Summary of findings 1. Comparison of interim PET‐negative and interim PET‐positive individuals with Hodgkin Lymphoma.
| Comparison of interim PET‐positive and interim PET‐negative participants with Hodgkin lymphoma | ||||||
| Population: Individuals with Hodgkin lymphoma Setting: Eleven studies recruited participants from a total of 28 haemato‐oncology treatment centres/hospitals in Brazil (N = 1), China (N = 1), Denmark (N = 4), France (N = 4), Italy (N = 3), Poland (N = 11), UK (N = 2) and the USA (N = 2). One study (Straus 2011) included participants from 29 institutions, but did not report the countries. One study (Simon 2016) reported the country (Hungary) but not the number of centres. One multi‐centre study (Hutchings 2014) recruited participants from four countries (USA, Italy, Poland and Denmark). One RCT (Kobe 2018) included participants from 301 hospitals and private practices in Germany, Switzerland, Austria, the Netherlands, and the Czech Republic. | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with Interim PET‐negative | Risk with Interim PET‐positive | |||||
| Overall survival Follow up: 3 years |
Low | HR 5.09 (2.64 to 9.81) | 1802 (9 studies) | ⊕⊕⊕⊝ MODERATE 2 3 4 | ||
| 900 per 1.000 1 | 585 per 1.0001 (356 to 757) | |||||
| High | ||||||
| 980 per 1.000 1 | 902 per 1.0001 (820 to 948) | |||||
| Progression‐free survival Follow up: 3 years |
Low | HR 4.90 (3.47 to 6.90) | 2079 (14 studies) | ⊕⊝⊝⊝ VERY LOW6 7 8 | ||
| 850 per 1.000 5 | 451 per 1.000 5 (326 to 569) | |||||
| High | ||||||
| 940 per 1.000 5 | 738 per 1.000 5 (653 to 807) | |||||
| 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 (2 studies) | ⊕⊕⊕⊝ MODERATE 9 | ||
| 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 (4 studies)10 | ⊕⊕⊝⊝ LOW 11 12 | ||
| *The survival in the PET‐positive group (and its 95% confidence interval) is based on the assumed survival in the PET‐negative group. CI: Confidence interval; HR: Hazard ratio; PET: positron emission tomography | ||||||
| GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect | ||||||
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.