Search

We report the long-term results of Tokyo Children's Cancer Study Group's studies L84-11, L89-12, L92-13, and L95-14 for 1846 children with acute lymphoblastic leukemia, which were conducted between 1984 and 1999. The value of event-free survival (EFS)±s.e. was 67.2±2.2% at 10 years in L84-11, which was not improved in the following two studies, and eventually improved to 75.0±1.8% at 10 years in L95-14 study. The lower EFS of the L89-12 reflected a high rate of induction failure because of infection and delayed remission in very high-risk patients. The L92-13 study was characterized by short maintenance therapy; it resulted in poor EFS, particularly in the standard-risk (SR) group and boys. Females did significantly better than males in EFS in the early three studies. The gender difference was not significant in overall survival, partly because >60% of the males survived after the testicular relapse. Randomized studies in the former three protocols revealed that intermediate- or high-dose methotrexate therapy significantly reduced the testicular relapse rate. In the L95-14 study, gender difference disappeared in EFS. Contrary to the results of larger-scale studies, the randomized control study in the L95-14 reconfirmed with updated data that dexamethasone 8 mg/m2 had no advantage over prednisolone 60 mg/m2 in the SR and intermediate-risk groups. Prophylactic cranial irradiation was assigned to 100, 80, 44, and 44% of the patients in the studies, respectively. Isolated central nervous system relapse rates decreased to <2% in the last two trials. Secondary brain tumors developed in 12 patients at 8–22 years after cranial irradiation. Improvement of the remission induction rates and the complete omission of irradiation are currently main objectives in our studies. [ABSTRACT FROM AUTHOR]

Objective: The prognostic significance of O(6)-methylguanine DNA methyltransferase (MGMT) was evaluated by analysis of both MGMT promoter methylation and protein expression in a series of patients with newly diagnosed glioblastoma., Methods: Seventy-three patients with glioblastomas treated with alkylating agents were analyzed for MGMT expression by immunohistochemistry. Genomic DNA was isolated from frozen surgical specimens obtained from 62 of 73 patients. MGMT promoter methylation was determined by methylation-specific polymerase chain reaction. The prognostic significance of MGMT was evaluated together with other well-known prognostic factors., Results: MGMT promoter hypermethylation was detected in 35 of 62 patients (56.4%). MGMT immunoreactivity was low in 26 (35.6%) tumors, moderate in 24 (32.9%), and high in 23 (31.5%). Significant correlation was observed between MGMT expression and MGMT promoter methylation (P < 0.001). Both MGMT promoter methylation and low MGMT expression were independently associated with better progression-free survival but not with longer overall survival. However, in the subgroup analysis, MGMT promoter hypermethylation was significantly associated with longer overall survival in patients treated with temozolomide (TMZ) after nimustine hydrochloride (ACNU) treatment., Conclusions: Low MGMT expression and MGMT promoter methylation are both predictive markers for slower tumor progression in patients with glioblastoma.

Background: This study was undertaken to analyze the practice process of thoracic radiotherapy (TRT) and evaluate changes in patterns of care for patients with limited-stage small-cell lung cancer (LS-SCLC) in Japan., Methods and Materials: The Patterns of Care Study (PCS) conducted the second nationwide survey of care process for patients with LS-SCLC treated by using TRT between 1999 and 2001., Results: The PCS collected data for 139 patients with LS-SCLC (man-woman ratio, 5:1; median age, 69 years; age > 70 years, 43%; Karnofsky Performance Status > 70, 73%; and Stage III, 88%). Median total dose was 50 Gy. Twice-daily TRT was used in 44% of patients. Median field size was 12 x 14 cm. The most commonly used photon energy was 10 MV (77%), whereas obsolete techniques using (60)Co or X-ray energy less than 6 MV comprised 12%. Three-dimensional conformal therapy was used with 12% of patients. Computed tomography simulation was performed in 40% of cases. Only 12 patients (8.6%) received prophylactic cranial irradiation (PCI). Concurrent chemotherapy and TRT (CCRT) was used for 94 patients (68%). Only 6 patients (4.4%) entered clinical trials. Compared with the previous PCS 95-97, significant increases in the use of CCRT (34-68%; p < 0.0001), twice-daily TRT (15-44%; p < 0.0001), and PCI (1.7-8.6%; p =0.0045) were observed, although the absolute number of patients receiving PCI was still extremely low., Conclusions: Evidence-based CCRT and twice-daily TRT has penetrated into clinical practice. However, PCI is not yet widely accepted in Japan.

