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The Cochrane Database of Systematic... Jan 2020Hodgkin 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 survival Twelve (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. Four studies were assessed as low risk, and eight studies as high risk of bias for the domain other prognostic factors (covariates). Nine studies were assessed as low risk, and three 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 low risk, and ten studies as high risk of bias for the domain other prognostic factors (covariates). Eight studies were assessed as high risk, thirteen 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 events No 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; Decision Making; Disease Progression; Disease-Free Survival; Hodgkin Disease; Humans; Positron Emission Tomography Computed Tomography; Prognosis; Young Adult
PubMed: 31930780
DOI: 10.1002/14651858.CD012643.pub3 -
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 -
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 -
Hematology Reports Mar 2022Infertility as a consequence of therapy presents a high psychosocial burden for HL patients. In the cohort of our analyzed patients, within the post-ABVD surviving...
Reproductive Issues in Long-Term Surviving Patients following Therapy for Hodgkin's Disease in the Republic of North Macedonia: Risks of Infertility According to First-Line Treatment Regimens.
Infertility as a consequence of therapy presents a high psychosocial burden for HL patients. In the cohort of our analyzed patients, within the post-ABVD surviving patients, alterations of the spermogram were documented in a total of 6.1% of the male patients and 5.4% of the female patients developed amenorrhea. On the other hand, within the subgroup of surviving patients following BEACOPP chemotherapy, 60% of the male patients manifested defects in their spermogram, and as high as 28.6% of the female survivors reported loss of their monthly cycle. It has been reported on several occasions that even prior to treatment, the sperm of HL patients manifests poorer quality characteristics when analyzed against control specimens from healthy male donors. The analyzed results in ABVD-treated male HL patients confirm ABVD to be a safe regimen for males of all age categories, as well as for female patients under the age of thirty. In women above the age of 30, the infertility risk rate is relatively low (14%), which leaves the decision of preserving fertility to themselves. For all BEACOPP-treated female, as well as male patients, a consult with a reproductive medicine specialist is warranted prior to therapy, due to the high infertility risk, and the final decision should be made on an individual basis.
PubMed: 35466177
DOI: 10.3390/hematolrep14020013 -
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 -
British Journal of Haematology Jul 2020
Topics: Adult; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Betacoronavirus; Bleomycin; COVID-19; Coronavirus Infections; Cyclophosphamide; Cytarabine; Dacarbazine; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Hydroxychloroquine; Idarubicin; Mediastinal Neoplasms; Pandemics; Pneumonia, Viral; Positron-Emission Tomography; Prednisone; Procarbazine; SARS-CoV-2; Treatment Outcome; Vinblastine; Vincristine
PubMed: 32379903
DOI: 10.1111/bjh.16798