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CD30 is overexpressed in several lymphoma types, including classic Hodgkin lymphoma (cHL), some peripheral T-cell lymphomas (PTCL), and some cutaneous T-cell lymphomas. The antibody–drug conjugate brentuximab vedotin targets CD30-positive cells and has been evaluated for the treatment of various lymphoma entities. This narrative review summarizes 10 years of experience with brentuximab vedotin for the treatment of CD30-positive lymphomas, discusses novel therapies targeting CD30 in development, and highlights remaining controversies relating to CD30-targeted therapy across lymphoma types. The collective body of evidence for brentuximab vedotin demonstrates that exploitation of CD30 can provide sustained benefits across a range of different CD30-positive lymphomas, in both clinical trials and real-world settings. Preliminary experience with brentuximab vedotin in combination with immune checkpoint inhibitors for relapsed/refractory cHL is encouraging, but further exploration is required. The optimal use of brentuximab vedotin for first-line therapy of PTCL remains to be determined. Further research is required on brentuximab vedotin treatment in high-risk patient populations, and in rare lymphoma subtypes, for which no standard of care exists. Novel therapies targeting CD30 include chimeric antigen receptor therapies and bispecific antibody T-cell engagers, which may be expected to further improve outcomes for patients with CD30-positive lymphomas in the coming years. [ABSTRACT FROM AUTHOR]

Background: Patients with relapsed or refractory B-cell non-Hodgkin lymphoma have few treatment options. We aimed to establish the safety and recommended phase 2 dose of epcoritamab, a novel bispecific antibody that targets CD3 and CD20 and induces T-cell-mediated cytotoxic activity against CD20+ malignant B cells.Methods: For the dose-escalation part of this phase 1/2 study, we enrolled adults (aged ≥18 years) with relapsed or refractory CD20+ B-cell non-Hodgkin lymphoma at ten sites across four countries (Denmark, the Netherlands, the UK, and Spain). Eligible patients received priming and intermediate doses followed by full doses of subcutaneous epcoritamab administered in 28-day cycles; each subsequent cohort involved escalation of the priming, intermediate, or full dose (0·0128-60 mg). The primary objectives were to determine the maximum tolerated dose and the recommended phase 2 dose. Safety, antitumour activity, pharmacokinetics, and immune biomarkers were also assessed. This study is registered with ClinicalTrials.gov, NCT03625037, with the dose-expansion part ongoing.Findings: Between June 26, 2018, and July 14, 2020, we enrolled 73 patients with relapsed, progressive, or refractory CD20+ mature B-cell non-Hodgkin lymphoma. 68 patients received escalating full doses (0·0128-60 mg) of subcutaneous epcoritamab. No dose-limiting toxic effects were observed, and the maximum tolerated dose was not reached; the full dose of 48 mg was identified as the recommended phase 2 dose. All 68 patients received at least one dose of epcoritamab and were included in safety analyses: common adverse events were pyrexia (47 patients [69%]), primarily associated with cytokine release syndrome (CRS; 40 [59%], all grade 1-2), and injection site reactions (32 [47%]; 31 grade 1). There were no grade 3 or higher CRS events. No discontinuations occurred due to treatment-related adverse events or treatment-related deaths. Overall response rate in patients with relapsed or refractory diffuse large B-cell lymphoma was 68% (95% CI 45-86), with 45% achieving a complete response at full doses of 12-60 mg. At 48 mg, the overall response rate was 88% (47-100), with 38% achieving a complete response. Patients with relapsed or refractory follicular lymphoma had an overall response rate of 90% (55-100), with 50% achieving a complete response at full doses of 0·76-48 mg. Epcoritamab induced robust and sustained B-cell depletion, and CD4+ and CD8+ T-cell activation and expansion, with modest increases in cytokine levels.Interpretation: Single-agent subcutaneous epcoritamab for treatment of patients with relapsed or refractory B-cell non-Hodgkin lymphoma merits investigation in ongoing phase 2 and phase 3 studies.Funding: Genmab and AbbVie. [ABSTRACT FROM AUTHOR]

The use of routine imaging for patients with classical Hodgkin lymphoma ( HL) in complete remission ( CR) is controversial. In a population-based study, we examined the post-remission survival of Danish and Swedish HL patients for whom follow-up practices were different. Follow-up in Denmark included routine imaging, usually for a minimum of 2 years, whereas clinical follow-up without routine imaging was standard in Sweden. A total of 317 Danish and 454 Swedish comparable HL patients aged 18-65 years, diagnosed in the period 2007-2012 and having achieved CR following ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)/ BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) therapy, were included in the study. The cumulative progression rates in the first 2 years were 4% (95% confidence interval [ CI] 1-7) for patients with stage I-II disease vs. 12% (95% CI 6-18) for patients with stage III-IV disease. An imaging-based follow-up practice was not associated with a better post-remission survival in general ( P = 0·2) or in stage-specific subgroups ( P = 0·5 for I-II and P = 0·4 for III-IV). Age ≥45 years was the only independent adverse prognostic factor for survival. In conclusion, relapse of HL patients with CR is infrequent and systematic use of routine imaging in these patients does not improve post-remission survival. The present study supports clinical follow-up without routine imaging, as encouraged by the recent Lugano classification. [ABSTRACT FROM AUTHOR]

18F-Fluorodeoxyglucose positron emission tomography/ computed tomography (PET/CT) is a highly accurate staging method in classical Hodgkin lymphoma (cHL). We retrospectively compared the staging results obtained in two large cohorts of patients with cHL diagnosed before ( n = 324) and after ( n = 406) the introduction of PET/CT staging in a retrospective study. In PET/CT staged patients, stage I disease was less frequent (16% vs. 27%, p < 0.001) while stage IV disease was more frequent (17% vs. 10%, p = 0.02). Imaging-detected skeletal involvement was recognized more often in PET/CT staged patients (17% vs. 2%, p < 0.001), and the presence of focal skeletal PET/CT lesions was associated with higher risk of progression (hazard ratio [HR] 1.96, 95% confidence interval [CI]: 1.14-3.36). The German Hodgkin Study Group (GHSG) risk classification (early, intermediate, advanced disease) predicted outcome in PET/CT staged patients. In conclusion, PET/CT led to higher disease stages, and the more frequently diagnosed skeletal lesions may be an adverse prognostic factor. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET)/computerised tomography (CT) has proved useful in a number of haematological malignancies, particularly in Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphomas (NHL). It is recommended in the staging of HL and aggressive NHL, it has been shown to be prognostically important early during treatment, and it has been incorporated in the response criteria. However, treatment modification based on early scans is still experimental, and routine use in follow up cannot be recommended. The use of PET/CT in other lymphoma types and other haematological malignancies is still under evaluation. [ABSTRACT FROM AUTHOR]

