Early neurological complications after stereotactic radiosurgery/radiotherapy.

OBJECTIVE: To evaluate the neurological complications after stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). MATERIAL AND METHOD: The Ramathibodi Radiosurgery Unit started its service in August 1997, using the linear-accelerator based system. There were 144 patients treated from August 1997 to October 1999. Single fraction SRS was performed in 56 cases consisting of 46 arteriovenous malformations (AVMs), 4 cranial nerve (CN) schwannomas, 3 pituitary adenomas, 2 meningiomas, and 1 multiple hemangioblastomas. Eighty eight patients received multifractionated SRT, including 27 meningiomas, 17 pituitary adenomas, 13 benign and malignant gliomas, 8 brain metastasi(e)s, 5 CA nasopharynx, 5 craniopharyngiomas, 5 CN schwannomas, 2 AVMs, 2 chordomas, and 4 others. After treatment the patients were clinically evaluated every 1-6 months and MRI was scheduled at 6 or 12-month interval or when there were abnormal clinical signs/symptoms. The complications included any new neurological complaints or findings during and after treatment. RESULTS: Median follow-up time was 9.5 (0-20) months. Of 138 patients with available follow-up data, there were 23 (13 SRS and 10 SRT) cases who experienced new neurological symptoms at 3 weeks - 20 months (median = 3 months) from the time treatment started. Symptoms included headache, seizure, weakness, decreased vision, vertigo with/without ataxia, diplopia, dizziness, impaired memory, hemifacial spasm, decreased sensation and facial palsy. Three AVM patients had intraventricular hemorrhage from the patent nidi. After symptomatic treatment there were 15 cases with complete recovery (including seizure control) and 6 with partial recovery. There were 2 deaths from ruptured AVM and progressive metastatic brain lesion. There were 79 patients who had at least 1 follow-up MRI, and changes were detected in T2-weighted images in 19 cases at 3-18 months after treatment. Ten cases had symptoms corresponding to the image changes, the other 9 patients were asymptomatic. CONCLUSIONS: Longer follow-up time is needed to fully evaluate the complications after SRS/SRT, however, preliminary results showed that most of the complications were mild and transient. There was a tendency of a higher complication rate in the SRS group. Not all patients with post treatment image changes developed symptoms.

Factors affecting chemistry of reduction-mediated 99mTc-labelling of monoclonal antibodies and polyclonal human immunoglobulins.

In developing a new method for preparing a radiopharmaceutical for clinical investigation, a thorough understanding of reaction stoichiometry is crucial in optimizing the labelling chemistry. Factors determining labelling efficiency of the 2-mercaptoethanol (2-ME)-mediated 99mTc-labelling of antibody molecules were elucidated using anti-tumor monoclonal antibodies of different IgG subclasses (i.e. IOR-CEA(IgG1), M170(IgG1), 3F8(IgG3) and EMD (IgG2a)) and polyclonal human immunoglobulins (Sandoglobulin). Antibodies which were sensitive to 2-ME reduction (i.e. required 500-1000 molar excess of 2-ME) could tag 99mTc with high efficiency since they possessed abundant reactive sites (i.e. sulfydryl groups) for 99mTc binding. Reduction sensitivity of antibodies was unlikely to be affected by IgG subclass and could be rated as follows: Sandoglobulin > IOR-CEA > 3F8 > M170 > EMD. Concentrations of the reduced antibodies for effective labelling appeared to be related to the reduction sensitivity, i.e. 0.2, 0.4 and 0.6 mg/ml were required for labelling of IOR-CEA, 3F8 and M170 respectively. In addition, susceptibility to 2-ME reduction seemed to reflect the rate of antibody labelling. For 2-ME resistant molecules, i.e. M170 and EMD, successful labelling could be achieved by using a slow 99mTc reducing agent such as SnCl2 instead of SnF2 which reacted more rapidly. Since 2-ME generates reactive sulfhydryl groups that are distal to antigen binding sites, the immunoreactivity of the modified antibody was not affected by the effect of reduction.

