Tomotherapy for neurofibromatosis Type 2: case report and review of the literature.

Neurofibromatosis 2 (NF2) results in multiple central nervous system tumours. In this case report, the patient has one vestibular schwannoma, one trigeminal schwannoma and two meningiomas developed before the age of 30. Aiming to treat three targets at one fraction with minimal interaction and overlapping doses to normal tissue, the sophisticated equipment of tomotherapy was utilised for frameless stereotaxy; tomotherapy delivered intensity-modulated, rotational radiation therapy using a fan-beam delivery. Daily CT scans with the inbuilt CT scanner were also performed as part of the image-guided radiotherapy. The course of fractionated stereotactic radiotherapy consisted of eight fractions given three times per week with an overall treatment time of 17 days. For the meningioma over left parietal vertex, 4.5 Gy per fraction was given at 36 Gy/8 Fr/17 days. For the meningioma over anterior cerebral falx, 4 Gy per fraction was given at 32 Gy/8 Fr/17 days. For the two schwannomas as one target, 5 Gy per fraction was given at 40 Gy/8 Fr/17 days. The acute effect of the treatment was alopecia and mild headache. Subsequent follow-up confirmed clinical improvement. This is the first reported case of clinical experience with tomotherapy in the management of NF2.

External beam radiation therapy for inoperable hepatocellular carcinoma with portal vein thrombosis.

Portal vein thrombosis (PVT) in patients with hepatocellular carcinoma (HCC) has a poor impact on prognosis. Many of these tumors may cause intrahepatic and extrahepatic metastases. From January 1991 to December 1996, 41 unresectable HCC patients with PVT underwent transcatheter arterial chemoembolization (TACE) and external beam radiation therapy (EBRT) to the portion of PVT. The irradiated field, with a mean equivalent field size of 6.6 x 7.1 cm2, was localized and simulated by abdominal sonography, angiography and computed tomography. Radiation dose ranged from 36 to 66 Gy (mean dose: 51.4 Gy), in a daily fraction of 1.8 to 2 Gy. The response of EBRT was evaluated by abdominal sonography within 3 months of completion of EBRT. The response rates of the PVT after treatment were 39% for complete response (CR), 41% for partial response (PR), and 19% for no response (NR), respectively. The median overall survival time from start of radiotherapy was 10 months for all patients, 17 months for CR patients, 8 months for PR patients and 4 months for NR patients. By multivariate analysis, response of PVT resulted in a significant improvement in survival. (P = 0.001) There was no occurrence of severe complication of radiation-induced liver disease. The results obtained with combined treatment modality of EBRT and TACE in the treatment of HCC patients with PVT are encouraging.

Recovery of the hematopoietic system by Si-Jun-Zi-Tang in whole body irradiated mice.

The herbal formulation Si-Jun-Zi-Tang reduced the decrease of leukocytes, erythrocytes, thrombocytes and hematocrit in irradiated mice. In general, its protection was more effective in leukocytes and thrombocytes than other hematocytes. Protection of bone marrow stem cells by Si-Jun-Zi-Tang was markedly enhanced by increased radiotolerance under the dose ranging from 0 to 5 Gy. This increased radiotolerance led to a prolonged shoulder in the survival curve but did not influence the D0 value. Si-Jun-Zi-Tang exerted a beneficial effect on clinical syndromes such as anemia. From the results in this study, we concluded preliminarily that the most effective concentration with least toxicity was about 20 mg/20 g body weight. At this dose, levels of leukocytes as well as thrombocytes were enhanced significantly after chi-irradiation. Elevation of erythrocytes and hematocrits could also be found but was not significant.

Patterns of distant metastases in nasopharyngeal carcinoma.

