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1Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Korea
2Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
3Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
4Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
5Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
6Lunit, Seoul, Korea
7Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
8Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
9Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
10Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
Copyright © 2024 Korean Endocrine Society
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICTS OF INTEREST
Chang Ho Ahn in Lunit as a medical director and has a stock option in the firm. Jung Hee Kim is a deputy editor of the journal. But she was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.
AUTHOR CONTRIBUTIONS
Conception or design: S.H.L., J.H.K. Acquisition, analysis, or interpretation of data: S.K.B., S.H.L., S.S.P., C.H.A., S.H.K., W.W.K., Y.M.L., S.J.K., D.E.S., T.Y.S., K.E.L., J.H.K., K.C.J., J.M.K. Drafting the work or revising: S.K.B., S.H.L., J.H.K. Final approval of the manuscript: S.K.B., S.H.L., S.S.P., C.H.A., S.H.K., W.W.K., Y.M.L., S.J.K., D.E.S., T.Y.S., K.E.L., J.H.K., K.C.J., J.M.K.
Variable | Available | Value |
---|---|---|
Women | 114 (100.0) | 67 (58.8) |
Age at diagnosis, yr | 114 (100.0) | 51.0 (41.0–62.0) |
≥50 | 114 (100.0) | 61 (53.5) |
BMI, kg/m2 | 105 (92.1) | 23.6 (22.0–25.9) |
Size, cm | 111 (97.4) | 7.9 (5.5–11.0) |
Symptom | 111 (97.4) | 55 (48.2) |
ENSAT stage | 114 (100.0) | |
1 | 13 (11.4) | |
2 | 54 (47.4) | |
3 | 17 (14.9) | |
4 | 30 (26.3) | |
Ki67 index or mitotic count | ||
Ki67 index | 79 (69.3) | 10.0 (4.0–18.5) |
Mitotic counts/50 HPF | 96 (84.2) | 20.0 (5.0–46.5) |
Additional treatmentb | 114 (100.0) | 61 (53.5) |
Adjuvant mitotane | 114 (100.0) | 35 (30.7) |
Mitotane dose, mg | 32 (94.1) | 2,000 (1,500–3,000) |
Mitotane level, mg/L | 9 (26.5) | 11.8 (7.1–13.5) |
Mitotane blood level >14 mg/L | 9 (26.5) | 6 (66.7) |
Resection status | 114 (100.0) | |
R0 | 70 (61.4) | |
RX | 7 (6.1) | |
R1 | 7 (6.1) | |
R2 | 30 (26.3) |
Values are expressed as number (%) or median (interquartile range).
ACC, adrenocortical carcinoma; mS-GRAS, modified Stage, Grade, Resection status, Age, Symptom; BMI, body mass index; ENSAT, European Network for the Study of Adrenal Tumour; HPF, high powered field.
a mS-GRAS components: ENSAT stage (S), modified grading (mG), resection status (R), age (A), and tumor- or hormone-related symptoms (S);
b Additional treatment included the adjuvant treatment with mitotane, additional operation, and other chemotherapy/radiation.
Scores | Variable | No. (%) | No. of relapse (%) | HR (95% CI) | P value | Harrell’s C-index (95% CI) | P valuec | P valued |
---|---|---|---|---|---|---|---|---|
S | ENSAT stage | 114 (100.0) | 70 (61.4) | 0.782 (0.716‒0.833)e | 0.037e | 0.115 | ||
0 | 1‒2 | 67 (58.8) | 33 (49.3) | Ref | ||||
1 | 3 | 17 (14.9) | 7 (41.2) | 1.12 (0.49–2.56) | 0.786 | |||
2 | 4 | 30 (26.3) | 30 (100.0) | NA | 0.994 | |||
Modified G | Ki67 index (%) or mitotic count, mitoses/50 HPF | 114 (100.0) | 70 (61.4) | 0.644 (0.558‒0.715)e | <0.001e | <0.001e | ||
0 | 0‒9 or ≤5 | 44 (38.6) | 21 (47.7) | Ref | ||||
1 | 10‒19 or 6‒20 | 33 (28.9) | 21 (63.6) | 1.67 (0.91–3.07) | 0.097 | |||
2 | ≥20 or >20 | 37 (32.5) | 28 (75.7) | 2.99 (1.67–5.35)e | <0.001e | |||
R | Resection status | 114 (100.0) | 70 (61.4) | 0.814 (0.755‒0.867)e | 0.333 | 0.832 | ||
0 | R0 | 70 (61.4) | 30 (42.9) | Ref | ||||
1 | RX | 7 (6.1) | 6 (85.7) | 3.29 (1.35–8.03)e | 0.009e | |||
2 | R1 | 7 (6.1) | 4 (57.1) | 2.15 (0.76–6.14) | 0.151 | |||
3 | R2 | 30 (26.4) | 30 (100.0) | NA | 0.995 | |||
A | Age, yr | 114 (100.0) | 70 (61.4) | 0.526 (0.480‒0.583) | <0.001e | <0.001e | ||
0 | <50 | 54 (47.4) | 35 (64.8) | Ref | ||||
1 | ≥50 | 60 (52.6) | 35 (58.3) | 0.89 (055–1.42) | 0.614 | |||
S | Symptom | 114 (100.0) | 70 (61.4) | 0.628 (0.563‒0.691)e | <0.001e | <0.001e | ||
0 | No | 60 (52.6) | 28 (46.7) | Ref | ||||
1 | Yes | 54 (47.4) | 42 (77.8) | 2.26 (1.40–3.65)e | 0.001e | |||
mS-GRAS | 114 (100.0) | 70 (61.4) | 1.90 (1.65–2.18)e | <0.001e | 0.829 (0.759‒0.880)e | Ref | ||
mS-GRAS group | 114 (100.0) | 70 (61.4) | 0.815 (0.751‒0.864)e | Ref | ||||
0–1 | 28 (24.6) | 10 (35.7) | Ref | |||||
2–3 | 43 (37.7) | 22 (51.2) | 1.84 (0.87–3.90) | 0.109 | ||||
4–5 | 11 (9.6) | 7 (63.6) | 3.18 (1.19–8.48)e | 0.021e | ||||
6–9 | 32 (28.1) | 31 (96.9) | 69.51 (25.99–185.86)e | <0.001e |
PFS, progression-free survival; HR, hazard ratio; mS-GRAS, modified Stage, Grade, Resection status, Age, Symptom; CI, confidence interval; ENSAT, European Network for the Study of Adrenal Tumour; HPF, high powered field; R0, complete resection; RX, uncertain resection; R1, microscopic incomplete resection; R2, macroscopic incomplete resection.
