Lack of durable disease control with chemotherapy for mycosis fungoides and Sézary syndrome: a comparative study of systemic therapy.

Numerous systemic treatment options exist for patients with mycosis fungoides (MF) and Sézary syndrome (SS), but no large comparative studies are published. To study the efficacy of treatments, a retrospective analysis of our cutaneous lymphoma database was undertaken, with 198 MF/SS patients undergoing systemic therapies. The primary end point was time to next treatment (TTNT). Patients with advanced-stage disease made up 53%. The median follow-up time from diagnosis for all alive patients was 4.9 years (range 0.3-39.6), with a median survival of 11.4 years. Patients received a median of 3 lines of therapy (range 1-13), resulting in 709 treatment episodes. Twenty-eight treatment modalities were analyzed. The median TTNT for single- or multiagent chemotherapy was only 3.9 months (95% confidence interval [CI] 3.2-5.1), with few durable remissions. α-interferon gave a median TTNT of 8.7 months (95% CI 6.0-18.0), and histone deacetylase inhibitors (HDACi) gave a median TTNT of 4.5 months (95% CI 4.0-6.1). When compared directly with chemotherapy, interferon and HDACi both had greater TTNT (P < .00001 and P = .01, respectively). This study confirms that all chemotherapy regimens assessed have very modest efficacy; we recommend their use be restricted until other options are exhausted.

Health-related quality of life in patients with high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study.

BACKGROUND: Temozolomide chemotherapy versus radiotherapy in patients with a high-risk low-grade glioma has been shown to have no significant effect on progression-free survival. If these treatments have a different effect on health-related quality of life (HRQOL), it might affect the choice of therapy. We postulated that temozolomide compromises HRQOL and global cognitive functioning to a lesser extent than does radiotherapy. METHODS: We did a prospective, phase 3, randomised controlled trial at 78 medical centres and large hospitals in 19 countries. We enrolled adult patients (aged ≥18 years) with histologically confirmed diffuse (WHO grade II) astrocytoma, oligodendroglioma, or mixed oligoastrocytoma, with a WHO performance status of 2 or lower, without previous chemotherapy or radiotherapy, who needed active treatment other than surgery. We randomly assigned eligible patients (1:1) using a minimisation technique, stratified by WHO performance status (0-1 vs 2), age (<40 years vs ≥40 years), presence of contrast enhancement on MRI, chromosome 1p status (deleted vs non-deleted vs indeterminate), and the treating medical centre, to receive either radiotherapy (50·4 Gy in 28 fractions of 1·8 Gy for 5 days per week up to 6·5 weeks) or temozolomide chemotherapy (75 mg/m2 daily, for 21 of 28 days [one cycle] for 12 cycles). The primary endpoint was progression-free survival (results published separately); here, we report the results for two key secondary endpoints: HRQOL (assessed using the European Organisation for Research and Treatment of Cancer's [EORTC] QLQ-C30 [version 3] and the EORTC Brain Cancer Module [QLQ-BN20]) and global cognitive functioning (assessed using the Mini-Mental State Examination [MMSE]). We did analyses on the intention-to-treat population. This study is closed and is registered at EudraCT, number 2004-002714-11, and at ClinicalTrials.gov, number NCT00182819. FINDINGS: Between Dec 6, 2005, and Dec 21, 2012, we randomly assigned 477 eligible patients to either radiotherapy (n=240) or temozolomide chemotherapy (n=237). The difference in HRQOL between the two treatment groups was not significant during the 36 months' follow-up (mean between group difference [averaged over all timepoints] 0·06, 95% CI -4·64 to 4·75, p=0·98). At baseline, 32 (13%) of 239 patients who received radiotherapy and 32 (14%) of 236 patients who received temozolomide chemotherapy had impaired cognitive function, according to the MMSE scores. After randomisation, five (8%) of 63 patients who received radiotherapy and three (6%) of 54 patients who received temozolomide chemotherapy and who could be followed up for 36 months had impaired cognitive function, according to the MMSE scores. No significant difference was recorded between the groups for the change in MMSE scores during the 36 months of follow-up. INTERPRETATION: The effect of temozolomide chemotherapy or radiotherapy on HRQOL or global cognitive functioning did not differ in patients with low-grade glioma. These results do not support the choice of temozolomide alone over radiotherapy alone in patients with high-risk low-grade glioma. FUNDING: Merck Sharp & Dohme-Merck & Co, National Cancer Institute, Swiss Cancer League, National Institute for Health Research, Cancer Research UK, Canadian Cancer Society Research Institute, National Health and Medical Research Council, European Organisation for Research and Treatment of Cancer Cancer Research Fund.

Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study.

BACKGROUND: Outcome of low-grade glioma (WHO grade II) is highly variable, reflecting molecular heterogeneity of the disease. We compared two different, single-modality treatment strategies of standard radiotherapy versus primary temozolomide chemotherapy in patients with low-grade glioma, and assessed progression-free survival outcomes and identified predictive molecular factors. METHODS: For this randomised, open-label, phase 3 intergroup study (EORTC 22033-26033), undertaken in 78 clinical centres in 19 countries, we included patients aged 18 years or older who had a low-grade (WHO grade II) glioma (astrocytoma, oligoastrocytoma, or oligodendroglioma) with at least one high-risk feature (aged >40 years, progressive disease, tumour size >5 cm, tumour crossing the midline, or neurological symptoms), and without known HIV infection, chronic hepatitis B or C virus infection, or any condition that could interfere with oral drug administration. Eligible patients were randomly assigned (1:1) to receive either conformal radiotherapy (up to 50·4 Gy; 28 doses of 1·8 Gy once daily, 5 days per week for up to 6·5 weeks) or dose-dense oral temozolomide (75 mg/m2 once daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles). Random treatment allocation was done online by a minimisation technique with prospective stratification by institution, 1p deletion (absent vs present vs undetermined), contrast enhancement (yes vs no), age (<40 vs ≥40 years), and WHO performance status (0 vs ≥1). Patients, treating physicians, and researchers were aware of the assigned intervention. A planned analysis was done after 216 progression events occurred. Our primary clinical endpoint was progression-free survival, analysed by intention-to-treat; secondary outcomes were overall survival, adverse events, neurocognitive function (will be reported separately), health-related quality of life and neurological function (reported separately), and correlative analyses of progression-free survival by molecular markers (1p/19q co-deletion, MGMT promoter methylation status, and IDH1/IDH2 mutations). This trial is closed to accrual but continuing for follow-up, and is registered at the European Trials Registry, EudraCT 2004-002714-11, and at ClinicalTrials.gov, NCT00182819. FINDINGS: Between Sept 23, 2005, and March 26, 2010, 707 patients were registered for the study. Between Dec 6, 2005, and Dec 21, 2012, we randomly assigned 477 patients to receive either radiotherapy (n=240) or temozolomide chemotherapy (n=237). At a median follow-up of 48 months (IQR 31-56), median progression-free survival was 39 months (95% CI 35-44) in the temozolomide group and 46 months (40-56) in the radiotherapy group (unadjusted hazard ratio [HR] 1·16, 95% CI 0·9-1·5, p=0·22). Median overall survival has not been reached. Exploratory analyses in 318 molecularly-defined patients confirmed the significantly different prognosis for progression-free survival in the three recently defined molecular low-grade glioma subgroups (IDHmt, with or without 1p/19q co-deletion [IDHmt/codel], or IDH wild type [IDHwt]; p=0·013). Patients with IDHmt/non-codel tumours treated with radiotherapy had a longer progression-free survival than those treated with temozolomide (HR 1·86 [95% CI 1·21-2·87], log-rank p=0·0043), whereas there were no significant treatment-dependent differences in progression-free survival for patients with IDHmt/codel and IDHwt tumours. Grade 3-4 haematological adverse events occurred in 32 (14%) of 236 patients treated with temozolomide and in one (<1%) of 228 patients treated with radiotherapy, and grade 3-4 infections occurred in eight (3%) of 236 patients treated with temozolomide and in two (1%) of 228 patients treated with radiotherapy. Moderate to severe fatigue was recorded in eight (3%) patients in the radiotherapy group (grade 2) and 16 (7%) in the temozolomide group. 119 (25%) of all 477 patients had died at database lock. Four patients died due to treatment-related causes: two in the temozolomide group and two in the radiotherapy group. INTERPRETATION: Overall, there was no significant difference in progression-free survival in patients with low-grade glioma when treated with either radiotherapy alone or temozolomide chemotherapy alone. Further data maturation is needed for overall survival analyses and evaluation of the full predictive effects of different molecular subtypes for future individualised treatment choices. FUNDING: Merck Sharpe & Dohme-Merck & Co, Canadian Cancer Society, Swiss Cancer League, UK National Institutes of Health, Australian National Health and Medical Research Council, US National Cancer Institute, European Organisation for Research and Treatment of Cancer Cancer Research Fund.

