Resultados provisionales de la TEP para el pronóstico en adultos con linfoma de Hodgkin: revisión sistemática y metanálisis de los estudios de factores pronósticos
Información
- DOI:
- https://doi.org/10.1002/14651858.CD012643.pub3Copiar DOI
- Base de datos:
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- Cochrane Database of Systematic Reviews
- Versión publicada:
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- 13 enero 2020see what's new
- Tipo:
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- Prognosis
- Etapa:
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- Review
- Grupo Editorial Cochrane:
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Grupo Cochrane de Hematología
- Copyright:
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- Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cifras del artículo
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Autores
Contributions of authors
Angela Aldin: screening and selection of studies, development of data extraction form, data extraction, 'Risk of bias' assessment, GRADE assessment, data analysis interpretation, 'Summary of findings' tables, writing and drafting of the review, communication with and between authors.
Lisa Umlauff: 'Risk of bias' assessment, characteristics of included and excluded studies (texts and tables), abstract and Plain language summary, proofread and commented on the draft.
Karel Moons: methodological input on reviews of prognosis studies.
Lise J Estcourt: screening and selection of studies, data extraction, risk of bias assessment, clinical and methodological input.
Andreas Engert: medical and content input, particularly on the clinical comparability of studies and subgroup analysis.
Carsten Kobe: nuclear medical input on PET‐CT.
Bastian von Tresckow: clinical input, particularly on the clinical comparability of studies and subgroup analysis.
Gary Collins: methodological input on reviews of prognostic studies.
Madhuri Haque: screening and selection of studies.
Farid Foroutan: input on risk of bias and GRADE assessment of prognostic factor studies.
Nina Kreuzberger: 'Risk of bias' assessment, proofread and commented on the review draft.
Marialena Trivella: screening and selection of studies, data extraction, risk of bias assessment, statistical analysis, proofread and commented on the review draft.
Nicole Skoetz: protocol development, screening and selection of studies, data extraction, risk of bias assessment, GRADE assessment, proofread and commented on the review draft.
Sources of support
Internal sources
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University Hospital of Cologne, Germany
Cochrane Haematological Malignancies, Department 1 of Internal Medicine
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NHS Blood and Transplant, UK
External sources
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Federal Ministry of Education and Research, Germany
Funding Number 01KG1709
Declarations of interest
Angela Aldin: award of the grant by Federal Ministry of Education and Research for the University Hospital of Cologne to perform this systematic review does not lead to a conflict of interest.
Lisa Umlauff: award of the grant by Federal Ministry of Education and Research for the University Hospital of Cologne to perform this systematic review does not lead to a conflict of interest.
Karel Moons: none known.
Lise J Estcourt: award of the grant by Federal Ministry of Education and Research to the University of Oxford to perform this systematic review does not lead to a conflict of interest.
Andreas Engert: award of the grant by Federal Ministry of Education and Research for the University Hospital of Cologne to perform this systematic review does not lead to a conflict of interest. Principal investigator of the HD18 trial, does not lead to a conflict of interest. Received funds from Takeda Pharma GmbH, BMS and MSD for consultancy and educational presentations, but these were not related to the intervention in this review. No competing interests.
Carsten Kobe: award of the grant by Federal Ministry of Education and Research for the University Hospital of Cologne to perform this systematic review does not lead to a conflict of interest.
Bastian von Tresckow: award of the grant by Federal Ministry of Education and Research for the University Hospital of Cologne to perform this systematic review does not lead to a conflict of interest. Received funds from Novartis Pharma GmbH, Takeda Pharma GmbH and MSD for consultancy and educational presentations, but these were not related to the intervention in this review. No competing interests.
Gary Collins: supported by the NIHR Biomedical Research Centre, Oxford, and Cancer Research UK (programme grant: C49297/A27294). No conflict of interest.
Madhuri Haque: award of the grant by Federal Ministry of Education and Research for the University Hospital of Cologne to perform this systematic review does not lead to a conflict of interest.
Farid Foroutan: none known.
Nina Kreuzberger: award of the grant by Federal Ministry of Education and Research for the University Hospital of Cologne to perform this systematic review does not lead to a conflict of interest.
