Clinical characteristics of patients with B-cell lymphoma enrolled in clinical trials for aggressive lymphoma in Japan: Japan Clinical Oncology Group - Lymphoma Study Group study - JCOG0108A.

The clinical characteristics of B-cell lymphoma (BCL) were studied through the combined analysis of six clinical trials conducted by the Japan Clinical Oncology Group - Lymphoma Study Group (JCOG-LSG) for aggressive lymphoma in the 1990s, before the introduction of rituximab. Through a central pathological review, 829 patients were diagnosed with BCL according to the World Health Organization classification and treated with doxorubicin-containing combination chemotherapies. Of these patients, 642, 104, 30, and 24 patients were diagnosed with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL), respectively. The overall survival (OS) of FL and MZL patients was higher than that of patients with DLBCL and MCL. The OS of the MCL patients was higher than that of DLBCL patients in the first 5 years, but MCL had the lowest survival after 5 years. The OS of DLBCL patients was clearly stratified by the international prognostic index and showed data compatible with that of aggressive lymphoma in the pre-rituximab era. These results established the clinical aspects of BCL in a large number of patients treated in prospective studies during the pre-rituximab era in Japan.

Ultra-high sensitivity HBsAg assay can diagnose HBV reactivation following rituximab-based therapy in patients with lymphoma.

BACKGROUND & AIMS: HBV reactivation is a risk in patients receiving anti-CD20 antibodies for the treatment of lymphoma. The purpose of this post hoc analysis was to evaluate the efficacy of an ultra-high sensitivity HBsAg assay to guide preemptive antiviral treatment in patients with lymphoma and resolved HBV infections using prospectively stored samples from an HBV DNA monitoring study. METHODS: HBV reactivation (defined as HBV DNA levels of ≥11 IU/ml) was confirmed in 22 of 252 patients. A conventional HBsAg assay (ARCHITECT, cut-off value: 0.05 IU/ml) and an ultra-high sensitivity HBsAg assay employing a semi-automated immune complex transfer chemiluminescence enzyme technique (ICT-CLEIA, cut-off value: 0.0005 IU/ml) were performed at baseline, at confirmed HBV reactivation and monitored after HBV reactivation. RESULTS: Baseline HBsAg was detected using ICT-CLEIA in 4 patients; in all of whom precore mutants with high replication capacity were reactivated. Of the 6 patients with HBV DNA detected below the level of quantification at baseline, 5 showed HBV reactivation and 3 of the 5 had precore mutations. Sensitivity for detection by ARCHITECT and ICT-CLEIA HBsAg assays at HBV reactivation or the next sampling after HBV reactivation was 18.2% (4 of 22) and 77.3% (17 of 22), respectively. Of the 5 patients undetectable by ICT-CLEIA, HBV reactivation resolved spontaneously in 2 patients. All 6 patients reactivated with precore mutations including preS deletion could be diagnosed by ICT-CLEIA HBsAg assay at an early stage of HBV reactivation. Multivariate analysis showed that an anti-HBs titer of less than 10 mIU/ml, HBV DNA detected but below the level of quantification, and HBsAg detected by ICT-CLEIA at baseline were independent risk factors for HBV reactivation (adjusted hazard ratios, 15.4, 31.2 and 8.7, respectively; p <0.05). CONCLUSIONS: A novel ICT-CLEIA HBsAg assay is an alternative method to diagnose HBV reactivation. CLINICAL TRIAL NUMBER: UMIN000001299. LAY SUMMARY: Hepatitis B virus can be reactivated in lymphoma patients receiving anti-CD20 antibodies such as rituximab. Currently, reactivation requires the monitoring of HBV DNA, but monitoring of the surface antigen (HBsAg) could provide a relatively inexpensive, quick and easy alternative. We assessed the performance of an ultra-high sensitivity HBsAg assay and showed that it could be effective for the diagnosis and monitoring of HBV reactivation.

Complications and outcomes in diffuse large B-cell lymphoma with gastric lesions treated with R-CHOP.