A transesophageal echocardiography examination clarifies the cause of cardiovascular collapse during scoliosis surgery in a child.

PURPOSE: The prone position is required for posterior spinal fusion surgery and may be associated with cardiovascular changes, including a decrease in venous return and cardiac index. We report a case of a patient who developed cardiovascular collapse, increased central venous pressure (CVP), and massive bleeding during posterior spinal fusion surgery. A transesophageal echocardiography examination (TEE) documented a right ventricular outflow tract (RVOT) obstruction associated with the use of transverse bolsters. CLINICAL FEATURES: We describe a case of a healthy 14-yr-old male with idiopathic scoliosis who developed severe intraoperative cardiovascular instability and massive bleeding. The surgery was suspended, and the patient was transferred to the intensive care unit. The patient subsequently underwent TEE in the supine and prone positions. The echocardiogram appeared normal in the supine position; however, in the prone position with transverse bolsters, we identified a significant decrease in the diameter of the RVOT that worsened with pressure applied against the thoracic spine. The central venous pressure increased from 10-24 mmHg simultaneously. We found appreciably less impact to the RVOT, RV size and flow, and CVP (10 to 14 mmHg) using longitudinal bolsters both with and without pressure to the back. This position was recommended for the patient's reoperation, which was uneventful. CONCLUSION: A TEE confirmed a RVOT obstruction in the prone position that was associated, in this case, with the use of transverse bolsters. The RVOT obstruction was explained by the chest deformity, compliant chest cage, bolstering, and pressure applied to the patient's back by the surgeon. This positional RVOT obstruction may explain the increase in the CVP and the secondary massive bleeding during the first operation. The TEE was useful to diagnose the patient's condition and to guide his positioning for the second operation.

Long-term outcomes of patients with advanced-stage cutaneous T-cell lymphoma and large cell transformation.

Although mycosis fungoides (MF) is typically an indolent disease, patients with advanced-stage disease (stages IIB-IVB), including Sézary syndrome (SS), often have a poor outcome. A 31-year, retrospective analysis of our cutaneous lymphoma database, of 297 patients with MF and SS, was undertaken to study long-term outcomes and identify clinical predictors of outcome in patients with advanced-stage disease (ASD, n = 92) and large cell transformation (LCT, n = 22). Two-thirds of patients with ASD presented with de novo ASD. The median overall survival (OS) for ASD was 5 years with a 10-year predicted OS of 32%. Age at initial diagnosis (P = .01), tumor stage (P = .01), and clinical stage (P = .001) were found to be significant predictors of outcome. Patients who presented with de novo ASD demonstrated better outcomes that were not statistically significant than those with a prior diagnosis of early-stage MF (P = .25). Transformation developed in 22 of the 297 MF/SS patients (7.4%), with a transformation rate of only 1.4% in patients with early-stage disease, compared with stage IIB (27%) and stage IV (56%-67%) disease. The median OS from diagnosis of LCT was 2 years. We confirm that the incidence of LCT is strongly dependent on tumor stage at diagnosis, and we demonstrate a much lower overall risk of LCT than previously reported.

