A Phase 0 Microdosing PET/CT Study Using O-[18F]Fluoromethyl-d-Tyrosine in Normal Human Brain and Brain Tumor.

PURPOSE: The aim of the present study was to obtain information about distribution, radiation dosimetry, toxicity, and pharmacokinetics of O-[18F]fluoromethyl-d-tyrosine (d-18F-FMT), an amino acid PET tracer, in patients with brain tumors. PATIENTS AND METHODS: A total of 6 healthy controls (age = 19-25 years, 3 males and 3 females) with brain PET images and radiation dosimetry and 12 patients (median age = 60 years, 6 males and 6 females) with primary (n = 5) or metastatic brain tumor (n = 7) were enrolled. We acquired 60-minute dynamic brain PET images after injecting 370 MBq of d-18F-FMT. Time-activity curves of d-18F-FMT uptake in normal brain versus brain tumors and tumor-to-background ratio were analyzed for each PET data set. RESULTS: Normal cerebral uptake of d-18F-FMT decreased from 0 to 5 minutes after injection, but gradually increased from 10 to 60 minutes. Tumoral uptake of d-18F-FMT reached a peak before 30 minutes. Tumor-to-background ratio peaked at less than 15 minutes for 8 patients and more than 15 minutes for 4 patients. The mean effective dose was calculated to be 13.2 µSv/MBq. CONCLUSIONS: Using d-18F-FMT as a PET radiotracer is safe. It can distinguish brain tumor from surrounding normal brain tissues with a high contrast. Early-time PET images of brain tumors should be acquired because the tumor-to-background ratio tended to reach a peak within 15 minutes after injection.

Incidental 18F-Florapronol Uptake in Meningioma.

ABSTRACT: A 76-year-old woman underwent 18F-florapronol (18F-FC119S, an amyloid ß imaging PET agent) PET, owing to cognitive impairment. 18F-florapronol PET images revealed an incidental 18F-florapronol uptake in the right frontal lobe. A well-enhancing extra-axial mass in the right frontal lobe was observed on MRI scans, suggesting a meningioma. After excision of the tumor, the biopsy results confirmed it as a meningothelial meningioma.

A Case of Sporadic Suprasellar Hemangioblastoma Mimicking Meningioma.

Hemangioblastoma (HBL) in the suprasellar region is very rare and a few cases have been reported. Suprasellar HBL without von Hippel-Lindau disease is much rarer. A 76-year old male patient presented progressively deteriorating visual disturbance. MRI demonstrated solid suprasellar mass of 20 mm in diameter, broadly based to planum sphenoidale and diaphragm sella and dural tail sign after the administration of gadolinium diethylene triamine penta-acetic acid (Gd-DTPA). Preoperative diagnosis was meningioma. Total resection of the tumor was not accomplished because of massive hemorrhage, and the histopathologic examination revealed the tumor to be HBL. The visual disturbance of the patient was not improved. The authors reviewed the literature and considered a differential diagnosis of suprasellar tumors and treatment of suprasellar HBL.

Prediction of Response to Stereotactic Radiosurgery for Brain Metastases Using Convolutional Neural Networks.

BACKGROUND: It is unclear whether radiomic phenotypes of brain metastases (BM) are related to radiation therapy prognosis. This study assessed whether a convolutional neural network (CNN)-based radiomics model which learned computer tomography (CT) image features with minimal preprocessing, could predict early response of BM to radiosurgery. MATERIALS AND METHODS: Tumor images of 110 BM post stereotactic-radiosurgery (SRS) (within 3 months) were assessed (Response Evaluation Criteria in Solid Tumor, version 1.1) as responders (complete or partial response) or non-responders (stable or progressive disease). Datasets were axial planning CT images containing the tumor center, and the tumor response. Datasets were randomly assigned to training, validation, or evaluation groups repeatedly, to create 50 dataset combinations that were classified into five groups of 10 different dataset combinations with the same evaluation datasets. The CNN learned using training-group images and labels. Validation datasets were used to choose the model that best classified evaluation images as responders or non-responders. RESULTS: Of 110 tumors, 57 were classified as responders, and 53 as non-responders. The area under the receiver operating characteristic curve (AUC) of each CNN model for 50 dataset combinations ranged from 0.602 [95% confidence interval (CI)=36.5-83.9%] to 0.826 [95% CI, 64.3-100%]. The AUC of ensemble models, which averaged prediction results of 10 individual models within the same group, ranged from 0.761 (95% CI=55.2-97.1%) to 0.856 (95% CI=68.2-100%). CONCLUSION: A CNN-based ensemble radiomics model accurately predicted SRS responses of unlearned BM images. Thus, CNN models are able to predict SRS prognoses from small datasets.

