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 carcinoma.

BACKGROUND: Endometrial adenocarcinoma is a common gynaecological cancer, but a comparatively small proportion of patients present with or develop recurrent or advanced disease. Progestogens are widely used, with little evidence of their efficacy. Co-morbidity including obesity and cardiac disease and concerns over toxicity have prevented more extensive studies of cytotoxic chemotherapy, although there are a number of active agents. OBJECTIVES: To assess any benefits or adverse effects of cytotoxic chemotherapy in women with advanced, recurrent or metastatic endometrial adenocarcinoma. SEARCH STRATEGY: The major medical literature databases were searched for all known randomised controlled trials (RCTs), as were trials registers and reference lists of relevant publications. SELECTION CRITERIA: RCTs comparing chemotherapy versus another intervention (including different chemotherapy) in advanced disease were considered. Trials of adjuvant treatment or for sarcomatous tumours were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted from the papers by reviewers and authors of included studies contacted for further information. MAIN RESULTS: Eleven eligible trials were identified which entered 2288 patients between 1974 and 2000. A meta-analysis of the 6 trials comparing more with less chemotherapy with combination was possible and included 1135 patients. Progression-free survival (PFS) was significantly improved (Hazard Ratio (HR) = 0.80, 95% Confidence Interval (CI) 0.71 to 0.90, p = 0.004), but there was only a trend toward improved survival (HR = 0.90, 95% CI 0.80 to 1.03). Toxicity was in general higher with the combination chemotherapy regimens. Only one trial showed a significant survival benefit from the addition of paclitaxel to combination chemotherapy, but this was at the expense of increased toxicity. There was insufficient evidence to assess whether there was any benefit from cytotoxic chemotherapy in terms of symptom control or quality of life (QOL) compared with best supportive care. There were no comparative trials of chemotherapy with endocrine therapy AUTHORS' CONCLUSIONS: The optimum cytotoxic drug regimen for advanced endometrial adenocarcinoma has still to be defined although our review suggests that it may contain paclitaxel or platinum. These mainly North American and European trial populations represent a highly selected subgroup of the 10, 000 women dying annually from this disease. Future trials should include measures of QOL and symptom control in addition to PFS and overall survival (OS). They should should also consider comparison of of endocrine therapy and cytotoxic chemotherapy in patients with no prior drug therapy. Stratification of patients should take into account other prognostic factors including co-morbidity and prior radiation treatment.

Chemotherapy for advanced, recurrent or metastatic endometrial carcinoma.

BACKGROUND: Endometrial adenocarcinoma is a common gynaecological cancer, but a comparatively small proportion of patients present with or develop recurrent or advanced disease. Progestogens are widely used, with little evidence of their efficacy. Co-morbidity including obesity and cardiac disease and concerns over toxicity have prevented more extensive studies of cytotoxic chemotherapy, although there are a number of active agents. OBJECTIVES: To assess any benefits or adverse effects of cytotoxic chemotherapy in women with advanced, recurrent or metastatic endometrial adenocarcinoma. SEARCH STRATEGY: The major medical literature databases were searched for all known randomised controlled trials (RCTs), as were trials registers and reference lists of relevant publications. SELECTION CRITERIA: RCTs comparing chemotherapy versus another intervention (including different chemotherapy) in advanced disease were considered. Trials of adjuvant treatment or for sarcomatous tumours were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted from the papers by reviewers and authors of included studies contacted for further information. MAIN RESULTS: Eleven eligible trials were identified which entered 2288 patients between 1974 and 2000. A meta-analysis of the 6 trials comparing more with less chemotherapy with combination was possible and included 1135 patients. Progression-free survival (PFS) was significantly improved (Hazard Ratio (HR) = 0.80, 95% Confidence Interval (CI) 0.71 to 0.90, p = 0.004), but there was only a trend toward improved survival (HR = 0.90, 95% CI 0.80 to 1.03). Toxicity was in general higher with the combination chemotherapy regimens. Only one trial showed a significant survival benefit from the addition of paclitaxel to combination chemotherapy, but this was at the expense of increased toxicity. There was insufficient evidence to assess whether there was any benefit from cytotoxic chemotherapy in terms of symptom control or QOL compared with best supportive care. There were no comparative trials of chemotherapy with endocrine therapy. AUTHORS' CONCLUSIONS: The optimum cytotoxic drug regimen for advanced endometrial adenocarcinoma has still to be defined although our review suggests that it may contain paclitaxel or platinum. These mainly North American and European trial populations represent a highly selected subgroup of the 10,000 women dying annually from this disease. Future trials should include measures of QOL and symptom control in addition to PFS and overall survival (OS). They should also consider comparison of endocrine therapy and cytotoxic chemotherapy in patients with no prior drug therapy. Stratification of patients should take into account other prognostic factors including co-morbidity and prior radiation treatment.