Durable Complete Remission and Long-Term Survival in FDG-PET Staged Patients with Stage III Follicular Lymphoma, Treated with Wide-Field Radiation Therapy.

Advanced-stage follicular lymphoma (FL) is generally considered incurable with conventional systemic therapies, but historic series describe long-term disease-free survival in stage III disease treated with wide-field radiation therapy (WFRT), encompassing all known disease sites. We report outcomes for patients staged with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and treated with CT-planned WFRT, given as either comprehensive lymphatic irradiation (CLI) or total nodal irradiation (TNI). This analysis of a prospective cohort includes PET-staged patients given curative-intent WFRT as a component of initial therapy, or as sole treatment for stage III FL. Thirty-three PET-staged patients with stage III FL received WFRT to 24-30Gy between 1999 and 2017. Fifteen patients also received planned systemic therapy (containing rituximab in 11 cases) as part of their primary treatment. At 10 years, overall survival and freedom from progression (FFP) were 100% and 75%, respectively. None of the 11 rituximab-treated patients have relapsed. Nine relapses occurred; seven patients required treatment, and all responded to salvage therapies. A single death occurred at 16 years. The principal acute toxicity was transient hematologic; one patient had residual grade two toxicity at one year. With FDG-PET staging, most patients with stage III FL experience prolonged FFP after WFRT, especially when combined with rituximab.

Mantle cell lymphoma with central nervous system involvement: frequency and clinical features.

Reported rates of central nervous system (CNS) involvement in mantle cell lymphoma (MCL) are highly variable but substantial (4-26%). Data is lacking regarding risk factors for CNS relapse, and for those patients in whom CNS prophylaxis could be beneficial. We present single institution retrospective analysis of data of baseline features, clinical course, rate of CNS disease and putative risk factors in 62 patients with MCL (18 female, 44 male). CNS disease (all cases were symptomatic) occurred in four patients at a median of 12 months (range 1-58) from diagnosis, with a crude incidence of 6.5% and 5-year actuarial incidence of 5 +/- 3%. Two cases had blastic MCL at diagnosis. Survival after CNS relapse ranged from 2-9 months. Patients who developed CNS disease had a significantly shorter survival from diagnosis than those who did not (P = 0.0024). Symptomatic CNS disease in patients with MCL either at presentation or relapse is an uncommon but devastating complication. In younger patients, more aggressive immuno-chemotherapy regimens containing CNS-penetrating agents may reduce the incidence of CNS disease. While not routinely justified for all patients, CNS prophylaxis may particularly benefit patients with blastic histology at diagnosis, or those with systemic relapse after first-line treatment.

Histone deacetylase inhibitor panobinostat induces clinical responses with associated alterations in gene expression profiles in cutaneous T-cell lymphoma.

PURPOSE: Histone deacetylase inhibitors can alter gene expression and mediate diverse antitumor activities. Herein, we report the safety and activity of the histone deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma (CTCL) and identify genes commonly regulated by panobinostat. EXPERIMENTAL DESIGN: Panobinostat was administered orally to patients with CTCL on Monday, Wednesday, and Friday of each week on a 28-day cycle. A dose of 30 mg was considered excessively toxic, and subsequent patients were treated at the expanded maximum tolerated dose of 20 mg. Biopsies from six patients taken 0, 4, 8, and 24 h after administration were subjected to microarray gene expression profiling and real-time quantitative PCR of selected genes. RESULTS: Patients attained a complete response (n = 2), attained a partial response (n = 4), achieved stable disease with ongoing improvement (n = 1), and progressed on treatment (n = 2). Microarray data showed distinct gene expression response profiles over time following panobinostat treatment, with the majority of genes being repressed. Twenty-three genes were commonly regulated by panobinostat in all patients tested. CONCLUSIONS: Panobinostat is well tolerated and induces clinical responses in CTCL patients. Microarray analyses of tumor samples indicate that panobinostat induces rapid changes in gene expression, and surprisingly more genes are repressed than are activated. A unique set of genes that can mediate biological responses such as apoptosis, immune regulation, and angiogenesis were commonly regulated in response to panobinostat. These genes are potential molecular biomarkers for panobinostat activity and are strong candidates for the future assessment of their functional role(s) in mediating the antitumor responses of panobinostat.

