Primary cutaneous B-cell lymphoma in Nottinghamshire U.K.: prognosis of subtypes defined in the WHO-EORTC classification.

BACKGROUND: Primary cutaneous B-cell lymphomas (PCBCL), with the exception of large B-cell lymphoma of leg type and intravascular large B-cell lymphoma, are associated with an excellent prognosis. These lymphomas have become much better understood in recent years leading to the publication in 2005 of the World Health Organization-European Organisation for Research and Treatment of Cancer classification. OBJECTIVES: To determine the relative frequency of occurrence of subtypes of PCBCL in a defined population, and the survival of patients with these subtypes. METHODS: During the period 1987-2009, 61 consecutive patients with PCBCL were identified from the Nottingham Lymphoma Registry (population 1·1 million). After histological review, the number of patients with each subtype was as follows: marginal zone, 18; follicle centre, 14; diffuse large B cell, leg type, 16; diffuse large B cell, other sites, 12; and intravascular large B cell, one. RESULTS: The 5- and 10-year lymphoma-specific survival for patients with marginal zone lymphoma was 100%. The only patient with intravascular large B-cell lymphoma died from widespread disease in spite of chemotherapy. The 4-year lymphoma-specific survival for follicle centre cell lymphoma was 90%. Patients with the other subtypes had the following 5-year lymphoma-specific survival rates: diffuse large B cell, leg type, 61% and diffuse large B cell, other, 40%. The median age at diagnosis for patients with diffuse large B-cell lymphoma, leg type was 82 years and as a consequence the 5-year overall survival was only 15%. There was a 3·4-fold increase in the incidence of PCBCL from the period 1987-1997 to the period 1998-2009. CONCLUSIONS: PCBCL is a rare disease (incidence around three per million population per year). It is, in our view, essential that it is diagnosed by a pathologist with an interest in cutaneous lymphoma and that the very different prognosis of the individual subtypes is appreciated by the treating clinician.

Chemotherapy for advanced, recurrent or metastatic endometrial cancer: a systematic review of Cochrane collaboration.

BACKGROUND: Cytotoxic chemotherapy has a limited place in the management of advanced or recurrent endometrial cancer. Commonly used agents include cisplatin and doxorubicin, but the side-effect profile may be unacceptable for many patients. The feasibility of administration of combination chemotherapy is limited in many patients on account of significant co-morbidity. While early-stage endometrial adenocarcinoma is a common gynaecological cancer with a favourable prognosis, advanced or recurrent disease presents a difficult management problem. The platinum and anthracycline compounds have been widely used for many years, but their impact on progression-free survival (PFS) and overall survival (OS) is not clear. This systematic review aimed to evaluate both the benefits and adverse effects of cytotoxic chemotherapy in these women. PATIENTS AND METHODS: We carried out systematic searches for randomised controlled trials (RCTs) comparing chemotherapy with another intervention. Data were extracted from trial reports or supplied by investigators. Where possible, hazard ratios (HRs) were calculated for OS and PFS and odds ratios (ORs) were calculated for acute toxicity. The impact of more versus less intensive chemotherapy on OS, PFS and acute toxicity was assessed in a meta-analysis. RESULTS: Eleven eligible RCTs were identified that recruited 2288 patients. A meta-analysis of six of these trials found that PFS [HR = 0.80, 95% confidence interval (CI) 0.71-0.90; P = 0.004], but not OS (HR = 0.90, 95% CI 0.80-1.03; P = 0.12), was significantly improved when more intensive chemotherapy was compared with less intensive chemotherapy. OS was improved when doxorubicin, cisplatin and other drugs were compared with doxorubicin and cisplatin. Toxicity was generally higher with more chemotherapy. There was insufficient evidence to assess the effect of chemotherapy on symptom control or quality of life (QoL). Platinums, anthracyclines and taxanes were the most studied in phase II trials and combinations gave the best responses, but patient selection and pre-treatment was very variable. CONCLUSIONS: More intense combination chemotherapy significantly improves the disease-free survival and the data indicate a modest improvement in OS. The addition of anthracyclines (e.g. doxorubicin) or the taxanes [e.g. paclitaxel (Taxol)] to cisplatin increases the response rate. More intensive regimens are associated with the gain in survival. However, grade 3 and 4 myelosuppression and gastrointestinal toxicity are also increased. Future developments are likely to exploit specific molecular characteristics of endometrial cancers, including their hormone dependence, growth factor target overexpression and PTEN loss. While no one drug or regimen offers a clear benefit for women with advanced endometrial cancer, platinum drugs, anthracyclines and paclitaxel seem the most promising agents. Future trials should address the impact of such agents on QoL and symptom control in addition to survival. Chemotherapy and endocrine therapy need to be compared directly in an RCT.

Concomitant hydroxyurea plus radiotherapy versus radiotherapy for carcinoma of the uterine cervix: a systematic review.

We identified eight randomised control trials of hydroxyurea and radiation versus radiotherapy alone (six published in full and two abstracts). Most concluded that outcomes were improved by use of hydroxyurea. However, methodological problems associated with these trials included small sample size, a large number of patient exclusions post randomisation, differing outcome definitions, subgroup analyses of already small numbers of patients and questionable rules for censoring, particularly a failure to include treatment related deaths in the survival analysis. All but two studies were of less than 50 patients. Patients were excluded from some analyses for treatment related reasons. The exclusion of such patients undoubtedly altered the conclusions of the studies. Even if there was a survival advantage attributed to hydroxyurea, overall survival was somewhat poor. We found the evidence regarding the use of hydroxyurea and radiotherapy to be inadequate for assessing its role in the treatment of cervical cancer.