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).
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.
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).
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.
CD20(+)CD27(+)CD43(+) B (CD43(+) B) cells have been newly defined among PBMCs and proposed to be human B1 cells. However, it is controversial as to whether they are orthologs of murine B1 cells and ...how they are related to other B-cell populations, particularly CD20(+)CD27(+)CD43(-) memory B cells and CD20(low)CD27(high)CD43(high) plasmablasts. Our objective is to identify phenotypically the position of CD43(+) B cells among peripheral B-lineage cell compartments in healthy donors, with reference to B-cell subsets from patients with systemic lupus erythematosus (SLE). We found that CD43(+) B cells among PBMCs from healthy subjects were indistinguishable phenotypically from memory B cells in terms of surface markers, and spontaneous in vitro Ig and IL-10 secretion capability, but quite different from plasmablasts. However, a moderate correlation was found in the frequency of CD43(+) B cells with that of plasmablasts in healthy donors but not in SLE patients. An in vitro differentiation experiment indicated that CD43(+) B cells give rise to plasmablasts more efficiently than do memory B cells, suggesting that they are more closely related to plasmablasts developmentally than are memory B cells, which is also supported by quantitative PCR analysis of mRNA expression of B-cell and plasma cell signature genes. Thus, we conclude that, in healthy individuals, CD43(+) B cells are closely related not only to memory B cells phenotypically but also to plasmablasts developmentally, although the developmental origin of CD43(+) B cells is not necessarily the same as that of plasmablasts.
Purpose
: To clarify whether the percentage of pulmonary volume irradiated to >20 Gy (
V20) is related to the incidence and grade of radiation pneumonitis (RP) in cases of lung cancer treated with ...concurrent chemoradiation.
Methods and Materials
: The subjects comprised 71 patients with lung cancer who were treated with conventionally fractionated definitive concurrent chemoradiation. The chemotherapy agents were carboplatin or cisplatin combined with taxane for most patients. Radiotherapy was delivered at 1.8–2.0 Gy fractions once daily to a total of 48–66 Gy (median 60). We analyzed the relation between RP grade and
V20. Univariate and multivariate analyses were performed to assess patient- and treatment-related factors, including age, gender, smoking history, pulmonary function (forced expiratory volume in 1 s), tumor location (upper lobe vs. middle/lower lobe), chemotherapy regimen (platinum + taxane vs. other), total dose, overall radiation periods in addition to
V20.
Results
: With a median follow-up of 7.5 months, an RP grade of 0, 1, 2, 3, and 5 was observed in 16, 35, 17, 1, and 2 patients, respectively; the corresponding mean
V20 values were 20.1%, 22.0%, 26.3%, 27.0%, and 34.5%. The 6-month cumulative incidence of RP greater than Grade 2 was 8.7%, 18.3%, 51%, and 85% in patients with a
V20 of ≤20%, 21–25%, 26–30%, and ≥31%, respectively (
p <0.0001). According to both univariate and multivariate analyses,
V20 was the only factor associated with RP of Grade 2 or greater.
Conclusion
: The incidence and grade of RP are significantly related to the
V20 value. Thus,
V20 appears to be a factor that can be used to predict RP after concurrent chemoradiation for lung cancer.
Purpose
The purposes of the study are to compare safety specifications between Japan and the European Union (EU) and to identify the factors affecting categorization of important identified or ...potential risks.
Methods
Safety specifications were collected from orphan and nonorphan drugs approved in Japan between 2014 and 2016, and in the EU as of October 2017. Outcome was defined dichotomously as listed as important identified risks or potential risks. A mixed‐effects logistic regression was performed to estimate odds ratios of being listed as important identified risks.
Results
This study included 20 orphan and 33 nonorphan drugs. The number of safety specifications per drug and the distribution of risk categories were significantly different between Japan and the EU regardless of orphan status. In orphan drugs, the occurrence of serious adverse events (AEs) during clinical trials for new drug applications was associated with a higher probability of being listed as important identified risks in Japan, while AE rate (%) was positively associated with being listed as important identified risks in the EU. For nonorphan drugs in Japan, AE occurring at a high rate, adverse drug reactions (ADRs) listed as important identified risks in EU risk management plans, and clinically significant ADRs known in similar drugs were likely to be listed as important identified risks, whereas a ≥1.4 risk ratio was associated with a higher probability of being listed as important identified risks in the EU.
Conclusions
Factors affecting risk categories were different between Japan and the EU, which might contribute to the difference in safety specifications between these 2 regions.