Marialena Trivella: part of the grant from the Federal Ministry of Education and Research to the University Hospital of Cologne, was paid to the University of Oxford for author time spent working on this review. However, the funder played no part in the design and execution of the project and it does not constitute a conflict of interest.
Nicole Skoetz: award of the grant by Federal Ministry of Education and Research for the University Hospital of Cologne to perform this systematic review does not lead to a conflict of interest.
Acknowledgements
This review was published in collaboration with the Cochrane Fast‐Track Service. We particularly thank Helen Wakeford (Managing Editor) and Heather Maxwell (copy‐editor) for their support. The Fast‐Track Service team made comments on the review and managed the editorial process.
We thank Nicola Köhler of the Cochrane Haematological Malignancies (CHM) Editorial Base as well as the editors Dr. Julia Bohlius and PD Dr. Sebastian Theurich and the consumer editor Anne Lyddiatt for commenting on the protocol of this review.
We thank Ina Monsef of CHM for developing the search strategy and conducting the search for this review, and Marius Goldkuhle and Vanessa Piechotta for commenting on the first submitted draft of this review.
We thank Jill Hayden for her help with the QUIPS tool, and particularly for agreeing to our adaptation of the tool for the purpose of this review.
We thank Yu‐Tian Xiao for the translation of the Chinese publication (Ying 2014).
We thank all principal investigators who have replied to all of our questions and provided us with more information or data, thereby helping us to include as many studies as possible in our analysis. Hence, we want to thank Prof. Dr. Jan Maciej Zaucha, Prof. Dr. Andrea Gallamini, Prof. Dr. Peter Borchmann and his colleague Helen Görgen, Prof. Dr. Pier Luigi Zinzani, Dr. Martin Hutchings, Prof. Dr. Marc André and his colleague Dr. John Raemaekers.
We thank Kym Snell and Sarah Hodgkinson for commenting on the first submitted draft of this review, as well as Robin Featherstone for commenting on the search strategy.
We thank all external peer‐reviewers who read and commented on this review. We thank Robert Wolff, Bob Phillips, Michel Meignan, Tim Illidge, Julian Higgins and Ulrike Holtkamp who greatly helped to improve this review.
The research was supported by NHS Blood and Transplant and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
Version history
| Published | Title | Stage | Authors | Version |
| 2020 Jan 13 | Interim PET‐results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta‐analysis of prognostic factor studies | Review | Angela Aldin, Lisa Umlauff, Lise J Estcourt, Gary Collins, Karel GM Moons, Andreas Engert, Carsten Kobe, Bastian Tresckow, Madhuri Haque, Farid Foroutan, Nina Kreuzberger, Marialena Trivella, Nicole Skoetz | |
| 2019 Sep 16 | Interim PET‐results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta‐analysis of prognostic factor studies | Review | Angela Aldin, Lisa Umlauff, Lise J Estcourt, Gary Collins, Karel GM Moons, Andreas Engert, Carsten Kobe, Bastian von Tresckow, Madhuri Haque, Farid Foroutan, Nina Kreuzberger, Marialena Trivella, Nicole Skoetz | |
| 2017 Apr 26 | Interim PET for prognosis in adults with Hodgkin lymphoma: a prognostic factor exemplar review | Protocol | Nicole Skoetz, Gary Collins, Karel Moons, Lise J Estcourt, Andreas Engert, Carsten Kobe, Bastian von Tresckow, Marialena Trivella | |
Differences between protocol and review
We included studies that evaluated both adult and adolescent participants (the youngest being 13 years old), as opposed to including adult participants ( ≥ 18 years of age) only as stated in the protocol of this review. Hodgkin lymphoma is a disease with a typical onset in adolescence to mid‐adulthood, with little physiological differences between adolescents and adults. In the studies included in this review, participants under the age of 18 were treated in the same clinic and received the same treatment as participants over ≥ 18 years of age. We believe that the results regarding interim PET are equally relevant to adolescents as they are to adult participants and, therefore, did not see reasons against the inclusion of studies including both younger and older adults. Nevertheless, we did not include studies that evaluated solely paediatric participants. In studies where only paediatric participants are included, it is more likely they will be treated in paediatric clinics and receive a different treatment regimen than adult participants.
