To investigate whether bone marrow biopsy (BMB) adds useful information to (18)Ffluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) staging in patients with Hodgkin ...lymphoma (HL).
Newly diagnosed patients with HL undergoing a pretherapeutic staging that encompasses both PET/CT and BMB were included in this retrospective study. The pattern of skeletal FDG uptake was categorized as uni-, bi-, or multifocal (≥ three lesions). Clinical stage, risk assessment, and treatment plan were determined with and without the contribution of BMB results according to the Ann Arbor classification and the guidelines from the German Hodgkin Study Group.
A total of 454 patients with HL were included of whom 82 (18%) had focal skeletal PET/CT lesions and 27 (6%) had positive BMB. No patients with positive BMB were assessed as having stage I to II disease by PET/CT staging. BMB upstaged five patients, assessed as being stage III before BMB; none of the 454 patients would have been allocated to another treatment on the basis of BMB results. Focal skeletal PET/CT lesions identified positive and negative BMBs with a sensitivity and specificity of 85% and 86%, respectively. The positive and negative predictive values of focal skeletal PET/CT lesions for BMB results were 28% and 99%, respectively.
A consistent finding of this study was the absence of positive BMBs in PET/CT-assessed stage I to II disease. The omission of staging BMB would not have changed the risk assessment or treatment strategy in this cohort of 454 newly diagnosed patients with HL.
Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed ...whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis.
This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18–60 years, with stage I–II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0–1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1·4 mg/m2, with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1–5. Rituximab was given at a dose of 375 mg/m2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of −5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421.
Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42–100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94–99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy.
In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population.
Deutsche Krebshilfe.
The Danish National Lymphoma Register (LYFO) prospectively includes information on all lymphoma patients newly diagnosed at hematology departments in Denmark. The validity of the clinical information ...in the LYFO has never been systematically assessed.
To test the coverage and data quality of the LYFO.
The coverage was tested by merging data of the LYFO with the Danish Cancer Register and the Danish National Patient Register, respectively. The validity of the LYFO was assessed by crosschecking with information from medical records in subgroups of patients. A random sample of 3% (N = 364) was made from all patients in the LYFO. In addition, four subtypes of lymphomas were validated: CNS lymphomas, diffuse large B-cell lymphomas, peripheral T-cell lymphomas, and Hodgkin lymphomas. A total of 1,706 patients from the period 2000-2012 were included. The positive predictive values (PPVs) and completeness of selected variables were calculated for each subgroup and for the entire cohort of patients.
The comparison of data from the LYFO with the Danish Cancer Register and the Danish National Patient Register revealed a high coverage. In addition, the data quality was good with high PPVs (87% to 100%), and high completeness (92% to 100%).
The LYFO is a unique, nationwide clinical database characterized by high validity, good coverage and prospective data entry. It represents a valuable resource for future lymphoma research.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Purpose The use of anthracycline chemotherapy is associated with heart failure (HF) among survivors of non-Hodgkin lymphoma (NHL). We aimed to understand the contribution of preexisting ...cardiovascular risk factors to HF risk among NHL survivors. Methods Using Danish registries, we identified adults diagnosed with aggressive NHL from 2000 to 2010 and sex- and age-matched general-population controls. We assessed HF from 9 months after diagnosis through 2012. We used Cox regression analysis to assess differences in risk for HF between survivors and general population controls. Among survivors only, preexisting cardiovascular factors (hypertension, dyslipidemia, and diabetes) and preexisting cardiovascular disease were ascertained. We used multivariable Cox regression to model the association of preexisting cardiovascular conditions on subsequent HF. Results Among 2,508 survivors of NHL and 7,399 controls, there was a 42% increased risk of HF among survivors compared with general population controls (hazard ratio HR, 1.42; 95% CI, 1.07 to 1.88). Among survivors (median age at diagnosis, 62 years; 56% male), 115 were diagnosed with HF during follow-up (median years of follow-up, 2.5). Before NHL diagnosis, 39% had ≥ 1 cardiovascular risk factor; 92% of survivors were treated with anthracycline-containing regimens. In multivariable analysis, intrinsic heart disease diagnosed before lymphoma was associated with increased risk of HF (HR, 2.71; 95% CI, 1.15 to 6.36), whereas preexisting vascular disease had no association with HF ( P > .05). Survivors with cardiovascular risk factors had an increased risk of HF compared with those with none (for 1 v 0 cardiovascular risk factors: HR, 1.63; 95% CI, 1.07 to 2.47; for ≥ 2 v 0 cardiovascular risk factors: HR, 2.86; 95% CI, 1.56 to 5.23; joint P < .01). Conclusion In a large, population-based cohort of NHL survivors, preexisting cardiovascular conditions were associated with increased risk of HF. Preventive approaches should take baseline cardiovascular health into account.