Lack of Durable Remission with Conventional-Dose Total Skin Electron Therapy for the Management of Sezary Syndrome and Multiply Relapsed Mycosis Fungoides.

Mycosis fungoides (MF) and Sezary syndrome (SS) are multi-relapsing, morbid, cutaneous T-cell lymphomas. Optimal treatment sequencing remains undefined. Total skin electron therapy (TSE) is a highly technical, skin-directed treatment, uniquely producing symptom-free and treatment-free intervals. Recent publications favour low-dose TSE for reduced toxicity, but early data support conventional-dose TSE (cdTSE) for longer disease control. Patient selection requires weighing-up tolerability against response durability. We investigated duration of benefit from cdTSE in patients with poorer prognosis diseases: SS and heavily pre-treated MF. Endpoints were overall survival, and "time to next treatment" (TTNT) as surrogate for clinical benefit duration. Seventy patients (53 MF, 17 SS) were eligible: median prior treatments, 4; median cdTSE dose, 30 Gy; median follow-up, 5.8 years. SS patients had worse prognosis (HR = 5.0, p < 0.001) and shorter TTNT (HR = 4.5, p < 0.001) than MF patients; median TTNT was only 3.7 months. Heavily pre-treated MF patients had inferior prognosis (HR = 1.19 per additional line, p = 0.005), and shorter TTNT (HR = 1.13 per additional line, p = 0.031). Median TTNT for MF patients with ≥3 prior treatments was 7.1 months, versus 23.2 months for 0-2 prior treatments. In conclusion, cdTSE has a limited role in SS. TTNT is reduced in heavily pre-treated MF patients, suggesting greater benefit when utilized earlier in treatment sequencing.

Extracorporeal photopheresis for the treatment of Sézary syndrome using a novel treatment protocol.

Various studies have reported that extracorporeal photopheresis is effective in producing meaningful responses in patients with Sézary syndrome. A single-center, 5-year retrospective analysis was performed on our patients with Sézary syndrome who received extracorporeal photopheresis using a novel protocol. Thirteen patients were treated with extracorporeal photopheresis consistently for a minimum of 2 months. All patients received a modified protocol of one treatment per week for 6 sessions, one session every 2 weeks for 6 sessions, and then one session per month. The overall response rate was 62%: two patients achieved a complete response and 6 patients achieved a partial response. The median time to response was 10 months. The 2- and 4-year predicted overall survivals were 82%. This study was limited by its retrospective nature and small sample size. Response and survival compare favorably with those of previous studies. Our modified treatment protocol appears to produce outcomes similar to the two-day protocol.

Risk factors for the perpetration of child sexual abuse: a review and meta-analysis.

OBJECTIVES: Since the late 1980s, there has been a strong theoretical focus on psychological and social influences of perpetration of child sexual abuse. This paper presents the results of a review and meta-analysis of studies examining risk factors for perpetration of child sexual abuse published since 1990. METHOD: Eighty-nine studies published between 1990 and April of 2003 were reviewed. Risk factors were classified into one of the following six broad categories: family factors, externalizing behaviors, internalizing behaviors, social deficits, sexual problems, and attitudes/beliefs. Sex offenders against children (SOC) were compared to three comparison groups identified within the 89 studies: sex offenders who perpetrated against adults (SOA), non-sex offenders, and non-offenders with no history of criminal or sexual behavior problems. RESULTS: Results for the six major categories showed that SOC were not different from SOA (all d between -.02 and .14) other than showing lower externalizing behaviors (d=-.25). Sex offenders against children were somewhat different from non-sex offenders, especially with regard to sexual problems and attitudes (d=.83 and .51). Sex offenders against children showed substantial differences from non-offenders with medium sized effects in all six major categories (d's range from .39 to .58). CONCLUSION: Child sex offenders are different from non-sex offenders and non-offenders but not from sex offenders against adults. PRACTICE IMPLICATIONS: This study suggests that the presence of general risk factors may lead to a variety of negative behavioral outcomes, including the perpetration of child sexual offending. Family factors were strongly related to the perpetration of child sex offending (vs. non-sexual offending or non-offending) and may be valuable intervention points for interrupting the development of child sex offending, as well as other negative behaviors. Other potential points for intervention may focus on the development of appropriate social and emotional skills that contribute to sexual offending.