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.

Concomitant hydroxyurea plus radiotherapy versus radiotherapy for carcinoma of the uterine cervix.

BACKGROUND: A number of randomised studies suggest hydroxyurea given alongside radiotherapy improves survival in patients with locally advanced cervix cancer. Following publication of five large randomised trials in 1999 and 2000 concomitant chemoradiotherapy has become standard treatment for these patients. In two of the studies hydroxyurea was given to patients in both control and experimental arms. The precise role of this orally administered cytotoxic drug is not known. OBJECTIVES: To assess the effectiveness (survival and toxicity) of concomitant radiation and hydroxyurea compared with radiotherapy alone in treating locally advanced cervix cancer. SEARCH STRATEGY: We searched the following:Cochrane Gynaecological Cancer Group's Specialised RegisterCENTRAL (Cochrane Library on CD ROM, issue 4, 2002) MEDLINE (Silver Platter, from 1970 to 2001) EMBASE (from 1980 to 2001) CANCERLIT (from 1970 to 2001) PDQ (search for open and closed trials) LILACSMeta-register (ongoing trials)Searches were not language or publication restricted. Investigators of relevant trials were contacted for further information. SELECTION CRITERIA: Randomized controlled trials comparing concomitant radiotherapy (+/- surgery) with hydroxyurea versus radiotherapy (+/- surgery) for locally advanced cervix cancer. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed trials for inclusion and extracted data. Discussions on all aspects of data collection and analysis took place among all the authors at regular intervals. MAIN RESULTS: Seven studies were found to be suitable for inclusion from 33 identified as relevant. None of the trials provided adequate evidence to support the use of hydroxyurea owing to small sample size, large numbers of post-randomisation exclusions and questionable rules for censoring, particularly a failure to include treatment-related deaths in the survival analysis. Details of statistical analysis were limited and often confusing, and we felt meta-analysis would lead to unreliable and invalid conclusions. Most studies appeared to be double blind placebo-controlled studies but none give details of power calculations or reasons for stopping recruitment. Only two studies had more than 50 patients. Patients were excluded from analysis in most trials for treatment-related reasons; in one, less than half those recruited were used in the analysis, the remainder having been excluded because of tumour progression or treatment-related conditions e.g. septicaemia, worsening renal/hepatic function. In another trial five out of 20 in the hydroxyurea group died of treatment-related complications but the five-year survival group was presented as 94%. REVIEWER'S CONCLUSIONS: We found no evidence to support the use of hydroxyurea in addition to radiotherapy in the routine treatment of cervix cancer.

Induced visual motion: effects of fixation and retinal position.

In the first of two experiments (N = 33) on the effects on induced motion of target fixation and retinal position, better induced motion was always perceived in a target which was fixated and centered on the fovea than in nonfixated target stimuli which projected onto various locations on the periphery. A similar fixation effect was again observed in Exp. 2 (N = 29) when the nonfixated stimuli fell within the fovea. Ratings of induced motion tended to decrease as retinal eccentricity of the nonfixated stimulus increased in both experiments. The results indicate that target fixation and retinal position should be controlled in research on induced motion. Also, the data may emphasize the similarity of real and induced motion perception.

Latency of induced visual motion and fixation.

The effects of target fixation on induced visual motion were examined in two experiments. In Exp. 1, induced motion was generated by a moving frame, and fixation was disrupted by temporarily extinguishing the target and by requiring subjects temporarily to look at a distractor. Relative to a continuous fixation control, both manipulations increased the perceived latency of induced motion. These effects were confirmed and extended in Exp. 2. Results indicate that target fixation should be carefully controlled in research on induced motion.

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.