[Radiotherapy for Alleviation of Paraparesis due to Leptomeningeal and Cauda Equina Metastasis of HER2-Positive Breast Cancer: A Case Report].

Leptomeningeal metastasis is a rare entity and its diagnosis is often difficult. Moreover, evidence-based therapeutic strategies have not yet been established. A 52-year-old woman presented with high fever and was diagnosed with bacterial meningitis at first examination;although her fever was alleviated, she experienced motor weakness in both of her lower extremities. Ga scintigraphy highlighted the hot-spot areas of the disease in the cranial bone. She was then transferred to our department. Open biopsy of the skull showed metastasis of the cancer. Chest CT results indicated right breast cancer and Gd-DTPA imaging showed obvious enhancement of the pia mater around the conus medullaris and cauda equina. However, cerebrospinal fluid(CSF)cytological examination did not show the presence of any positive cells;consequently, mastectomy was performed in the thoracic surgical department. The severity of paraparesis and pain in her legs increased;however, repeat MRI 1 month later showed no evidence of any change. Therefore, we performed biopsy of the cauda equina and arachnoid lesions. The pathological diagnosis was metastasis of breast cancer with positive human epidermal growth factor receptor 2(HER2)immunological staining. The results of a repeat cytological examination of the CSF during the surgery were negative. Local radiotherapy(25 Gy/5 Fr)as a monotherapy was selected for the patient, because her family did not approve of the combination of radiotherapy and chemotherapy. The severity of both paraparesis and limb pain decreased immediately after the radiotherapy.

Cell type-specific reciprocal regulation of HIF1A gene expression is dependent on 5'- and 3'-UTRs.

In the present study, we demonstrated the reciprocal regulation of hypoxia-inducible factor 1 alpha (HIF1A) gene expression via untranslated region-(UTR) dependent mechanisms. A 151 nucleotide sequence found in the HIF1A 5'-UTR is sufficient for significant translational up-regulation. On the other hand, the 3'-UTR of HIF1A has been implicated in mRNA degradation. In the non-metastatic breast cancer cell line MCF7, the 3'-UTR-dependent down-regulatory machinery predominates over the 5'-UTR-dependent up-regulation of HIF1A. However, 5'-UTR-dependent up-regulation is dominant among metastatic cell lines (MDA-MB453, U87MG). It is therefore likely that the predominance of 5'-UTR-dependent translational enhancement of HIF1A is critical for the malignant phenotype of cancer cells. PTBP-1, but not HuR, is a candidate RNA binding protein for the translational control of HIF1A.

Lysyl oxidase: from basic science to future cancer treatment.

In this mini-review, we discuss the physiological and pathological roles of lysyl oxidase (LOX) and its family, LOX-like proteins (LOXL), in relation to prognosis of major cancers. The number of reports on LOX family is numerous. We have decided to review the articles that were recently published (i.e. past 5 years). Experimental techniques in molecular biology have advanced surprisingly in the past decade. Accordingly, the results of the studies are more reliable. Most studies reached the same conclusion; a higher LOX- or LOXL- expression is associated with a poor prognosis. Molecular experiments have already started aiming for clinical application, and the results are encouraging. Suppressing LOX or LOXL activities resulted in lower cell motility in collagen gel and, moreover, succeeded in reducing metastases in mice. LOX family members were originally recognized as molecules that cross-link collagen fibers in the extracellular matrix. Recent studies demonstrated that they are also involved in a phenomenon called Epithelial Mesenchymal Transition (EMT). This may affect cell movement and cancer cell invasiveness. LOX and LOXL2 are regulated by hypoxia, a major factor in the failure of cancer treatment. Here we discuss the molecular biology of the LOX family in relation to its role in tumor biology.

Radiation-induced cancer cell repopulation: a possible mechanism implied by experiments using transplantable mouse-derived sarcoma cell line.

