Primary CNS lymphoma treated with combined intra-arterial ACNU and radiotherapy.

OBJECT: To assess whether nimustine (ACNU), a drug that can cross the blood brain barrier, combined with radiotherapy, improved the survival of patients with primary central nervous system lymphoma (PCNSL). CLINICAL MATERIALS AND METHODS: Between 1995 and 2005, we treated 63 immunocompetent PCNSL patients with combination therapy consisting of intra-arterial ACNU (100 mg/m(2)) and whole brain radiotherapy (36-50 Gy). Their median age was 60 years (range 28-81). The median follow-up was 24 months. FINDINGS: With this regimen we achieved a complete response rate of 75% (43 of 57 patients). Kaplan-Meier estimates for median progression-free survival and median overall survival were 26 and 39 months, respectively. The 3- and 5-year survival rates were 51% (95% confidence interval [CI], 36-65%) and 32% (95% CI, 17-47%), respectively. By multivariate analysis, age (<60 vs. > or =60 years) was the only statistically significant prognostic factor; the WBRT dose, sex, and number of tumors were not significant prognostic factors in this study. Myelosuppression was the most frequent side effect, 60% of patients experienced grade 3-4 leukopenia. Late neurotoxicity as a result of treatment was observed in 14 of 43 patients (34%) and higher age (>60) was associated with a high risk of neurotoxicity. CONCLUSION: The intra-arterial administration of ACNU combined with radiation therapy yielded a high response rate at acceptable toxicity levels in younger patients with PCNSL. However, late neurotoxicity was a serious complication in patients above 60 years of age.

Radiation therapy for loco-regionally recurrent esophageal cancer after surgery.

PURPOSE: To evaluate the treatment outcome of radiation therapy for 33 loco-regionally recurrent esophageal cancer patients. METHODS: Between 1988 and 1997, 33 patients with loco-regional recurrence of esophageal cancer after curative surgery received radiation therapy at an average total dose of 61 Gy. The site of recurrence was the supraclavicular region in 14 patients, the mediastinal region in 13 patients, and both the supraclavicular and mediastinal regions in six patients. If patients had ether distant metastasis or malignant pleural effusion, they were excluded from analysis. Patients who received prophylactic postoperative irradiation were also excluded from analysis. RESULTS: The median survival period was 7 months. The survival rates at 1, 2, and 3 years were 33, 15, and 12%, respectively. In univariate analysis, patients with a short time interval between surgery and recurrence (P=0.0098) and patients with recurrence in both the supraclavicular and mediastinal regions (P=0.036) had a worse prognosis. In multivariate analysis, the time interval between surgery and recurrence (P<0.001) and age (worse prognosis in younger patients, P=0.019) were the significant prognostic factors. Complete or partial responses were observed in nine (27%) and 21 (64%) of the patients, respectively. Changes in clinical symptoms, such as dysphagia, chest pain and back pain, could be evaluated in 11 patients, and improvement in symptoms was obtained in eight (73%) patients. CONCLUSIONS: The prognosis of patients who received radiation therapy for postoperative loco-regional recurrence of esophageal cancer is poor. However, there is symptomatic relief in a significant proportion of such patients, and long-term survival is possible in some patients.

Retrospective multi-institutional study of radiotherapy for intracranial non-germinomatous germ cell tumors.

The treatment outcome of 24 patients with pathologically-proven non-germinomatous germ cell tumor was retrospectively investigated to determine the effectiveness of radiotherapy. The patients were divided into three groups as follows: group 1, five patients with mature teratoma with or without germinoma; group 2, six patients with immature teratoma with or without germinoma; group 3, 13 patients with other highly malignant tumors. The overall actuarial survival and relapse-free rates at 5 years were 82% and 59%, respectively, with a median follow-up period of 62 months. The actuarial relapse-free rate at 5 years was 100% for group 1, 63% for group 2 and 44% for group 3. There was no difference in the relapse-free rates between total resection and partial resection. Usage of chemotherapy was adversely related to survival probably due to selection bias. No local failure was observed with 10 Gy or more for group 1,40 Gy or more for group 2 and 54 Gy or more for group 3. In groups 1 and 2, there was no spinal relapses without craniospinal irradiation. In group 3, three of eight patients who did not receive craniospinal irradiation and none of five patients who received craniospinal irradiation experienced spinal relapse. In conclusion, highly malignant GCTs show a high incidence of spinal metastasis and craniospinal irradiation may reduce the risk of spinal metastasis. Radiation dose and volume are to be determined according to the histopathological aggressiveness.

Pathologically-proven intracranial germinoma treated with radiation therapy.

