Standardized response criteria are needed to interpret and compare clinical trials and for approval of new therapeutic agents by regulatory agencies.
The International Working Group response criteria (Cheson et al, J Clin Oncol 17:1244, 1999) were widely adopted, but required reassessment because of identified limitations and the increased use of [18F]fluorodeoxyglucose-positron emission tomography (PET), immunohistochemistry (IHC), and flow cytometry. The International Harmonization Project was convened to provide updated recommendations.
New guidelines are presented incorporating PET, IHC, and flow cytometry for definitions of response in non-Hodgkin's and Hodgkin's lymphoma. Standardized definitions of end points are provided.
We hope that these guidelines will be adopted widely by study groups, pharmaceutical and biotechnology companies, and regulatory agencies to facilitate the development of new and more effective therapies to improve the outcome of patients with lymphoma.
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"All lesion assessments, whether by physical examination or radiologic methods, were repeated by the same methods at least 4 weeks following the initial observation of an objective response for response confirmation. Responses were recorded based on Response Evaluation Criteria in Solid Tumors,version 1.0 (RECIST 1.0), and Revised Response Criteria for Malignant Lymphoma [38, 39]. "
[Show abstract][Hide abstract]ABSTRACT: Purpose:
This study was conducted to assess the pharmacokinetics and safety of enzastaurin in native Chinese patients with refractory solid tumors and lymphoma.
Eligible patients received 500 mg of enzastaurin orally once daily. The pharmacokinetics of enzastaurin and its metabolites were assessed on days 14 to 18. Patients were allowed to continue receiving the agent in a safety extension phase until disease progression or presentation with unacceptable toxicity.
Twenty-five patients received at least 1 dose of enzastaurin, and twenty-one patients completed the pharmacokinetic phase. Fifteen patients entered the safety extension phase. Except for transient, asymptomatic grade 3 QT interval prolongation in one patient who had baseline grade 2 QT prolongation, other adverse events were of grade 1 to 2. The t1/2, Cav, ss, and AUCτ,ss for enzastaurin and its primary active metabolite LSN326020 were 14 and 42 h, 1,210 and 907 nmol/L, and 29,100 and 21,800 nmol•h/L, respectively. One patient with relapsed diffuse large B-cell lymphoma achieved a partial response that lasted for 8.1 months.
The pharmacokinetics of enzastaurin in Chinese cancer patients were consistent with those observed in previous studies abroad. Enzastaurin 500 mg daily was well tolerated by Chinese patients. We recommend 500 mg daily as the phase II dose in this population. Its efficacy in lymphoma deserves further investigation.
"Associations between miRNA expression and BAGS, REGS, and ABC/GCB were investigated using ANOVA, Pearson's correlation, and/or Student's t tests. The impact of expression of miR-34a on overall survival (OS) and progression-free survival (PFS), as defined by Cheson et al.  , was evaluated with Kaplan–Meier estimates , log-rank tests, and Cox proportional hazards regression analyses. The impact of overexpression of miR-34a by lentiviral transduction in response to doxorubicin was evaluated with Student's t test. "
[Show abstract][Hide abstract]ABSTRACT: The standard treatment of diffuse large B-cell lymphoma (DLBCL) patients is the immunochemotherapy-based R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). Resistance to treatment, intrinsic or acquired, is observed in approximately 40% of DLBCL patients who thus require novel interventions to survive. To identify biomarkers for cytotoxic response assessment, microRNAs (miRNAs) associated with doxorubicin sensitivity were determined by combining global miRNA expression profiling with systematic dose-response screens in 15 human DLBCL cell lines. One candidate, miR-34a, was tested in functional in vitro studies and in vivo in a retrospective clinical cohort. High expression of miR-34a was observed in cell lines sensitive to doxorubicin and upregulation of miR-34a is documented here to increase doxorubicin sensitivity in in vitro lentiviral transduction assays. High expression of miR-34a showed prognostic impact using overall survival as outcome. Using risk stratification of DLBCL samples based on resistance gene signatures (REGS), doxorubicin-responsive samples had statistically significant upregulated miR-34a expression. Classification of the DLBCL samples into subset-specific B-cell-associated gene signatures (BAGS) showed differentiation-specific expression of miR-34a. Our data further support FOXP1 as a target of miR-34a suggesting that downregulation of FOXP1 may sensitize DLBCL cells to doxorubicin. We conclude that miRNAs, in particular miR-34a, may have clinical utility in DLBCL patients as both predictive and prognostic biomarkers.
Full-text · Article · Feb 2016 · Experimental hematology
"Compliance to national guidelines was also reported by the ten largest haematology/oncology centres in Sweden, although we cannot formally exclude that individual physicians used other strategies. Finally, we included patients with CR determined by either conventional or PET/CT-based response criteria (Cheson et al, 1999Cheson et al, , 2007). PET/CT restaging was used in 70% of the Danish patients and 86% of the Swedish patients (P < 0Á01) but patients with PET/CT-based CR had similar OS as patients with CR by conventional response (Fig 4 and Table SI). "
[Show abstract][Hide abstract]ABSTRACT: 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.
Full-text · Article · Feb 2016 · British Journal of Haematology