Positron emission tomography using [18F]-fluoro-2-deoxy-d-glucose (FDG-PET) is an important tool for staging and treatment response assessment in malignant lymphomas. In Hodgkin lymphoma (HL), FDG-PET precisely predicts the therapy response when performed very early during standard ABVD chemotherapy. However, it is unclear whether FDG-PET retains this role if therapy is changed as a consequence of the scan, or if performed during a more intensive chemotherapy regimen such as BEACOPPesc, which is used for HL. This brief review presents the up-to-date evidence for the use and interpretation of early interim FDG-PET in HL, including recent preliminary results on early interim FDG-PET during BEACOPPesc therapy. [ABSTRACT FROM AUTHOR]

Background: Early-stage Hodgkin lymphoma (HL) has excellent survival rates but carries a high risk of late treatment-related adverse effects. Modern, individualised therapeutic strategies require an accurate determination of the extent of the disease. This study investigated the potential impact of 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computerised tomogrpahy (FDG-PET/CT) in the planning of involved field radiotherapy (IFRT). Patients and methods: Thirty patients received staging FDG-PET/CT before therapy, and IFRT after a short course of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy. IFRT planning was performed using only the CT data from the FDG-PET/CT scan. Later, the IFRT planning was performed anew using the FDG-PET/CT data as basis for contouring. Results: In 20 out of 30 patients, the radiotherapy (RT) course was unaffected by the addition of FDG-PET/CT. FDG-PET/CT would have increased the irradiated volume in seven patients where the volume receiving a minimum of 90% of the target dose was increased by 8–87%. FDG-PET/CT decreased the volume in two patients where the volume was reduced by 18% and 30%. Conclusions: When used for RT planning, FDG-PET/CT results in larger IFRT treatment volumes. If FDG-PET/CT is introduced to RT planning, the method should be accompanied by a change in RT treatment strategy, aiming at more targeted therapy in order to best avoid radiation to normal tissues. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) is a molecular functional imaging technique that provides qualitative and quantitative information about the localization and activity of pathophysiological processes. The most commonly used tracer for oncological purposes is 2-[18F]fluoro-2-deoxy-d-glucose (FDG). FDG-PET has within recent years become the most important nuclear medicine imaging modality in the management of lymphoma. This review summarizes the data published so far concerning the value of FDG-PET in staging, treatment monitoring, therapy planning, and follow-up of Hodgkin lymphoma (HL). FDG-PET detects more disease sites and involved organs than conventional staging procedures including computerized tomography (CT) and has a large influence on staging. FDG-PET during and after therapy appears to provide considerable prognostic information. However, the impact on patient outcome is not clear since no controlled trials are conducted and follow-up periods are generally short. The value of dual-modality PET/CT and its potential role in the radiotherapy planning is discussed. [Copyright &y& Elsevier]

Summary The documented treatment‐induced excess mortality in Hodgkin lymphoma (HL) has spurred important treatment changes over recent decades. This study aimed to examine mortality among young HL patients treated with contemporary strategies, including historical data comparison. This nationwide study included 1348 HL patients, diagnosed in 1995–2015 and aged 15–40 at diagnosis. Among the patients, 66.5% had Ann Arbor stage I–II and 33.5% had stage III–IV disease. With a median follow‐up of 14.76 years, 139 deaths occurred, yielding a 5‐year overall survival of 94.6%. Older age, advanced disease, earlier treatment periods and extensive regimens were associated with higher overall mortality risk. The cumulative risk of HL‐related death showed an initial sharp rise, with a plateau at 5.3% 10‐year post‐diagnosis. Deaths due to cardiovascular or pulmonary diseases and second cancers initially had minimal risk, gradually reaching 1.2% and 2.0% at the 20‐year mark respectively. HL cases had a 7.5‐fold higher mortality hazard than the background population. This study suggests that contemporary HL treatment still poses excess mortality risk, but recent changes have notably reduced overall and cause‐specific mortality compared to earlier eras. Balancing treatment efficacy and toxicity remains crucial, but our findings highlight improved outcomes with modern treatment approaches. [ABSTRACT FROM AUTHOR]

Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT. The open-label, randomised, three-arm, parallel-group, superiority TRIANGLE trial was performed in 165 secondary or tertiary clinical centres in 13 European countries and Israel. Patients with previously untreated, stage II–IV mantle cell lymphoma, aged 18–65 years and suitable for ASCT were randomly assigned 1:1:1 to control group A or experimental groups A+I or I, stratified by study group and mantle cell lymphoma international prognostic index risk groups. Treatment in group A consisted of six alternating cycles of R-CHOP (intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous cyclophosphamide 750 mg/m2 on day 1, intravenous doxorubicin 50 mg/m2 on day 1, intravenous vincristine 1·4 mg/m2 on day 1, and oral prednisone 100 mg on days 1–5) and R-DHAP (or R-DHAOx, intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1–4, intravenous cytarabine 2 × 2 g/m2 for 3 h every 12 h on day 2, and intravenous cisplatin 100 mg/m2 over 24 h on day 1 or alternatively intravenous oxaliplatin 130 mg/m2 on day 1) followed by ASCT. In group A+I, ibrutinib (560 mg orally each day) was added on days 1–19 of R-CHOP cycles and as fixed-duration maintenance (560 mg orally each day for 2 years) after ASCT. In group I, ibrutinib was given the same way as in group A+I, but ASCT was omitted. Three pairwise one-sided log-rank tests for the primary outcome of failure-free survival were statistically monitored. The primary analysis was done by intention-to-treat. Adverse events were evaluated by treatment period among patients who started the respective treatment. This ongoing trial is registered with ClinicalTrials.gov , NCT02858258. Between July 29, 2016 and Dec 28, 2020, 870 patients (662 men, 208 women) were randomly assigned to group A (n=288), group A+I (n=292), and group I (n=290). After 31 months median follow-up, group A+I was superior to group A with 3-year failure-free survival of 88% (95% CI 84–92) versus 72% (67–79; hazard ratio 0·52 [one-sided 98·3% CI 0–0·86]; one-sided p=0·0008). Superiority of group A over group I was not shown with 3-year failure-free survival 72% (67–79) versus 86% (82–91; hazard ratio 1·77 [one-sided 98·3% CI 0–3·76]; one-sided p=0·9979). The comparison of group A+I versus group I is ongoing. There were no relevant differences in grade 3–5 adverse events during induction or ASCT between patients treated with R-CHOP/R-DHAP or ibrutinib combined with R-CHOP/R-DHAP. During maintenance or follow-up, substantially more grade 3–5 haematological adverse events and infections were reported after ASCT plus ibrutinib (group A+I; haematological: 114 [50%] of 231 patients; infections: 58 [25%] of 231; fatal infections: two [1%] of 231) compared with ibrutinib only (group I; haematological: 74 [28%] of 269; infections: 52 [19%] of 269; fatal infections: two [1%] of 269) or after ASCT (group A; haematological: 51 [21%] of 238; infections: 32 [13%] of 238; fatal infections: three [1%] of 238). Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined. Janssen and Leukemia & Lymphoma Society. [ABSTRACT FROM AUTHOR]

The article focuses on the Hodgkin lymphoma (HL) disease. Topics include the introduction of positron emission tomography (PET) represents the most important improvement in the management of HL; PET could identify patients with excellent response who might benefit from a reduction of treatment intensity; and mentions that the duration of treatment was reduced in patients who were PET negative after 2 cycles of eBEACOPP by the German Hodgkin Study Group (GHSG) HD18 study.

Summary Late toxicities can impact survivorship in patients with classical Hodgkin lymphoma (cHL) with pulmonary toxicity after bleomycin‐containing chemotherapy being a concern. The incidence of pulmonary diseases was examined in this Danish population‐based study. A total of 1474 adult patients with cHL treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or BEACOPP (bleomycin, vincristine, etoposide, doxorubicin, cyclophosphamide, procarbazine and prednisone) between 2000 and 2018 were included along with 7370 age‐ and sex‐matched comparators from the background population. Median follow‐up was 8.6 years for the patients. Patients with cHL had increased risk of incident pulmonary diseases (HR 2.91 [95% CI 2.30–3.68]), with a 10‐year cumulative risk of 7.4% versus 2.9% for comparators. Excess risks were observed for interstitial lung diseases (HR 15.84 [95% CI 9.35–26.84]) and chronic obstructive pulmonary disease (HR 1.99 [95% CI 1.43–2.76]), with a 10‐year cumulative risk of 4.1% and 3.5% respectively for patients. No excess risk was observed for asthma (HR 0.82 [95% CI 0.43–1.56]). Risk factors for interstitial lung diseases were age ≥60 years, the presence of B‐symptoms and low albumin. These findings document a significant burden of pulmonary diseases among patients with cHL and emphasize the importance of diagnostic work‐up of pulmonary symptoms. [ABSTRACT FROM AUTHOR]

PURPOSE: Patients diagnosed with advanced-stage Hodgkin lymphoma (aHL) have historically been risk-stratified using the International Prognostic Score (IPS). This study investigated if a machine learning (ML) approach could outperform existing models when it comes to predicting overall survival (OS) and progression-free survival (PFS). PATIENTS AND METHODS: This study used patient data from the Danish National Lymphoma Register for model development (development cohort). The ML model was developed using stacking, which combines several predictive survival models (Cox proportional hazard, flexible parametric model, IPS, principal component, penalized regression) into a single model, and was compared with two versions of IPS (IPS-3 and IPS-7) and the newly developed aHL international prognostic index (A-HIPI). Internal model validation was performed using nested cross-validation, and external validation was performed using patient data from the Swedish Lymphoma Register and Cancer Registry of Norway (validation cohort). RESULTS: In total, 707 and 760 patients with aHL were included in the development and validation cohorts, respectively. Examining model performance for OS in the development cohort, the concordance index (C-index) for the ML model, IPS-7, IPS-3, and A-HIPI was found to be 0.789, 0.608, 0.650, and 0.768, respectively. The corresponding estimates in the validation cohort were 0.749, 0.700, 0.663, and 0.741. For PFS, the ML model achieved the highest C-index in both cohorts (0.665 in the development cohort and 0.691 in the validation cohort). The time-varying AUCs for both the ML model and the A-HIPI were consistently higher in both cohorts compared with the IPS models within the first 5 years after diagnosis. CONCLUSION: The new prognostic model for aHL on the basis of ML techniques demonstrated a substantial improvement compared with the IPS models, but yielded a limited improvement in predictive performance compared with the A-HIPI. Machine-Learning based advanced-stage Hodgkin lymphoma (aHL) prognosis surpasses International Prognostic Score, competes with aHL international prognostic index in overall survival and progression-free survival prediction. [ABSTRACT FROM AUTHOR]

A study published in the British Journal of Haematology examined the impact of COVID-19 on patients with B-cell non-Hodgkin lymphoma (B-NHL) who received bispecific antibodies. The study included 130 Danish patients who were treated with glofitamab or epcoritamab. Of the 43 patients who were infected with COVID-19, the majority were in complete remission at the time of diagnosis. The severity of COVID-19 symptoms varied, with 2 patients experiencing critical symptoms, 2 experiencing severe symptoms, and 30 experiencing non-severe symptoms. Hospitalization was required for 16 patients, and the most common treatments prescribed were sotrovimab and remdesivir. Overall, the study found low mortality rates from COVID-19 infection in patients with B-NHL after bispecific CD20xCD3 therapy. The study also compared the mortality rates of patients who received bispecific antibodies to those treated with CAR-T-cell therapy, finding that bispecific antibody patients had a lower mortality rate. The study concludes that bispecific CD20xCD3 antibodies can be safely prescribed to lymphoma patients who have been vaccinated for COVID-19 with currently circulating virus variants. [Extracted from the article]

The author discusses a study by A. Rothe and colleagues regarding Hodgkin lymphoma (HL) immunotherapy. Topics include the mechanism of Hodgkin Reed-Sternberg (RS) cell through cytokine and chemokine activity, the programmed cell death protein 1 which is targeted by monoclonal antibodies, and the use of the CD30 receptor as HL therapy's target.