The Effect of Perioperative Radiation Therapy on Spinal Bone Fusion Following Spine Tumor Surgery.

INTRODUCTION: Perioperative irradiation is often combined with spine tumor surgery. Radiation is known to be detrimental to healing process of bone fusion. We tried to investigate bone fusion rate in spine tumor surgery cases with perioperative radiation therapy (RT) and to analyze significant factors affecting successful bone fusion. METHODS: Study cohort was 33 patients who underwent spinal tumor resection and bone graft surgery combined with perioperative RT. Their medical records and radiological data were analyzed retrospectively. The analyzed factors were surgical approach, location of bone graft (anterior vs. posterior), kind of graft (autologous graft vs. allograft), timing of RT (preoperative vs. postoperative), interval of RT from operation in cases of postoperative RT (within 1 month vs. after 1 month) radiation dose (above 38 Gy vs. below 38 Gy) and type of radiation therapy (conventional RT vs. stereotactic radiosurgery). The bone fusion was determined on computed tomography images. RESULT: Bone fusion was identified in 19 cases (57%). The only significant factors to affect bony fusion was the kind of graft (75% in autograft vs. 41 in allograft, p=0.049). Other factors proved to be insignificant relating to postoperative bone fusion. Regarding time interval of RT and operation in cases of postoperative RT, the time interval was not significant (p=0.101). CONCLUSION: Spinal fusion surgery which was combined with perioperative RT showed relatively low bone fusion rate (57%). For successful bone fusion, the selection of bone graft was the most important.

Clinical Outcome of Treatment for Patients with Giant Cell Tumor in Spine.

OBJECTIVE: The treatment of giant cell tumor (GCT) is mainly performed surgically. However, GCT in spine seems difficult to treat because of the limited surgical accessibility and proximity. In this report, we analyzed the outcome of GCT treatment in spine. METHODS: Between 2000 and 2012, 19 patients received treatment for GCT in spine. Median age at their first diagnosis was 31 years, 10 patients were male, and 9 female. Fourteen tumors were located in the sacrum, 1 in cervical, 1 in thoracic and 3 in lumbar spine. As primary treatment, gross total removal (GTR) was done in 6 patients, and subtotal removal (STR) in 13 patients. Radiation therapy (RT) as an adjuvant therapy was performed in 2 cases in GTR group and 10 cases in STR group. RESULTS: During the follow-up, 7 patients had local recurrence (36.8%). The average period until recurrence after primary treatment was 14 months. No recurrence was detected in GTR group. Recurrence was noted in 7 out of 13 patients who underwent STR. These differences were statistically significant (p=0.024). A median of recurrence free period (RFP) was 84 months. Also average RFP of the RT group was 112 months, and non-RT group was 65 months. These differences were statistically significant (p=0.041). CONCLUSION: Treatment of choice for GCT in spine is a complete removal of tumor without neurological deficits. In case of incomplete removal, radiation therapy may be a useful adjuvant treatment modality.

Two Cases of Dedifferentiated Chordoma in the Sacrum.