Standard therapy for gastric diffuse large B-cell lymphoma (DLBCL) is considered to be chemotherapy with or without involved-field radiation therapy. Although R-CHOP therapy alone is widely used for DLBCL with gastric lesions (DLBCL-GL), the outcome and incidence of treatment-related gastric complications following R-CHOP are not well known. This study aimed to evaluate the outcome after R-CHOP therapy in patients with gastric DLBCL including gastric complications and to identify risk factors for the complications. Consecutive patients with newly diagnosed DLBCL-GL treated with R-CHOP between 2003 and 2014 were retrospectively evaluated. DLBCL-GL was defined only when pathologically confirmed in the stomach. Of the 96 patients with DLBCL-GL, 63 patients were diagnosed with gastric symptoms. Eighty-eight patients (92%) completed six to eight cycles of R-CHOP. The complete remission (CR) rate was 86%, and 3-year and 5-year overall survival rates were 80% and 73%, respectively. Patients were well stratified according to the Revised International Prognostic Index (R-IPI). Complication rate was 8% (8/96); seven patients had bleeding and three had stenosis. No patients had gastric perforation. Bleeding occurred during the first cycle of R-CHOP in five patients (5/7, 71%). Patients with gastric complications had a lower R-CHOP completion rate (50%, P = 0.001) and a lower CR rate (25%, P < 0.001) than those without complications. A low serum albumin level at diagnosis was the only risk factor identified for gastric complications (P = 0.001) and six of the eight patients with complications were shown to be at stage IV. Further studies of DLBCL-GL are warranted to identify patients at high risk for gastric complications and to provide better treatment strategies.

Randomized phase II study of a bendamustine monotherapy schedule for relapsed or refractory low-grade B-cell non-Hodgkin lymphoma or mantle cell lymphoma (RABBIT-14).

The aim of this randomized phase II study was to improve the treatment delays and discontinuations associated with bendamustine use by comparing the effect of Benda-14 (intravenous bendamustine, 120 mg/m2 on days 1 and 15, repeated every 4 weeks for a total of 6 cycles) with those of the standard treatment in relapsed indolent lymphoma and/or mantle cell lymphoma. Forty-six patients were randomly assigned to the treatments from September 2012 to February 2016. Treatment accomplishment rate and median relative dose intensity were similar in both arms: 38 and 63.4% in the Benda-14 arm and 41 and 66.3% in the standard treatment arm, respectively. The overall response rate and median progression-free survival, respectively, were 83% and 21.0 months for Benda-14, and 77% and 15.5 months for the standard treatment. Benda-14 induced favorable responses with less frequent hematological toxicities.

Japanese phase II study of rituximab maintenance for untreated indolent B-cell non-Hodgkin lymphoma with high tumor burden.

Recent large-scale randomized clinical trials in Europe and the US demonstrated that maintenance therapy with rituximab significantly improved the progression-free survival (PFS) in indolent B-cell non-Hodgkin lymphoma (B-NHL) patients, especially those with follicular lymphoma (FL). However, rituximab maintenance has not been approved in Japan, because there are no clinical data supporting the benefit of rituximab maintenance in Japanese patients. Therefore, we conducted a single-arm, multicenter bridging study in previously untreated indolent B-NHL patients with high tumor burden. The primary endpoint was 4-year PFS and was expected to be 70 % based on previous studies. Sixty-two patients, including 55 FL patients, were enrolled and received induction therapy with CHOP combined with rituximab (R-CHOP). Fifty-eight patients responding to R-CHOP induction received rituximab at 375 mg/m2 every 8 weeks for 2 years as for the rituximab maintenance arm in the PRIMA study. A 4-year PFS of 69.8 % was obtained (95 % confidence interval 55.9-80.0 %). Rituximab maintenance was well tolerated and common adverse events were infections, neutropenia, and/or leukopenia that were manageable with conventional supportive care. No patients died. These data were compatible with the PRIMA data. R-CHOP induction followed by rituximab is useful in Japanese patients with untreated indolent B-NHL having high tumor burden. Clinical trial number UMIN000001191.

Monitoring of Hepatitis B Virus (HBV) DNA and Risk of HBV Reactivation in B-Cell Lymphoma: A Prospective Observational Study.