Primary non-Hodgkin's lymphoma of the breast: retrospective analysis of prognosis and patterns of failure in two Australian centers.

The breast is an uncommon site of presentation for primary non-Hodgkin's lymphoma, with prognosis and patterns of relapse still not clearly defined. A retrospective analysis of 21 patients presenting to 2 Australian centers during a 20-year period is presented. All patients were women and had a median age of 62 years. Fifteen patients (71%) had localized disease (12 unilateral and 3 bilateral), and 6 (29%) had regional lymph-node involvement. Histology was predominantly intermediate grade, with diffuse large B-cell lymphoma (DLBL) in 16 cases (76%). The most common treatment program was partial mastectomy followed by chemotherapy and radiation therapy (n = 12). Complete response (CR) to treatment was exhibited in 19 patients (90%), 11 of whom subsequently experienced relapse. Including the 2 patients who failed to exhibit an initial CR, the median time to disease progression was 23.4 months (range, 0-143 months), with a 5-year disease-free survival rate of 38% (+/- 12%). The actuarial median survival of all patients was 3.8 years, with bilateral breast involvement at presentation the only significant prognostic factor. The contralateral breast was the site of initial relapse in 3 patients (17%), all of whom subsequently died of disease. The actuarial rate of central nervous system (CNS) recurrence at 8 years was 39% (+/- 14%), occurring only in patients with diffuse large-cell histology. Our analysis suggests that DLBL presenting in the breast has a poor prognosis and characteristic patterns of failure. Targeted strategies such as CNS prophylaxis and contralateral breast irradiation might therefore improve prognosis and should be prospectively studied.

Long-term follow-up of salvage radiotherapy in Hodgkin's lymphoma after chemotherapy failure.

PURPOSE: To evaluate the long-term results of salvage radiotherapy (SRT) for Hodgkin's lymphoma after chemotherapy failure. METHODS AND MATERIALS: We reviewed 81 patients undergoing SRT for persistent or recurrent Hodgkin's lymphoma after chemotherapy; 19 also received conventional-dose salvage chemotherapy. RESULTS: At SRT, the median patient age was 31 years. Of the 81 patients, 81% had Stage I-II, 25.9% had B symptoms, 14.8% had bulky disease, and 7.4% had extranodal disease. A less than a complete response (CR) to the last chemotherapy regimen occurred in 47%. SRT was generally limited to one side of the diaphragm, and the median dose was 36 Gy. After SRT, 75% of patients achieved a CR, with 82% retaining durable in-field control. In-field failure was associated with less than a CR to the last chemotherapy regimen (p = 0.0287). Most failures were at distant sites, with 60% in previously involved sites. The 10-year freedom from treatment failure and overall survival rates were 32.8% and 45.7%, respectively. The adverse prognostic factors for freedom from treatment failure were age >50 years (p < 0.001), B symptoms (p < 0.001), extranodal disease (p = 0.012), and less than a CR to the last chemotherapy regimen (p = 0.001). The adverse prognostic factors for overall survival were male gender (p = 0.034), age >50 years (p < 0.001), B symptoms (p = 0.002), and less than a CR to the last chemotherapy regimen (p = 0.002). Favorable cohorts had a 10-year freedom from treatment failure rate of 51% and overall survival rate of 92%. CONCLUSIONS: Salvage radiotherapy is effective for selected patients with Hodgkin's lymphoma after chemotherapy failure and should be considered for incorporation into salvage programs.