PURPOSE: Treatment with any cytotoxic agent can trigger surviving cells in a tumor to divide faster than before. This phenomenon is widely recognized as "repopulation". To better clarify the mechanism, gene expression profiling and pathological experiments were performed. MATERIALS AND METHODS: A mouse fibrosarcoma cell line, QRsP, was used. Cells were irradiated with 10 Gy. Colony assay and cloning were performed. Six clones were established. cDNA analysis was performed on the clone that showed the largest number of colonies on the 2nd 10 Gy irradiation. Mouse transplantation experiment was then carried out. RESULTS: cDNA analysis showed that cyclin-dependent kinase inhibitors, p16 and p57 were down-regulated; 14.8- and 12.0-fold, respectively for the tolerant clone. Matrix metalloproteinase 3 and 13 were up-regulated; 22.5- and 25.8-fold, respectively. Transplantation ratio was 100% (5/5) for the tolerant clone whereas it was 40% (2/5) for the parent. Under light microscope, the mean mitotic cell number was 4.0+/-3.9 for the parent, and 12.8+/-3.4 for the tolerant clone (p<0.01, Student's t-test). CONCLUSIONS: This study implies that repopulation is not a temporary reaction to irradiation. It is caused probably by "clonal" gene-expression changes, though it remains unknown whether the changes are attributable to tolerant cell selection or to gene mutation/modification.

Clinical characteristics and computed tomography findings in children with 2009 pandemic influenza A (H1N1) viral pneumonia.

In this article we review the clinical characteristics and computed tomography (CT) findings in children with 2009 pandemic H1N1 influenza viral pneumonia. The medical charts of 88 children with pandemic H1N1 influenza virus infection, admitted to our hospital in Japan from 10 August to 28 December 2009, were reviewed; we compared the clinical features of these children with those of 61 children admitted with seasonal influenza A during the previous 3 seasons. Of 88 patients, 53 (60%) had radiographic findings consistent with pneumonia and 34 patients underwent a chest computed tomography (CT) scan. Pneumonia was a more frequent complication in children with pandemic H1N1 influenza compared with those with seasonal influenza (60% vs 11%; p < 0.001). The predominant CT findings were unilateral or bilateral multifocal consolidation (15/34; 44%) associated with ground-glass opacities in the peribronchovascular region. The second most common CT finding was unilateral diffuse consolidation or atelectasis in 1 or more lung zones (12/34; 35%). The chest CT findings of unilateral or bilateral multifocal consolidation often associated with ground-glass opacities were commonly seen in children with pandemic H1N1 influenza viral pneumonia. Atelectasis was seen in patients who required oxygen administration.

Integrin beta1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix.

Radiotherapy is one of the effective therapies used for treating various malignant tumors. However, the emergence of tolerant cells after irradiation remains problematic due to their high metastatic ability, sometimes indicative of poor prognosis. In this study, we showed that subcloned human lung adenocarcinoma cells (A549P-3) that are irradiation-tolerant indicate high invasive activity in vitro, and exhibit an integrin beta1 activity-dependent migratory pattern. In collagen gel overlay assay, majority of the A549P-3 cells displayed round morphology and low migration activity, whereas a considerable number of A549P-3IR cells surviving irradiation displayed a spindle morphology and high migration rate. Blocking integrin beta1 activity reduced the migration rate of A549P-3IR cells and altered the cell morphology allowing them to assume a round shape. These results suggest that the A549P-3 cells surviving irradiation acquire a highly invasive integrin beta1-dependent phenotype, and integrin beta1 might be a potentially effective therapeutic target in combination with radiotherapy.

Novel function of transcription factor ATF5: blockade of p53-dependent apoptosis induced by ionizing irradiation.

PURPOSE: To find a new molecule that affects p53-dependent radiosensitivity. METHODS AND MATERIALS: A mouse sarcoma cell line, QRsP(p53+/+), was used. From this cell line, we established a radiosensitive clone and a radioresistant one. Colony assay, p53 gene transfer, a luciferase assay for p53 and p21, animal transplantation experiment, and DNA array analyses were performed. RESULTS: Microarray showed marked reduction of a transcription factor, ATF5, both in vitro and in vivo for the radiosensitive clone. Interestingly, flow cytometric analysis demonstrated marked apoptosis for the radiosensitive clone by p53 cloned adenovirus infection. Luciferase reporter assay revealed that ATF5 suppressed the transactivational activity of p53 and p63. By ATF5 gene transfer, the radiosensitive clone regained resistance to both ionizing-radiation and Ad-p53 infection-induced cell death. Surprisingly, time-lapse cell migration observation revealed greater cell motility for ATF5-transfected radiosensitive clone. CONCLUSIONS: It seems likely that ATF5 is a potent repressor of p53 and elevated expression of ATF5 in a tumor may relate to enhanced malignant phenotypes, such as radioresistance or greater cell motility.