BACKGROUND AND PURPOSE: A retrospective multi-institutional study was conducted to survey what percentage of intracranial germinomas were treated with pathological confirmation before radiotherapy and to investigate the influence of field selection on outcome. MATERIALS AND METHODS: Thirty-seven percent of patients (41 of 110 patients) were pathologically confirmed before radiotherapy during the past 16 years at eight institutions in Northern Japanese prefectures. Pathological confirmation was obtained in 26, 37 and 53% of cases during 1978-1983, 1984-1989 and 1990-1994, respectively. All 110 patients were examined using computed tomography (CT) scans. Among the 41 patients with pathologically confirmed germinoma, radiation fields were craniospinal in 23 patients, whole-brain in 10 patients and local without ventricle inclusion in eight patients. RESULTS: For the 41 patients with pathologically confirmed germinoma, the actuarial and cause-specific survival rates were 91/94% at 5 years and 87/90% at 10 years, respectively. The relapse-free survival rate at 10 years was 90. 76 and 22% for the craniospinal field, whole-brain field and local field without ventricle inclusion, respectively. CONCLUSION: Pathological confirmation was obtained in only 37% of CT-scan era cases, although the confirmations were more commonly carried out later in the study period. Limited local irradiation alone without ventricle inclusion cannot be recommended for localized tumors even with the help of CT scanning.

Reirradiation of locally recurrent carcinoma of the maxillary sinus.

The changes in radiosensitivity of locally recurrent cancer and in normal tissue tolerance are not established. So, determining the optimal therapy is often very difficult in the treatment of locally recurrent maxillary cancer. In this study, we reviewed the retreatment results of 19 patients with locally recurrent maxillary cancer. The time interval between the first and the second irradiation ranged from four to 23 months (mean 11.1 months). The total radiation dose of the first and the second irradiation ranged from 56 to 123 Gy (mean 87.0 Gy). The survival rates for all patients at one, two and five years were 43.1%, 28.7% and 28.7%, respectively. The extent of tumor resection and the clinical stages were the major prognostic factors. Severe late complications such as brain necrosis or bone necrosis did not develop in any patients who survived more than one year. Although we compared the radioresponses of the initial and the recurrent tumors in five patients, a definite conclusion about the changes in radioresponse could not be drawn.

Intraoperative radiation-therapy combined with hyperthermia for pancreatic-carcinoma.

Seventeen patients with pancreatic carcinoma were treated with intraoperative radiation therapy (IORT) combined with hyperthermia. Their treatment results were compared with those of 56 patients treated with the IORT alone (control group). The pain relief rate and the local tumor control rate of the hyperthermia group were slightly better than the control group. The survival rate of all patients was 13.7% at one year, 1.4% at two years (median, 5.0 months). The survival of the hyperthermia group was marginally better than that of the control group. Only 29% of the patients of the hyperthermia group was successfully heated, and if hyperthermia were given successfully to all patients, their prognoses would have been possibly improved.

Allopurinol hypersensitivity syndrome associated with systemic cytomegalovirus infection and systemic bacteremia.

A 43-year-old man developed fever, skin rash, eosinophillia, and severe renal and liver dysfunction following treatment with allopurinol. The patient died after 3 months of hospitalization. Autopsy revealed systemic cytomegalovirus infection and bacteremia.

[Effects of combination chemoradiotherapy with daily low-dose CDDP for esophageal cancer--results of a randomized trial].

Between 1994 and 1996, 24 patients with esophageal carcinoma were entered in a randomized clinical trial comparing radiotherapy (RT) only (arm A) versus RT and a daily low dose of CDDP (5 mg/m2) (arm B). For arm B group, CDDP was injected within 30 min after irradiation. All patients were irradiated with a total dose of 60 Gy /30fr. at first, and some patients were boosted. An overall response rate of 75.0% (complete response rate of 25.0%) was observed in arm A and 91.7% (complete response rate of 16.7%) in arm B, respectively. The survival rate at 1 year was 23.8% in arm A and 40.0% in arm B. Median survival time was 7 months in arm A and 9 months in arm B. Toxicity was acceptable and no significant difference was noted between arm A and arm B.

Prognostic factors in radiation-treated esophageal carcinoma.

Prognostic factors in esophageal carcinoma treated with irradiation were examined. The prognosis of 111 patients without metastasis who had received more than 60 Gy was analyzed. Significant associations were found between survival rates and tumor length, stage, radioresponse of the primary tumor and the s.c. X-P classification based on barium contrast radiography; superficial type (tumor limited to the surface of the esophageal wall), tumorous type (solid mass without ulceration), Ul-A type (tumor with shallow ulceration with regular margin), Ul-B type (tumor with deep ulceration or irregular ulcer margin), and funneled type (tumor invading the esophageal wall in a scirrhous pattern). In multiple regression analysis, the X-P classification had the strongest correlation with survival and the survival rates of patients with the superficial type, the tumorous type and the s.c. Ul-A type were significantly higher than those of patients with the other tumor types (p < 0.001).