The efficacy of chemically-stabilized chlorite-matrix (TCDO) in the management of late postradiation cystitis.

Carcinoma of the uterine cervix is the most common cancer of women in Thailand. The most frequent complication after pelvic radiation for uterine cancer is radiation cystitis. The management of severe late postradiation cystis is far from satisfactory. The objective of this study was to evaluate the efficacy of chemically-stabilized chlorite-matrix (TCDO) in patients with severe radiation cystitis. This study was conducted at the Department of Obstetrics and Gynecology, Ramathibodi Hospital and the Department of Radiology, Siriraj Hospital between September 1997 and September 1998. Twenty patients with grade 3 radiation cystitis after radiotherapy were enrolled into this study. TCDO was administered at a dose of 0.5 ml/kg body weight per day on 5 consecutive days as intravenous infusion over 4 hours. The response rate after the first cycle was 80 per cent with 30 per cent of the patients showing complete response. The follow-up time (13 patients) ranging from 1-9 months revealed no recurrent bleeding. There were no side effects from TCDO therapy. The result suggests good efficacy of TCDO in the treatment of postradiation cystitis.

Dental management in irradiated head and neck cancers.

Seventy three head and neck cancer patients were radiated between 1987 and 1993 at the Faculty of Medicine, Ramathibodi Hospital, Mahidol University. The incidence of dental extraction was much decreased after fluoride treatment regardless of the method of treatment with 54.8 per cent of the patients followed-up for more than 36 months. There was no significant difference of the dental status between application of fluoride gel, fluoride solution month rinse and combination of gel and solution. The incidence of dental extraction decreased to 6.9-22.7 per cent but dental filling increased to 54.5-68.2 per cent. We would like to conclude that continuing dental care with daily home fluoride month rinse and 3-6 months follow-up by the dentists will be the proper way to prevent radiation dental caries.

The experience in using whole pelvic irradiation in management of massive bleeding from carcinoma of the uterine cervix.

At the Radiation Therapy Section, Ramathibodi Hospital, from June 1, 1981 to May 31, 1991, there were 35 out of 1,683 new cases of carcinoma of the uterine cervix which presented with massive bleeding per vagina. All were treated via cobalt-60 teletherapy covering the whole pelvic region by 12 x 12 cm2 or 16 x 16 cm2 field sizes. Eighteen cases received a radiation dose of 300 cGy/fraction while 16 cases received 400 cGy and one case received 600 cGy. All had bleeding controlled within 2-6 fractions, twenty-two cases (62.9%) within 3 fractions and 34 cases (97.1%) within 5 fractions. There was no severe acute complication in all patients. In 10 patients who were followed up to the range of 3-70 months, median 16.5 showed no severe late complications.

Treatment of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma is a common cancer among Thai males. When first seen, the disease is almost always locoregional. Evaluation of the tumor volume at the nasopharynx by computerized axial tomogram must be done prior to therapy. Treatment is done by radiation therapy to the nasopharynx and cervical lymph nodes, and is effective. Chemotherapy has high activity in this disease. However, more studies are needed to define its role. Side effects of treatment are radiation related, and confined to the area of previous radiation. They can be minimized if the patients strictly adhere to the physician's advice. Causes of treatment failure and death can be due to both locoregional failure and distant metastasis, notably to bone, liver and lungs.

Nasopharyngeal carcinoma: results of treatment by radiotherapy vs chemotherapy plus radiotherapy.