BACKGROUND: There is no standard management of reactivation of hepatitis B virus (HBV) infection in HBV-resolved patients without hepatitis B surface antigen (HBsAg), but with antibodies against hepatitis B core antigen and/or antibodies against HBsAg (anti-HBs). METHODS: We conducted a prospective observational study to evaluate the occurrence of HBV reactivation by serial monthly monitoring of HBV DNA and to establish preemptive therapy guided by this monitoring in B-cell non-Hodgkin lymphoma (B-NHL) treated with rituximab plus corticosteroid-containing chemotherapy (R-steroid-chemo). The primary endpoint was the incidence of HBV reactivation defined as quantifiable HBV DNA levels of ≥ 11 IU/mL. RESULTS: With a median HBV DNA follow-up of 562 days, HBV reactivation was observed in 21 of the 269 analyzed patients. The incidence of HBV reactivation at 1.5 years was 8.3% (95% confidence interval, 5.5-12.4). No hepatitis due to HBV reactivation was observed in patients who received antiviral treatment when HBV DNA levels were between 11 and 432 IU/mL. An anti-HBs titer of <10 mIU/mL and detectable HBV DNA remaining below the level of quantification at baseline were independent risk factors for HBV reactivation (hazard ratio, 20.6 and 56.2, respectively; P < .001). Even in 6 patients with a rapid increase of HBV due to mutations, the monthly HBV DNA monitoring was effective at preventing HBV-related hepatitis. CONCLUSIONS: Monthly monitoring of HBV DNA is useful for preventing HBV reactivation-related hepatitis among B-NHL patients with resolved HBV infection following R-steroid-chemo (UMIN000001299).

Prognostic biomarkers in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy.

Concurrent chemoradiotherapy has become one of the standard management approaches for newly diagnosed localized nasal natural killer (NK)/T-cell lymphoma (NKTCL). Few data are available on the prognostic biomarkers of NKTCL among patients treated with concurrent chemoradiotherapy. To evaluate the prognostic significance of immunophenotypic biomarkers for patients treated with concurrent chemoradiotherapy, latent membrane protein 1 (LMP1), cutaneous lymphocyte antigen (CLA) and cell origin were examined in samples from 32 patients who were enrolled in the Japan Clinical Oncology Group 0211 trial and treated with concurrent chemoradiotherapy. LMP1 and CLA were positive in 66% (19/29) and 29% (9/31) of the cases examined, respectively. The median follow-up duration was 68 months (range, 61-94). The patients with LMP1-positive tumors showed a better overall survival (OS) than the patients with LMP1-negative tumors (hazard ratio, 0.240; 95% confidence interval [CI], 0.057-1.013; 80% CI, 0.093-0.615; P = 0.035). All five patients with LMP1-negative tumors who experienced disease progression died of lymphoma, and both patients with local failure had LMP1-negative tumors. There was no significant difference in OS according to CLA expression. A total of 27 (84%) cases were of NK-cell origin, two were of αß T-cell origin and three were of γδ T-cell origin. In contrast to those with tumors of NK-cell origin, all five patients with NKTCL of T-cell origin were alive without relapse at the last follow up. Our results indicate that LMP1 expression is a favorable prognostic marker and suggest that a T-cell origin of the tumor may be a favorable prognostic marker for patients with localized NKTCL treated with concurrent chemoradiotherapy.

A multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma.

Although initial rituximab-containing chemotherapies achieve high response rates, indolent B-cell non-Hodgkin lymphoma (B-NHL), such as follicular lymphoma (FL), is still incurable. Therefore, new effective agents with novel mechanisms are anticipated. In this multicentre phase II study, patients with relapsed/refractory indolent B-NHL and mantle cell lymphoma (MCL) received vorinostat 200 mg twice daily for 14 consecutive days in a 21-d cycle until disease progression or unacceptable toxicity occurred. The primary endpoint was overall response rate (ORR) in FL patients and safety and tolerability in all patients. Secondary endpoints included progression-free survival (PFS). Fifty-six eligible patients were enrolled; 50 patients (39 with FL, seven with other B-NHL, and four with MCL) were evaluable for ORR, and 40 patients had received rituximab-containing prior chemotherapeutic regimens. For the 39 patients with FL, the ORR was 49% [95% confidence interval (CI): 32·4, 65·2] and the median PFS was 20 months (95% CI: 11·2, 29·7). Major toxicities were manageable grade 3/4 thrombocytopenia and neutropenia. Vorinostat offers sustained antitumour activity in patients with relapsed or refractory FL with an acceptable safety profile. Further investigation of vorinostat for clinical efficacy is warranted.