The article notes the high incidence of treatment-related late morbidity and mortality among patients treated for Hodgkin lymphoma, and discusses efforts to identify patients in which treatment-related toxicity could be reduced by means of lower treatment intensity. Particular attention is given to a study that found a potential link between the intensity of the PET (positron emission tomography) in Hodgkin lymphoma and the expression of glucose transporters.

Genetic testing has been applied for decades in clinical routine diagnostics of hematological malignancies to improve disease (sub)classification, prognostication, patient management, and survival. In recent classifications of hematological malignancies, disease subtypes are defined by key recurrent genetic alterations detected by conventional methods (i.e., cytogenetics, fluorescence in situ hybridization, and targeted sequencing). Hematological malignancies were also one of the first disease areas in which targeted therapies were introduced, the prime example being BCR::ABL1 inhibitors, followed by an increasing number of targeted inhibitors hitting the Achilles' heel of each disease, resulting in a clear patient benefit. Owing to the technical advances in high‐throughput sequencing, we can now apply broad genomic tests, including comprehensive gene panels or whole‐genome and whole‐transcriptome sequencing, to identify clinically important diagnostic, prognostic, and predictive markers. In this review, we give examples of how precision diagnostics has been implemented to guide treatment selection and improve survival in myeloid (myelodysplastic syndromes and acute myeloid leukemia) and lymphoid malignancies (acute lymphoblastic leukemia, diffuse large B‐cell lymphoma, and chronic lymphocytic leukemia). We discuss the relevance and potential of monitoring measurable residual disease using ultra‐sensitive techniques to assess therapy response and detect early relapses. Finally, we bring up the promising avenue of functional precision medicine, combining ex vivo drug screening with various omics technologies, to provide novel treatment options for patients with advanced disease. Although we are only in the beginning of the field of precision hematology, we foresee rapid development with new types of diagnostics and treatment strategies becoming available to the benefit of our patients. [ABSTRACT FROM AUTHOR]

The author discusses the study of G. A. Abel and colleagues which examines the significance and patterns of surveillance imaging in patients with diffuse large B-cell lymphoma (DLBCL) in remission. They mention that the multi-institutional survey has focused on first two years of post-treatment via surveillance imaging. They say that those patients who were randomised to low-intensity surveillance imaging have a risk relapse compared to those who have DLBCL in remission following chemotherapy.

The article comments on a study on routine bone marrow biopsy for Hodgkin lymphoma (HL) by S. Richardson and colleagues published in this journal. The study included 392 patients with HL, including 190 patients with advanced stage disease and 202 patients with early stage disease. The author observes that the result revealed that BMB should not be performed routinely in HL patients undergoing positron emission tomography staging.

In this article the author discusses the retrospective Czech experience of Dr. Mocikova and colleagues in the application of pre-transplant positron emission tomography (PET) and computed tomography (CT) on patients with relapsed Hodgkin lymphoma (HL). It notes the higher 2-year progression-free survival (PFS) in PET-negative patients than PET-positive patients. It also highlights the use of histone deacetylase (HDAC) inhibitors and brentuximab vedotin (SG-35) on pretreated HL patients.

In this article the author discusses the study of T. El-Galaly and colleagues which presents the efficacy of routine post-treatment surveillance with positron emission tomography/computed tomography (PET/CT) to aggressive non-Hodgkin lymphoma (NHL) patients. He states that the addition of PET/CT to routine surveillance showed an early detection of one single relapse. He also explores two studies which use chest X-ray and CT scans and both confirmed that most of the relapses were symptomatic.

Disease-specific studies on the impact of Hodgkin lymphoma (HL) on education or work interruption and resumption are lacking. In a cross-sectional study conducted among long-term HL survivors enrolled from 1964 to 2004 in nine randomised EORTC-LYSA trials, the interruption and resumption of education/work was investigated. Survivors alive 5–44 years after diagnosis who were studying or working at time of diagnosis were included (n = 1646). Patient and treatment characteristics were obtained from trial records. Education and work outcomes were collected using the Life Situation Questionnaire. Logistic regression was used to model education or work interruption; Cox regression was used to study resumption rates. Among survivors studying at time of diagnosis (n = 323), 52% (95% CI: 46–57%) interrupted their education; however, it was resumed within 24 months by 92% (95% CI: 87–96%). The probability of interruption decreased with time: the more recent the treatment era, the lower the risk (OR 0.70 per 10 years, 95% CI: 0.49–1.01). Treatment with radiotherapy (yes vs. no) was associated with a higher education resumption rate (HR 2.01, 95% CI 1.07–3.78) whereas age, sex, stage, radiotherapy field and chemotherapy were not. Among survivors working at time of diagnosis (n = 1323), 77% (95% CI: 75–79%) interrupted their work. However, it was resumed within 24 months by 86% (95% CI: 84%-88%). Women were more likely to interrupt their work as compared to men (OR 1.90, 95% CI: 1.44–2.51) and, when interrupted, less likely to resume work (HR 0.70, 95% CI: 0.61–0.80). Survivors with a higher educational level were less likely to interrupt their work (OR 0.68 for university vs. no high school, 95% CI: 0.46–1.03); and when interrupted, more likely to resume work (HR 1.50 for university vs. no high school, 95% CI: 1.21–1.86). Increasing age was also associated with lower resumption rates (HR 0.62 for age ≥50 vs. 18–29 years, 95% CI: 0.41–0.94). An interruption in education/work was common among long-term HL survivors. However, most of the survivors who interrupted their studies or work had resumed their activities within 24 months. In this study, no associations between survivors' characteristics and failure to resume education were observed. Female sex, age ≥50 years, and a lower level of education were found to be associated with not resuming work after treatment for HL. [ABSTRACT FROM AUTHOR]

