Patterns of relapse and long-term outcome in patients treated with a curative intent for advanced Hodgkin lymphoma

Figures & data

Figure 1. Rigid co-registration of the staging- and relapse scans for two patients (a–e and f–h). (a) Staging PET/CT-scan. Arrow pointing to an initially involved PET positive supraclavicular lymph node. (b) CT part of the staging PET/CT-scan. Delineation of the PET positive (cyan) and the anatomically involved volume (red). (c) Relapse PET/CT-scan. Arrow pointing to a PET positive relapsed supraclavicular lymph node. (d) CT part of the relapse PET/CT-scan. Delineation of the PET positive (yellow) and the anatomically involved volume (blue). (e) Fusion of the staging- and the relapse PET/CT-scans. The relapse is in the exact same lymph node as initially involved. (f) CT part of the staging PET/CT-scan. Delineation of a PET positive (cyan) and two anatomically involved mediastinal lymph nodes (red). (g) CT part of the relapse PET/CT-scan. Delineation of a PET positive (yellow) and anatomically involved (blue) mediastinal lymph node. (h) Fusion of the staging- and the relapse scans. The relapse is in the exact same lymph node as initially involved.CT: computed tomography; PET: positron emission tomography.

Table 1. Details of relapse locations.

Patient	Relapse in initially involved site(s)	Relapse in other than initially involved site(s)	Relapse in initially irradiated site(s)	Dose to initially involved site(s) with later relapse (Gy)	Largest size of initially involved site with later relapse (cm)	Largest size of any initially involved site (cm)	SUVmax in initially involved site(s) with later relapse (range)	Highest SUVmax in any initially involved site	Largest size of residual CT abnormality after chemo-therapy in initially involved site with later relapse (cm)	Largest size of any residual CT abnormality after chemo-therapy (cm)
1	Yes	Yes	Yes	36/4^a	2.5	5.2	19.6	23.4	1.0	1.0^b
2	Yes	Yes	No RT	N/A	3.1	13.5	2.5–5.4	12.4	N/A*	2.0
3	Yes	Yes	No RT	N/A	1.4	6.6	7.4	22.5	N/A**	N/A**
4	Yes	Yes	No RT	N/A	7.5	7.5	1.8–12.8	14.8	N/A***	N/A***
5	Yes	Yes	No RT	N/A	2.9	5.2	6.7	23.4	N/A**	N/A**
6	Yes	No	No RT	N/A	8.4	8.4	2.7–7.0	15.9	N/A**	N/A**
7	Yes	No	No RT	N/A	4.8	4.8	4.4–13.6	16.7	2.7	2.7
8	Yes	No	No RT	N/A	16.5	16.5	15.5–20.9	20.9	9.1	9.1
9	No	Yes	No RT	N/A	N/A	N/A	N/A	N/A	N/A	N/A

CT: computed tomography; Gy: Gray; N/A: not applicable; RT: radiotherapy; SUV_max: maximum Standardized Uptake Value.

^a One of two initially involved sites with a later relapse, was at the margin of the treatment field, in an area that received at most at total dose of 4 Gy.

^b Only CT thorax available post chemotherapy.

* Relapse not in residual disease.

** No residual disease on CT-scan.

*** Evaluation of residual disease on CT not possible due to scan without contrast.

Table 2. Baseline characteristics.

	All patients		Irradiated patients
	Total		Total
	N	%	N		%
No. of patients	133	100.0	23		100.0
Relapse	9	6.8	1		4.3
Sex
Male	87	65.4	13		56.5
Female	46	34.6	10		43.5
Age, year, median, range	44	16–81	39		17–75
Histology
NS	73	54.9	18		78.3
MC	31	23.3	2		8.7
LR	3	2.3	1		4.3
LD	1	0.8	–		–
cHL, NOS	25	18.8	2		8.7
Clinical stage
III	53	39.8	10		43.5
IV	80	60.2	13		56.5
B-symptoms
No	44	33.1	9		39.1
Yes	88	66.2	14		60.1
Unknown	1	0.8	–		–
Performance status
0	69	51.9	11		47.8
1	51	38.3	11		47.8
2	7	5.3	1		4.3
3	3	2.3	–		–
4	3	2.3	–		–
Bulky disease
≥10 cm	14	10.5	7		30.4
Risk stratification
IPS group
0-3	81	60.9	17		73.9
4-7	48	36.1	6		26.1
Unknown^a	4	3.0	–		–

cHL, NOS: classical Hodgkin lymphoma not otherwise specified; IPS: International Prognostic Score; LD: lymphocyte depletion; LR: lymphocyte rich; MC: mixed cellularity; NS: nodular sclerosis.

^a Patients scoring 3 but with one missing value, why they could be either group had the value been known.

Table 3. Treatment characteristics.

	All patients		Irradiated patients
	Total		Total
	N	%	N	%
No. of patients	133	100.0	23	100.0
Chemotherapy
ABVD^a	76	57.1	11	47.8
A-AVD^b	1	0.8	–	–
BEACOPP	51	38.3	11	47.8
ABVD/BEACOPP	3	2.3	–	–
PVAG	2	1.5	1	4.3
No. of cycles
1–5	13	9.8	–	–
≥6	120	90.2	23	100.0
Radiation therapy
No	110	82.7	–	–
Yes	23	17.3	23	100.0
Dose, Gy, median, range	–	–	36.0	18^c–36
3D-CRT	–	–	22	95.7
VMAT	–	–	1	4.3

A-AVD: brentuximab vedotin, adriamycin, vinblastine, dacarbazine; ABVD: adriamycin, bleomycin, vinblastine, dacarbazine; BEACOPP: bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin, procabazine, prednisone; PVAG: prednisone, vinblastine, adriamycin, gemcitabine; 3D-CRT: three-dimensional conformal radiotherapy; VMAT: volumetric modulated arc therapy.

^a One patient received rituximab in addition to ABVD due to transformation from chronic lymphatic leukemia and CD20 antigens.

^b Patient treated in the ECHELON-1 protocol.

^c One patient died (unknown reason) during radiotherapy and did not receive the fully planned dose.

Figure 2. Overall survival (a) and time to progression (b) for all patients. Overall survival (c) and time to progression (d) stratified on IPS groups. Four patients could not be stratified to a group due to missing values in the IPS and were left out of the stratified analyses. IPS: International Prognostic Score.

Data availability statement

The data generated during the current study are not publicly available due to regulations on personal data protection but are available from the corresponding author on reasonable request.