Increased motility and invasiveness in tumor cells that survive 10 Gy irradiation.

Radiotherapy is an important noninvasive treatment for many types of cancer. However, it has been reported that the proliferative, invasive, and metastatic capacities of tumor cells can be increased in the repopulated tumors that survive radiotherapy. We have previously established a radiation-surviving cell model for the human non-small cell lung cancer cell line H1299 by harvesting relic cells 14 days after irradiation (IR cells). Here, we report that cell invasion, cell migration, and cell adhesion are enhanced in these surviving cancer cells. The mRNA expression levels of matrix metalloproteinases (MMPs), including mmp1, mmp2, and mmp9, were upregulated in IR cells compared with parental cells. A gelatin zymogram, wound healing assay, and invasion assay showed increased MMP activity, cell motility, and invasiveness in IR cells, respectively. Moreover, IR cells adhered more tightly to collagen-coated dishes than parental cells. Consistently, paxillin, phosphorylated FAK, integrin beta1, and vinculin were strongly localized at focal adhesions in IR cells, as visualized by immunofluorescence. In this report, we identify molecules responsible for the malignant properties of tumor cells that survive irradiation. These molecules may be important therapeutic targets for the control of repopulated tumors after radiotherapy.

Exhale fluctuation in respiratory-gated radiotherapy of the lung: a pitfall of respiratory gating shown in a synchronized internal/external marker recording study.

PURPOSE: For optimal respiratory-gated radiotherapy, exhale fluctuation was assessed by monitoring internal fiducials in a synchronized internal/external marker detection system. METHODS: Synchronized internal/external position data were collected during the entire course of treatments for 12 lung patients with 24 fiducials. Baseline was determined in the exhale phase during pre-treatment observation time, and a gating level of external waves was set in each treatment session in a simulation of respiratory-gated radiotherapy. Patients were treated under a real-time tumor-tracking (RTRT) system with an external (abdominal) respiratory motion detector. In the simulation, external gating windows were defined as those below the 30% amplitude level (i.e., imaginary beams would be triggered when part of the respiratory wave falls into this window). Exhale fluctuation (EF) was defined as the phenomenon in which the lowest point of the external wave crossed downward past the pre-determined baseline. Gating efficiency (GE) was defined as the ratio between the amount of gate-ON time and the total treatment time. RESULTS: EF occurred in 18.4% of total measurements. EF varied depending on the patient, fiducial sites, and treatment session. The mean incidence of EF for each patient varied from 2.9% to 37.5% (18.4+/-9.9). The EF magnitude was 0.2-12.2 mm in the left-right direction, 0.7-12.7 mm in the cranio-caudal direction, and 0.4-9.7 mm in the anterior-posterior direction. Total fiducial movement was 0.5-28.7 mm. GE was 36.1-69.2% (55.4+/-11.0). EF magnitude correlated with total fiducial movement. CONCLUSION: This study showed that EF is not a rare phenomenon and needs to be taken into consideration for individualized precise 4D radiotherapy.

[Squamous cell carcinoma of the lower lip, completely responding to concurrent chemoradiotherapy with S-1].

Concurrent chemoradiotherapy (CCRT) can be used in order to increase both the local and systemic control of head and neck carcinoma. This report shows for the first time the assessment of CCRT with S-1 as a treatment modality for squamous cell carcinoma (SCC) of the lower lip. Surgical excision is usually the first choice for the treatment of SCC of the lower lip, followed by reconstruction. Such a treatment choice more or less compromises the cosmetic and/or functional status of the lip. We present our experience of utilizing CCRT with S-1 as a mode of treatment for SCC of the lower lip that yielded significant results while preserving the integrity of the lip.