CONTEXT In patients with brain metastases, it is unclear whether adding up-front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or ...neurologic function compared with SRS alone. OBJECTIVE To determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death. DESIGN, SETTING, AND PATIENTS Randomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003. INTERVENTIONS Patients were randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients). MAIN OUTCOME MEASURES The primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death. RESULTS The median survival time and the 1-year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7%-50.3%) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6%-39.2%) for SRS alone (P = .42). The 12-month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for SRS alone group (P<.001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29) (P<.001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone (P = .64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation. CONCLUSIONS Compared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Consequently, salvage treatment is frequently required when up-front WBRT is not used. TRIAL REGISTRATION umin.ac.jp/ctr Identifier: C000000412
Background and purpose: The incidence and extent of radiation esophagitis were assessed endoscopically in patients treated with concurrent chemoradiotherapy.
Patients and methods: Eighty-two patients ...who received thoracic radiotherapy for lung, thymic, or esophageal cancer were investigated endoscopically from July 1991 to the end of 1997. Among them, 23 esophageal cancer patients were treated with radiation alone, and the others were treated with concurrent chemoradiotherapy. Esophageal endoscopy was performed during or just after radiotherapy. The presence of radiation esophagitis was assessed and assigned an endoscopic score (i.e. grade 0 for normal, 1 for erythema, 2 for erosion or sloughing, 3 for ulcer, hemorrhage, or stricture). The symptomatic grade was assessed using the RTOG (Radiation Therapy Oncology Group) acute radiation morbidity score.
Results: A correlation was seen between endoscopic and RTOG scores. However, even some patients with RTOG grade 0 to 1 had endoscopic grade 3 esophagitis. Endoscopic grade 3 was observed in 16 (27.1%) patients in the concurrent chemoradiotherapy group, whereas it did not occur in any patient in the radiation alone group (
P=0.004).
Conclusions: Our results suggest that (1) RTOG score correlates closely to esophageal mucosal damage, and (2) more severe esophagitis occurs in those undergoing radiotherapy alone.
Purpose: To clarify the role of radiotherapy and chemotherapy in the treatment of patients with localized aggressive non-Hodgkin’s lymphomas (NHL) originating in the nasal cavity.
Methods and ...Materials: The survey, administered at 25 Japanese institutes in 1998, enabled us to collect the clinical data for 787 patients with localized aggressive NHL who were treated between 1988 and 1992.
Results: There were 42 patients (5%) with nasal lymphomas. Twelve of these patients received radiotherapy alone, and 30 were treated with a combination of radiotherapy and chemotherapy. The median radiation dose was 47 Gy (22–66). Twelve patients were reviewed histopathologically according to REAL (Revised European-American Classification of Lymphoid neoplasms) classification. T-cell or natural killer (NK) cell lymphomas were detected in 9 patients (75%), and diffuse large B-cell lymphomas in 3 (25%). The 5-year overall and disease-free survival (DFS) rates of all patients were 57% and 59%, respectively. The 5-year DFS rate for the 30 patients treated with the combined therapy was 64% and that for the 12 patients treated with radiotherapy alone was 46% (
p = 0.021). For the 34 patients with stage-modified International Prognostic Index (m-IPI) 0–1, the 5-year DFS rates of those treated with the combined therapy and radiotherapy alone were 68% and 45%, respectively (
p = 0.020), but there was no difference in DFS rate among the two groups of patients with m-IPI 2–3. The 5-year local control rates of the patients who received >46 Gy (
n = 22) and ≤46 Gy (
n = 20) were 95% and 76% (
p = 0.087), respectively. There was no significant difference among the 5-year DFS rates (62% vs. 67%) and local control rates (87% vs. 100%) of the patients with T-cell or NK-cell lymphoma and diffuse large B-cell lymphoma.
Conclusions: Patients with nasal lymphomas (m-IPI 0–1) should be treated with combined therapy. For the patients with high risk (m-IPI 2–3), the effectiveness of combined therapy was not clarified because of the small number of the patients. A high radiation dose >46 Gy may need to be used to achieve good local control.
The purpose of this study was to evaluate the results of two sequential total body irradiation (TBI) regimens, especially focusing on pulmonary complications.
Patients with malignant disease who ...underwent TBI followed by bone marrow transplantation were retrospectively reviewed. There were 86 patients (51 males, 35 females). Altogether, 36 patients were treated on twice-daily fractions of 2 Gy for 3 days to a total 12 Gy (group A). Another 50 patients were treated on once-daily fractions of 2.4 or 3.0 Gy for 4 or 5 days to a total 12 Gy (group B).