Dedifferentiated chordoma (DC) is defined as a chordoma containing sarcoma components. DC is distinguished from conventional chordoma by the rapidity of tumor growth and the potential for distant metastasis. We report two cases of DC, which are developed in the sacrum. We reviewed the medical records and imaging studies of 2 patients diagnosed with DC and the literature published. In the first case, percutaneous biopsy revealed that it was conventional chordoma in the sacrum. Patient underwent radiation therapy (RT). Six years after the RT, the tumor recurred. Surgical removal was performed and the recurrent tumor was diagnosed as DC in histopathologic examination. In the second case, a patient underwent gross total resection of sacral tumor, which was diagnosed with conventional chordoma. Aggravated tumor was detected after 4 months, and patient underwent reoperation. The second operation revealed the transformation of the tumor into DC. The survival time of the patients after the diagnosis was 10 and 31 months. Dedifferentiated chordoma is a rare and highly aggressive tumor. De novo type exists, but it usually transformed from recurrent chordoma after surgical resection or radiation.

Intracavitary radiation therapy for recurrent cystic brain tumors with holmium-166-chico : a pilot study.

OBJECTIVE: Intracavitary injection of beta-emitting radiation source for control of cystic tumors has been tried with a benefit of localized internal radiation. The authors treated cystic brain tumor patients with Holmium-166-chitosan complex (Ho-166-chico), composed of a beta-emitting radionuclide Holmium-166 and biodegradable chit polymer, and evaluated the safety and effective measurement for response. METHODS: Twenty-two patients with recurrent cystic brain tumor and/or located in a deep or eloquent area were enrolled in this pilot study. The cyst volume and wall thickness were determined on CT or MRI to assess radiological response. The activity of Ho-166-chico injected via Ommaya reservoir was prescribed to be 10-25 Gy to the cyst wall in a depth of 4 mm. RESULTS: There was neither complications related to systemic absorption nor leakage of Ho-166-chico in all 22 patients. But, two cases of oculomotor paresis were observed in patients with recurrent craniopharyngioma. Radiological response was seen in 14 of 20 available follow-up images (70%). Seven patients of 'evident' radiological response experienced more than 25% decrease of both cyst volume and wall thickness. Another 7 patients with 'suggestive' response showed decrease of cyst volume without definitive change of the wall thickness or vice versa. All patients with benign tumors or low grade gliomas experienced symptomatic improvement. CONCLUSION: Ho-166-chico intracavitary radiation therapy for cystic tumor is a safe method of palliation without serious complications. The determination of both minimal effective dosage and time interval of repeated injection through phase 1 trial could improve the results in the future.

Radiosurgery using the Cyberknife for benign spinal tumors: Korea Cancer Center Hospital experience.

This study evaluated clinical outcome and safety of radiosurgery using the Cyberknife for treatment of benign spinal tumors. The authors treated 30 benign spinal tumors in 20 patients with the Cyberknife (Accuray, Inc., Sunnyvale, CA, USA) from 2002 to 2008. Among these there were 20 neurogenic tumors, eight hemangioblastomas, and two meningiomas. Four patients with neurofibromatosis (NF) type 2 and four patients with Von Hippel Lindau disease were also included. Radiosurgery was done as primary treatment for 22 lesions, for postoperative residual tumor control for four lesions, and for the remaining four lesions with image-based progression after initial subtotal resection. The distribution of lesions was cervical (18 tumors), thoracic (six), and cauda equina level (six). Follow-up data included imaging studies, clinical findings, and radiotherapy data. Tumor volume ranged from 0.04 to 33.65 cm³ (mean, 4.52 cm³). A 14-33 Gy marginal dose was delivered in 1-5 fractions. The mean follow-up period was 35.6 months (range, 12-84 months). On follow-up, most lesions decreased in size (57%) or remained unchanged (33%). Two lesions initially decreased, then increased later. One lesion increased without response. With regard to clinical aspects, radicular pain and myelopathic pain improved after radiosurgery in most cases (94%). Motor weakness recovered in two out of five patients and recovery of sensory change occurred in four out of ten patients. In two patients, symptoms were aggravated by tumor enlargement and the occurrence of new lesion. Mean spinal cord volumes receiving more than 10 and 8 Gy were 0.40 ± 0.4 and 0.81 ± 0.7 cm³, respectively. Stereotactic radiosurgery (SRS) using the Cyberknife showed the ability to control benign spinal tumors without complication in most cases.