Summary Background The MInT study was the first to show improved 3-year outcomes with the addition of rituximab to a CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen in ...young patients with good-prognosis diffuse large-B-cell lymphoma. Extended follow-up was needed to establish long-term effects. Methods In the randomised open-label MInT study, patients from 18 countries (aged 18–60 years with none or one risk factor according to the age-adjusted International Prognostic Index IPI, stage II–IV disease or stage I disease with bulk) were randomly assigned to receive six cycles of a CHOP-like chemotherapy with or without rituximab. Bulky and extranodal sites received additional radiotherapy. Randomisation was done centrally with a computer-based tool and was stratified by centre, bulky disease, age-adjusted IPI, and chemotherapy regimen by use of a modified minimisation algorithm that incorporated a stochastic component. Patients and investigators were not masked to treatment allocation. The primary endpoint was event-free survival. Analyses were by intention to treat. This observational study is a follow-up of the MInT trial, which was stopped in 2003, and is registered at ClinicalTrials.gov , number NCT00400907. Findings The intention-to-treat population included 410 patients assigned to chemotherapy alone and 413 assigned to chemotherapy plus rituximab. After a median follow-up of 72 months (range 0·03–119), 6-year event-free survival was 55·8% (95% CI 50·4–60·9; 166 events) for patients assigned to chemotherapy alone and 74·3% (69·3–78·6; 98 events) for those assigned to chemotherapy plus rituximab (difference between groups 18·5%, 11·5–25·4, log-rank p<0·0001). Multivariable analyses showed that event-free survival was affected by treatment group, presence of bulky disease, and age-adjusted IPI and that overall survival was affected by treatment group and presence of bulky disease only. After chemotherapy and rituximab, a favourable subgroup (IPI=0, no bulk) could be defined from a less favourable subgroup (IPI=1 or bulk, or both; event-free survival 84·3% 95% CI 74·2–90·7 vs 71·0% 65·1–76·1, log-rank p=0·005). 18 (4·4%, 95% CI 2·6–6·9) second malignancies occurred in the chemotherapy-alone group and 16 (3·9%, 2·2–6·2) in the chemotherapy and rituximab group (Fisher's exact p=0·730). Interpretation Rituximab added to six cycles of CHOP-like chemotherapy improved long-term outcomes for young patients with good-prognosis diffuse large-B-cell lymphoma. The definition of two prognostic subgroups allows a more refined therapeutic approach to these patients than does assessment by IPI alone. Funding Hoffmann–La Roche.
•Relapses in early-stage Hodgkin lymphoma are uncommon.•Relapses rarely occur in irradiated lymph nodes.•Without radiation relapses occur preferentially in initially involved lymph nodes.•All ...initially involved lymph nodes should be irradiated.
Involved node radiation therapy (INRT) in the combined modality treatment for early-stage Hodgkin lymphoma (ESHL) has reduced the irradiated volume dramatically. Limiting the irradiated volume further based on initial disease bulk, 18F-fluoro-deoxy-glucose (FDG)-avidity, or residual computed tomography (CT) abnormality after chemotherapy seems attractive. In a cohort of patients treated with INRT a meticulous pattern-of-relapse analysis was performed to examine these options.
Patients treated for ESHL in our institution from 2005 to 2014 who achieved complete remission with chemotherapy were included. Patient characteristics, treatment details and clinical outcome were registered. For relapsed patients, rigid co-registration of the positron emission tomography/computed tomography-scans from the time of diagnosis and at relapse was done to visually assess the relapse location relative to initial involvement and, if irradiated, the irradiated volume. Size and maximum Standardized Uptake Value of the initial node(s) with later relapse, and residual CT abnormalities after chemotherapy in those locations were measured.