The 5-year overall survival rate was 49.2%, and relapse-free survival was 44.3%. There were no significant differences between the two groups regarding overall survival (P = 0.1237) or relapse-free survival (P = 0.1548). Two patients in group A had interstitial pneumonitis of grade 3 or higher severity compared with three patients in group B. There was no significant difference between patients in group A (5-year probability rate was 7.6%) and patients in group B (5-year probability rate was 13.9%) (P = 0.9519).
We concluded that our once-daily TBI regimen is feasible and had the benefit of reducing the complexity of TBI. We believe that further investigation of the TBI regimen is needed.
Purpose: To identify the prognostic factors that specifically predict survival rates of patients with localized aggressive non-Hodgkin’s lymphoma (NHL).
Methods and Materials: The survey was carried ...out at 25 radiation oncology institutions in Japan in 1998. The 5-year event-free (EFS) and overall survival rates (OAS) were calculated, and univariate and multivariate analyses were done to identify which of the following factors, namely, gender, age, performance status (PS), serum lactate dehydrogenase (LDH) level, Stage (I vs. II), tumor bulk (maximum diameter), and treatment, were significant from the viewpoint of prognosis.
Results: A total of 1141 patients with Stage I and II NHL were treated by the Japanese Lymphoma Radiation Therapy Group between 1988 and 1992. Of them, 787 patients, who were treated using definitive radiotherapy with or without chemotherapy for intermediate- and high-grade lymphomas in working formulation, constituted the core of this study. Primary tumors arose mainly from extranodal organs (71%) in the head and neck (Waldeyer’s ring: 36% and sinonasal cavities: 9%). The factors associated with poorer prognosis were age over 60 years old (
p < 0.0001), radiation therapy alone (
p < 0.0001), PS = 2–4 (
p = 0.0011), (sex male,
p = 0.0078), a bulky tumor more than 6 cm in maximum diameter (
p = 0.0088), elevated LDH (
p = 0.0117), and stage II (
p = 0.0642). A median dose of 42 Gy was delivered mainly to the involved fields. Short-course chemotherapy was provided in 549 (70%) patients. The 5-year OAS and EFS rates for all patients were 71% and 67%, respectively. According to the stage-modified International Prognostic Index, the 5-year EFS of the patients with risk factors from 0 to 1 was 76%, 61% for patients with two risk factors, and 26% for patients with three or more risk factors.
Conclusion: Extranodal presentation, especially Waldeyer’s ring and sinonasal cavities, is encountered more frequently in Japan than in Western countries. Tumor bulk is an important prognostic factor in patients with localized aggressive extranodal NHL. Short course chemotherapy followed by radiation therapy was associated with prolonged survival in patients with localized aggressive NHLs of extranodal origin and 0–1 risk factor.
Human CD43 super(+) B cells resemble both memory B cells and plasmablastsCD20 super(+)CD27 super(+)CD43 super(+) B (CD43 super(+) B) cells have been newly defined among PBMCs and proposed to be human ...B1 cells. However, it is controversial as to whether they are orthologs of murine B1 cells and how they are related to other B-cell populations, particularly CD20 super(+)CD27 super(+)CD4 3 super(-) memory B cells and CD20 super(low)CD27 super(high)CD43 super(high) plasmablasts. Our objective is to identify phenotypically the position of CD43 super(+) B cells among peripheral B-lineage cell compartments in healthy donors, with reference to B-cell subsets from patients with systemic lupus erythematosus (SLE). We found that CD43 super(+) B cells among PBMCs from healthy subjects were indistinguishable phenotypically from memory B cells in terms of surface markers, and spontaneous in vitro Ig and IL-10 secretion capability, but quite different from plasmablasts. However, a moderate correlation was found in the frequency of CD43 super(+) B cells with that of plasmablasts in healthy donors but not in SLE patients. An in vitro differentiation experiment indicated that CD43 super(+) B cells give rise to plasmablasts more efficiently than do memory B cells, suggesting that they are more closely related to plasmablasts developmentally than are memory B cells, which is also supported by quantitative PCR analysis of mRNA expression of B-cell and plasma cell signature genes. Thus, we conclude that, in healthy individuals, CD43 super(+) B cells are closely related not only to memory B cells phenotypically but also to plasmablasts developmentally, although the developmental origin of CD43 super(+) B cells is not necessarily the same as that of plasmablasts.
PDF