Long-term survival of diffuse large B cell lymphoma of the trigeminal region extending to the Meckel's cave treated by CHASER therapy: case report.

A 52-year-old man with a history of malignant lymphoma of the cecum presented with lancinating facial pain in the left. Magnetic resonance imaging (MRI) revealed a tumor in the Meckel's cave extending along the trigeminal nerve. The tumor was partially removed via left retrosigmoid lateral suboccipital craniotomy. Histological examination showed findings consistent with diffuse large B cell lymphoma, which was later confirmed to be metastatic lesion from the cecal lesion. Postoperative chemotherapy with cyclophosphamide, high dose, cytarabine, steroid (dexamethasone), etoposide, and rituximab (CHASER) followed by whole brain irradiation (30 Gy) resulted in complete remission. Although facial pain persisted, the patient's general condition remained favorable and he did not experience recurrence over the 51-month follow-up period. Histological confirmation and awareness of malignant lymphoma are very important to determine the therapeutic strategy and to avoid misdiagnosis or delayed diagnosis. Long-term survival of patients with metastatic malignant lymphoma in the Meckel's cave extending along the trigeminal nerve was very rare. In addition, metastatic malignant lymphoma in the extra-axial and peripheral nervous tissue might be different from primary central nervous system lymphoma in the white matter, since the efficacy of chemotherapeutic agents against malignant lymphomas in the extra-axial regions is not attenuated by the blood brain barrier.

First experience of active surveillance before systemic target therapy in patients with metastatic renal cell carcinoma.

OBJECTIVE: To reveal the outcomes of initial active surveillance (AS), followed by deferred systemic target therapy, in a subpopulation of patients with indolent metastatic renal cell carcinoma (mRCC). METHODS: We retrospectively reviewed the clinical and pathologic data of patients with mRCC, who initially were monitored by planned AS before systemic therapy because of their preference and asymptomatic or slowly progressive disease, at our institution between 2000 and 2011. The primary outcome measures were progression-free survival (PFS) and overall survival (OS). RESULTS: Twenty-nine patients with a metastatic lesion at start of AS were eligible for this analysis. The median age at the start of AS was 69 years. Of these patients, 65% had recurrent disease and 35% were in stage IV. All patients had undergone nephrectomy and 86% had clear-cell carcinoma. No patients were categorized into a poor risk according to Memorial Sloan-Kettering Cancer Center (MSKCC) and Heng criteria. The median follow-up period was 35.4 months. Disease progression was observed in 72% of patients, but only 14% died during the follow-up period. The median PFS time was 26.1 months. After disease progression was observed, only 58% of these patients received treatment. The median OS had not been reached, but 12, 24, and 48 months OS rates were 96.4%, 88.7%, and 83.8%, respectively. CONCLUSION: PFS and OS of patients who underwent AS were acceptable. AS might be a reasonable approach, particularly for patients with prolonged, indolent course of the disease. Further observational studies with a larger sample size might be needed.

A multicenter clinical study evaluating the confirmed complete molecular response rate in imatinib-treated patients with chronic phase chronic myeloid leukemia by using the international scale of real-time quantitative polymerase chain reaction.

