathological findings].

OBJECTIVE: To retrospectively evaluate the effects of Gamma knife in the treatment of cerebral hemangioblastomas. METHODS: From 1993 to 1996, seventeen patients with 29 hemangioblastomas were treated with Gamma knife. The patients mean age was 35 years (range: 16 - 61 years). The mean tumor diameter was 16 mm (range: 6 - 55 mm). Thirteen patients had recurrent or residual hemangioblastomas. Four with primary hemangioblastomas were diagnosed using CT, MRI and DSA. The maximum dose to the tumors was 21.0 - 50.0 Gy, with mean dose of 33.7 Gy. The radiation dose to the periphery of tumors was 12.0 - 24.0 Gy, with mean dose of 17.6 Gy. RESULTS: All the patients had been followed up for 18 to 62 months, with mean 46 months. Five patients experienced clinical improvement and reduction in tumor volume, and 5 remained stable and tumor unchanged in volume during the follow-up period. Three patients died of tumor progression, surgery and cancer after treatment 18, 22, 25 months respectively. Four patients underwent surgery respectively at 3, 4, 29 and 48 months after gamma knife operation. The local control rate of the tumors at 1 year was 92%, 2 years 88%, 3 years 80% and 4 years 75%. Pathological findings in these patients showed varying degrees of small vessel thickening and occlusion together with degeneration, necrosis in the center of tumor and loss of tumor cells at periphery. CONCLUSIONS: Gamma knife is not adequately reliable for the control of hemangioblastoma cysts, it is an effective treatment of small or medium-size solid tumors, but long-term follow-up is needed. The recommended dose is 16 to 20 Gy.

Gamma knife radiosurgery for jugular foramen schwannomas.

OBJECT: The purpose of this study was to evaluate the effect on tumor growth and symptom relief in patients with jugular foramen schwannomas after undergoing gamma knife radiosurgery (GKS). METHODS: Between November 1993 and December 2000, 27 patients were treated for jugular foramen schwannomas. The results of GKS in these cases are reviewed. Twelve patients had undergone previous tumor resection and the others underwent GKS as their primary treatment. The mean tumor volume was 13.5 cm3 (range 4.7-35.7 cm3). The mean margin dose was 14.6 Gy (range 9.8-20 Gy). The mean maximum dose was 32.6 Gy (range 25.4-50 Gy). The prescription isodose was 35 to 55%. Twenty-five patients were followed for a mean period of 38.7 months (range 9-90 months). Tumors shrank in 11 patients, remained stable in 13, and enlarged in one patient who underwent a second GKS procedure. Sixteen patients improved and nine remained at their pre-GKS clinical status. No patient developed new cranial nerve deficits after GKS. CONCLUSIONS: The follow-up results indicate that GKS is a safe and effective primary or adjuvant treatment method for the control of jugular foramen schwannomas.