The distant metastasis in nasopharyngeal carcinoma has remained the major cause of mortality and treatment failure despite better locoregional control of the disease in the past decades. Between 1987 and 1992, 125 out of 629 cases of nasopharyngeal carcinoma were found to have distant metastasis. The location of metastatic site, the timing and median survival were analyzed. The diagnosis of distant metastasis in the retrospective study was based on radiography, computed tomography, skeletal scintigraphy, abdominal sonography and pathology reports. The results showed that the frequencies of metastases were as follows: bone (75% of total metastatic patients), lung (46%), liver (38%), retroperitoneal lymph nodes (10%). Multiple organ involvement was high (57%). Most of the distant metastases (95%) occurred within 3 years after completion of radiotherapy, the first year (52%), the second year (23%) and the third year (20%). The median survival time from the discovery of distant metastasis was 11.2 months for bone metastasis, 16.3 months for pulmonary metastasis, and 3.2 months for hepatic metastasis. The results revealed that the skeletal system was the most common site of distant metastasis, followed by lung and liver. The incidence of retroperitoneal lymphadenopathy is higher than previous reports.

Changes of serum copper and zinc levels in patients with nasopharyngeal carcinoma by radiotherapy.

Serum copper levels (SCL) and serum zinc levels (SZL) were evaluated in 128 patients with nasopharyngeal carcinoma (NPC) of varying stages before, during, and after radiotherapy, and then compared with normal age-matched subjects. Among these patients, there were 119 undifferentiated squamous cell carcinoma, 5 differentiated squamous cell carcinoma, and 4 moderately differentiated squamous cell carcinoma, respectively. Before radiotherapy, SCLs were significantly higher in NPC patients than in normal subjects, but the difference of SZLs was not significant. The ratio of Cu/Zn also showed a significant difference between normal subjects and NPC patients preradiotherapy. Moreover, except stage II, patients with more advanced stages of the disease had more elevated Cu/Zn ratios. During and after the period of radiotherapy, the SCL decreased as compared with the level of preradiotherapy. The Cu/Zn ratio also decreased after radiotherapy but not significant. However, Cu/Zn ratio of expired patients at least 2 yr after radiotherapy did not show the significant decrease in contrast to the alive ones.

The effect of external radiotherapy in treatment of portal vein invasion in hepatocellular carcinoma.

To investigate the effect of external radiotherapy in the control of portal vein invasion (PVI) in hepatocellular carcinoma (HCC), ten patients with cytologically confirmed unresectable HCC were recruited for study. All of the patients were assigned Pugh's classification A, and all had only unilateral PV involvement. The main tumors were treated by transcatheter arterial embolization. The PVI was irradiated with a dose of 3000-5000 cGY using a linear accelerator under localization by real-time ultrasound. All ten patients responded to the external irradiation, with complete disappearance of the PVI occurring in five and partial shrinkage, in the other five. However, the HCC extended to the contralateral PV in two patients, although the irradiated lesion had shrunk. Both patients had shown involvement of the main PV in the initial study. Six patients died after 3, 6, 7, 7, 8, and 10 months, respectively, due to advance of the HCC, rupture, liver failure, and respiratory failure. The others survived for longer than 6 months and remain under follow-up. The branch of PVI at discovery might have an important bearing on the effect of the radiotherapy. No postirradiation hepatitis or other complication was observed.

The effects on basal anterior pituitary hormone concentrations by cranial irradiation in patients with nasopharyngeal carcinoma.

Hypopituitarism occurring in patients who received external cranial radiation therapy (RT) have been increasingly recognized. Fourteen healthy patients were collected as control Group I, and 25 patients with nasopharyngeal carcinoma (NPC) were enrolled as Group II. Another 18 NPC patients were enrolled as Group III. Blood was sampled from Group I, Group IIB (before RT), Group IIA (one week after RT) and Group IIIA (1 to 1.5 years after RT). The basal samples were taken for growth hormone (GH), adrenocorticotropic hormone (ACTH), cortisol, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyrotropin (TSH), triiodothyronine (T3) and thyroxine (T4). The results showed the T3 level was statistically low in Group IIB compared with Group I. The serum GH and FSH (male only) levels were higher and with statistical significance in Group IIA compared Group IIB. Both GH and ACTH levels decreased and PRL increased with statistical significance in Group IIIA compared with Group IIA. The ACTH decreased with statistical significance in Group IIIA compared with Group IIB. Clinical damage to the pituitary is usually manifested months to years after RT. Therefore, a careful exclusion of these glands from radiation treatment fields is recommended whenever possible.