Summary: Due to improvements in early detection and treatment of malignant disease, the population of cancer survivors is constantly expanding. Cancer survivors are faced with chemotherapy‐related long‐term side effects, including irreversible cardiac injury with risk of heart failure (HF). Numerous antineoplastic regimens are associated with risk of cardiac side effects, but anthracyclines in particular carry a severe risk of cardiotoxicity. Currently, serial echocardiographic evaluation of resting left ventricular ejection fraction (LVEF) is the gold standard for monitoring anthracycline‐induced cardiac side effects from chemotherapy. LVEF measurements are, however, limited by their low sensitivity. A normal LVEF does not exclude cardiotoxicity and declines in LVEF are usually not observed before the occurrence of irreversible cardiomyopathy. Hence, a clinically applicable high‐sensitivity diagnostic tool for early detection of chemotherapy‐related cardiotoxicity is still lacking and alternative non‐invasive imaging modalities are therefore being investigated. 123I‐MIBG is a noradrenaline (NA) analogue used for evaluation of cardiac adrenergic function, including assessment of HF prognosis and evaluation of HF treatment response. However, the role of 123I‐MIBG for monitoring chemotherapy‐related cardiotoxicity is still unclear. Here, we review the value of 123I‐MIBG imaging for early detection and prevention of anthracycline‐induced cardiomyopathy. [ABSTRACT FROM AUTHOR]

Studies have shown higher survival rates for patients with Hodgkin lymphoma (HL) treated within clinical trials compared to patients treated outside clinical trials. However, endpoints are often limited to overall survival (OS). In this retrospective cohort study, we investigated the effect of trial participation on OS, the incidence of relapse, second cancer, and cardiovascular disease (CVD). The study population consisted of patients with HL, aged between 14 and 51 years at diagnosis, who started their treatment between 1962 and 2002 at three Dutch cancer centres. Patients were either included in the EORTC Lymphoma Group trials (H1–H9) or treated according to standard guidelines at the time. After adjusting for differences in baseline characteristics, trial participation was associated with longer OS (median OS: 29.4 years [95%CI: 27.0–31.6] for treatment inside trials versus 27.4 years [95%CI: 26.0–28.5] for treatment outside trials, p =.046), a lower incidence of relapse (HR = 0.79, 95%CI: 0.63–0.98, p =.036) and a higher incidence of CVD (HR = 1.49, 95%CI: 1.23–1.79, p <.001). The trial effect for CVD was present only for patients treated before 1983. No evidence of differences in the incidence of second cancer was found. Consequently, essential results from clinical trials should be implemented into standard practice without undue delay. [ABSTRACT FROM AUTHOR]

Involvement of the internal female reproductive organs by diffuse large B-cell lymphoma ( DLBCL) is uncommon, and there are sparse data describing the outcomes of such cases. In total, 678 female patients with DLBCL staged with positron emission tomography/computed tomography and treated with rituximab-containing chemotherapy were identified from databases in Denmark, Great Britain, Australia, and Canada. Overall, 27/678 (4%) had internal reproductive organ involvement: uterus ( n = 14), ovaries ( n = 10) or both ( n = 3). In multivariate analysis, women with uterine DLBCL experienced inferior progression-free survival and overall survival compared to those without reproductive organ involvement, whereas ovarian DLBCL was not predictive of outcome. Secondary central nervous system ( CNS) involvement ( SCNS) occurred in 7/17 (41%) women with uterine DLBCL (two patients with concomitant ovarian DLBCL) and 0/10 women with ovarian DLBCL without concomitant uterine involvement. In multivariate analysis adjusted for other risk factors for SCNS, uterine involvement by DLBCL remained strongly associated with SCNS (Hazard ratio 14·13, 95% confidence interval 5·09-39·25, P < 0·001). Because involvement of the uterus by DLBCL appears to be associated with a high risk of SCNS, those patients should be considered for CNS staging and prophylaxis. However, more studies are needed to determine whether the increased risk of secondary CNS involvement also applies to women with localized reproductive organ DLBCL. [ABSTRACT FROM AUTHOR]

Focuses on causes and effects of the disease Lemierre's syndrome, which is a malignant complication of pharyngitis. Symptoms of the disease; Factors responsible for causing Lemierre's syndrome; Therapy to cure the disease; Procedure to determine the extent and localization of Lemierre's syndrome.

Background: Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available.Methods: We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has been reported previously. The key secondary end point was overall survival in the intention-to-treat population. Safety was also assessed.Results: A total of 664 patients were assigned to receive A+AVD and 670 to receive ABVD. At a median follow-up of 73.0 months, 39 patients in the A+AVD group and 64 in the ABVD group had died (hazard ratio, 0.59; 95% confidence interval [CI], 0.40 to 0.88; P = 0.009). The 6-year overall survival estimates were 93.9% (95% CI, 91.6 to 95.5) in the A+AVD group and 89.4% (95% CI, 86.6 to 91.7) in the ABVD group. Progression-free survival was longer with A+AVD than with ABVD (hazard ratio for disease progression or death, 0.68; 95% CI, 0.53 to 0.86). Fewer patients in the A+AVD group than in the ABVD group received subsequent therapy, including transplantation, and fewer second cancers were reported with A+AVD (in 23 vs. 32 patients). Primary prophylaxis with granulocyte colony-stimulating factor was recommended after an increased incidence of febrile neutropenia was observed with A+AVD. More patients had peripheral neuropathy with A+AVD than with ABVD, but most patients in the two groups had resolution or amelioration of the event by the last follow-up.Conclusions: Patients who received A+AVD for the treatment of stage III or IV Hodgkin's lymphoma had a survival advantage over those who received ABVD. (Funded by Takeda Development Center Americas and Seagen; ECHELON-1 ClinicalTrials.gov number, NCT01712490; EudraCT number, 2011-005450-60.). [ABSTRACT FROM AUTHOR]

We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International Harmonization Project criteria (IHP), Deauville 5-point scale (D 5PS) with scores 1-3 considered negative (D 5PS > 3) and D 5PS with scores 1-4 considered negative (D 5PS = 5). Ratios of tumor maximum standardized uptake value (SUVmax) to liver SUVmax were also analyzed. We found no difference in progression-free survival (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS > 3. The 2-year PFS using D 5PS = 5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group ( p = 0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET-positive and PET-negative patients in different prognostic groups. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the relapse detection pattern in primary central nervous system lymphomas (PCNSLs), with a focus on the value of routine magnetic resonance imaging (MRI) studies. Topics include the minimum testing for patients with PCNSL in remission, categories of MRI studies, and conclusion on the limited role of routine follow-up (FU) procedures in detecting relapsed PCNSL.