To determine the efficacy of neoadjuvant chemotherapy over radiotherapy alone in locally advanced nasopharyngeal carcinoma, a prospective non-randomized study was performed from 1 January 1982 to 31 December 1985 at Ramathibodi Hospital, Thailand. There were 69 new cases who completed treatment and were followed up at least once. Thirty-three cases were treated by radical radiotherapy (RT) alone and 36 cases by chemotherapy (CT) + RT. CT were by the combination of cis-diamminedichloroplatinum II and 5 fluorouracil. Of 32 cases, 2 courses of CT were given before RT and 1 after. The other 4 received 3 courses prior to RT. For both groups, RT technique and dosage were similar. Follow-up time of both groups ranged from 6-104 months (mean 50.3, median 50) and 8-100 months (mean 52.2, median 54.5), and total failures were 18/33 and 13/36, respectively, with no statistical difference (p greater than 0.05). Estimated actual survival and disease free survival from Kaplan-Meier curves at 3 years were about 75 per cent vs 75 per cent and 65 per cent vs 65 per cent, respectively, with no statistical differences (Log-Rank test). Therefore, we concluded that induction chemotherapy had some benefit but no statistical significance over RT alone. However, the role of maintenance chemotherapy is now being studied.

Nasopharyngeal carcinoma: value of bone and liver scintigraphy in the pre-treatment and follow-up period.

Nasopharyngeal carcinoma (NPC) is a disease with a high potential of distant metastasis, especially to bone and liver. To evaluate the routine use of bone and liver scintigraphy in the evaluation of metastatic disease during the pre-treatment and follow-up period, 112 new cases of NPC were enrolled. The pre-treatment scintigraphs were performed at the time of staging evaluation, while the follow-up ones were performed once a year and whenever clinically indicated. At the pre-treatment period, 3/112 cases showed a true positive result, all at bony sites. At the 3 years follow-up, 10/83 and 8/83 cases respectively showed a true positive result in the bone and liver. All of the positive cases had definite symptoms and signs of metastases, which correlated well with the scintigraphic findings. All without clinical evidence showed a negative finding. Therefore, we conclude that, without clinical indication, routine bone and liver scintigraphy are of limited value.

Cervical cancer survival at Ramathibodi Hospital 1979-1983.

Carcinoma of the cervix is the most common malignant neoplasm among the female population. The treatment is surgery for stage IB and radiotherapy for all stages of disease. In a developing country like Thailand, the percentage of lost to follow-up after complete treatment is usually high. The purpose of this study is to present the follow-up and survival rate of patients with carcinoma of the cervix at Ramathibodi Hospital. From 1979 to 1983 there were 323 patients with carcinoma of the cervix who had been treated at Ramathibodi Hospital. The majority of patients (51.9%) were in stage II. The 5-year follow-up rate was 87.73 per cent which is better than the previous reports from Thailand. The 5-year survival rate was 93.75 per cent for stage I, 63.12 per cent for stage II and 42.22 per cent for stage III with an overall survival rate of 61.65 per cent. The 5-year survival rate in this study is not different from other reports.

Pattern of treatment failure among patients who died of invasive carcinoma of the uterine cervix.

During January 1979 to December 1982, 78 cases of invasive carcinoma of the uterine cervix (stage IB-IV) whose causes of death were established have been reviewed. The major causes of death were either pelvic failure, extrapelvic failure and the combination of both pelvic and extrapelvic failure, which were 47.5, 32.0 and 17.9 per cent respectively. Most of the patients died within 3 years after the established diagnosis of residual or recurrence or metastases of disease, more than half were dead within 12 months. To improve survival rate of the patients, ways must be found to overcome pelvic as well as extrapelvic failures.

Combined radiotherapy and hysterectomy in the treatment of high risk stage II invasive carcinoma of the uterine cervix: a preliminary report.

From January 1979 to December 1983, 187 cases of stage II, invasive carcinoma of the uterine cervix were studied prospectively to evaluate survival rate and treatment sequelae. Forty-one cases with any of these conditions; (a) partial response or inadequate radium insertion from obliterated cervical os; (b) endometrial extension; (c) enlarged cervical mass over 5 cm or barrel-shaped; and (d) with pelvic mass, were treated by the combination of radiotherapy and simple abdominal hysterectomy with bilateral salpingoophorectomy (group I), while the rest of 146 cases (group II) were treated by definitive radiotherapy alone. The 5-year follow-up rates were 87.8 per cent in group I and 70.6 per cent group II, respectively. The recurrence free survival rates at 5 years were 80.6 per cent in group I and 63.1 per cent in group II. The immediate and late sequelae were the same in both groups. We concluded that combined treatment was more effective than radiation alone in cases with a poorer prognosis.