Chemotherapy for malignant gliomas based on histoculture drug response assay : a pilot study.

OBJECTIVE: The Histoculture Drug Response Assay (HDRA), which measures chemosensitivity using minced tumor tissue on drug-soaked gelfoam, has been expected to overcome the limitations of in vitro chemosensitivity test in part. We analyzed interim results of HDRA in malignant gliomas to see if the test can deserve further clinical trials. METHODS: Thirty-three patients with malignant gliomas were operated and their tumor samples were examined for the chemosensitivity to 10 chosen drugs by HDRA. The most sensitive chemotherapy regimen among those pre-established was chosen based on the number of sensitive drugs or total inhibition rate (IR) of the regimen. The response was evaluated by 3 month magnetic resonance image. RESULTS: Among 13 patients who underwent total resection of the tumor, 12 showed no evidence of disease and one patient revealed progression. The response rate in 20 patients with residual tumors was 55% (3 complete and 8 partial responses). HDRA sensitivity at the cut-off value of more than one sensitive drug in the applied regimen showed a sensitivity of 100%, specificity of 60% and predictability of 70%. Another cut-off value of >80% of total IR revealed a sensitivity of 100%, specificity of 69%, and predictability of 80%. For 12 newly diagnosed glioblastoma patients, median progression-free survival of the HDRA sensitive group was 21 months, while that of the non-sensitive group was 6 months (p=0.07). CONCLUSION: HDRA for malignant glioma was inferred as a feasible method to predict the chemotherapy response. We are encouraged to launch phase 2 clinical trial with chemosensitivity on HDRA.

Clinical outcomes after percutaneous vertebroplasty for pathologic compression fractures in osteolytic metastatic spinal disease.

OBJECTIVE: Percutaneous vertebroplasty (VP) can provide immediate stabilization in pathologic fractures of spinal tumors. However, long term follow-up data in cases of pathologic fractures are lacking. The authors report follow-up results of VP in 185 pathologic fractures of 102 spinal tumor patients. METHODS: Percutaneous VP was performed at 185 vertebral bodies of 102 patients from 2001 to 2007. Retrospective analysis was done with medical records and radiological data. The change of visual analogue score (VAS), vertebral body (VB) height and kyphotic angle were measured preoperatively and on postoperative one day and at 3, 6, and 12 months. RESULTS: The patients were composed of metastatic spine tumors (81%) and multiple myeloma (19%). Involved spinal segments were between T6 and L5. Mean follow-up period was 12.2 months. VAS for back pain was 8.24 preoperatively, 3.59 (postoperative one day), 4.08 (three months) and 5.22 (one year). VB compression ratio changed from 21.33% preoperatively to 13.82% (postoperative one day), 14.36% (three month), and 16.04% (one year). Kyphotic angle changed from 15.35 degrees preoperatively to 12.03 degrees (postoperative one day), 13.64 degrees (three month), and 15.61 degrees (one year). CONCLUSION: Immediate pain relief was definite after VP in pathologic compression fracture of osteolytic spinal disease. Although VAS was slightly increased on one year follow-up, VP effect was maintained without significant change. These results indicate that VP could be a safe and effective procedure as a palliative treatment of the spinal tumor patients.

Radiosurgery for recurrent brain metastases after whole-brain radiotherapy : factors affecting radiation-induced neurological dysfunction.