The aim of this study was to evaluate the prognostic value of clinician interpretation of positron emission tomography/computed tomography (PET/CT) reports at mid-therapy, interim PET (I-PET) and after the end of first-line therapy (E-PET) in patients with diffuse large B-cell lymphoma (DLBCL). Four hundred and thirty patients were enrolled in this study comprising a total of 617 PET reports. Each report was evaluated by three expert hematologists randomly selected from a panel of nine. Reports were labeled positive or negative if all three interpreters agreed. All others were considered indeterminate. Indeterminate reports accounted for 59% of I-PET and 49% of E-PET reports. Two-year overall survival (OS) for patients with a positive, indeterminate and negative I-PET was 58%, 87% and 89% ( p < 0.001), respectively. Two-year OS for patients with E-PET was 41%, 89% and 97% ( p < 0.001) for positive, indeterminate and negative interpretation of PET/CT reports. Progression-free survival and OS did not differ significantly in patients with a negative and an indeterminate I-PET report. The use of well-defined reporting criteria, e.g. the Deauville five-point scale, is likely to reduce the number of scans perceived as indeterminate. [ABSTRACT FROM AUTHOR]

Objectives: To provide reference values for the European Organisation for Treatment and Research of Cancer (EORTC) Quality of Life Questionnaire (QLQ‐C30) in advanced‐stage Hodgkin lymphoma (HL) patients and 5‐year HL survivors. The QLQ‐C30 is the most widely used cancer‐specific questionnaire to assess Health‐Related Quality of Life (HRQoL). Methods: The EORTC database was searched to identify HL RCTs in which patients' and survivors' HRQoL was assessed by the QLQ‐C30. HRQoL mean scores were calculated and stratified by age and gender. Minimal important differences were used to assess the clinical relevance of the findings. Data from one RCT with HRQoL scores available at baseline (n = 343) and four RCTs with HRQoL scores available at follow‐up (n = 1665) were analyzed. Results: Patients reported worse HRQoL scores than survivors across most functioning scales and symptoms' scales. These scores varied as a function of gender but not age. Survivors' HRQoL reports were comparable to the ones of the general population. Conclusions: These values provide an assessment framework for the comparison and interpretation of QLQ‐C30 scores in advanced‐stage HL. Our findings suggest that although HL patients' HRQoL scores are worse than the general population, HRQoL scores may normalize over long‐term survival. [ABSTRACT FROM AUTHOR]

Segmentation of lymphoma lesions in FDG PET/CT images is critical in both assessing individual lesions and quantifying patient disease burden. Simple thresholding methods remain common despite the large heterogeneity in lymphoma lesion location, size, and contrast. Here, we assess 11 automated PET segmentation methods for their use in two scenarios: individual lesion segmentation and patient-level disease quantification in lymphoma. Lesions on 18F-FDG PET/CT scans of 90 lymphoma patients were contoured by a nuclear medicine physician. Thresholding, active contours, clustering, adaptive region-growing, and convolutional neural network (CNN) methods were implemented on all physician-identified lesions. Lesion-level segmentation was evaluated using multiple segmentation performance metrics (Dice, Hausdorff Distance). Patient-level quantification of total disease burden (SUVtotal) and metabolic tumor volume (MTV) was assessed using Spearman's correlation coefficients between the segmentation output and physician contours. Lesion segmentation and patient quantification performance was compared to inter-physician agreement in a subset of 20 patients segmented by a second nuclear medicine physician. In total, 1223 lesions with median tumor-to-background ratio of 4.0 and volume of 1.8 cm3, were evaluated. When assessed for lesion segmentation, a 3D CNN, DeepMedic, achieved the highest performance across all evaluation metrics. DeepMedic, clustering methods, and an iterative threshold method had lesion-level segmentation performance comparable to the degree of inter-physician agreement. For patient-level SUVtotal and MTV quantification, all methods except 40% and 50% SUVmax and adaptive region-growing achieved a performance that was similar the agreement of the two physicians. Multiple methods, including a 3D CNN, clustering, and an iterative threshold method, achieved both good lesion-level segmentation and patient-level quantification performance in a population of 90 lymphoma patients. These methods are thus recommended over thresholding methods such as 40% and 50% SUVmax, which were consistently found to be significantly outside the limits defined by inter-physician agreement. [ABSTRACT FROM AUTHOR]

Background: Response to modern treatment strategies, which combine cytotoxic compounds with immune stimulatory agents and targeted treatment is highly variable among MCL patients. Thus, providing prognostic and predictive markers for risk adapted therapy is warranted and molecular information that can help in patient stratification is a necessity. In relapsed MCL, biopsies are rarely available and molecular information from tumor tissue is often lacking. Today, the main tool to access risk is the MCL international prognostic index (MIPI), which does not include detailed biological information of relevance for different treatment options. To enable continuous monitoring of patients, non-invasive companion diagnostic tools are needed which can further reduce cost and patient distress and enable efficient measurements of biological markers.Methods: We have assessed if serum-based protein profiling can identify immune related proteins that stratify relapsed MCL patients based on risk. Overall, 371 scFv targeting 158 proteins were assessed using an antibody microarray platform. We profiled patients (n = 44) who had been treated within the MCL6-Philemon trial combining targeted and immune-modulatory treatment.Results: The downstream processing led to the identification of the relapsed immune signature (RIS) consisting of 11 proteins with potential to stratify patients with long and short overall survival (OS). Moreover, in this population, MIPI alone failed to separate high, intermediate and low risk patients, but a combined index based on MIPI together with RIS, MIPIris, showed improved performance and significantly stratified all three risk groups based on OS.Conclusions: Our results show that addition of biological parameters to previous prognostic indices improves patient stratification among patients treated with BTK inhibitor triplet combination, particularly, in the identification of an extreme high risk group. [ABSTRACT FROM AUTHOR]