Preventing violence and trauma in the next generation.

Research in recent times has clearly demonstrated that violence is predictable and preventable; however, the primary prevention of abusive and violent behavior will not occur without personal, interpersonal, and social change. This article reviews the empirical research supporting hypotheses for primary prevention of many risks associated with children becoming abusive.

Fluorine-18 fluorodeoxyglucose positron emission tomography, gallium-67 scintigraphy, and conventional staging for Hodgkin's disease and non-Hodgkin's lymphoma.

PURPOSE: To compare fluorine-18 fluorodeoxyglucose positron emission tomography (PET) and gallium scanning with each other and with conventional staging, for patients with Hodgkin's disease or non-Hodgkin's lymphoma. SUBJECTS AND METHODS: Fifty patients had PET, gallium scanning, and conventional staging of newly diagnosed or progressive Hodgkin's disease or non-Hodgkin's lymphoma. Disease sites, stage, and treatment plans were assessed retrospectively. RESULTS: Positron emission tomography and gallium scanning each upstaged 14% of patients (n = 7). Management was altered by PET in 9 cases (18%) and by gallium scanning in 7 (14%, P = 0.6). Disease was evident in 117 sites in 42 patients. The case positivity rate for conventional assessment was 90%; for PET, 95%; for gallium scanning, 88%; for conventional assessment plus PET, 100%; and for conventional assessment plus gallium scanning, 98%. Site positivity rates for conventional assessment were 68%; for PET, 82%; for gallium scanning, 69% (conventional vs. PET, P = 0.01; conventional vs. gallium scanning, P = 0.9; PET vs. gallium scanning, P = 0.01); for conventional assessment plus PET, 96%; and for conventional assessment plus gallium scanning, 94%. Positron emission tomography and gallium scanning were entirely concordant in 31 patients; in the other 19 patients, PET identified 25 sites missed by gallium scanning, whereas gallium scanning identified 10 sites missed by PET. CONCLUSION: In this retrospective study, PET demonstrated a higher site positivity rate than did gallium scanning, with similar case positivity rates. These data support the use of PET in place of gallium scanning for the staging of patients with Hodgkin's disease or non-Hodgkin's lymphoma.

A randomised phase III study of palliative radiation with concomitant carboplatin for brain metastases from non-small cell carcinoma of the lung.

PURPOSE: To determine if the addition of carboplatin chemotherapy to whole brain irradiation improves response and survival in patients with brain metastases from non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-two patients with brain metastases from NSCLC and performance status ECOG 0-2 were randomised to receive either whole brain radiotherapy (WBRT) alone (20Gy in five fractions) or the same radiotherapy plus concomitant carboplatin (70 mg/m(2) intravenously for 5 days). RESULTS: The median survival was 4.4 months in the radiotherapy alone (RT) arm and 3.7 months in the combined treatment (RTC) arm (P = 0.64). The objective response rates of 10% on the RT arm and 29% on the RTC arm were not significantly different (P = 0.24). The trial was closed early because of poor accrual. CONCLUSIONS: Although no firm conclusions can be made regarding the efficacy of the combined treatment, this prospective study highlights the poor objective response rates and relatively poor symptom control despite standard treatment of brain metastases from NSCLC.

Cutaneous lymphomas: which pathological classification?

Cutaneous lymphomas are rare and although some are a manifestation of systemic lymphoma, the majority arise primarily from the skin. These primary cutaneous lymphomas comprise predominantly T cell subtypes and represent a wide spectrum of disorders. Pathologists can currently choose to label these conditions according to three classifications (REAL, EORTC or WHO) but each has shortcomings. Nonetheless, in an attempt to unify the field, we would recommend that pathologists make every attempt to categorise these conditions according to the WHO classification. This classification can encompass all the conditions and aligns the cutaneous lymphomas with the broader systemic lymphoproliferative conditions.