Prognostic impact of the period between surgery and postoperative irradiation in esophageal carcinoma.

One hundred and sixty-two esophageal carcinomas curatively resected and followed by postoperative irradiation were analyzed to investigate whether the delay of postoperative irradiation affected the patients' prognosis. The period of 40 or more days between surgery and postoperative irradiation caused significantly worse survival rates, and this fact was true even if the survival rates were corrected by the other significantly important prognostic factors: age and tumor staging. The incidence of infield recurrence and cancerous death were higher in the patients with the waiting period of 40 or more days. Significant repopulation of residual tumor cells in curatively resected esophageal carcinomas begins 40 days after surgery, therefore, postoperative irradiation should be started within 40 days after a radical resection. The difference of survival rates as related to the waiting period became clear after the follow-up of more than four years. The prognostic difference of subclinical tumors seems to be uncovered several years after treatment.

[Radiation therapy for low-grade astrocytomas: survival and QOL].

From 1980 to 1994, 59 patients with a diagnosis of lowgrade astrocytoma were treated in our hospital. We analyzed survival, prognostic factors and quality of life (QOL) in survivors who had been recurrence free for at least 2 years. The overall 2-, 5- and 10-year survival rates were 75, 65 and 49 % respectively. The major prognostic factors were field size (the smaller, the better) and age (the younger, the better) according to Cox regression analysis. Quality of life was evaluated in the 20 patients who had survived at least 2 years without tumor regrowth. Performance status was good in most of the patients, and 17(85%) patients were intellectually and physically normal. Headache, fatigue and memory difficulties were the major clinical complaints of these patients and were observed in 7(35%), 6(30%) and 7(35%) of the patients, respectively, although severe symptoms were rare.

Radiotherapy for malignant fistula to other tract.

Radiotherapy was applied to 14 esophageal carcinomas with respiratory tract fistulas using various treatment regimens. Closure of the fistulas was observed in four cases after irradiation at a daily dose of 1.5 Gy. The period of closure was transient in two cases but long-term in the other two. One long-term closure case underwent low-dose rate telecobalt therapy (LDRT)(1 Gy per hour, 7 Gy per day; a total dose of 28 Gy) as a boost. His cancer has been well controlled and he is still alive without recurrence at 74 months after fistula formation.

Prognostic significance of CT scan in malignant glioma.

In 91 malignant gliomas treated with radiation therapy, CT scan which was taken before treatment was reviewed to examine the significance as a prognostic indicator. The irradiation methods and the surgical resectability did not affect the survival. Similarly, the tumor location and the grade of the low density area (LDA) surrounding the contrast enhanced area (CEA) had no significance on the prognosis. As a result of the multi-variate analysis, the histopathologic diagnosis, the CEA size and the CEA pattern were significantly important prognostic factors. Astrocytoma grade III, a CEA diameter of under 4 cm and a homogeneous CEA were favorable indicators of the malignant gliomas. Tumors with a heterogeneous or a ring-like CEA in the diameter of more than 4 cm have the worse prognosis and should be treated extensively by radiation therapy.

[Radiation therapy for superficial type esophageal carcinoma].

During the period from 1984 through 1991, fifteen patients with superficial esophageal carcinoma were treated with radiation therapy. The clinical stage of these patients was I in 13 cases and IV in two cases. We analyzed the treatment results of 13 patients with stage I disease. Seven patients were treated with external irradiation only and six patients with external irradiation plus high dose rate intracavitary irradiation. The survival rates at one, two and five years were 73.3%, 73.3% and 30.6%, respectively. The relapse-free survival rates at one, two and five years were 76.9%, 76.9% and 76.9%, respectively. Combination chemotherapy and combined therapy with intracavitary irradiation did not improve the local control rate or survival. At present, six patients have already died. The cause of death was uncontrolled primary lesion in one, radiation-induced esophageal ulcer in one, other causes in three and unknown cause in one patient. Local control was achieved in 84.6%(11/13). Radiation therapy for superficial esophageal carcinoma seems as effective as surgical therapy and may become a curative alternative.

Low-dose rate telecobalt therapy as a boost against esophageal carcinomas.

The results of treating 54 esophageal carcinomas with low-dose rate telecobalt therapy (LDRT) as a boost were compared with those of treating 97 esophageal carcinomas with conventionally fractionated irradiation alone (CFI). The LDRT (100 cGy/hr, 500 to 700 cGy/day, a total dose of 1400 to 2000 cGy) was boosted at 10 days after 6000 cGy of the CFI dose. Although the LDRT group included more advanced cases than the CFI group, local effects and survival rates in the former group were slightly better than in the latter group. Late complications were more severe in the LDRT group. However, they were acceptable when the total dose administered to this group was less than 8000 cGy. Using LDRT as a boost against esophageal carcinomas was found to be satisfactory therapeutically.