Purpose: We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials. Patients and methods: Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression‐free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT). Results: About 1227 patients were included. The 7‐year OS was 84.3% (95% CI 80.8‐87.2) for ABVD vs 87.7% (95% CI 84.5‐90.2) for BEACOPP. Two follow‐up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HRABVD vs BEACOPP = 1.59; 95% CI 1.09‐2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P =.0185; IPI score, P =.0107). The 7‐year PFS was 71.1% (95% CI 67.1‐74.6) for ABVD vs 81.1% (95% CI 77.5‐84.2) for BEACOPP (P <.001). After ABVD, 25 secondary cancers (4.0%) were reported with no myelodysplasia (MDS)/acute myeloid leukemia (AML) compared to 36 (6.5%) after BEACOPP, which included 13 patients with MDS/AML. Following ABVD, 86 patients (13.8%) received ASCT vs 39 (6.4%) for BEACOPP. Conclusions: This analysis showed a slight improvement in OS for BEACOPP and confirmed a PFS benefit. Frontline use of BEACOPP instead of ABVD increased secondary leukemia incidence but halved the requirement for ASCT. [ABSTRACT FROM AUTHOR]

Cancer‐related psychological distress may lead to depression and anxiety among survivors. The vast majority of patients with Hodgkin lymphoma (HL) become long‐term survivors, but the risk of mental health problems after HL is not well‐characterized. Using national population‐based registries, we investigated the cumulative incidence of psychotropic drug (antidepressants, antipsychotics, and anxiolytics) use (proxies for depression and anxiety) in HL patients as well as if an increased risk would normalize over time for patients in remission. The study included 945 HL patients aged 18‐92 years and 4725 matched persons. In total, 215 HL patients (22.8%) received a prescription of any psychotropic drug (PD) at some point after date of diagnosis compared to 545 persons (11.5%) in the matched cohort. Cumulative incidences with death/relapse as competing risk confirmed that HL patients were at higher risk of receiving psychotropic drug prescriptions, but the increased risk was transient and normalized to the matched population 5 years into survivorship. Increased age, Eastern Cooperative Oncology Group performance status, and disease stage were associated with higher risk of psychotropic drug prescriptions. Given the increased rate of psychotropic drug prescriptions after HL diagnosis, screening for symptoms of depression and anxiety is warranted after HL diagnosis and first years into survivorship. [ABSTRACT FROM AUTHOR]

We tested baseline positron emission tomography (PET)/computed tomography (CT) as a measure of total tumor burden to better identify high-risk patients with early-stage Hodgkin lymphoma (HL). Patients with stage I-II HL enrolled in the standard arm (combined modality treatment) of the H10 trial (NCT00433433) with available baseline PET and interim PET (iPET2) after 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine were included. Total metabolic tumor volume (TMTV) was measured on baseline PET. iPET2 findings were reported negative (DS1-3) or positive (DS4-5) with the Deauville scale (DS). The prognostic value of TMTV was evaluated and compared with baseline characteristics, staging classifications, and iPET2. A total of 258 patients were eligible: 101 favorable and 157 unfavorable. The median follow-up was 55 months, with 27 progression-free survival (PFS) and 12 overall survival (OS) events. TMTV was a prognosticator of PFS (P < .0001) and OS (P = .0001), with 86% and 84% specificity, respectively. Five-year PFS and OS were 71% and 83% in the high-TMTV (>147 cm3) group (n = 46), respectively, vs 92% and 98% in the low-TMTV group (≤147 cm³). In multivariable analysis including iPET2, TMTV was the only baseline prognosticator compared with the current staging systems proposed by the European Organization for Research and Treatment of Cancer/Groupe d'Etude des Lymphomes de l'Adulte, German Hodgkin Study Group, or National Comprehensive Cancer Network. TMTV and iPET2 were independently prognostic and, combined, identified 4 risk groups: low (TMTV≤147+DS1-3; 5-year PFS, 95%), low-intermediate (TMTV>147+DS1-3; 5-year PFS, 81.6%), high-intermediate (TMTV≤147+DS4-5; 5-year PFS, 50%), and high (TMTV>147+DS4-5; 5-year PFS, 25%). TMTV improves baseline risk stratification of patients with early-stage HL compared with current staging systems and the predictive value of early PET response as well. [ABSTRACT FROM AUTHOR]

A review of the article "2-[18F]fluoro-2-deoxyd-glucose positron emission tomography/computed tomography examination in patients with chronic lymphocytic leukemia may reveal Richter transformation," by T. Papajík, M. Mysliveček, R. Urbanová and others is presented.

Purpose Development of secondary central nervous system involvement (SCNS) in patients with diffuse large B-cell lymphoma is associated with poor outcomes. The CNS International Prognostic Index (CNS-IPI) has been proposed for identifying patients at greatest risk, but the optimal model is unknown. Methods We retrospectively analysed patients with diffuse large B-cell lymphoma diagnosed between 2001 and 2013, staged with PET/CT and treated with R-CHOP(-like) regimens. Baseline clinicopathologic characteristics, treatments, and outcome data were collected from clinical databases and medical files. We evaluated the association between candidate prognostic factors and modelled different risk models for predicting SCNS. Results Of 1532 patients, 62 (4%) subsequently developed SCNS. By multivariate analysis, disease stage III/IV, elevated serum LDH, kidney/adrenal and uterine/testicular involvement were independently associated with SCNS. There was a strong correlation between absolute number of extranodal sites and risk of SCNS; the 144 patients (9%) with >2 extranodal sites had a 3-year cumulative incidence of SCNS of 15.2% (95% confidence interval [CI] 9.2–21.2%) compared with 2.6% (95% CI 1.7–3.5) among those with ≤2 sites ( P < 0.001). The 3-year cumulative risks of SCNS for CNS-IPI defined risk groups were 11.2%, 3.1% and 0.4% for high-, intermediate- and low-risk patients, respectively. All risk models analysed had high negative predictive values, but only modest positive predictive values. Conclusions Patients with >2 extranodal sites or high-risk disease according to the CNS-IPI should be considered for baseline CNS staging. Clinical risk prediction models suffer from limited positive predictive ability, highlighting the need for more sensitive biomarkers to identify patients at highest risk of this devastating complication. [ABSTRACT FROM AUTHOR]