Carcinoma of the floor of the mouth: a case treated with precisely controlled external beam radiotherapy.

A new external radiotherapy system has been developed for head and neck cancer and a case with T2 oral floor carcinoma treated with this system is presented in this report. The system consists of real-time tumor-tracking equipment and a gold-marker implanted mouthpiece. Accuracy of the order of 2 mm was achieved during the entire course of fractionated radiotherapy (a total of 52.5 Gy in 15 fractions). Planning target volume became smaller compared to the conventional parallel-opposed technique. Dose-volume histogram analysis demonstrated a significant reduction in the dose to the mandible bone compared to the conventional technique. A confluent fibrinous mucositis developed in the oral floor mucosa that corresponded to 90% dose area. Mucositis in the lower gum was minimal and analgesics were not required. The patient is currently free from both tumor and complication during a follow-up period of 48 months. External radiotherapy can be an option as a curative treatment for early stage carcinoma of the floor of the mouth provided that patient set-up is rigid and reproducible.

X-ray irradiation altered chemosensitivity of a p53-null non-small cell lung cancer cell line.

Radiotherapy is an effective approach to treating many types of cancer. Recent progress in radiotherapy technology, such as intensity-modulated radiation therapy (IMRT) and three-dimensional (3D) radiotherapy, allow precise energy transfer to the tumor, which has improved local control rates. However, the emergence of tolerant cells during or after radiotherapy remains problematic. In the present study, we first established a cell population from H1299, the p53-null non-small cell lung cancer cell line, by 10 Gy irradiation using 6 MV X-rays. The radio- and chemosensitivity of this cell population (referred to as H1299-IR) was determined using colony formation analyses and MTS assays. Compared with the parental cell line, the radiosensitivity of H1299-IR was apparently the same. H1299 and H1299-IR were both more radio tolerant than the A549 cell line. However, H1299-IR became significantly more sensitive to cisplatin, an antitumor agent. After exposure to 25 mug/ml cisplatin for 2 h, parental cells steadily grew during the MTS assay, whereas the sensitivity of H1299-IR cells doubled both at 24 and 48 h. Microarray analysis of over 30,000 H1299-IR genes (Agilent Technology) revealed that 12 and 15 genes were up- (> 2.0) and down- (< 2.0) regulated, respectively. Rad51d (homologous recombination repair protein) gene was down-regulated 2.8-fold, whereas matrix metalloproteinase 1 (collagenase-1) gene was up-regulated 4.4-fold. These results indicated that some p53-null non-small cell lung cancers could be successfully treated when X-ray radiotherapy was administered with subsequent or concurrent cisplatin chemotherapy.

Uncertainty in treatment of head-and-neck tumors by use of intraoral mouthpiece and embedded fiducials.

PURPOSE: To reduce setup error and intrafractional movement in head-and-neck treatment, a real-time tumor tracking radiotherapy (RTRT) system was used with the aid of gold markers implanted in a mouthpiece. METHODS AND MATERIALS: Three 2-mm gold markers were implanted into a mouthpiece that had been custom made for each patient before the treatment planning process. Setup errors in the conventional immobilization system using the shell (manual setup) and in the RTRT system (RTRT setup) were compared. Eight patients with pharyngeal tumors were enrolled. RESULTS: The systematic setup errors were 1.8, 1.6, and 1.1 mm in the manual setup and 0.2, 0.3, and 0.3 mm in the RTRT setup in right-left, craniocaudal, and AP directions, respectively. Statistically significant differences were observed with respect to the variances in setup error (p <0.001). The systematic and random intrafractional errors were maintained within the ranges of 0.2-0.6 mm and 1.0-2.0 mm, respectively. The rotational systematic and random intrafractional errors were estimated to be 2.2-3.2 degrees and 1.5-1.6 degrees , respectively. CONCLUSIONS: The setup error and planning target volume margin can be significantly reduced using an RTRT system with a mouthpiece and three gold markers.

Involvement of UTR-dependent gene expression in the maintenance of cancer stem cell like phenotypes.

