Impact of Therapy & Age in Choroidal Cancers: A Retrospective Cohort Analysis of 7722 Patients from a US National Database

Figures & data

Table 1 Baseline Demographical & Clinical Characteristics

Variable	Value	Frequency	Percent	p-value
Age (years)	0–24	95	1.2	p < 0.001
	25–49	1576	20.4
	50–74	4698	60.8
	75+	1353	17.5
Sex	Male	4104	53.1	p = 0.146
	Female	3618	46.9
Marital Status	Married	4772	61.8	p = 0.002
	Single	958	12.4
	Widowed	818	10.6
	Divorced	551	7.1
	Other/Unknown	623	8.1
Race/ethnicity	White	7462	96.6	p < 0.001
	Non-white	260	3.4
Hispanic Origin	Spanish-Hispanic-Latino	376	4.9	p = 0.008
	Non-Spanish-Hispanic-Latino	7346	95.1
Laterality Recode	Left	3842	49.8	p = 0.393
	Right	3811	49.4
	Other/Unknown	69	0.9
Grade	Well-differentiated; Grade I	60	0.8	p = 0.42
	Moderately differentiated; Grade II	7512	97.3
	Poorly differentiated; Grade III	94	1.2
	Undifferentiated; anaplastic	34	0.4
	Grade IV and B-cell; pre-B; B-precursor	22	0.3
ICD-10-Behavior	8720/3: Malignant melanoma, NOS	5610	72.6	p < 0.001
	8770/3: Mixed epithelioid and spindle cell melanoma	780	10.1
	8774/3: Spindle cell melanoma, type B	477	6.2
	8772/3: Spindle cell melanoma, NOS	467	6
	8771/3: Epithelioid cell melanoma	261	3.4
	8730/3: Amelanotic melanoma	58	0.8
	8773/3: Spindle cell melanoma, Type A	20	0.3
	Other/Unknown	49	0.6
Diagnostic confirmation	Positive histology	3993	51.7	p < 0.001
	Radiography without microscopic confirmation	1423	18.4
	Direct visualization without microscopic confirmation	1184	15.3
	Positive exfoliative cytology, no positive histology	512	6.6
	Clinical diagnosis only	481	6.2
	Other/Unknown	129	1.7
Chemotherapy	Yes	139	1.8	p < 0.001
	No/Unknown	7583	98.2
Radiation recode	Radioactive implants	2468	32
	Beam Radiation	1325	17.2
	Radioisotopes	671	8.7	p = 0.006
	Other	205	2.7
	None/Unknown	3053	39.5
Radiation sequence recode	Radiation prior to surgery	7183	93	p = 0.002
	Radiation after surgery	271	3.5
	No radiation and/or cancer-directed surgery	215	2.8
	Other	22	0.3
Type of follow-up expected	Active follow-up	7711	99.9	p = 0.203
	Autopsy/death certificate only cases	2	0
	SF/Oakland only (originally inactive/now active)	9	0.1

Note: Statistical significance was achieved at p-value < 0.05.

Table 2 Univariable Cox Regression Results

Age	Other-Cause Survival		Cause-Specific Survival
	HR* (95% CI*)	p-value*	HR* (95% CI*)	p-value*
75+ years	Ref.	Ref.	Ref.	Ref.
50–74 years	0.210 (0.188, 0.235)	<0.001	0.701 (0.622, 0.789)	< 0.001
25–49 years	0.029 (0.023, 0.038)	< 0.001	0.414 (0.355, 0.483)	< 0.001
0–24 years	0.006 (0.001, 0.043)	< 0.001	0.685 (0.469, 1.001)	0.051

Notes: *Hazards ratio, 95% confidence interval. *Statistical significance achieved at p < 0.05.

Figure 1 Kaplan-Meier plot shows the differences in cumulative cause-specific survival over time for choroidal cancer patients between 25 and 49 years of age. (top, red line) as compared to patients aged 75+ (bottom, orange line). The log-rank (Mantel-Cox) test showed that the cause-specific survival distributions for the different levels of aged groups at diagnosis are significantly different (p < 0.001).

Figure 2 Kaplan-Meier plot shows the differences in cumulative other-cause survival over time for choroidal cancer patients aged 25–49 (red line) as compared to aged 75+ patients (bottom, orange line). The log-rank (Mantel-Cox) test showed that the other-cause survival distributions for the different levels of aged groups at diagnosis are significantly different (p < 0.001).

