Real-World Data Analysis of Survival Outcomes and Central Nervous System Relapses in Testicular Diffuse Large B Cell Lymphoma

Figures & data

Table 1 Baseline Demographics and Disease Characteristics at Diagnosis (n = 65)

Characteristics		n (%)
Age, years	Median, range	65 (33–83)
	< 60	23 (35.4%)
	≥ 60	42 (64.6%)
	< 70	44 (67.7%)
	≥ 70	21 (32.3%)
ECOG-PS	0–1	62 (95.4%)
	2–4	3 (4.6%)
Location	Left	29 (44.6%)
	Right	31 (47.7%)
	Bilateral	5 (7.7%)
Ann Arbor stage	I	43 (66.2%)
	≥ II	22 (33.8%)
Extra-nodal involvement outside testis	Lymphoma involvement in more than two sites	11 (16.9%)
	Bone marrow involvement	3 (4.6%)
	CNS involvement	1 (1.5%)
	Kidney/adrenal gland involvement	3 (4.6%)
Serum LDH	Elevated	25 (38.4%)
Serum β-2 microglobulin	Elevated	16 (24.6%)
IPI score	0–1	42 (64.6%)
	2–5	23 (35.4%)
CNS-IPI score	Low to intermediate	55 (84.6%)
	High	10 (15.4%)
Cell of origin of lymphoma	Non-GCB type	37 (56.9%)
	GCB type	16 (24.6%)
	Not evaluable	12 (18.5%)
Double-expressor phenotype	Present	19 (29.2%)
Double/triple-hit phenotype	Present	1 (1.5%)

Abbreviations: ECOG-PS, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase; IPI, International Prognostic Index; CNS, central nervous system; GCB, germinal center B-cell.

Figure 1 (A) Treatment modalities for patients according to disease stage. (B) Overall and progression-free survival. (C) Comparison of overall and progression-free survival between stage I and stage II–IV.

Abbreviations: Op, orchiectomy; ChT, chemotherapy; RT, radiation therapy; CNS Px, central nervous system prophylaxis therapy.

Figure 2 (A) Comparison of overall and progression-free survival between patients with IPI score 0 or 1 and patients with IPI ≥ 2. (B) Comparison of overall and progression-free survival according to the involved sites of testis.

Abbreviations: IPI, international prognostic index; Rt, right; Lt, left.

Figure 3 (A) Comparison of overall survival according to cycles of chemotherapy. (B) Comparison of overall survival according to use of radiation therapy to contralateral testis. (C) Comparison of cumulative incidence of CNS recurrence according to CNS prophylaxis. (D) Comparison of overall survival according to combined modality treatment.

Abbreviations: RT, radiotherapy; CNS, central nervous system.

Table 2 Univariate and Multivariate Analyses

Variables	Univariate		Multivariate
	HR (95% CI)	p	HR (95% CI)	p
OS
Age ≥ 60 years	3.505 (1.093–11.241)	0.030	1.277 (0.243–6.714)	0.773
Age ≥ 70 years	3.740 (1.233–11.340)	0.017	1.844 (0.300–11.341)	0.509
ECOG-PS ≥ 2	4.278 (1.386–13.202)	0.009	6.424 (1.502–27.475)	0.012
IPI score ≥ 2	2.933 (0.993–8.666)	0.048	2.159 (0.379–12.308)	0.386
High CNS-IPI score	1.490 (0.372–5.973)	0.572	-
Ann Arbor stage ≥ II	2.424 (0.821–7.162)	0.105	-
Bilateral testicular involvement	3.500 (0.538–22.765)	0.168	-
Bone marrow involvement	1.050 (0.090–12.275)	0.969	-
Elevated β-2 microglobulin	1.944 (0.606–6.241)	0.260	-
Elevated serum LDH	1.758 (0.609–5.069)	0.294	-
Addition of rituximab	0.208 (0.058–0.750)	0.012	0.404 (0.084–1.934)	0.256
CNS prophylaxis	0.417 (0.141–1.232)	0.109	-
Radiation to contralateral testis	0.092 (0.027–0.314)	< 0.001	0.070 (0.017–0.287)	< 0.001
PFS
Age ≥ 60 years	1.705 (0.623–4.666)	0.297	-
Age ≥ 70 years	1.747 (0.612–4.990)	0.295	-
ECOG-PS ≥ 2	3.714 (1.226–11.252)	0.017	4.333 (1.239–15.151)	0.022
IPI score ≥ 2	2.340 (0.829–6.609)	0.105	-
High CNS-IPI score	1.391 (0.361–5.369)	0.631	-
Ann Arbor stage ≥ II	2.696 (0.938–7.753)	0.062	-
Bilateral testicular involvement	6.000 (0.632–57.004)	0.083	-
Bone marrow involvement	2.769 (0.238–32.184)	0.398	-
Elevated β-2 microglobulin	2.870 (0.894–9.220)	0.071	-
Elevated serum LDH	1.385 (0.505–3.793)	0.526	-
Addition of rituximab	0.256 (0.069–0.945)	0.033	-
CNS prophylaxis	0.711 (0.265–1.908)	0.497	-
Radiation to contralateral testis	0.153 (0.051–0.460)	0.001	0.138 (0.042–0.448)	0.001

Note: The bolded text represents the P value < 0.05.

Abbreviations: OS, overall survival; ECOG-PS, Eastern Cooperative Oncology Group performance status; IPI, International Prognostic Index; CNS, central nervous system; LDH, lactate dehydrogenase; PFS, progression-free survival.

Figure 4 Clinical characteristics and subsequent treatments of relapsed patients.

Abbreviations: Lt, left; Rt, right; RT, radiotherapy; IT MTX, intrathecal methotrexate; CNS, central nervous system; P, parenchyma; L, leptomeninges; LN, lymph node; ENs, other extranodal site; HD MTX, high-dose methotrexate; ChT, chemotherapy; Auto, autologous stem cell transplantation.

Figure 5 Paired analysis of mutation profiles in eight patients (A) and their swimmer plot (B).

Data Sharing Statement

All data are available upon request to the corresponding authors.