Treatment results by uneven fractionated irradiation, low-dose rate telecobalt therapy as a boost, and intraoperative irradiation for malignant glioma.

The prognosis of malignant glioma is extremely poor. We applied conventionally fractionated irradiation combined with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), uneven fractionated irradiation with ACNU, low dose rate telecobalt therapy as a boost, and intraoperative irradiation against 110 malignant gliomas to investigate the efficacy of these methods as alternative treatments for malignant glioma. Although local tumor control by uneven fractionated irradiation was better than that by the other methods, no significant improvement was obtained in survival rates. As a result of multiple regression analysis, age and histology were major factors for survival rates, and the difference of treatment methods was not important. Both low-dose rate telecobalt therapy as a boost and intraoperative irradiation showed little advantage because of the high risk of brain necrosis associated with them.

Intraoperative radiation therapy combined with hyperthermia against pancreatic carcinoma.

Fourteen patients with pancreatic carcinoma were treated by intraoperative radiation therapy (IORT) combined with hyperthermia (hyperthermia group). Their treatment results were compared with those of fifty five patients treated by IORT without hyperthermia (control group). Most of patients underwent some kind of chemotherapy for the carcinoma and some of them received post-operative irradiation. Although there was no significant difference in pain relief between hyperthermia group and control group, the local tumor control rate of the former group was a little better. The survival rate of all patients was 14.5% at one year, 2.9% at two years, 2.9% at three years and 0% at four years after surgery. The survival rate of the hyperthermia group was 21.4% at one year and 7.1% at two years and that of the control group was 12.7% at one year and 1.8% at two years. The survival of the hyperthermia group was a little better than that of control group, but the difference was not significant. Only 36% of patients of hyperthermia group were successfully heated, and if hyperthermia were given successfully to all patients, their prognoses would be possibly improved.

Radioresponse and prognosis of malignant glioma.

Radioresponse and prognosis of 91 malignant gliomas were studied to examine the efficacy of radiotherapy. There was no case of complete response. No statistically significant difference was observed among the prognoses of patients with various radiation methods. General survival rate was significantly higher than relapse-free survival rate both in astrocytoma grade III and in glioblastoma. This means that the retreatment after relapse is exceedingly important in any malignant glioma. In comparison with reported resection alone data, the efficiency of radiotherapy was evident in astrocytoma grade III and a part of glioblastoma; cases with minimal or no contrast enhanced area (CEA) in CT scans prior to irradiation. Poor radioresponders of glioblastoma with CEA should be reoperated.

Fatal hemorrhage in irradiated esophageal cancer patients.

Between 1980 and 1994, 423 patients with esophageal cancer were given curative radiation therapy. Of these patients, 31 died of massive hemorrhage and were used as the subjects of analysis in this study. The incidence of massive hemorrhage in all patients was 7% (31/423). In the 31 patients who died of massive hemorrhage, 27 had local tumors and two had no tumors at hemorrhage (two unknown cases). The mean time interval from the start of radiation to hemorrhage was 9.2 months. In 9 autopsy cases the origin of hemorrhage was a tear of the aorta in 5 cases, necrotic local tumor in 3 cases and esophageal ulcer in 1 case. The positive risk factors for this complication seemed to be excess total dose, infection, metallic stent, and tracheoesophageal fistula. Chest pain or sentinel hemorrhage proceeding to massive hemorrhage was observed in about half of the patients.

[Simple method of stereotactic radiotherapy without stereotactic body frame for extracranial tumors].

Thirty-five patients with metastatic lung cancer(46 lesions) and twenty patients with primary lung cancer (21 lesions) have been treated with a simple method of stereotactic radiotherapy (SRT) without stereotactic body frame. Tumor size ranged from 1-4 cm in diameter. We used Vac-Lok cushion(Med-Tek) as a immobilization system. To be sure to include the respiratory movement of tumor to planning target volume(PTV), every patients were examined by fluoroscopy and radio-opaque catheters with the same length of tumor movement were attached on the anterior and lateral chest wall before CT simulation. A gold grain was implanted into a tumor that was invisible on fluoroscopy, as a radiomaker. Protocol of 60 Gy/8 fractions/2 weeks and 45 Gy/3 fractions/3-6 days were mainly used. The median follow-up period was 15 months for primary lung cancer and 19 months for metastatic lung cancer. Local control rates were 91% for metastatic lung cancer, 89% for primary lung cancer and 85% for T1, 2N0M0 cases. All patients developed mild pneumonitis or fibrosis about 4.5 months after SRT just in the treatment volume. Only three patients was symptomatic.