Changes in T-staging of nasopharyngeal carcinoma by CT-scan.

To evaluate the value of computerized axial tomogram (CT-scan) of the nasopharynx in the management of patients with nasopharyngeal carcinoma (NPC), comparisons between clinical T-staging by means of indirect or direct nasopharyngeal examination, and CT-scan were performed in 101 cases. CT-scan has upstaged clinical T-staging in 83.9 per cent of Tx-T3 cases, or 80 per cent in Tx, 98 per cent in T1, 65.4 per cent in T2, and 50 per cent in T3 cases. CT-scan was also able to show the destruction of the base of the skull in 85.7 per cent of T4 cases. With regard to tumor extensions into the surrounding regions, the CT-scan proved to out-perform clinical T-staging by 82.2, 57.4, and 25.7 per cent respectively in superior, anterior, and lateral and inferior extensions. We, therefore, recommend that a CT-scan be done in every new case of NPC, because it provides more accurate T-staging, and more details of tumor extension, which is essential in the management of NPC, especially in the proper planning of radical radiotherapy.

Lethal midline granuloma and lymphoproliferative disorders.

Seventeen patients, who presented with unhealing ulcers or destructive lesions of the upper aero-digestive tract at Ramathibodi hospital from 1977 to 1985 were reported. Lesions caused by infection, Wegener's granulomatosis or non-hematopoietic malignancy were excluded. A spectrum of histopathologic findings were evident in our patients, ranging from acute and chronic inflammatory changes with or without necrosis, polymorphic reticulosis or lymphamatoid granulomatosis, and malignant lymphoma of the non-Hodgkin's type (NHL). Although some initial histopathologic findings were non-specific, evidence of lymphoproliferative disorders finally emerged. These malignant lymphoid cells had a predilection for the GI tract and skin. Lymphoma staging should thus be done. Bleeding from the lesion, treatment-induced leucopenia, and sepsis were common in these patients. Early aggressive treatment including adequate antibiotic coverage for superimposed infection, improved nutritional status, and early radiation to the primary lesion are suggested for those diseases.

Challenge of the two neural tumors: neuroblastoma and retinoblastoma.

Fifty cases of neuroblastoma and 29 retinoblastoma patients who had additional chemotherapy were analyzed retrospectively. Male:Female ratio were 1:1 and 0.8:1, the ages ranged from birth to 14 years (4 +/- 3.42 year) for neuroblastoma, and one month to 5.5 years (2.4 +/- 1.4 year) for retinoblastoma. More than 70%-90% of them came in advanced stages. The treatment consisted of surgical resection, enucleation or exenteration if feasible. Radiation therapy and chemotherapy were given as specific and palliative measures. All of the neuroblastoma who were younger than 8 months old survived long-term. Various chemotherapeutic agents did not seem to effect the outcome of the advanced cases of these two diseases. The retinoblasts did not seem to be sensitive to MTX and Ara-C. Thio-tepa intrathecally seems to be worth trying. Since these two tumors are not sensitive to treatment and are still a great challenge to the developed countries, awareness of the diseases, early diagnosis and early treatment are appropriate approaches for the developing countries.

Chemo-radiotherapy in nasopharyngeal carcinoma at Ramathibodi Hospital, Bangkok.

Combined chemotherapy (Cis-platinum and 5 FU) and radiation therapy were given to 11 patients with stage IV (except 1) nasopharyngeal carcinoma. None had distant metastasis. Mean duration of follow-up was 16.2 months. Objective response (CR+PR) at the primary lesion were 10 out of 11 (90.9%), while CR was 7 out of 11 (63.6%). CR+PR at the regional node were 10 out of 10 (100%), while CR was 9 out of 10 (90%). There has been no recurrence so far. One patient died of hepatocellular carcinoma. Side effects, mainly from radiation therapy, were clinically acceptable. One had transient cervical myelitis, which improved after medical treatment. There was no significant myelosuppression.