OBJECTIVE: We retrospectively analyzed survival, local control rate, and incidence of radiation toxicities after radiosurgery for recurrent metastatic brain lesions whose initial metastases were treated with whole-brain radiotherapy. Various radiotherapeutical indices were examined to suggest predictors of radiation-related neurological dysfunction. METHODS: In 46 patients, total 100 of recurrent metastases (mean 2.2, ranged 1-10) were treated by CyberKnife radiosurgery at average dose of 23.1 Gy in 1 to 3 fractions. The median prior radiation dose was 32.7 Gy, the median time since radiation was 5.0 months, and the mean tumor volume was 12.4 cm(3). Side effects were expressed in terms of radiation therapy oncology group (RTOG) neurotoxicity criteria. RESULTS: Mass reduction was observed in 30 patients (65%) on MRI. After the salvage treatment, one-year progression-free survival rate was 57% and median survival was 10 months. Age (<60 years) and tumor volume affected survival rate (p=0.03, each). Acute (6 months) toxicity occurred in 21%, respectively. Less acute toxicity was observed with small tumors (<10 cm(3), p=0.03), and less chronic toxicity occurred at lower cumulative doses (<100 Gy, p=0.004). "Radiation toxicity factor" (cumulative dose times tumor volume of <1,000 Gyxcm(3)) was a significant predictor of both acute and chronic CNS toxicities. CONCLUSION: Salvage CyberKnife radiosurgery is effective for recurrent brain metastases in previously irradiated patients, but careful evaluation is advised in patients with large tumors and high cumulative radiation doses to avoid toxicity.

Clinical results of cyberknife(r) radiosurgery for spinal metastases.

OBJECTIVE: Primary treatment of spinal metastasis has been external beam radiotherapy. Recent advance of technology enables radiosurgery to be extended to extracranial lesions. The purpose of this study was to determine the clinical effectiveness and safety of stereotactic radiosurgery using Cyberknife in spinal metastasis. METHODS: From June, 2002 to December, 2007, 129 patients with 167 spinal metastases were treated with Cyberknife. Most of the patients (94%) presented with pain and nine patients suffered from motor deficits. Twelve patients were asymptomatic. Fifty-three patients (32%) had previous radiation therapy. Using Cyberknife, 16-39 Gy in 1-5 fractions were delivered to spinal metastatic lesions. Radiation dose was not different regarding the tumor pathology or tumor volume. RESULTS: After six months follow-up, patient evaluation was possible in 108 lesions. Among them, significant pain relief was seen in 98 lesions (91%). Radiological data were obtained in 83 lesions. The mass size was decreased or stable in 75 lesions and increased in eight lesions. Radiological control failure cases were hepatocellular carcinoma (5 cases), lung cancer (1 case), breast cancer (1 case) and renal cell carcinoma (1 case). Treatment-related radiation injury was not detected. CONCLUSION: Cyberknife radiosurgery is clinically effective and safe for spinal metastases. It is true even in previously irradiated patients. Compared to conventional radiation therapy, Cyberknife shows higher pain control rate and its treatment process is more convenient for patients. Thus, it can be regarded as a primary treatment modality for spinal metastases.

Extraskeletal Ewing's sarcoma of the head and neck presenting as blindness.

Extraskeletal Ewing's sarcoma is rarely found in the head and neck regions. We report an unusual case of extraskeletal Ewing's Sarcoma of the parapharynx region in a 49-year-old man who presented with blindness. MRI examination showed marked enhancement of tumor thrombosis involving the superior sagittal sinus, straight sinus, transverse sinus, sigmoid sinus, and internal jugular vein. The final diagnosis was extraskeletal Ewing's sarcoma after biopsy of the internal jugular vein thrombosis by histopathological evaluation and immunohistochemical assay. In addition, the patient was diagnosed as having adenocarcinoma of the rectum by biopsy of the rectal mass. The patient was treated with systemic chemotherapy and showed improved response with durable remission. The patient's visual acuity, however, did not improve.

ACNU-cisplatin continuous infusion chemotherapy as salvage therapy for recurrent glioblastomas: phase II study.