Purpose: To determine how the omission of whole brain radiotherapy (WBRT) affects the neurocognitive function of patients with one to four brain metastases who have been treated with stereotactic radiosurgery (SRS)., Methods and Materials: In a prospective randomized trial between WBRT+SRS and SRS alone for patients with one to four brain metastases, we assessed the neurocognitive function using the Mini-Mental State Examination (MMSE). Of the 132 enrolled patients, MMSE scores were available for 110., Results: In the baseline MMSE analyses, statistically significant differences were observed for total tumor volume, extent of tumor edema, age, and Karnofsky performance status. Of the 92 patients who underwent the follow-up MMSE, 39 had a baseline MMSE score of < or =27 (17 in the WBRT+SRS group and 22 in the SRS-alone group). Improvements of > or =3 points in the MMSEs of 9 WBRT+SRS patients and 11 SRS-alone patients (p = 0.85) were observed. Of the 82 patients with a baseline MMSE score of > or =27 or whose baseline MMSE score was < or =26 but had improved to > or =27 after the initial brain treatment, the 12-, 24-, and 36-month actuarial free rate of the 3-point drop in the MMSE was 76.1%, 68.5%, and 14.7% in the WBRT+SRS group and 59.3%, 51.9%, and 51.9% in the SRS-alone group, respectively. The average duration until deterioration was 16.5 months in the WBRT+SRS group and 7.6 months in the SRS-alone group (p = 0.05)., Conclusion: The results of the present study have revealed that, for most brain metastatic patients, control of the brain tumor is the most important factor for stabilizing neurocognitive function. However, the long-term adverse effects of WBRT on neurocognitive function might not be negligible.

Purpose: To examine in retrospect prognostic factors influencing meningeal dissemination relapse of medulloblastoma (MB) and to estimate time parameter gamma/alpha of the biologically effective dose for fractionated craniospinal irradiation (CSI)., Materials and Methods: Fifty-eight patients with MB who had been treated at our six hospitals from 1980 to 1990, were analyzed by the proportional hazards model consisting of radiation factors of both CSI and local irradiation (LI), sequential CSI time-lag, and eight non-radiation factors (gender, age, performance status, T-stage, dissemination score, extent of resection, and use of chemotherapy and immunotherapy). The gamma/alpha for CSI was estimated by the profile likelihood method using the maximum value of conditionally calculated time-incorporated biologically effective dose, tBEDmax, of the field treated with the least dose., Results: Dissemination relapse was seen in 23 (40%) patients. Nineteen disseminations occurred within four years, and the cumulative dissemination-free rate was 64% at five years. The site of initial dissemination relapse was both cranial and spinal in 13 patients (57%). Dissemination relapse was accompanied with local failure in 43% (10/23) of patients, and four of them were seen later than four years. In the multivariate analysis, significant prognostic factors were dissemination score (p=0.0008) and total dose of CSI (p=0.018). The estimate of gamma/alpha for CSI was about 0.2 Gy/day in BED units. In another multivariate analysis including the best-fitted tBEDmax, significant prognostic factors were dissemination score and the tBEDmax of both CSI (p=0.021) and LI (p=0.024)., Conclusion: This analysis indicated that the dissemination score, total dose of CSI, and tBEDmax of both CSI and LI were significantly prognostic for dissemination relapse of MB. The estimate of gamma/alpha for CSI was smaller than that derived from our previous analysis for LI. However, in order to estimate the time factor for CSI more precisely, a larger group of patients treated with concurrent CSI is needed.

A survey was undertaken to analyze osseointegrated implants placed in irradiated maxillae and mandibles. It was found that nine centers in Japan and two centers in the United States had placed 228 implants in 44 patients. Of 228 implants, 59 were placed in the maxilla, 169 in the mandible. Three of 169 implants placed in irradiated mandibles were removed; 17 of 59 were removed from maxillae. One hundred nineteen implants were placed in the mandible without adjunctive hyperbaric oxygen treatment, of which only 2 were removed. From these results, it is suggested that osseointegrated implants can be placed in the irradiated mandibles of selected patients without hyperbaric oxygen treatment.

The outcomes in 32 cases of histologically diagnosed primary central nervous system lymphoma were investigated. The 1-, 2-, and 5-year survival rates were 54, 36, and 8%, respectively. Good outcome was indicated by extensive surgical removal with 50-Gy irradiation and lower ages. 61% of patients receiving radiation therapy suffered recurrence within 1 year. The incidence of multiple lesions increased at recurrence. These lesions were almost all remote from the initial site in the brain, occurring more frequently in the central part of the supratentorial regions near the ventricle. Multiple lesions recurred more rapidly than single lesions. Longer survival times were indicated by a long tumor-free period after initial treatment. Extensive surgical removal results in long survival times for patients with a localized single tumor in the early stage. Radiochemotherapy should be given as part of the initial treatment.