The effects of radiation therapy on salivary function in patients with head and neck cancer.

Eighty nasopharyngeal carcinoma (NPC) patients and another eighty head and neck cancer (HNC, non-NPC) patients were enrolled as two experimental groups to study their salivary function by using Tc99m sialography. Twenty healthy subjects were also employed as a control group. The patients received an intravenous injection of 4 mCi of 99mTc-pertechnetate (Tc-99mO4-). The data were collected at a rate of 1 frame per 15 seconds for the total time of 30 minutes, and the patients received stimulations for salivary secretion by ingesting 0.5cc of lemon juice 15 min after the start of data acquisition. The salivary function was measured on Pre-RT (radiation therapy), During-RT and Post-RT periods. The results showed no statistical significance for maximum uptake (%) and excretion rate (%) between Control and Pre-RT group on parotid or submandibular glands function. This was the same in the age groups (age below 40 and age above 40) and sex groups. The NPC group had a decreasing maximum uptake (%) 3 months after RT on both parotid glands and submandibular glands, whereas the HNC group showed no obvious difference. The excretion rate (%) of both parotid and submandibular glands reached its lowest mark after 3-6 months in both the NPC and HNC groups and then started to recover progressively. For NPC patients, the radiation damage to the parotid glands was greater than to the submandibular glands, whereas the effect was reversed on HNC patients. It is important that the radiation therapist should preserve salivary function whenever possible.

Commissioning Varian 2100C medical linear accelerator.

One Varian 2100C medical linear accelerator (LINAC) was installed at Kaohsiung Medical College Hospital last summer. The outputs of this LINAC are 6 and 10 MV X-ray beams, and 6, 9, 12, 16, and 20 MeV electron beams. A commissioning procedure including acceptance tests, dose data, environmental radiation survey was executed when the LINAC installation was completed. The acceptance tests organized as a sequential were performed by the medical physicist and Varian's engineers. Dose determination and environmental radiation survey were measured with ion chamber, phantom and survey meters. Radiation dose was calculated following the protocal of the Task Group 21, Radiation Therapy Committee of the American Association of the Physicists in Medicine (AAPM). After the commissioning procedure, the license application to operate the LINAC was submitted to the Atomic Energy Council (AEC) of Executive Yuan. When the license was authorized by the AEC last November, a quality assurance (QA) program was established and performed continuously in order to keep the Varian LINAC with high quality of radiation therapy.

Preliminary study on the anti-radiation effect of jen-sheng-yang-yung-tang.

Six to seven week old male mice of ICR strain were exposed to different doses of x-rays to determine if jen-sheng-yang-yung-tang could be a modifier in the elimination of radiation damage. Colony forming units of bone marrow cells in the spleen (CFUs) were measured before and after x-ray irradiation with intraperitoneal injection of 10 mg/20 g or 20 mg/20 g body weight of jen-sheng-yang-yung-tang, once a day for seven consecutive days. The recovery of CFUs and hemocytes counts by 4 Gy irradiation with jen-sheng-yang-yung-tang administration was faster for a concentration of 20 mg/20 g than 10 mg/20 g. The measurement of 10-day CFUs showed an increase of radiotolerance in the treatment of 20 mg/20 g administration before x-ray irradiation. The injection of jen-sheng-yang-yung-tang accelerated the recovery of hemocyte counts in mice irradiated with 4 Gy x-ray; the effect was especially profound for leukocytes with 20 mg/20 g jen-sheng-yang-yung-tang administration after irradiation.

Regulation of arginase production by glucocorticoid in three human gastric cancer cell lines.