Background and purpose:In early-stage classical Hodgkin lymphoma (HL) the target volume nowadays consists of the volume of the originally involved nodes. Delineation of this volume on a post-chemotherapy CT-scan is challenging. We report on the interobserver variability in target volume definition and its impact on resulting treatment plans. Materials and methods:Two representative cases were selected (1: male, stage IB, localization: left axilla; 2: female, stage IIB, localizations: mediastinum and bilateral neck). Eight experienced observers individually defined the clinical target volume (CTV) using involved-node radiotherapy (INRT) as defined by the EORTC-GELA guidelines for the H10 trial. A consensus contour was generated and the standard deviation computed. We investigated the overlap between observer and consensus contour [Sørensen-Dice coefficient (DSC)] and the magnitude of gross deviations between the surfaces of the observer and consensus contour (Hausdorff distance). 3D-conformal (3D-CRT) and intensity-modulated radiotherapy (IMRT) plans were calculated for each contour in order to investigate the impact of interobserver variability on each treatment modality. Similar target coverage was enforced for all plans. Results:The median CTV was 120 cm3(IQR: 95–173 cm3) for Case 1, and 255 cm3(IQR: 183–293 cm3) for Case 2. DSC values were generally high (>0.7), and Hausdorff distances were about 30 mm. The SDs between all observer contours, providing an estimate of the systematic error associated with delineation uncertainty, ranged from 1.9 to 3.8 mm (median: 3.2 mm). Variations in mean dose resulting from different observer contours were small and were not higher in IMRT plans than in 3D-CRT plans. Conclusions:We observed considerable differences in target volume delineation, but the systematic delineation uncertainty of around 3 mm is comparable to that reported in other tumour sites. This report is a first step towards calculating an evidence-based planning target volume margin for INRT in HL. [ABSTRACT FROM AUTHOR]

The survival of patients diagnosed with Hodgkin lymphoma ( HL) has improved from 70% to 90% in clinical trials. However, population-based data has shown lower survival. In this study, clinical trial data were linked with cancer registry to identify trial and non-trial participants and differences in overall survival and associated factors were assessed. In 1986-2004, 27% of HL patients aged 15-70 years participated in clinical trials. Compared to non-trial participants, trial participants were younger (median age, 31 vs. 34 years), had staging registered more accurately and had an 8% higher 20-year survival rate (73% vs. 65%). After adjusting for baseline differences, no differences in survival (hazard ratio = 0·96, 95% confidence interval 0·82-1·12), or in subgroup analysis according to stage, remained. Over time, increased administration of chemotherapy in combination with radiotherapy, together with the decreased use of radiotherapy alone was observed among the trial population. This trend was later followed in non-trial participants, coinciding with a similar 'take-up' in survival. The observed superior survival among patients with HL treated in clinical trials can be largely explained by the differences in baseline characteristics, particularly younger age. High trial participation rate and centralized expertise facilitates the implementation of trial findings to real-world practice. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics including the involvement of bone marrow in Hodgkin lymphoma, the metabolic response in interim positron emission tomography (PET) during Hodgkin lymphoma treatment, and the outcome of aggressive non-Hodgkin lymphoma patients with negative pretreatment PET scan.

Watch and wait ( WAW) is a common approach for asymptomatic, advanced stage follicular lymphoma ( FL), but single-agent rituximab is an alternative for these patients. In this nationwide study we describe the outcome of patients selected for WAW. A cohort of 286 out of 849 (34%) stage III- IVA FL patients seen between 2000 and 2011, were managed expectantly and included. The 5-year progression-free survival ( PFS) was 35% [95% confidence interval ( CI) 29-42]. The 10-year overall survival ( OS) was 65% (95% CI 54-78), and the cumulative risk of dying from lymphoma within 10 years of diagnosis was 13% (95% CI 7-20). Elevated lactate dehydrogenase and > four nodal regions involved were associated with a higher risk of lymphoma treatment and death from lymphoma. The WAW patients and a matched background population had similar OS during the first 50 months after diagnosis ( P = 0·7), but WAW patients had increased risk of death after 50 months ( P < 0·001). The estimated loss of residual life after 10 years was 6·8 months. The 10-year cumulative risk of histological transformation was 22% (95% CI 15-29) and the 3-year OS after transformation was 71% (95% CI 58-87%). In conclusion, advanced stage FL managed by WAW had a favourable outcome and abandoning this strategy could lead to overtreatment in some patients. [ABSTRACT FROM AUTHOR]

Abstract: A number of novel fused thiophene derivatives have been prepared and identified as potent inhibitors of MEK. The SAR data of selected examples and the in vivo profiling of compound 13h demonstrates the functional activity of this class of compounds in HT-29 PK/PD models. [Copyright &y& Elsevier]

The preparation of the selective VEGF-R2 kinase inhibitor 10 (JNJ- 17029259) is described in which the key precursor, 4-(5-isoxazolyl)benzonitrile, undergoes clean transformation to the corresponding cumylamine derivative with CeCI3- MeLi in THF. This high-yielding cerium mediated transfor- mation is robust, reproducible, and readily scalable based on a requirement for the anhydrous CeCI3 to be milled and subjected to ultrasound treatment prior to addition of methyl lithium. [ABSTRACT FROM AUTHOR]

The jatrophane class of natural products exhibit a wide range of biological activities with certain members of this family of complex sesquiterpenes being P-glycoprotein inhibitors. Considerable attention has been paid to the synthesis of biologically active jatrophanes although very few have succumbed to total synthesis. Herein we report a synthesis of the cyclopentane core of pepluanin A, a potent P-glycoprotein inhibitor, that features an iodocarbocyclization and an invertive acetal formation as key steps. Image 1 • Synthesis of the core of the P-glycoprotein inhibitor pepluanin A reported. • Key methods involve selective iodocyclization and invertive acetal formation. • Exploration of cylization - lactonization reported. [ABSTRACT FROM AUTHOR]