We included 182 patients. Twelve (6.6%) patients relapsed, five in previously involved nodes (two irradiated, three not irradiated). Relapses did not occur preferentially in initially bulky disease, in lymph node(s) with the highest FDG-uptake, or in residual CT abnormalities after chemotherapy.
Modern treatment with brief chemotherapy and limited radiotherapy provides excellent long-term disease control in ESHL. Neither bulk, high FDG-uptake, nor residual CT abnormality after chemotherapy could predict initially involved lymph nodes with a high risk of relapse.
Immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become standard of care for patients with diffuse large B-cell lymphoma (DLBCL). This ...randomized trial assessed whether rituximab intensification during the first 4 cycles of R-CHOP could improve the outcome of these patients compared with standard R-CHOP.
A total of 574 patients with DLBCL age 18 to 80 years were randomly assigned to induction therapy with 6 or 8 cycles of R-CHOP-14 with (RR-CHOP-14) or without (R-CHOP-14) intensification of rituximab in the first 4 cycles. The primary end point was complete remission (CR) on induction. Analyses were performed by intention to treat.
CR was achieved in 254 (89%) of 286 patients in the R-CHOP-14 arm and 249 (86%) of 288 patients in the RR-CHOP-14 arm (hazard ratio HR, 0.82; 95% CI, 0.50 to 1.36;
= .44). After a median follow-up of 92 months (range, 1-131 months), 3-year failure-free survival was 74% (95% CI, 68% to 78%) in the R-CHOP-14 arm versus 69% (95% CI, 63% to 74%) in the RR-CHOP-14 arm (HR, 1.26; 95% CI, 0.98 to 1.61;
= .07). Progression-free survival at 3 years was 74% (95% CI, 69% to 79%) in the R-CHOP-14 arm versus 71% (95% CI, 66% to 76%) in the RR-CHOP-14 arm (HR, 1.20; 95% CI, 0.94 to 1.55;
= .15). Overall survival at 3 years was 81% (95% CI, 76% to 85%) in the R-CHOP-14 arm versus 76% (95% CI, 70% to 80%) in the RR-CHOP-14 arm (HR, 1.27; 95% CI, 0.97 to 1.67;
= .09). Patients between ages 66 and 80 years experienced significantly more toxicity during the first 4 cycles in the RR-CHOP-14 arm, especially neutropenia and infections.
Early rituximab intensification during R-CHOP-14 does not improve outcome in patients with untreated DLBCL.
Summary
Cardiotoxicity is a known risk of anthracycline treatment. However, the relative contribution of anthracyclines to the development of congestive heart failure (CHF), when included in a ...poly‐chemotherapy regimen, is unclear. We examined cardiotoxicity in adult patients with diffuse large B‐cell lymphoma and follicular lymphoma undergoing first‐line immunochemotherapy from 2000–2012. In total, 2440 patients without previous heart disease were identified from the Danish Lymphoma Registry, of which 1994 (81·7%) were treated with anthracycline‐containing chemotherapy R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R‐CHOEP (R‐CHOP + etoposide) and 446 (18·3%) were treated without anthracyclines (reference group). Compared to the reference group, the adjusted hazard ratio of CHF after 3–5 cycles of R‐CHOP/CHOEP was 5·0 95% confidence interval (CI) 1·4; 18·5, 6 cycles 6·8 (95% CI 2·0; 23·3) and >6 cycles 13·4 (95% CI 4·0; 45·0). The cumulative 5‐year risk of CHF with all‐cause mortality as competing risk was 4·6% after 3–5 cycles of R‐CHOP/CHOEP, 4·5% after 6 and 7·9% after more than 6 cycles. Cumulative 5‐year risk for patients treated without anthracyclines was 0·8%. Using anthracyclines in first‐line lymphoma treatment increases risk of CHF in patients without previous history of heart disease. In particular, treatment with >6 cycles of R‐CHOP/CHOEP is associated with a significant increase in CHF rate.
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