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Australian Journal of General Practice Dec 2019
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Dyspnea; Etoposide; Hematuria; Hepatomegaly; Hodgkin Disease; Humans; Lower Urinary Tract Symptoms; Lymphadenopathy; Male; Marfan Syndrome; Mediastinum; Neoplasm Staging; Pectus Carinatum; Pleural Effusion; Prednisone; Procarbazine; Splenomegaly; Tomography, X-Ray Computed; Vinblastine; Vincristine; Young Adult
PubMed: 31774988
DOI: 10.31128/AJGP-07-19-5019 -
The Cochrane Database of Systematic... Sep 2019Hodgkin lymphoma (HL) is one of the most common haematological malignancies in young adults and, with cure rates of 90%, has become curable for the majority of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hodgkin lymphoma (HL) is one of the most common haematological malignancies in young adults and, with cure rates of 90%, has become curable for the majority of individuals. Positron emission tomography (PET) is an imaging tool used to monitor a tumour's metabolic activity, stage and progression. Interim PET during chemotherapy has been posited as a prognostic factor in individuals with HL to distinguish between those with a poor prognosis and those with a better prognosis. This distinction is important to inform decision-making on the clinical pathway of individuals with HL.
OBJECTIVES
To determine whether in previously untreated adults with HL receiving first-line therapy, interim PET scan results can distinguish between those with a poor prognosis and those with a better prognosis, and thereby predict survival outcomes in each group.
SEARCH METHODS
We searched MEDLINE, Embase, CENTRAL and conference proceedings up until April 2019. We also searched one trial registry (ClinicalTrials.gov).
SELECTION CRITERIA
We included retrospective and prospective studies evaluating interim PET scans in a minimum of 10 individuals with HL (all stages) undergoing first-line therapy. Interim PET was defined as conducted during therapy (after one, two, three or four treatment cycles). The minimum follow-up period was at least 12 months. We excluded studies if the trial design allowed treatment modification based on the interim PET scan results.
DATA COLLECTION AND ANALYSIS
We developed a data extraction form according to the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). Two teams of two review authors independently screened the studies, extracted data on overall survival (OS), progression-free survival (PFS) and PET-associated adverse events (AEs), assessed risk of bias (per outcome) according to the Quality in Prognosis Studies (QUIPS) tool, and assessed the certainty of the evidence (GRADE). We contacted investigators to obtain missing information and data.
MAIN RESULTS
Our literature search yielded 11,277 results. In total, we included 23 studies (99 references) with 7335 newly-diagnosed individuals with classic HL (all stages).Participants in 16 studies underwent (interim) PET combined with computed tomography (PET-CT), compared to PET only in the remaining seven studies. The standard chemotherapy regimen included ABVD (16) studies, compared to BEACOPP or other regimens (seven studies). Most studies (N = 21) conducted interim PET scans after two cycles (PET2) of chemotherapy, although PET1, PET3 and PET4 were also reported in some studies. In the meta-analyses, we used PET2 data if available as we wanted to ensure homogeneity between studies. In most studies interim PET scan results were evaluated according to the Deauville 5-point scale (N = 12).Eight studies were not included in meta-analyses due to missing information and/or data; results were reported narratively. For the remaining studies, we pooled the unadjusted hazard ratio (HR). The timing of the outcome measurement was after two or three years (the median follow-up time ranged from 22 to 65 months) in the pooled studies.Eight studies explored the independent prognostic ability of interim PET by adjusting for other established prognostic factors (e.g. disease stage, B symptoms). We did not pool the results because the multivariable analyses adjusted for a different set of factors in each study.Overall survivalTwelve (out of 23) studies reported OS. Six of these were assessed as low risk of bias in all of the first four domains of QUIPS (study participation, study attrition, prognostic factor measurement and outcome measurement). The other six studies were assessed as unclear, moderate or high risk of bias in at least one of these four domains. Nine studies were assessed as high risk, and three studies as moderate risk of bias for the domain study confounding. Eight studies were assessed as low risk, and four studies as high risk of bias for the domain statistical analysis