Gastric cancer tissues have high levels of glucocorticoid receptors (GR) and arginase. To investigate the interrelation of glucocorticoid, GR and arginase, three human gastric cancer cell lines (AZ-521, NUGC-3, KATO-III) were treated with hydrocortisone in the presence or absence of a glucocorticoid antagonist RU38486. GR were found to be present in all three lines, and hydrocortisone significantly increased the production of total arginase in all 3 lines. The induction of arginase production by hydrocortisone was inhibited by RU38486. These findings suggest that the regulation of arginase production by hydrocortisone in gastric cancer cells is mediated through GR.

Radiotherapy in the treatment of hepatocellular carcinoma and its metastases.

A study was conducted to evaluate the effect of external radiation therapy on hepatocellular carcinoma (HCC) and its metastatic lesions. A total of 33 patients with cytopathologically proven HCC were subjected to radiation therapy over a 4-year period, and treatment was discontinued in 8 cases due to jaundice, severe discomfort, or early mortality. Thus, 25 patients with 28 lesions underwent irradiation with a total dose ranging between 3000 and 5600. Of these, seven were irradiated for liver tumors, and the results showed that two lesions decreased in size, the symptoms improved in 1 case, and another patient maintained stable disease for 4 months. Among the 21 metastatic lesions treated, only 2 patients failed respond to the treatment. Nine subjects were irradiated for bone metastases, and the bone pain subsided in all but one case. The survival for bone metastasis was as long as 23 months when the primary tumor was treated effectively. Three of the four cases of irradiated skin nodules disappeared and had not recurred after 5 months, 1 year, and 4 years, respectively. Tumor shrinkage or symptoms of relief were noted for three abdominal lymph nodes, one neck lymph node, one pleural tumor, and one lung tumor. Clinical improvement associated with a stable lesion was observed in two patients with brain metastasis. Follow-up revealed regrowth of the tumor or recurrence of symptoms in most of the patients. However, none of the patients died as a direct result of a metastatic lesion. Although external radiation therapy is palliative in intent, it appears to be useful in the treatment of HCC and its metastatic lesions.

[Evaluation of urinary polyamines in patients with nasopharyngeal carcinoma].

A new and simple enzymatic assay utilizing an acylpolyamine amidohydrolase and putrescine oxidase was adopted for measuring urinary polyamines (U-Pa). Serum carcinoembryonic antigen (S-CEA) was determined for comparison. The study population consisted of patients with pathologically proven nasopharyngeal carcinoma (NPC) who were referred to Kaohsiung Medical College Hospital. We found that polyamine levels were markedly elevated during radiotherapy but declined when the treatment was completed. Thus mean polyamines and the positive rate of polyamine elevation was higher in patients suffering from an active stage of the disease than in patients whose cancer had stabilized. However, the level of carcinoembryonic antigen was not elevated whilst undergoing radiotherapy. Therefore, routine measurement of polyamine levels may have a clinical utility in monitoring the disease state of the tumor. However, the low sensitivity of U-Pa test (22%) precludes its use as an effective screening method for this condition. Nevertheless, because of its simplicity, convenience and rapidity for monitoring NPC, U-Pa test should be considered a valuable tool in the clinical investigation of NPC patients.

Preliminary study on antiradiation effect of kuei-pi-tang.

In order to evaluate the potential action of Kuei-Pi-Tang as an antiradiation agent, colony forming units of bone marrow cells in the spleen (CFUs) were used. Different sequences of X-ray irradiation with or without Kuei-Pi-Tang administration in the groups of ICR strain mice were intraperitoneally injected 10mg/20g or 20mg/20g, once a day, for consecutive seven days before or after 4Gy X-ray irradiation. After the different treatments, whole blood was collected from the tail endings to observe the fluctuation of leukocytes, erythrocytes and thrombocytes. The administration of 20mg/20g was more effective than that of 10mg/20g. Lower radiosensitivity was observed with the treatment of 20mg/20g of Kui-Pi-Tang than that of 10mg/20g. The injection of Kuei-Pi-Tang accelerated the recovery of blood cell counts of leukocytes, erythrocytes and thrombocytes in mice irradiated with 4Gy, especially for leukocytes under the treatments with 20mg/20g of Kuei-Pi-Tang administered after irradiation.

