Relapse in stage I(E) diffuse large B-cell lymphoma.

Despite a general favourable outcome in limited stage diffuse large B-cell lymphoma (DLBCL), relapses occur in about 10 to 20% of patients. Prognostic models only partially identify patients at risk for relapse. Moreover, it is not known whether the outcome after such a relapse is similar to the outcome after relapse in advanced stages. From January 2004 through December 2012, all newly diagnosed patients with stage I(E) DLBCL were retrospectively analysed from 2 clinical databases to investigate the relapse pattern and outcome in relation to initial treatment and clinical characteristics. In 126 patients (median age 64 years), histologically confirmed stage I(E) DLBCL was diagnosed. With a median follow-up of 53 months (range 5-132 months), 1 progressive disease and 18 relapses occurred. The 5-year time to tumour progression and disease-specific survival were 85% (95% CI 79-91%) and 92% (95% CI 87%-97%), respectively. We observed no significant difference in relapse localization, time to tumour progression, and disease-specific survival between patients treated with abbreviated R-CHOP plus involved field radiotherapy or with 6 to 8 cycles of R-CHOP. Analysis of relapses showed relapse >5 years after initial treatment (late relapse) in 5 of 19 patients (26%). Six of 19 patients (32%) had central nervous system relapse. Three of 11 relapsed cases available for analysis (28%) showed an MYC translocation, suggesting an overrepresentation in the relapse group. Outcome of patients with a relapse was poor with a median survival after relapse of 8 months. Only 1 patient (5%) underwent successful autologous stem cell transplantation. To improve outcome in these patients, early identification of new biological factors such as a MYC translocation or a high risk for CNS dissemination might be helpful. Moreover, treatment of any relapse after stage I disease should be taken seriously. Salvage treatment should be similar to relapses after advanced DLBCL.

Comorbidity is an independent prognostic factor in patients with advanced-stage diffuse large B-cell lymphoma treated with R-CHOP: a population-based cohort study.

An observational population-based cohort study was performed to investigate the role of comorbidity on outcome and treatment-related toxicity in patients with newly diagnosed advanced-stage diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Data for the clinical characteristics of 154 patients (median age 69 years), including Charlson Comorbidity Index (CCI), treatment, toxicity and outcome were evaluated. Forty-five percent of the patients had an International Prognistic index ≥3 and 16% had a CCI ≥2. The planned R-CHOP schedule was completed by 84% and 75% reached complete remission (CR). In those with CCI ≥2, 67% completed treatment with 46% CR. In patients with a CCI <2, overall survival (OS) after 1, 2 and 5 years was 84%, 79% and 65% respectively and it was 64%, 48% and 48% for those with CCI ≥2. Grade III/IV toxicity was documented in 53%, most frequently febrile neutropenia (27%) and infections (23%). In multivariate analysis CCI ≥2 and IPI ≥3 were independent risk indicators for OS and grade III/IV toxicity. In conclusion, comorbidity is an independent risk indicator for worse OS in patients with advanced DLBCL treated with R-CHOP by interference with intensive treatment schedules and more grade III/IV toxicity. Future studies are warranted to determine the optimal treatment approach in patients with significant comorbidities.

The clinicopathological roles of alpha-B-crystallin and p53 expression in patients with head and neck squamous cell carcinoma.

AIMS: The aim of the study was to investigate the expression of alpha-B-crystallin and p53 in head and neck squamous cell carcinoma (HNSCC). METHODS: Alpha-B-crystallin and p53 expressions from 118 HNSCC were studied by immunohistochemistry and correlated with clinicopathological parameters. RESULTS: Alpha-B-crystallin expression was seen in 28% (n = 33) of HNSCC. All except one poorly differentiated HNSCC were negative for alpha-B-crystallin. p53 expression was seen in 63% (n = 73) of HNSCC and was more common in moderately/poorly differentiated HNSCC (p = 0.034). The proportion of cases with positive staining for either alpha-B-crystallin or p53 was different in different anatomical locations in the head and neck. Patients with HNSCC having a high portion of tumour cells expressing p53 had a shorter survival than the other groups (p = 0.032). CONCLUSION: The expression of p53 and alpha-B-crystallin were related to the differentiation and site of the HNSCC. Alpha-B-crystallin was not a prognostic marker for HNSCC.

No outcome disparities in patients with diffuse large B-cell lymphoma and a low socioeconomic status.

INTRODUCTION: In patients with diffuse large B-cell lymphoma (DLBCL) socioeconomic status (SES) is associated with outcome in several population-based studies. The aim of this study was to further investigate the existence of disparities in treatment and survival. METHODS: A population-based cohort study was performed including 343 consecutive patients with DLBCL, diagnosed between 2005 and 2012, in the North-west of the Netherlands. SES was based on the socioeconomic position within the Netherlands by use of postal code and categorized as low, intermediate or high. With multivariable logistic regression and Cox proportional hazard models the association between SES and respectively treatment and overall survival (OS) was evaluated. RESULTS: Two-third of patients was positioned in low SES. Irrespective of SES an equal proportion of patients received standard immunochemotherapy. SES was not a significant risk indicator for OS (intermediate versus low SES: hazard ratio (HR) 1.31 (95%CI 0.78-2.18); high versus low SES: HR 0.83 (95%CI 0.48-1.46)). The mortality risk remained significantly increased with higher age, advanced performance status, elevated LDH and presence of comorbidity. CONCLUSION: Within the setting of free access to health care, in this cohort of patients with DLBCL no disparities in treatment and survival were seen in those with lower SES.

Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone is beneficial but toxic in very elderly patients with diffuse large B-cell lymphoma: a population-based cohort study on treatment, toxicity and outcome.

To assess treatment strategies, toxicity and outcome in very elderly patients (aged ≥ 75 years) diagnosed with diffuse large B-cell lymphoma (DLBCL) in the rituximab era, an observational population-based cohort study was performed. From 103 patients with a median age of 81 years, data of clinical characteristics, treatment, toxicity and outcome were evaluated. Advanced stage DLBCL was documented in 74 patients. In 80 patients chemotherapy was initiated; 70 patients received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP). In this group, 39 patients completed all cycles and 30 patients achieved a complete remission. Severe chemotherapy-related toxicity occurred in 69%. Two-year overall survival was 70% for elderly patients who completed chemotherapy, 28% for those treated with incomplete or suboptimal chemotherapy and 21% for those receiving palliative radiotherapy or supportive care. In conclusion, the ability to complete R-CHOP was associated with better overall survival compared to other treatment strategies at the expense of severe treatment-related toxicity.