The present study demonstrated the acquisition of additional malignant characteristics in irradiated mouse fibrosarcoma cells compared with the parent cells. Several reporter assays indicated that hypoxia-inducible factor (HIF)-1α, activator protein-1 and Ets-dependent transcription were activated in irradiated cells. The cis-elements in the 5'-untranslated region (UTR) of these transcription factors plays a major role in their expression in surviving irradiated cancer cells. By contrast, there were no evident differences between the 3'-UTR-dependent repression demonstrated by parent cells and irradiated cells. A small population of parental fibrosarcoma cells was also found to exhibit the same enhanced 5'-UTR-dependent HIF-1α expression as that demonstrated by irradiated cells. These observations may indicate that high-dose X-ray irradiation affects the majority of proliferating cancer cells, but not the cancer stem cells (CSCs), and an increased CSC population may explain the progressive phenotypes of the irradiated cells. It appears likely that the transcription factors that maintain stemness are regulated by the same 5'-UTR-dependent mechanism.

Clinical significance of 3D reconstruction of arteriovenous malformation using digital subtraction angiography and its modification with CT information in stereotactic radiosurgery.

PURPOSE: A three-dimensional (3D) reconstruction method of arteriovenous malformation (AVM) nidus from digital subtraction angiography (DSA) in combination with CT and/or MRI was developed, and its usefulness was evaluated in this study. MATERIALS AND METHODS: The contour of the AVM nidus was delineated on two orthogonal projected DSA images. First, the volume and center of the AVM nidus were calculated in a classic DSA plan using three maximal lengths of the nidus in three perpendicular directions, assuming that the nidus had a prolate ellipsoid shape. Second, in the 3D-DSA plan, the contours of the AVM nidus on the two orthogonal projected DSA images were segmented to be compatible with the slice thickness of the CT image. Assuming that each segment of the nidus has an ellipsoid pillar shape, the volume and center of each segment were calculated. The volume and 3D shape of the nidus were calculated by 3D reconstruction in the 3D-DSA plan. Third, in the CT-DSA plan, the contour based on the segmented DSA was superimposed on the corresponding transaxial CT image slice by slice. The cylindrical shape of the nidus in the transaxial image was modified using the enhanced CT images in the CT-DSA plan. These three planning methods were compared using dose-volume statistics from real patients' data. Eighteen patients with intracranial AVMs in different brain locations who had been treated by radiosurgery were the subjects of this study. To examine the visibility (validity) of the nidus on the CT image, the "nidus" was delineated on an enhanced CT image without DSA superposition in the CT plan and compared with the CT-DSA plan. RESULTS: The variance in the distance between coordinates determined by the CT plan and those determined by the classic DSA plan was significantly larger than the variance in the CT-DSA plan (p < 0.0001 for lateral, AP, and craniocaudal directions). The difference in the variance was not reduced by the addition of MRI (p < 0.0001 for each direction). The mean volume +/- SD of the nidus calculated was 5.9 +/- 8.0 cm(3) in the classic DSA plan, 4.0 +/- 5.6 cm(3) in the 3D-DSA plan, and 3.6 +/- 5.2 cm(3) in the CT-DSA plan. The 3D-DSA plan significantly reduced the mean nidus volume 31.8% +/- 12.7% from the classic DSA plan (p = 0.0054). The CT-DSA plan further significantly reduced the volume 9.8% +/- 8.8% from the 3D-DSA plan (p = 0.0021). The mean overlapping volume of the nidus between the CT plan and CT-DSA plan was 2.6 +/- 4.3 cm(3) (range 0.17-18.9), corresponding to 63.7% +/- 19.2% (range 11.4-85.3%) of the volume in the CT-DSA plan. CONCLUSIONS: The superposition of the segmented DSA information on CT was shown to be an important tool to determine the precise shape of the nidus and is suggested to be useful to reduce partial occlusion of the AVM or radiation complications in radiosurgery.

Calculation of rotational setup error using the real-time tracking radiation therapy (RTRT) system and its application to the treatment of spinal schwannoma.