Achievement of complete molecular response in patients with chronic phase chronic myeloid leukemia has been recognized as an important milestone in therapy cessation and treatment-free remission; the identification of predictors of complete molecular response in these patients is, therefore, important. This study evaluated complete molecular response rates in imatinib-treated chronic phase chronic myeloid leukemia patients with major molecular response by using the international standardization for quantitative polymerase chain reaction analysis of the breakpoint cluster region-Abelson1 gene. The correlation of complete molecular response with various clinical, pharmacokinetic, and immunological parameters was determined. Complete molecular response was observed in 75/152 patients (49.3%). In the univariate analysis, Sokal score, median time to major molecular response, ABCG2 421C>A, and regulatory T cells were significantly lower in chronic phase chronic myeloid leukemia patients with complete molecular response than in those without complete molecular response. In the multivariate analysis, duration of imatinib treatment (odds ratio: 1.0287, P=0.0003), time to major molecular response from imatinib therapy (odds ratio: 0.9652, P=0.0020), and ABCG2 421C/C genotype (odds ratio: 0.3953, P=0.0284) were independent predictors of complete molecular response. In contrast, number of natural killer cells, BIM deletion polymorphisms, and plasma trough imatinib concentration were not significantly associated with achieving a complete molecular response. Several predictive markers for achieving complete molecular response were identified in this study. According to our findings, some chronic myeloid leukemia patients treated with imatinib may benefit from a switch to second-generation tyrosine kinase inhibitors (ClinicalTrials.gov, UMIN000004935).

Phase II study of ABV (doxorubicin with increased dose, bleomycin and vinblastine) therapy in newly diagnosed advanced-stage Hodgkin lymphoma: Japan Clinical Oncology Group study (JCOG9705).

The role of dacarbazine in ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) therapy in Hodgkin lymphoma (HL) remains unclear. This phase II study assessed the efficacy and safety of ABV therapy with an increased doxorubicin dose (30 mg/m(2)) in advanced-stage HL. The primary endpoint was complete response rate (%CR). Patients received six or eight cycles of ABV every 4 weeks followed by involved-field radiation therapy (IFRT) in residual disease and initial bulky mass. Seventy-two patients were enrolled. An interim analysis in 46 assessable patients showed that %CR had exceeded the stopping criteria.However, the 2-year progression-free survival (%PFS) rate of 49.4% (95% confidence interval [CI] 32.2-66.6) was markedly lower than the 79.2% PFS (95% CI 70.6-87.7) seen in our previously reported study (JCOG9305) of ABVd with two-thirds the dose of dacarbazine of the original ABVD. Therefore, the study was closed early. The %CR in the 70 eligible patients after ABV was 31.4% (95% CI 20.9-43.6) and was increased to 70.0% (95% CI 57.9-80.4) after the addition of IFRT. ABV was inferior to ABVd for PFS in patients with advanced HL, suggesting that dacarbazine is indispensable in ABVD/ABVd.

Comparison between neoadjuvant and adjuvant gemcitabine plus cisplatin chemotherapy for muscle-invasive bladder cancer.

AIM: Radical cystectomy plus platinum-based perioperative chemotherapy is a standard treatment for patients with clinically localized muscle-invasive bladder cancer. The standard perioperative chemotherapy is methotrexate, vinblastine, doxorubicin and cisplatin (MVAC). However, no prospective randomized trial has been published that compares neoadjuvant and adjuvant chemotherapy for bladder cancer. Moreover, the efficacy of perioperative chemotherapy with gemcitabine plus cisplatin (GC) has not been clarified. In this study we have compared the clinical outcomes between neoadjuvant and adjuvant chemotherapy in patients receiving GC. METHODS: We retrospectively reviewed the records of patients who were scheduled to be treated with a radical cystectomy plus perioperative chemotherapy with GC from 2005 to 2010 at our institution. The primary outcome measure was recurrence-free survival (RFS). RESULTS: A total of 42 patients received perioperative chemotherapy with GC (25 neoadjuvant, 17 adjuvant). The median number of cycles of GC administered to the two groups was not significantly different. The median duration of follow up was 28.6 months. During the follow-up period, recurrence was observed in nine and three patients in the neoadjuvant and adjuvant groups, respectively. The RFS rate at median follow up was 67 and 76% in the neoadjuvant and adjuvant groups, respectively. No significant difference in RFS at median follow up was observed between the two groups (P = 0.124). CONCLUSION: Our results showed no statistically significant difference in RFS between neoadjuvant and adjuvant GC chemotherapy for muscle-invasive bladder cancer. We expect to validate these findings in a prospective randomized trial.