We used an amended version of the Quality in Prognostic Factor Studies (QUIPS) tool to assess the risk of bias of the included studies. In consultation with Hayden and colleagues (Hayden 2013), we adapted the QUIPS tool by adding 'unclear (no information)' as a fourth judgement in the tool. In addition, we renamed the fifth domain of the tool, originally named 'study confounding', into 'other prognostic factors (covariates)', to highlight the importance of adjusting for other prognostic factors and distinguish it from confounding. Lastly, we assessed all six domains (study participation, study attrition, prognostic factor measurement, outcome measurement, other prognostic factors (covariates), statistical analysis and reporting) per outcome (OS and PFS) in each study. The first three domains ended up always receiving the same judgement as they are indeed to be considered at study level. With regard to the outcomes, however, we identified differences in analysis and reporting within studies.
With regard to data extraction, we developed our own data extraction form specific to prognostic factor studies (particularly those that are included in this review), which includes more items than stipulated in the protocol of this review.
Lastly, we searched Embase as an additional database, as well as one trial registry (ClinicalTrials.gov).
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
Medical Subject Headings Check Words
Humans; Young Adult;
Study flow diagram according to PRISMA
'Risk of bias' assessment according to QUIPS (Quality in Prognostic Studies) by outcome.
Forest plot of comparison: 1 Univariable comparison of PET+ve vs. PET‐ve, outcome: 1.1 Overall survival
Forest plot of comparison: 1 Univariable comparison of PET+ve vs. PET‐ve, outcome: 1.2 Progression‐free survival
Comparison 1: Univariable comparison of PET+ve vs. PET‐ve, Outcome 1: Overall survival
Comparison 1: Univariable comparison of PET+ve vs. PET‐ve, Outcome 2: Progression‐free survival
Comparison 2: Subgroups in univariable comparison of OS: PET+ve vs. PET‐ve, Outcome 1: OS by radiotherapy
Comparison 2: Subgroups in univariable comparison of OS: PET+ve vs. PET‐ve, Outcome 2: OS by study design
Comparison 2: Subgroups in univariable comparison of OS: PET+ve vs. PET‐ve, Outcome 3: OS by chemotherapy
Comparison 2: Subgroups in univariable comparison of OS: PET+ve vs. PET‐ve, Outcome 4: OS for PET/CT vs PET
Comparison 2: Subgroups in univariable comparison of OS: PET+ve vs. PET‐ve, Outcome 5: OS by disease stage
Comparison 2: Subgroups in univariable comparison of OS: PET+ve vs. PET‐ve, Outcome 6: Timing of interim PET
Comparison 2: Subgroups in univariable comparison of OS: PET+ve vs. PET‐ve, Outcome 7: OS by HR type of estimation
Comparison 3: Subgroups in univariable comparison of PFS: PET+ve vs. PET‐ve, Outcome 1: PFS by study design
Comparison 3: Subgroups in univariable comparison of PFS: PET+ve vs. PET‐ve, Outcome 2: PFS by chemotherapy
Comparison 3: Subgroups in univariable comparison of PFS: PET+ve vs. PET‐ve, Outcome 3: PFS for PET/CT vs PET
Comparison 3: Subgroups in univariable comparison of PFS: PET+ve vs. PET‐ve, Outcome 4: PFS by disease stage