Table 3 Multivariable Cox Regression Results

Age	Other-Cause Survival		Cause-Specific Survival
	HR* (95% CI*)	p-value*	HR* (95% CI*)	p-value*
0–24 years	Ref.	Ref.	Ref.	Ref.
25–49 years	5.275 (0.730, 38.139)	0.099	0.694 (0.469, 1.027)	0.068
50–74 years	39.066 (5.459, 279.590)	< 0.001	1.173 (0.799, 1.721)	0.415
75+ years	178.764 (24.908, 1282.957)	< 0.001	1.718 (1.155, 2.555)	0.008

Notes: *Hazards ratio, 95% confidence interval. *Statistical significance achieved at p < 0.05.

Figure 3 Kaplan-Meier plot shows the differences in cumulative cause-specific survival over time for the choroidal cancer patients aged 25–49 years (top, red line) as compared to patients aged 75+ years (bottom, orange line), using Cox-model based estimates after adjusting for confounding variables.

Figure 4 Kaplan-Meier plot shows the differences in cumulative other-cause survival over time for choroidal cancer patients aged 0–24 years (top, blue line) as compared to patients aged 75+ years (bottom, orange line), using Cox-model based estimates after adjusting for confounding variables.

Table 4 Multi-Variable Cox Regression Results (Continued)

Variable Name	Value	Exp (B)	95.0% CI for Hazard Ratios		p-value
			Lower	Upper
Race/Ethnicity	White	ref	ref	ref	<0.001
	Non-White	0.496	0.346	0.713	<0.001
Hispanic Origin	Non-Spanish-Hispanic-Latino	ref	ref	ref	<0.001
	Spanish-Hispanic-Latino	0.749	0.606	0.926	0.008
Chemotherapy	Yes	0.328	0.252	0.427	<0.001
Laterality	Left	ref	ref	ref	0.393
	Right	1.033	0.944	1.131	0.48
	other	1.333	0.843	2.108	0.218
Grade	Unknown	ref	ref	ref	0.42
	Undifferentiated; anaplastic; Grade IV and B-cell; pre-B; B-precursor	1.343	0.668	2.7	0.407
	Poorly differentiated; Grade III	0.574	0.135	2.439	0.452
	Moderately differentiated; Grade II	1.217	0.484	3.065	0.676
	Well differentiated; Grade I	1.642	0.749	3.602	0.216
Marital Status	Married	ref	ref	ref	0.002
	Widowed	0.792	0.652	0.961	0.018
	Divorced	1.223	1.051	1.423	0.009
	Single	1.153	0.969	1.372	0.108
	Other/Unknown	1.075	0.927	1.246	0.339
Diagnostic Confirmation	Clinical diagnosis only	ref	ref	ref	<0.001
	Radiography without microscopic confirmation	1.41	0.885	2.246	0.148
	Positive histology	0.882	0.656	1.187	0.408
	Positive exfoliative cytology, no positive histology	2.375	1.804	3.125	<0.001
	Direct visualization without microscopic confirmation	1.79	1.276	2.511	0.001
Icd 10 behavior	8720/3: Malignant melanoma, NOS	ref	ref	ref	<0.001
	8730/3: Amelanotic melanoma	0.509	0.228	1.137	0.1
	8770/3: Mixed epithelioid and spindle cell melanoma	1.162	1.015	1.33	0.029
	8771/3: Epithelioid cell melanoma	1.58	1.304	1.915	<0.001
	8772/3: Spindle cell melanoma, NOS	0.469	0.375	0.586	<0.001
	8773/3: Spindle cell melanoma, type A	0.188	0.047	0.753	0.018
	8774/3: Spindle cell melanoma, type B	0.575	0.474	0.697	<0.001
	Other	0.901	0.384	2.112	0.811
Sex	Female	ref	ref	ref	0.25
	Male	0.933	0.849	1.025	0.146
Radiation	Beam Radiation	ref	ref	ref	0.006
	None/Unknown	1.046	0.78	1.402	0.765
	Radioactive implants	1.043	0.786	1.384	0.771
	Radioisotopes	0.81	0.607	1.08	0.15
	Other	0.952	0.693	1.308	0.76
Radiation sequence recode	Radiation prior to surgery	ref	ref	ref	0.002
	Radiation after surgery	1.31	0.975	1.759	0.073
	No radiation and/or cancer-directed surgery	0.846	0.669	1.069	0.161
	Other	1.212	0.607	2.422	0.586
Type of follow-up expected	1=SF/Oakland only (originally inactive/now active)	ref	ref	ref	0.251
	Active follow-up	0.564	0.234	1.362	0.203

Figure 5 Kaplan-Meier plot shows the differences in cumulative univariable cause-specific survival over time for choroidal cancer patients treated with radioactive implants (top, green line) as compared to patients treated with no or unknown treatments (bottom, red line) using Cox-model based estimates. The log-rank (Mantel-Cox) test showed that the cause-specific survival distributions for the different radiation treatment groups are significantly different (p < 0.001).