Impaired mental health among the bereaved spouses of cancer patients.

OBJECTIVE: Few cancer physicians routinely provide bereavement follow-up in clinical practice. The purpose of this study was to identify the prevalence of impaired mental health among the bereaved spouses over several years and explore the indicators for early detection of high-risk spouses during end-of life (EOL) care. METHODS: A cross-sectional mail survey was conducted for the bereaved spouses of patients who had died at the National Cancer Center Hospital of Japan. Bereaved spouses with potential psychiatric disorders were identified by the cut-off score of the 28-item General Health Questionnaire. Associated factors of potential psychiatric disorders were explored by logistic regression analysis. RESULTS: A total of 821 spouses experiencing bereavement from 7 months to 7 years returned the questionnaires. Overall mean prevalence of potential psychiatric disorders was 44% (360/821). Bereaved spouses 'under 55 years' (71%) or '2 years after bereavement' (59%) revealed a significantly higher prevalence (p < 0.01). Associated factors during EOL care were several characteristics such as 'spouses' history of psychiatric disorder (odds ratio (OR) = 3.19), 'patients' with stomach cancer (OR = 1.87), and 'patients' using psychiatric consultation services (OR = 1.52) as well as spouses' dissatisfaction with EOL care such as 'physicians' treatment of physical symptoms' (OR = 3.44) and 'time spent communicating with patients' (OR = 1.55). CONCLUSIONS: Nearly half the bereaved spouses showed potential psychiatric disorders even 7 years after bereavement. Patients' psychological distress, spouses' history of psychiatric disorder, and dissatisfaction with EOL care were indicators of high-risk spouses.

Phase II study of cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) therapy for newly diagnosed patients with low- and low-intermediate risk, aggressive non-Hodgkin's lymphoma: final results of the Japan Clinical Oncology Group Study, JCOG9508.

The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone, known as CHOP therapy, has been established as the standard treatment for aggressive non-Hodgkin's lymphoma (NHL). Although patients categorized as low (L) and low-intermediate (L-I) risk using the International Prognostic Index have favorable prognoses in Western countries, the efficacy and safety of CHOP therapy has not been prospectively evaluated in Japan. We conducted a phase II study of CHOP in L and L-I risk Japanese patients, evaluating overall survival (OS) as the primary endpoint. A total of 213 patients were enrolled and treated with eight courses of CHOP. Efficacy was evaluated in 168 eligible patients (L risk, 87; L-I risk, 81). Five-year OS rates in all eligible, L, and L-I risk patients were 68 % [95 % confidence interval (CI): 61-76 %], 73 % (95 % CI: 63-82 %), and 64 % (95 % CI: 53-74 %), respectively. The major toxicity observed was grade 4 neutropenia (64 %). Grade 4 non-hematological toxicities were observed as follows: one case each of paralytic ileus, convulsions, hypoxemia due to interstitial pneumonia, and reactivated fulminant hepatitis B. These results show reasonable efficacy and safety of the CHOP regimen in Japanese patients with lower risk aggressive NHL (UMIN-CTR Number C000000053).

Bortezomib-induced pneumonitis during bortezomib retreatment in multiple myeloma.

Bortezomib is a proteasome inhibitor and is active against multiple myeloma. Most toxicities associated with bortezomib are mild to moderate and manageable; however, bortezomib-induced pneumonitis has been reported in some multiple myeloma cases. Bortezomib-induced pneumonitis was reported to occur relatively soon after the first administration of bortezomib. A 64-year-old Japanese man with multiple myeloma received low-dose dexamethasone followed by bortezomib monotherapy as the initial therapy. He had no pulmonary complications during bortezomib treatment. Thereafter, he was treated with high-dose chemotherapy, followed by autologous peripheral blood stem cell transplantation. Ten months after autologous peripheral blood stem cell transplantation, his disease relapsed and he received bortezomib retreatment. On the fifth day after the second dose of weekly bortezomib, he complained of mild dyspnea, dry cough and fever. High-resolution computed tomography of the chest showed bilateral infiltrates with partial ground glass appearance in the lower lobes. The diagnosis of bortezomib-induced pneumonitis was made. His bortezomib-induced pneumonitis responded to steroid therapy and his respiratory symptoms disappeared. This is the first report in which bortezomib-induced pneumonitis occurred during bortezomib retreatment for relapsed multiple myeloma. Careful management is needed during bortezomib retreatment, even after the previous course of bortezomib was administered safely.