and reporting.We pooled nine studies with 1802 participants. Participants with HL who have a negative interim PET scan result probably have a large advantage in OS compared to those with a positive interim PET scan result (unadjusted HR 5.09, 95% confidence interval (CI) 2.64 to 9.81, I² = 44%, moderate-certainty evidence). In absolute values, this means that 900 out of 1000 participants with a negative interim PET scan result will probably survive longer than three years compared to 585 (95% CI 356 to 757) out of 1000 participants with a positive result.Adjusted results from two studies also indicate an independent prognostic value of interim PET scan results (moderate-certainty evidence).Progression-free survival Twenty-one studies reported PFS. Eleven out of 21 were assessed as low risk of bias in the first four domains. The remaining were assessed as unclear, moderate or high risk of bias in at least one of the four domains. Eleven studies were assessed as high risk, nine studies as moderate risk and one study as low risk of bias for study confounding. Eight studies were assessed as high risk, three as moderate risk and nine as low risk of bias for statistical analysis and reporting.We pooled 14 studies with 2079 participants. Participants who have a negative interim PET scan result may have an advantage in PFS compared to those with a positive interim PET scan result, but the evidence is very uncertain (unadjusted HR 4.90, 95% CI 3.47 to 6.90, I² = 45%, very low-certainty evidence). This means that 850 out of 1000 participants with a negative interim PET scan result may be progression-free longer than three years compared to 451 (95% CI 326 to 569) out of 1000 participants with a positive result.Adjusted results (not pooled) from eight studies also indicate that there may be an independent prognostic value of interim PET scan results (low-certainty evidence).PET-associated adverse eventsNo study measured PET-associated AEs.
AUTHORS' CONCLUSIONS
This review provides moderate-certainty evidence that interim PET scan results predict OS, and very low-certainty evidence that interim PET scan results predict progression-free survival in treated individuals with HL. This evidence is primarily based on unadjusted data. More studies are needed to test the adjusted prognostic ability of interim PET against established prognostic factors.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Disease Progression; Disease-Free Survival; Hodgkin Disease; Humans; Positron-Emission Tomography; Prognosis; Randomized Controlled Trials as Topic
PubMed: 31525824
DOI: 10.1002/14651858.CD012643.pub2 -
Scientific Reports Jul 2019Semiquantitative F-fluoro-2-deoxy-D-glucose positron emission tomography (F-FDG PET) parameters have been proposed as prognostic markers in classical Hodgkin lymphoma...
Semiquantitative F-fluoro-2-deoxy-D-glucose positron emission tomography (F-FDG PET) parameters have been proposed as prognostic markers in classical Hodgkin lymphoma (cHL). In non-Hodgkin lymphoma necrosis as assessed by F-FDG PET or computed tomography (CT) (necrosis) correlates with an adverse prognosis. We investigated whether semiquantitative F-FDG PET metrics correlate with necrosis, determined the incidence of necrosis and explored the prognostic impact of these factors in cHL. From 87 cHL cases treated with ABVD, (escalated) BEACOPP or CHOP chemotherapy between 2010 and 2017, 71 had both a NEDPAS/EARL accredited F-FDG PET and a contrast enhanced CT scan. Semiquantitative F-FDG PET parameters were determined using Hermes Hybrid 3D software. Necrosis, defined by photopenic tumor areas on F-FDG PET and attenuation values between 10 and 30 Hounsfield units (HUs) on CT, was assessed blinded to outcome. Univariate Cox regression survival analyses of progression free survival (PFS) were performed. Necrosis was observed in 18.3% of cHL patients. Bulky disease (tumor mass >10 cm in any direction) (P = 0.002) and TLG (P = 0.041) but no other semiquantitative parameters were significantly associated with necrosis. In exploratory univariate survival analysis for PFS the covariates IPS, bulky disease, MTV and TLG were prognostic, while necrosis was not.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Fluorodeoxyglucose F18; Hodgkin Disease; Humans; Male; Middle Aged; Necrosis; Positron-Emission Tomography; Prednisone; Prognosis; Progression-Free Survival; Survival Analysis; Vincristine; Young Adult
PubMed: 31363153
DOI: 10.1038/s41598-019-47453-5 -
Blood Oct 2019Patients with advanced-stage Hodgkin lymphoma (HL) demonstrated excellent 2-year progression-free survival (PFS) after receiving positron emission tomography... (Clinical Trial)
Clinical Trial