PURPOSE: The efficacy of a prototypic fluoroscopic real-time tracking radiation therapy (RTRT) system using three gold markers (2 mm in diameter) for estimating translational error, rotational setup error, and the dose to normal structures was tested in 5 patients with spinal schwannoma and a phantom. METHODS AND MATERIALS: Translational error was calculated by comparing the actual position of the marker closest to the tumor to its planned position, and the rotational setup error was calculated using the three markers around the target. Theoretically, the actual coordinates can be adjusted to the planning coordinates by sequential rotation of gamma degrees around the z axis, beta degrees around the y axis, and alpha degrees around the x axis, in this order. We measured the accuracy of the rotational calculation using a phantom. Five patients with spinal schwannoma located at a minimum of 1-5 mm from the spinal cord were treated with RTRT. Three markers were inserted percutaneously into the paravertebral deep muscle in 3 patients and surgically into two consecutive vertebral bones in two other patients. RESULTS: In the phantom study, the discrepancies between the actual and calculated rotational error were -0.1 +/- 0.5 degrees. The random error of rotation was 5.9, 4.6, and 3.1 degrees for alpha, beta, and gamma, respectively. The systematic error was 7.1, 6.6, and 3.0 degrees for alpha, beta, and gamma, respectively. The mean rotational setup error (0.2 +/- 2.2, -1.3 +/- 2.9, and -1.3 +/- 1.7 degrees for alpha, beta, and gamma, respectively) in 2 patients for whom surgical marker implantation was used was significantly smaller than that in 3 patients for whom percutaneous insertion was used (6.0 +/- 8.2, 2.7 +/- 5.9, and -2.1 +/- 4.6 degrees for alpha, beta, and gamma). Random translational setup error was significantly reduced by the RTRT setup (p < 0.0001). Systematic setup error was significantly reduced by the RTRT setup only in patients who received surgical implantation of the marker (p < 0.0001). The maximum dose to the spinal cord was estimated to be 40.6-50.3 Gy after consideration of the rotational setup error, vs. a planned maximum dose of 22.4-51.6 Gy. CONCLUSION: The RTRT system employing three internal fiducial markers is useful to reduce translational setup error and to estimate the dose to the normal structures in consideration of the rotational setup error. Surgical implantation of the marker to the vertebral bone was shown to be sufficiently rigid for the calculation of the rotational setup error. Fractionated radiotherapy for spinal schwannoma using the RTRT system may well be an alternative or supplement to surgical treatment.

Pilot study of modified version of CHOP plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck.

PURPOSE: To evaluate the safety and efficacy of a modified version of cyclophosphamide, doxorubicin, vincristine, prednisone (pirarubicin, cyclophosphamide, vincristine, and prednisone [THP-COP]) plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck. METHODS AND MATERIALS: Between December 1993 and December 1999, 41 patients with early-stage non-Hodgkin's lymphoma with intermediate-grade histologic features were enrolled in our study. The mean patient age was 51 years. Of the 41 patients, 27 had Stage I and 14 Stage II disease. The primary site was Waldeyer's ring, a neck node, or an extranodal site in 14, 11, and 16 patients, respectively. The immunophenotype was B cell in 29 and T cell in 12 patients. All patients were in the low-risk category according to the International Prognostic Index. Chemotherapy consisted of 40 mg/m(2) i.v. pirarubicin (THP-Adriamycin), 750 mg/m(2) i.v. cyclophosphamide, and 1.0 mg/m(2) i.v. vincristine, on Day 1 and 40 mg/m(2) p.o. prednisone on Days 1-5. The combination chemotherapy was given twice at a 14-day interval. Radiotherapy was given to involved areas at a fraction size of 2.0-2.5 Gy up to a total of 40 Gy within 4-5 weeks. The mean follow-up period was 63 months. RESULTS: The 5-year overall survival rate was 89%. The 5-year cause-specific survival and progression-free survival rate was 90% and 81%, respectively. The 5-year progression-free survival rate for patients with Waldeyer's ring primaries was 93%. Patients with tumor <5 cm in size had greater 5-year progression-free survival than those with tumor >5 cm in size (85% vs. 33%, p <0.05, log-rank test). Grade 4 neutropenia was seen in 12% of patients; however, 93% of patients (38 of 41) received chemotherapy as scheduled with the support of granulocyte colony-stimulating factor. CONCLUSION: Biweekly THP-COP plus radiotherapy is feasible and effective for Stage I-II low-risk non-Hodgkin's lymphoma.