PURPOSE: To evaluate the activity and the toxicity of ACNU (1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-cholroethyl)-3-nitrosourea hydrochloride) administered with cisplatin by intravenous infusion for 72 h in select patients with recurrent glioblastoma. PATIENTS AND METHODS: From April 1996 to 2002, 37 patients with histologically proven glioblastoma, who showed recurrence on image study after operation and radiation, met the eligibility criteria of our cohort. The mean time to recurrence was 9.7+/-7.0 (1-26 months). Treatment response was evaluated every 6 weeks using magnetic resonance imaging (MRI). Complete blood counts were collected every week to monitor and treat possible bone marrow suppression from the treatment. Survival rates were analyzed using the Kaplan-Meier and log rank test. RESULTS: Post-chemotherapy MRI was available in 36 of 37 patients. Response to treatment was observed in 19 patients (53%) including two cases of complete remission. Six patients (17%) showed progression (PD) and 11 patients (31%) had stable disease (SD). Two or more cycles of chemotherapy was the only factor that predicted response to treatment. The overall median survival for all patients was 17.0+/-5.5 months. Age (< 40 years) and time to recurrence (>or=1 year) were the clinical factors that predicted improved overall survival. Survival gain after chemotherapy was 9 months. Patients who responded and those with SD after treatment (11 months) had a longer median survival compared to PD (5 months) (P=0.01). Myelosuppression was severe (grade III/IV leukopenia in 15 patients (40%) and grade III/IV thrombocytopenia in 19 patients (52%)) but most recovered more than WHO grade II at the end of the chemotherapy cycles. There was only one fatality due to sepsis from pneumonia during the initial leukopenic state. CONCLUSION: ACNU and cisplatin chemotherapy can be an effective salvage therapy for recurrent glioblastoma patients. Myelosuppression from the chemotherapy regimen was the greatest side-effect but was manageable.

Hypofractionated stereotactic radiation therapy for skull base and upper cervical chordoma and chondrosarcoma: preliminary results.

INTRODUCTION: Chordoma and chondrosarcoma are rare tumors of the base of the skull and are difficult candidates for surgical treatment. They are also usually resistant to conventional radiation therapy. We report preliminary results of hypofractionated stereotactic radiation therapy (SRT) using the Cyberknife system (Accuray Inc., Sunnyvale, Calif., USA) for primary and recurrent chordomas and chondrosarcomas of the skull base and upper cervical region. MATERIAL AND METHODS: Nine pathologically proven chordoma/chondrosarcoma patients underwent Cyberknife treatment, and in 4 patients Cyberknife was performed as a primary adjuvant treatment after operation. Remainder of the patients had previously received conventional radiotherapy except 1 who had received Gamma Knife treatment. The prescribed tumor dose ranged from 21 to 43.6 Gy in three to five fractions. The dosimetric characteristics were evaluated for conformity and coverage indices. Dose volume histograms of both the tumor and the critical structure were obtained, and the dose delivered to a specific volume (25, 50 and 100%) of the critical structure was calculated in each case. Mass response was measured on follow-up MRI scans. Total tumor doses of different fractionation numbers were converted into single session equivalent doses and linear quadratic equivalent doses of conventional radiation for comparison among patient groups. RESULT: No significant complications were observed during the treatment and early follow-up periods except one instance of transient esophagitis and one instance of otitis. All treatment plans met the criteria for standard protocol of radiosurgery suggested by the Radiation Therapy Oncology Group, specifically in terms of conformity index, which ranged from 1.01 to 1.83. Three plans had a coverage index that was rated as a minor acceptable deviation. All patients were followed from 11 to 30 (median 24) months following the treatment with regular magnetic resonance images, and 4 patients showed mass reduction. Disease progression was not noted in any patient during the above follow-up period except 1 patient who showed asymptomatic recurrence on 27-month follow-up MRI. Dose volume histograms revealed that the relative dose to volume percent of critical structure, measured at 25, 50 and 100%, was apparently lower in the pretreatment surgical decompression group than in the nondecompression group. Two patients developed radiation-induced myelopathy. The delivered radiation dose to the critical structure calculated using the linear-quadratic formula was within the acceptable range in one case and exceeded 70 Gy at 50% volume of the spinal cord in the other. CONCLUSION: The hypofractionated Cyberknife SRT is effective in generating therapeutic response in these radioresistant tumors, with minimal toxicity during the procedure and early follow-up period. Repeated radiosurgical treatment may also be feasible for tumor recurrences but deserves great caution with respect to the biological effects of the accumulated dose on the adjacent critical structures. Cyberknife SRT may be a potentially valuable treatment option once the long-term results and appropriate dose calculators are optimally defined.