Psychological states and coping strategies after bereavement among spouses of cancer patients: a quantitative study in Japan.

PURPOSE: The purposes of this study were (1) to characterize psychological states and coping strategies after bereavement among spouses of cancer patients in Japan and (2) to explore the factors associated with psychological states in oncology settings. METHODS: In March 2009, questionnaires to assess spouses' psychological states, coping strategies, and mental health states (GHQ-28) were sent after patients died at the National Cancer Center of Japan. To address the first purpose, exploratory factor analysis, gender comparison, and calculation of correlation with age, time since bereavement, and mental health states were conducted. Hierarchical regression analysis was conducted to address the second purpose. RESULTS: A total of 821 spouses experiencing bereavement for 7 months to 7 years participated in the study. Psychological states revealed three factor structures: "Anxiety/Depression/Anger", "Yearning", and "Acceptance/Future-Oriented Feelings". Coping strategies also revealed three factor structures: "Distraction", "Continuing Bonds", and "Social Sharing/Reconstruction". Coping strategies represented 18 % to 34 % of each factor associated with psychological states, whereas the characteristics of bereaved spouses and deceased patients represented 6 % and less than 6 %, respectively. More "Distraction and Social Sharing/Reconstruction" and less "Continuing Bonds" were significantly associated coping strategies for achieving "Acceptance/Future-Oriented Feelings" (p < 0.01). CONCLUSIONS: Both psychological states and coping strategies after bereavement revealed three factor structures. Coping strategies was the primary, bereaved spouses' characteristics was the secondary, and deceased patients' characteristics was the tertiary factor associated with psychological states. Enhancing "Distraction" and "Social Sharing/Reconstruction", and reducing "Continuing Bonds" might be promising strategies for achieving positive psychological states of the bereaved.

Long-term outcome of pleurodesis with OK-432 in metastatic breast cancer: a new risk model for success from an analysis of 75 cases.

BACKGROUND: Malignant pleural effusion is a common and devastating complication of metastatic breast cancer. This occurs in about 30% of patients with metastatic breast cancer during the clinical course, and chemical pleurodesis is sometimes performed to relieve dyspnea. However, the long-term outcome of pleurodesis and factors affecting successful pleurodesis have not been clarified. OBJECTIVES: The aim of this analysis is to evaluate the long-term outcome of pleurodesis and to identify risk factors associated with success. METHODS: Data on 75 patients who had undergone chemical pleurodesis with OK-432 for pleural effusion due to metastatic breast cancer were reviewed retrospectively. The primary outcomes were success rate and pleural progression-free survival (PPFS) rate. RESULTS: The median duration of follow-up was 134 days (range 8-975 days). During this period, 22 patients re-accumulated pleural fluid. The overall success rate was 70.5%. The 4-, 8- and 12-week PPFS rates were 88.0, 84.0 and 78.7% respectively. Multivariate analysis identified three unfavorable factors that were independently associated with unsuccessful pleurodesis, including estrogen-receptor negative status, a 24-h drainage volume of more than 100 mL before extubation and NSAID use. The PPFS rate at median follow-up was 93.5% in the low-risk group (n = 41, 0 or 1 unfavorable factor) and 55.1% in the high-risk group (n = 34, 2 or 3 unfavorable factors). The difference between the PPFS curves of the two risk groups was statistically significant (P < 0.001). CONCLUSIONS: Pleurodesis for metastatic breast cancer was efficacious in controlling malignant pleural effusion. Our simple new risk model warrants further studies.