Comparison 3: Subgroups in univariable comparison of PFS: PET+ve vs. PET‐ve, Outcome 5: PFS by radiotherapy
Comparison 3: Subgroups in univariable comparison of PFS: PET+ve vs. PET‐ve, Outcome 6: Timing of interim PET
Comparison 3: Subgroups in univariable comparison of PFS: PET+ve vs. PET‐ve, Outcome 7: PFS by HR type of estimation
| Comparison of interim PET‐positive and interim PET‐negative participants with Hodgkin lymphoma | ||||||
| Population: Individuals with Hodgkin lymphoma | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with Interim PET‐negative | Risk with Interim PET‐positive | |||||
| Overall survival Follow up: 3 years | Low | HR 5.09 | 1802 | ⊕⊕⊕⊝ | ||
| 900 per 1.000 1 | 585 per 1.0001 | |||||
| High | ||||||
| 980 per 1.000 1 | 902 per 1.0001 | |||||
| Progression‐free survival Follow up: 3 years | Low | HR 4.90 | 2079 | ⊕⊝⊝⊝ | ||
| 850 per 1.000 5 | 451 per 1.000 5 | |||||
| High | ||||||
| 940 per 1.000 5 | 738 per 1.000 5 | |||||
| Adverse events associated with PET ‐ not reported | No study measured PET‐associated adverse events. | ‐ | ‐ | ‐ | ||
| Overall survival (adjusted effect estimate) | Two studies reported an adjusted effect estimate for overall survival after interim PET2: a hazard ratio of 3.2 (95% CI 1.3 to 8.4, P = 0.02) (Kobe 2018) and 11.51 (95% CI 3.14 to 42.86, P < 0.001) (Simon 2015) indicates the independent prognostic value of interim PET over and above other clinically relevant prognostic factors. | ‐ | 843 | ⊕⊕⊕⊝ | ||
| Progression‐free survival (adjusted effect estimate) | Eight studies conducted a multivariable analysis to test the independent prognostic value of interim PET over and above other clinically relevant prognostic factors. Four of these studies reported a hazard ratio as the adjusted effect estimate, of which the value ranges from 2.4 to 36.89, indicating the independent prognostic value of interim PET2.10 | ‐ | 996 | ⊕⊕⊝⊝ | ||
| *The survival in the PET‐positive group (and its 95% confidence interval) is based on the assumed survival in the PET‐negative group. | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 The assumed event‐free survival in the control group is based on the survival rate of the interim PET‐negative participants at 3 years in the studies included (the lowest survival rate from Cerci 2010 and the highest survival rate from Kobe 2018). 2 High risk of bias in seven studies for the domain 'other prognostic factors (covariates)', and high risk of bias in three studies for the domain 'statistical analysis and reporting'. Downgraded by 1 point for risk of bias. 3 For one study we used the reported hazard ratio. For seven studies we had to estimate the hazard ratio and for one study we re‐calculated it (Trivella 2006). Downgraded by 1 point for imprecision. 4 Upgraded by one point due to the large effect showing the large difference between interim PET‐negative and interim PET‐positive participants (HR 5.09, CI 2.64 to 9.81). 5 The assumed event‐free survival in the control group is based on the survival rate of the interim PET‐negative participants at 3 years in the studies included (the lowest survival rate from Rossi 2014 and the highest survival rate from Kobe 2018). 