Brain radiotherapy in patients treated for a newly diagnosed primary central nervous system lymphoma: professional practice evaluation in 19 French centers

Figures & data

Table 1. Demographic and tumoral characteristics at diagnosis.

	Total (n = 79)
Age, years
Median	56
Range	25–79
Sex, no. of patients
Male (%)	44 (55%)
Female (%)	35 (45%)
Pre-RT KPS
Median	80
Range	40–100
Histologically proven DLBCL, no. of patients
Yes (%)	76 (95%)
No (%)	3 (5%)
Ophthalmologic evaluation, no. of patients
Yes (%)	52 (65%)
No (%)	27 (35%)
HD-MTX based induction CT, no. of patients
Yes (%)	75 (95%)
No (%)	4 (5%)
Response to HD-MTX based induction CT, no. of patients	n = 75
CR (%)	54 (72%)
PR (%)	17 (23%)
SD/PD (%)	4 (5%)
Tumoral localization, no. of patients
Ocular (%)	1 (1.25%)
Cerebral (%)	70 (88.75%)
Ocular and cerebral (%)	8 (10%)
Intracerebral lesions, no. of patients	n = 78
Unique (%)	39 (50.6%)
Multiple (%)	39 (49.4%)
Lateralized (%)	57 (73.4%)
Median (%)	7 (8.9%)
Lateralized and median (%)	14 (17.7%)
Supratentorial (%)	57 (73.6%)
Infratentorial (%)	5 (6.4%)
Supra and infratentorial (%)	16 (20%)

RT: radiotherapy; KPS: Karnofsky performance status; DLBCL: diffuse large B-cell lymphoma; HD-MTX: high-dose methotrexate; CT: chemotherapy; CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease.

Figure 1. Evolution of irradiation volumes over time (A) and of the prescribed dose to WBRT (B) in patients who reached CR after HD MTX-based induction CT, according to the date and publications [15,19].

Table 2. Univariate and multivariate analysis of factors affecting overall and progression-free survival in patients treated with HD-MTX-based induction CT.

	Univariate analysis						Multivariate analysis
	OS			PFS			OS
	HR	CI 95%	p-val	HR	CI 95%	p-val	HR	CI 95%	p-val
Irradiation volume			.004			.6			.24
WB/WB plus boost/PB	2.07	1.25; 3.42		1.16	0.65; 2.07		1.48	0.76; 2.89
Total dose to the WB (Gy)			.82			.9
≤30
>30	0.91	0.42; 1.96		1.02	0.49; 2.13
Response to induction CT			.008			.07			.17
CR/PR	2.72	1.29; 5.71		1.96	0.92; 4.18		1.88	0.75; 4.71
Age (years)			<.001			.26			.02
≤60
>60	4.66	2.28; 9.49		1.55	0.72; 3.34		2.98	1.18; 7.51
Pre-RT KPS			.002			.13			.002
>80
≤80	3.59	1.57; 8.23		0.56	0.26; 1.19		3.87	1.61; 9.34
Sex			.052			.6			.57
M (1)
F (2)	0.45	0.21; 1.007		1.2	0.6; 2.38		0.77	0.3; 1.92
Presence of intraocular lymphomatous involvement at diagnosis			.23
No
Yes	0.29	0.03; 2.21		2.26	0.87; 5.84	.09

OS: overall survival; PFS: progression-free survival; HR: hazard ratio; CI: confidence interval; p-val: p value; WB: whole brain; PB: partial brain; RT: radiotherapy; CT: chemotherapy; CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; KPS: Karnofsky performance status.

Table 3. Review of the different published guidelines for the implementation of brain radiotherapy as consolidation treatment of newly diagnosed PCNSL.

	Irradiation dose and volume		Ocular irradiation (associated with brain radiotherapy)
	CR to HD-MTX based CT	PR to HD-MTX based CT	Intraocular lymphomatous involvement at diagnosis: no	Intraocular lymphomatous involvement at diagnosis: yes
French recommendations, LOC network, 2014–2015	WBRT [23–30] Gy [1.8–2] Gy/fr	WBRT 40 Gy [1.8–2] Gy/fr	Respect of the dose constraints: Dmax eyes <40 Gy Dmax lens <10 Gy
ILROG guidelines, 2015 (Yahalom et al.)[15]	WBRT 24 Gy 2 Gy/fr	WBRT [36–45] Gy 1.8 Gy/fr	Inclusion of the posterior third of the eyes in the irradiation target volume	Inclusion of full eyes in the irradiation target volume
Guidelines for the diagnosis and management of PCNSL, 2019 (Fox et al.)[14]	WBRT 36 Gy 1.8 Gy/fr Option: WBRT 23.4 Gy 1.8 Gy/fr	WBRT 36 Gy 1.8 Gy/fr + Boost to 45 Gy 1.8 Gy/fr	Irradiation of full eyes, 30 Gy	Irradiation of full eyes, 36 Gy
NCCN guidelines CNS Cancers, v3.2020	WBRT 23.4 Gy 1.8 Gy/fr	WBRT [30–36] Gy + Boost to 45 Gy 1.8 Gy/fr Option: PBRT 45 Gy 1.8 Gy/fr	Unspecified	Inclusion of full eyes in the irradiation target volume

CR: complete response; PR: partial response; HD-MTX: high-dose methotrexate; CT: chemotherapy; WBRT: whole-brain radiotherapy; PBRT: partial brain radiotherapy; LOC: lymphomes oculo-cérébraux; ILROG: international lymphoma radiation oncology group; PCNSL: primary central nervous system lymphoma; NCCN: national comprehensive cancer network.

Table 4. Proposal from our study for the implementation of brain radiotherapy as consolidation treatment of newly diagnosed PCNSL.

		Irradiation dose and volume		Ocular irradiation (associated with brain radiotherapy)
		CR to HD-MTX based CT	PR to HD-MTX based CT	Intraocular lymphomatous involvement at diagnosis: no	Intraocular lymphomatous involvement at diagnosis: yes
Proposal from our study	Volume	WBRT	WBRT + Boost	Inclusion of the posterior third of the eyes in the irradiation target volume	Inclusion of full eyes in the irradiation target volume
	Dose	23.4 Gy 1.8 Gy/fr	36 Gy 1.8 Gy/fr Boost to 45 Gy 1.8 Gy/fr	23. Gy or 36 Gy (according to the response to HD-MTX based induction CT) 1.8 Gy/fr

CR: complete response; PR: partial response; WBRT: whole brain radiotherapy; RT: radiotherapy; HD-MTX-based induction CT: high-dose methotrexate-based chemotherapy.

Yahalom J, Illidge T, Specht L, et al. Modern radiation therapy for extranodal lymphomas: field and dose guidelines from the international lymphoma radiation oncology group. Int J Radiat Oncol Biol Phys. 2015;92(1):11–31. doi: 10.1016/j.ijrobp.2015.01.009.

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Omuro AMP, DeAngelis LM, Karrison T, et al. Randomized phase II study of rituximab, methotrexate (MTX), procarbazine, vincristine, and cytarabine (R-MPV-A) with and without low-dose whole-brain radiotherapy (LD-WBRT) for newly diagnosed primary CNS lymphoma (PCNSL). Journal Clin Oncol. 2020;38:2501.

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Fox CP, Phillips EH, Smith J, et al. Guidelines for the diagnosis and management of primary Central nervous system diffuse large B-cell lymphoma. Br J Haematol. 2019;184(3):348–363. doi: 10.1111/bjh.15661.

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Data availability statement

The data that support the findings of this study are available from Dr Loïc Feuvret, LF, [email protected], upon reasonable request.