Patients with advanced-stage Hodgkin lymphoma (HL) demonstrated excellent 2-year progression-free survival (PFS) after receiving positron emission tomography (PET)-adapted therapy on SWOG S0816. Patients received 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Patients achieving complete response (CR) on PET scan following cycle 2 of ABVD (PET2) continued 4 additional cycles of ABVD. Patients not achieving CR on PET2 were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for 6 cycles. After a median follow-up of 5.9 years, a subset of 331 eligible patients with central review of PET2 was analyzed. PET2 was negative in 82% and positive in 18%. For all patients, the estimated 5-year PFS and OS was 74% (95% confidence interval [CI], 69%-79%) and 94% (95% CI, 91%-96%), respectively. For PET2- and PET2+ patients, the 5-year PFS was 76% (95% CI, 70%-81%) and 66% (95% CI, 52%-76%), respectively. Seven (14%) and 6 (2%) patients reported second cancers after treatment with eBEACOPP and ABVD, respectively (P = .001). Long-term OS of HL patients treated on S0816 remains high. Nearly 25% of PET2- patients experienced relapse events, demonstrating limitations ABVD therapy and of the negative predictive value of PET2. In PET2+ patients who received eBEACOPP, PFS was favorable, but was associated with a high rate of second malignancies compared with historical controls. Our results emphasize the importance of long-term follow-up, and the need for more efficacious and less toxic therapeutic approaches for advanced-stage HL patients. This trial was registered at www.clinicaltrials.gov as #NCT00822120.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Female; Follow-Up Studies; Hodgkin Disease; Humans; Male; Middle Aged; Neoplasm Staging; Positron-Emission Tomography; Prednisone; Procarbazine; Vinblastine; Vincristine; Young Adult
PubMed: 31331918
DOI: 10.1182/blood.2019000719 -
Annals of Oncology : Official Journal... Aug 2019The prognosis of Hodgkin lymphoma (HL) is excellent rendering research into treatment complications highly important. An important complication of cancer and its...
BACKGROUND
The prognosis of Hodgkin lymphoma (HL) is excellent rendering research into treatment complications highly important. An important complication of cancer and its treatment is thrombosis. Thrombotic events are regularly observed in HL patients but precise information on incidence and risk factors is lacking and the value of prophylactic anticoagulation unclear.
PATIENTS AND METHODS
Thus, we comprehensively studied thrombotic events in 5773 patients from the German Hodgkin Study Group (GHSG) HD13-15 trials in early-favorable, intermediate and advanced HL. We estimated the incidence of and identified risk factors for thrombotic events. Additionally, we provide detailed data on the time course and characteristics of thrombotic events.
RESULTS
A total of 193 thrombotic events occurred for an incidence of 3.3%. Out of these, 175 (90.7%) were venous thromboses, 3 (1.5%) newly emerging post-thrombotic syndromes and 15 (7.8%) arterial thromboses. There were 11 (0.7%) events in early-favorable, 27 (1.3%) in early-unfavorable and 155 (7.3%) in advanced patients, the latter incidence being significantly higher (P < 0.001). The most common locations were deep vein thrombosis of the arm (46.3%) and leg (24.6%). Most venous thrombotic events occurred during chemotherapy (78.9%). We observed 59 (30.6%) catheter-associated events and a descriptively increased risk of venous thrombotic events in patients with oral contraception use during treatment (6.8% versus 3.9%). In advanced HL, the incidence of venous thrombotic events was increased upon treatment with BEACOPP-14 (9.4%, P = 0.0079) compared with 5.1% with 6×BEACOPPesc and 5.7% with 8×BEACOPPesc. Among commonly applied risk factors, including the Khorana score, only age and smoking were prognostic.
CONCLUSIONS
The incidence of thrombotic events in advanced stage HL is comparable to other high-risk cancer patients, especially if treated with dose-dense regimens. Additional risk factors are higher age and smoking. Selected HL patients could benefit from prophylactic anticoagulation, however, further interventional studies are needed before general recommendations can be made.
Topics: Administration, Intravenous; Administration, Oral; Adolescent; Adult; Aged; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Catheters; Contraceptives, Oral; Female; Germany; Hodgkin Disease; Humans; Incidence; Male; Middle Aged; Neoplasm Staging; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Thrombosis; Young Adult
PubMed: 31132094
DOI: 10.1093/annonc/mdz168 -
British Journal of Haematology Aug 2019F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) is used for staging classical Hodgkin lymphoma (cHL) with high sensitivity for...