Image fusion between 18FDG-PET and MRI/CT for radiotherapy planning of oropharyngeal and nasopharyngeal carcinomas.

PURPOSE: Accurate diagnosis of tumor extent is important in three-dimensional conformal radiotherapy. This study reports the use of image fusion between (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG-PET) and magnetic resonance imaging/computed tomography (MRI/CT) for better targets delineation in radiotherapy planning of head-and-neck cancers. METHODS AND MATERIALS: The subjects consisted of 12 patients with oropharyngeal carcinoma and 9 patients with nasopharyngeal carcinoma (NPC) who were treated with radical radiotherapy between July 1999 and February 2001. Image fusion between 18FDG-PET and MRI/CT was performed using an automatic multimodality image registration algorithm, which used the brain as an internal reference for registration. Gross tumor volume (GTV) was determined based on clinical examination and 18FDG uptake on the fusion images. Clinical target volume (CTV) was determined following the usual pattern of lymph node spread for each disease entity along with the clinical presentation of each patient. RESULTS: Except for 3 cases with superficial tumors, all the other primary tumors were detected by 18FDG-PET. The GTV volumes for primary tumors were not changed by image fusion in 19 cases (89%), increased by 49% in one NPC, and decreased by 45% in another NPC. Normal tissue sparing was more easily performed based on clearer GTV and CTV determination on the fusion images. In particular, parotid sparing became possible in 15 patients (71%) whose upper neck areas near the parotid glands were tumor-free by 18FDG-PET. Within a mean follow-up period of 18 months, no recurrence occurred in the areas defined as CTV, which was treated prophylactically, except for 1 patient who experienced nodal recurrence in the CTV and simultaneous primary site recurrence. CONCLUSION: This preliminary study showed that image fusion between 18FDG-PET and MRI/CT was useful in GTV and CTV determination in conformal RT, thus sparing normal tissues.

High dose three-dimensional conformal boost (3DCB) using an orthogonal diagnostic X-ray set-up for patients with gynecological malignancy: a new application of real-time tumor-tracking system.

The feasibility and accuracy of high dose three-dimensional conformal boost (3DCB) using three internal fiducial markers and a two-orthogonal X-ray set-up of the real-time tumor-tracking system on patients with gynecological malignacy were investigated in 10 patients. The standard deviation of the distribution of systematic deviations (Sigma) was reduced from 3.8, 4.6, and 4.9 mm in the manual set-up to 2.3, 2.3 and 2.7 mm in the set-up using the internal markers. The average standard deviation of the distribution of random deviations (sigma) was reduced from 3.7, 5.0, and 4.5 mm in the manual set-up to 3.3, 3.0, and 4.2 mm in the marker set-up. The appropriate PTV margin was estimated to be 10.2, 12.8, and 12.9 mm in the manual set-up and 6.9, 6.7, and 8.3 mm in the gold marker set-up, respectively, using the formula 2Sigma + 0.7sigma. Set-up of the patients with three markers and two fluoroscopy is useful to reduce PTV margin and perform 3DCB.

Clinical study of a spacer to help prevent osteoradionecrosis resulting from brachytherapy for tongue cancer.

OBJECTIVE: We sought to describe a simple method to construct a spacer and to evaluate with the use of computed tomography the spacer's effectiveness in preventing osteoradionecrosis of the mandible. STUDY DESIGN: Fifty-three patients with oral tongue cancers who were treated by means of interstitial brachytherapy were included in this study. Patients underwent a computed tomography examination immediately after the implantation of radioactive sources, with the spacers in place. Distances between the radioactive sources and the lingual surfaces of the mandible were measured on transverse computed tomographs and were evaluated in terms of the development of osteoradionecrosis in the mandible. RESULTS: Statistically significant differences in the frequency of osteoradionecrosis were observed between patients who had received spacers equal to or thicker than 5 mm and those who had received spacers less than 5 mm thick. CONCLUSION: A spacer should have a minimum thickness of 5 mm on its lingual flange to prevent the development of osteoradionecrosis of the mandible.