6 High risk of bias in eight studies for the domain 'other prognostic factors (covariates)', and high risk of bias in six studies for the domain 'statistical analysis and reporting'. Downgraded by 1 point for risk of bias. 7The definition of PFS varied across studies, downgraded by 1 point for inconsistency 8 For three studies we used the reported hazard ratio. For ten studies we had to estimate the value, and for one study we had to re‐calculate it (Trivella 2006). Downgraded by 1 point for imprecision. 9 High risk of bias for the domains 'other prognostic factors (covariates)' and statistical analysis and reporting for one study (Simon 2016). Downgraded by 1 point for risk of bias. 10Hutchings 2006; Kobe 2018; Mesguich 2016; Simon 2016. 11 High risk of bias for the domains 'other prognostic factors (covariates)' and statistical analysis and reporting for one study (Simon 2016). Also high risk of bias for the domain study participation in one study (Hutchings 2006). Downgraded by 1 point for risk of bias. 12 Studies included a heterogenous set of covariates in the adjusted analyses. Downgraded by 1 point for inconsistency. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Overall survival Show forest plot | 9 | 1802 | Hazard Ratio (IV, Random, 95% CI) | 5.09 [2.64, 9.81] |
| 1.2 Progression‐free survival Show forest plot | 14 | 2079 | Hazard Ratio (IV, Random, 95% CI) | 4.90 [3.47, 6.90] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 OS by radiotherapy Show forest plot | 9 | 1802 | Hazard Ratio (IV, Random, 95% CI) | 5.09 [2.64, 9.81] |
| 2.1.1 Involved node and/or site | 3 | 548 | Hazard Ratio (IV, Random, 95% CI) | 3.45 [1.22, 9.72] |
| 2.1.2 involved field | 4 | 428 | Hazard Ratio (IV, Random, 95% CI) | 12.75 [4.98, 32.68] |
| 2.1.3 not specified | 2 | 826 | Hazard Ratio (IV, Random, 95% CI) | 2.80 [1.17, 6.67] |
| 2.2 OS by study design Show forest plot | 8 | 1717 | Hazard Ratio (IV, Random, 95% CI) | 4.63 [2.43, 8.80] |
| 2.2.1 Prospective | 3 | 406 | Hazard Ratio (IV, Random, 95% CI) | 5.35 [1.07, 26.68] |
| 2.2.2 Retrospective | 4 | 589 | Hazard Ratio (IV, Random, 95% CI) | 7.12 [3.14, 16.14] |
| 2.2.3 RCT | 1 | 722 | Hazard Ratio (IV, Random, 95% CI) | 2.60 [1.03, 6.56] |
| 2.3 OS by chemotherapy Show forest plot | 9 | 1802 | Hazard Ratio (IV, Random, 95% CI) | 5.09 [2.64, 9.81] |
| 2.3.1 ABVD | 5 | 801 | Hazard Ratio (IV, Random, 95% CI) | 5.19 [2.11, 12.72] |
| 2.3.2 ABVD and/or other | 3 | 279 | Hazard Ratio (IV, Random, 95% CI) | 10.30 [1.71, 62.13] |
| 2.3.3 BEACOPP | 1 | 722 | Hazard Ratio (IV, Random, 95% CI) | 2.60 [1.03, 6.56] |
| 2.4 OS for PET/CT vs PET Show forest plot | 8 | 1706 | Hazard Ratio (IV, Random, 95% CI) | 5.01 [2.50, 10.02] |
| 2.4.1 PET/CT | 5 | 595 | Hazard Ratio (IV, Random, 95% CI) | 4.70 [1.86, 11.86] |
| 2.4.2 PET only | 3 | 1111 | Hazard Ratio (IV, Random, 95% CI) | 6.99 [1.58, 30.90] |
| 2.5 OS by disease stage Show forest plot | 9 | 1802 | Odds Ratio (IV, Random, 95% CI) | 5.09 [2.64, 9.81] |
| 2.5.1 Stages I and II with A and B symptoms | 1 | 96 | Odds Ratio (IV, Random, 95% CI) | 9.21 [0.71, 120.03] |
| 2.5.2 All stages | 7 | 984 | Odds Ratio (IV, Random, 95% CI) | 6.28 [2.62, 15.05] |