F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) is used for staging classical Hodgkin lymphoma (cHL) with high sensitivity for skeletal involvement. However, it is unclear whether a single bone lesion carries the same adverse prognosis as multifocal lesions and if this is affected by type of chemotherapy [ABVD (adriamycin, bleomycin, vincristine, dacarbazine) versus BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone)]. We reviewed the clinico-pathological and outcome data from 209 patients with newly diagnosed cHL staged by FDG-PET/CT. Patterns of skeletal/bone marrow uptake (BMU) were divided into 'low' and 'high' diffuse BMU (i.e. without focal lesions), and unifocal or multifocal lesions. Additional separate survival analysis was performed, taking type of chemotherapy into account. Forty patients (19·2%) had skeletal lesions (20 unifocal, 20 multifocal). The 3-year progression-free-survival (PFS) was 80% for patients with 'low BMU', 87% for 'high BMU', 69% for 'unifocal' and 51% for 'multifocal' lesions; median follow-up was 38 months. The presence of bone lesions, both uni- and multifocal, was associated with significantly inferior PFS (log rank P = 0·0001), independent of chemotherapy type. Thus, increased diffuse BMU should not be considered as a risk factor in cHL, whereas unifocal or multifocal bone lesions should be regarded as important predictors of adverse outcome, irrespective of the chemotherapy regimen used.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Neoplasms; Disease-Free Survival; Female; Fluorodeoxyglucose F18; Hodgkin Disease; Humans; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Retrospective Studies; Sweden; Treatment Outcome; Young Adult
PubMed: 31115045
DOI: 10.1111/bjh.15933 -
Critical Reviews in Oncology/hematology Jun 2019Neutropenia, specifically febrile neutropenia (FN), can have profound sequelae (infection, hospitalization, mortality), and the risk of its development differs across... (Review)
Review
Neutropenia, specifically febrile neutropenia (FN), can have profound sequelae (infection, hospitalization, mortality), and the risk of its development differs across chemotherapy regimens/according to patient characteristics. We conducted a comprehensive literature review regarding neutropenia in frontline treatment of adults with advanced Hodgkin lymphoma. Guidelines state primary prophylaxis (PP) with colony-stimulating factors (CSFs) should be implemented when the risk of FN is ≥20%; CSF PP is given with standard-of-care escalated BEACOPP, but the risk of FN with standard-of-care ABVD does not necessitate routine PP. Notably, the risk of neutropenia (including FN) is higher in clinical practice versus clinical studies, and physicians overestimate their adherence to CSF guidelines. ECHELON-1 demonstrated higher FN rates with brentuximab vedotin plus AVD (A + AVD) compared with ABVD (19% vs 8%) and led to the recommendation of PP with granulocyte-CSF (G-CSF) for all A + AVD patients, highlighting the importance of readjusting our risk-assessment thinking as standard backbone regimens are modified.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Febrile Neutropenia; Female; Hodgkin Disease; Humans; Incidence; Risk Factors
PubMed: 31092364
DOI: 10.1016/j.critrevonc.2019.03.016 -
Polish Archives of Internal Medicine Apr 2019INTRODUCTION Escalated BEACOPP (escBEACOPP: bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) significantly improves overall...
Early chemotherapy de-escalation strategy in patients with advanced-stage Hodgkin lymphoma with negative positron emission tomography scan after 2 escalated BEACOPP cycles.