Radioprotective effect of Ganoderma lucidum (Leyss. ex. Fr.) Karst after X-ray irradiation in mice.

Six to seven week old male mice of ICR strain were exposed to 500 or 650 cGy of X-ray during experiments to determine if Ganoderma lucidum could be a factor in modification of radiation damage. Continuous intraperitoneal injection of the extract from Ganoderma lucidum before or after irradiation of 500 and 650 cGy of X-ray was found to improve the 30-day survival fractions of ICR mice, but wasn't significant by statistical analysis. The administration also enhanced the recoveries of the body weights and increased the recovery of hemograms of irradiated mice from radiation damage by injecting before or after radiation exposure, especially for the treatment of 500 cGy irradiation. The 10-day CFUs was significantly higher for Ganoderma lucidum treated groups than for untreated groups. However, the differences of radioprotective effect between the X-ray irradiated groups with Ganoderma lucidum pretreated and post-treated were not significant (p greater than 0.05).

A highly suspected radiation-associated thyroid cancer: report of 1 case.

The association between head and neck irradiation and the development of malignant thyroid tumor is well established. The first case was detected by Duff and Fitzgerald in 1950, and it was well documented in publications during the 1950's and early 1960's. But it was rarely reported in Taiwan. Incident rates of irradiation-induced thyroid cancer of 6% to 7% have been reported. These patients developed tumors on an average of 20 years after X-ray exposure and were nearly all under 35 years of age. We reported a case with a female patient, who was treated with 60Co for eosinophilic granuloma in her occipital area at the age of 4 to 5 years. Twenty years later, it was observed that she had developed thyroid cancer. We once again refer to the literature to draw the attention to the public in regard to radiation-associated thyroid cancer in Taiwan.

Serum copper and zinc levels in patients with nasopharyngeal carcinoma.

Serum copper levels (SCL) and serum zinc levels (SZL) were evaluated in 103 patients with nasopharyngeal carcinoma (NPC) of varying stages during radiotherapy, and compared with normal subjects. Ninety-nine of these patients were undifferentiated squamous cell carcinoma, 2 were differentiated squamous cell carcinoma and 2 were moderately differentiated squamous cell carcinoma. The serum copper levels were significantly higher in NPC patients than in normal subjects, but the difference of SZL was not significant. The ratio of Cu/Zn also showed a significant difference between normal subjects and NPC patients. There was no significant difference in SCL, Cu/Zn or SZL between men and women. Patients with more advanced stages of the disease had more elevated Cu/Zn ratios. It appears that SCL in NPC patients may be useful in evaluating the extent of the disease; furthermore, the Cu/Zn ratio may also provide some information in discriminating between normal subjects and patients with early or advanced stages of NPC.

Ultrastructural changes in the frontal cortex of mice after irradiation: a study of dose-rate and field size effect.

The dd-strain male mice were exposed to a dosage of 50 Gy high energy x-ray from a 6-MeV linear accelerator to elucidate the ultrastructural changes in the frontal cortex. After a single dose of whole body or head solely irradiation with a fixed rate of either 13.0 Gy/min. or 2.0 Gy/min., the frontal cortex was removed at different intervals and observed under electron microscope. The swelling of the astrocytic process and the damage of vasculoastrocytic units were observed with increasing degree following prolonged intervals of irradiation. Vacuolization, swelling of mitochondria, and the presence of electron dense particles in the cytoplasm of neuroglial cells were observed with these alterations being more prominent in the high dose-rate group. In addition, persistent degeneration was found in vasculoastrocytic units as well as neuroglial cells in this acute stage. Destruction of the presynaptic membrane or postsynaptic region, or an increase in number of the synaptic vesicles was not seen as time lapsed. Neurons were less vulnerable to radiation. Nerve fibers, moreover, seemed to be the most radioresistant at this dosage and high dose-rate irradiation.