| 2.5.3 Advanced | 1 | 722 | Odds Ratio (IV, Random, 95% CI) | 2.60 [1.03, 6.56] |
| 2.6 Timing of interim PET Show forest plot | 9 | 1802 | Hazard Ratio (IV, Random, 95% CI) | 5.09 [2.64, 9.81] |
| 2.6.1 PET2 | 6 | 1495 | Hazard Ratio (IV, Random, 95% CI) | 3.53 [1.97, 6.32] |
| 2.6.2 Other (including mixed) | 3 | 307 | Hazard Ratio (IV, Random, 95% CI) | 20.13 [5.04, 80.38] |
| 2.7 OS by HR type of estimation Show forest plot | 9 | 1802 | Hazard Ratio (IV, Random, 95% CI) | 5.09 [2.64, 9.81] |
| 2.7.1 precise | 7 | 1638 | Hazard Ratio (IV, Random, 95% CI) | 5.70 [2.60, 12.48] |
| 2.7.2 Imprecise | 2 | 164 | Hazard Ratio (IV, Random, 95% CI) | 3.60 [0.89, 14.64] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 PFS by study design Show forest plot | 13 | 1349 | Hazard Ratio (IV, Random, 95% CI) | 5.66 [4.02, 7.97] |
| 3.1.1 prospective | 3 | 357 | Hazard Ratio (IV, Random, 95% CI) | 3.95 [2.23, 7.00] |
| 3.1.2 retrospective | 8 | 827 | Hazard Ratio (IV, Random, 95% CI) | 6.85 [4.66, 10.08] |
| 3.1.3 RCT | 2 | 165 | Hazard Ratio (IV, Random, 95% CI) | 6.21 [2.87, 13.42] |
| 3.2 PFS by chemotherapy Show forest plot | 14 | 2079 | Hazard Ratio (IV, Random, 95% CI) | 4.90 [3.47, 6.90] |
| 3.2.1 ABVD | 7 | 945 | Hazard Ratio (IV, Random, 95% CI) | 5.13 [3.18, 8.27] |
| 3.2.2 ABVD and/or other | 4 | 265 | Hazard Ratio (IV, Random, 95% CI) | 7.07 [3.40, 14.70] |
| 3.2.3 other NON‐ABVD chemo | 3 | 869 | Hazard Ratio (IV, Random, 95% CI) | 3.64 [1.83, 7.24] |
| 3.3 PFS for PET/CT vs PET Show forest plot | 13 | 1983 | Hazard Ratio (IV, Random, 95% CI) | 5.08 [3.57, 7.21] |
| 3.3.1 PET/CT | 8 | 707 | Hazard Ratio (IV, Random, 95% CI) | 6.03 [3.68, 9.90] |
| 3.3.2 PET only | 5 | 1276 | Hazard Ratio (IV, Random, 95% CI) | 4.06 [2.33, 7.08] |
| 3.4 PFS by disease stage Show forest plot | 14 | 2079 | Hazard Ratio (IV, Random, 95% CI) | 4.90 [3.47, 6.90] |
| 3.4.1 Stages I and II with A and B symptoms | 2 | 184 | Hazard Ratio (IV, Random, 95% CI) | 3.88 [1.54, 9.83] |
| 3.4.2 All stages | 11 | 1173 | Hazard Ratio (IV, Random, 95% CI) | 5.81 [3.93, 8.57] |
| 3.4.3 Advanced | 1 | 722 | Hazard Ratio (IV, Random, 95% CI) | 2.27 [1.35, 3.82] |
| 3.5 PFS by radiotherapy Show forest plot | 14 | 2079 | Hazard Ratio (IV, Random, 95% CI) | 4.90 [3.47, 6.90] |
| 3.5.1 Involved node and/or site | 5 | 651 | Hazard Ratio (IV, Random, 95% CI) | 5.35 [2.94, 9.75] |
| 3.5.2 Involved field | 6 | 514 | Hazard Ratio (IV, Random, 95% CI) | 7.06 [4.15, 12.00] |
| 3.5.3 Not specified | 2 | 826 | Hazard Ratio (IV, Random, 95% CI) | 2.97 [1.48, 5.98] |
| 3.5.4 None | 1 | 88 | Hazard Ratio (IV, Random, 95% CI) | 5.09 [1.95, 13.29] |
| 3.6 Timing of interim PET Show forest plot | 14 | 2079 | Hazard Ratio (IV, Random, 95% CI) | 4.90 [3.47, 6.90] |
| 3.6.1 PET2 | 9 | 1677 | Hazard Ratio (IV, Random, 95% CI) | 4.68 [3.14, 6.98] |
| 3.6.2 Other (including mixed) | 5 | 402 | Hazard Ratio (IV, Random, 95% CI) | 6.32 [3.40, 11.75] |
| 3.7 PFS by HR type of estimation Show forest plot | 14 | 2079 | Hazard Ratio (IV, Random, 95% CI) | 4.90 [3.47, 6.90] |
| 3.7.1 precise | 9 | 1450 | Hazard Ratio (IV, Random, 95% CI) | 4.69 [2.84, 7.73] |
| 3.7.2 Imprecise | 5 | 629 | Hazard Ratio (IV, Random, 95% CI) | 5.66 [3.65, 8.77] |