INTRODUCTION Escalated BEACOPP (escBEACOPP: bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) significantly improves overall response rates (ORRs) and prolongs progression‑free survival (PFS) in patients with advanced‑stage Hodgkin lymphoma (HL). However, 6 to 8 cycles of escBEACOPP are associated with increased acute toxicity and late complications. OBJECTIVES We aimed to determine the role of early positron emission tomography-computed tomography (PET‑CT) response assessment in a de‑escalation strategy. PATIENTS AND METHODS We retrospectively analyzed 188 consecutive patients with advanced‑stage HL treated at diagnosis. Patients received 2 cycles of escBEACOPP followed by an early PET‑CT response assessment performed after 2 cycles of chemotherapy (PET2). Patients with an active disease continued therapy with escBEACOPP, while those with negative PET2 were de‑escalated to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Radiotherapy was allowed in patients with stage IIBX. RESULTS PET2 allowed for de‑escalation of therapy in 141 patients (75%). Their ORR was 92.2%, with a complete remission (CR) rate of 91.5%; 10‑year PFS and overall survival (OS) were 87.2% and 95%, respectively. In the whole cohort, ORR was 87.8% (CR, 85.6%), while the 10‑year PFS and OS were 79.3% and 89.4%, respectively. Hematological and thromboembolic complications were significantly more frequent in patients treated with 6 escBEACOPP cycles, including febrile neutropenia (25 patients, [53.2%] vs 7 [5%]), serious anemia (35 [74.5%] vs 11 [7.8%]), or thrombocytopenia (16 [34%] vs 7 [5%]) (P <0.001 for all comparisons with de‑escalation strategy) as well as pulmonary embolism (3 [6.4%] vs 0) (P = 0.02). CONCLUSIONS The early de‑escalation strategy allows for effective treatment of advanced HL, with a comparable efficacy to that of 6 to 8 cycles of escBEACOPP, but with significantly reduced toxicity.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Etoposide; Female; Follow-Up Studies; Hodgkin Disease; Humans; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Prednisone; Procarbazine; Retrospective Studies; Survival Analysis; Treatment Outcome; Vincristine
PubMed: 30945698
DOI: 10.20452/pamw.14786 -
Turkish Journal of Haematology :... May 2019
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Eruptions; Etoposide; Female; Hodgkin Disease; Humans; Prednisone; Procarbazine; Vincristine
PubMed: 30600679
DOI: 10.4274/tjh.galenos.2019.2018.0317 -
Cancer Management and Research 2018Combined chemotherapy is the cornerstone treatment for patients with advanced Hodgkin lymphoma (HL). The objective of our study was to perform a network meta-analysis of...
BACKGROUND
Combined chemotherapy is the cornerstone treatment for patients with advanced Hodgkin lymphoma (HL). The objective of our study was to perform a network meta-analysis of the efficacy of different chemotherapy regimens in adults with advanced-stage HL.
MATERIALS AND METHODS
We searched for relevant randomized controlled trials (RCTs) in titles/abstracts in PubMed, Embase, and the Cochrane Library. The search was last updated on April 3, 2018. RCTs that assessed the effectiveness of one of the following treatments were included: doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); four cycles of increased dose of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by two or four cycles of standard dose of BEACOPP (4× BEACOPP + 2 or 4× BEACOPP); brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD); doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone combined with radiation therapy (Stanford V); mechlorethamine (cyclophosphamide), vincristine, procarbazine, and prednisone (M[C] OPP); sequential or alternating chemotherapy regimens with ABVD as the footstone (eg, COPP/ABVD or mechlorethamine, vincristine, procarbazine, and prednisone [MOPP]/ABVD); eight cycles of BEACOPP; hybrid MOPP/ABV; and M[C]EC (M[C]OPP with epidoxorubicin, bleomycin, vinblastine [EBV], and lomustine, doxorubicin, and vindesine [CAD]).
RESULTS
Overall, we screened 3,564 citations and deemed 18 reports of 16 trials eligible and included them in our network meta-analysis. A total of 11,928 participants were randomly assigned to one of the 12 combinations of chemotherapy regimens, of which 11,476 participants were analyzed. For the overall survival (OS), no differences were observed within any interventions when the ABVD regimen was used as the reference treatment. Similarly, relative to A+AVD, 8× BEACOPP and 6× BEACOPP also showed no differences (HR =1.07, 95% credible interval (CrI): 0.58-1.95; HR =0.62, 95% CrI: 0.16-1.83; and HR =0.71, 95% CrI: 0.30-1.72, respectively). In terms of complete remission (CR), enough evidence exists to support a maximum clinical treatment effect for 6× BEACOPP (OR =1.88, 95% CrI: 1.20-2.96; and OR =3.43, 95% CrI: 1.87-6.24).
CONCLUSION
When compared across the 12 combined chemotherapy regimens, six cycles of BEACOPP may be the optimal treatment for patients with advanced-stage HL.
PubMed: 30538551
DOI: 10.2147/CMAR.S179356