The effect of radiotherapy on patients with advanced HL who have been treated with the ABVD regimen and have large mass lesions: the final results of the FIL HD0801 study are announced

The role of consolidation radiotherapy (RT) in patients with advanced Hodgkin's lymphoma (HL) is still controversial, mainly because of conflicting results in randomized studies
.

Before the advent of functional imaging, the efficacy of consolidation radiotherapy was only confirmed in patients with large mass lesions at baseline or patients with partial remission after chemotherapy.
At present, with the use of PET/CT, the assessment of remission after chemotherapy is more accurate.
Its uncertainty increases
.

In addition, concerns about the increase in late-stage side effects (especially secondary malignancies and heart disease) have also led to a gradual decrease in the use of radiotherapy
.

Although technological advances have significantly reduced the radiation doses to healthy organs, they may not completely eliminate the risk of long-term complications associated with radiotherapy
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Therefore, many research groups have proposed PET-driven strategies for advanced HL after treatment
.

German researchers conducted the Fondazione Italiana Linfomi HD0801 study to explore the efficacy of consolidation radiotherapy for patients with advanced HL who achieved complete molecular remission (CMR) after chemotherapy and had large mass lesions at baseline.
The results have been announced recently
.

The editor organizes the main content as follows for the reference of readers
.

Research Methods The HD0801 study is a multi-center study.
The inclusion criteria include: age 18-70 years old, newly treated patients with classic HL (except for subtypes predominantly nodular lymphocytes), and Ann Arbor stage IIB-IV , Have at least 1 measurable lesion
.

All patients received first-line treatment with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) regimen and received interim PET2 evaluation
.

The study aims to explore two specific questions: Compared with the data in the literature, whether the early PET-guided rescue treatment consisting of high-dose chemotherapy combined with autologous bone marrow transplantation is safe and effective (phase 2), and the completion of the 6-cycle ABVD program After treatment, whether patients with large mass lesions that remain PET2-negative benefit from consolidation radiotherapy (stage 3)
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The results of the second phase of the study have been announced.
This article mainly introduces the results of the third phase of the study
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In the third phase of the study, patients who achieved CMR after 2 and 6 cycles of ABVD treatment and had large mass lesions (maximum diameter ≥5cm) were randomly assigned to receive consolidation radiotherapy (dose 30Gy) or observation (OBS)
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The primary endpoint is the 2-year event-free survival (EFS) rate, and the secondary endpoint is the 2-year progression-free survival (PFS) rate
.

Research results From September 2008 to April 2013, a total of 520 patients participated in the study.
Finally, 116 patients were randomly assigned to receive consolidation radiotherapy (RT group, 58 patients) or OBS (OBS group, 58 patients)
.

The baseline disease characteristics of randomly assigned patients are shown in Table 1
.

Nine patients assigned to the RT group did not receive consolidation radiotherapy and were excluded from the PP analysis
.

None of the patients assigned to the OBS group received consolidation radiotherapy
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The median size of large mass lesions in the RT group and OBS group were 8.
15 cm and 8.
25 cm (range, 5-20 cm), respectively
.

The median radiation dose is 30 Gy (range, 25-40 Gy)
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Table 1 Survival analysis of patients with baseline characteristics: For EFS, 23 patients recorded at least one event: 14 patients in the RT group and 9 patients in the OBS group
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Disease progression occurred in 17 patients: 9 in the RT group and 8 in the OBS group
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Table 2 details the events recorded according to random grouping
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It is worth noting that of the 9 patients who did not receive the assigned radiotherapy treatment, 5 had disease progression
.

Table 2 Events recorded by the two groups of patients In the ITT analysis, the 2-year EFS rates of the RT group and the OBS group were 87.
8% (95% CI, 76.
0-94.
0) and 85.
8% (95% CI, 73.
6-92.
6), respectively.
HR It was 1.
5 (95% CI, 0.
6-3.
5; stratified log-rank test P=0.
34; Figure 1A)
.

PP analysis showed that the 2-year EFS rates of the RT group and OBS group were 89.
6% (95% CI, 76.
8-95.
6) and 85.
8% (95% CI, 73.
6%-92.
6%), respectively, and the HR was 1.
1 (95% CI, 0.
4-2.
8; Hierarchical log-rank test P=0.
7; Figure 1B)
.

Figure 1 EFS rate (A) ITT analysis; (B) PP analysis In the ITT analysis, the 2-year PFS rates of the RT group and OBS group were 91.
3% (95% CI, 80.
3-96.
3) and 85.
8% (95%) CI, 73.
6-92.
6), HR was 1.
2 (95% CI, 0.
5-3; hierarchical log-rank test P=0.
7; Figure 2A)
.

PP analysis showed that the 2-year PFS rates of the RT group and OBS group were 93.
8% (95% CI, 81.
9-98.
0) and 85.
8% (95% CI, 73.
6-92.
6), respectively, and the HR was 0.
7 (95% CI, 0.
2- 2.
1; Hierarchical log-rank test P=0.
5; Figure 2B)
.

Figure 2 PFS rate (A) ITT analysis; (B) PP analysis toxicity: no acute toxicity events related to radiotherapy were found
.

Regarding late toxicity, only 7 events were recorded in 116 randomly assigned patients: 3 patients (2 in the RT group and 1 in the OBS group) developed a second tumor (1 case of breast cancer, 1 case of follicular lymph) Tumor, 1 case unknown), 1 patient (OBS group) experienced myocardial infarction, 1 patient (RT group) was suspected of having myelodysplastic syndrome and severe respiratory failure, and 1 patient (RT group) had persistent Sexual severe neutropenia (suspected myelodysplastic syndrome), 1 case (RT group) had severe neutropenia and thrombocytopenia
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Only one patient died of myocardial infarction (although he was randomly assigned to the RT group, he did not receive RT treatment)
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Study conclusions The study failed to show the difference in the effect of patients with large mass lesions on EFS and PFS when they received or did not receive consolidation radiotherapy
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In addition, studies have shown that patients who achieve CMR after 6 cycles of ABVD treatment and do not undergo consolidation radiotherapy have a good prognosis
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However, these results are still unclear and cannot directly prove the non-inferiority of OBS.
It cannot be ruled out that some patients will benefit from consolidation radiotherapy.
The next step in the study may be to merge similar studies with updated follow-ups and conduct a meta-analysis of patient data.
The goal is to obtain stronger evidence on the role of consolidation radiotherapy in different risk subgroups
.

Reference source: Umberto Ricardi, Mario Levis, Andrea Evangelista, et al.
Blood Adv (2021) 5 (21): 4504–4514.
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