a mS-GRAS components: ENSAT stage (S), modified grading (modified G), resection status (R), age (A), and tumor- or hormone-related symptoms (S);
b Patients subjected to mS-GRAS analysis who underwent adrenalectomy and had data for all variables included in modified S-GRAS scores;
c P values comparing Harrell’s C-index of the variable with that of the mS-GRAS score;
d P values comparing Harrell’s C-index of the variable with that of the SGRAS groups;
e Significant results (P<0.05).
Scores | Variable | No. (%) | No. of death (%) | HR (95% CI) | P value | Harrell’s C-index (95% CI) | P valuec | P valued |
---|---|---|---|---|---|---|---|---|
S | ENSAT stage | 114 (100.0) | 55 (48.2) | 0.700 (0.627‒0.754)e | 0.047e | 0.050e | ||
0 | 1‒2 | 67 (58.2) | 22 (32.8) | Ref | ||||
1 | 3 | 17 (14.9) | 8 (47.1) | 2.36 (0.62–8.94) | 0.205 | |||
2 | 4 | 30 (26.3) | 25 (83.3) | 8.23 (2.47–27.50)e | 0.001e | |||
Modified G | Ki67 index (%) or mitotic count, mitoses/50 HPF | 114 (100.0) | 55 (48.2) | 0.634 (0.553‒0.694)e | 0.001e | 0.004e | ||
0 | 0‒9 or ≤5 | 44 (38.6) | 14 (31.8) | Ref | ||||
1 | 10‒19 or 6‒20 | 33 (28.9) | 14 (42.4) | 1.41 (0.67–2.96) | 0.365 | |||
2 | ≥20 or >20 | 37 (32.5) | 27 (73.0) | 3.44 (1.79–6.58)e | <0.001e | |||
R | Resection status | 114 (100.0) | 55 (48.2) | 0.713 (0.636‒0.769)e | 0.148 | 0.141 | ||
0 | R0 | 70 (61.4) | 21 (30.0) | Ref | ||||
1 | RX | 7 (6.1) | 5 (71.4) | 2.91 (1.09–7.75)e | 0.033e | |||
2 | R1 | 7 (6.1) | 4 (57.1) | 2.39 (0.82–6.96) | 0.112 | |||
3 | R2 | 30 (26.4) | 25 (83.3) | 6.33 (3.48–11.50)e | <0.001e | |||
A | Age, yr | 114 (100.0) | 55 (48.2) | 0.545 (0.490‒0.612) | <0.001e | <0.001e | ||
0 | <50 | 54 (47.4) | 22 (40.7) | Ref | ||||
1 | ≥50 | 60 (52.6) | 33 (55.0) | 1.56 (0.91–2.69) | 0.106 | |||
S | Symptom | 114 (100.0) | 55 (48.2) | 0.551 (0.484‒0.613) | <0.001e | <0.001e | ||
0 | No | 60 (52.6) | 27 (45.0) | Ref | ||||
1 | Yes | 54 (47.4) | 28 (51.9) | 1.32 (0.78–2.25) | 0.298 | |||
mS-GRAS | 114 (100.0) | 55 (48.2) | 1.37 (1.25–1.50)e | <0.001e | 0.747 (0.684‒0.805)e | Ref | ||
mS-GRAS group | 114 (100.0) | 55 (48.2) | 0.746 (0.673‒0.795)e | Ref | ||||
0–1 | 28 (24.6) | 5 (17.9) | Ref | |||||
2–3 | 43 (37.7) | 17 (39.5) | 2.32 (0.85–6.28) | 0.099 | ||||
4–5 | 11 (9.6) | 5 (45.5) | 3.22 (0.93–11.15) | 0.065 | ||||
6–9 | 32 (28.1) | 28 (87.5) | 13.14 (5.01–34.50)e | <0.001e |
OS, overall survival; HR, hazard ratio; mS-GRAS, modified Stage, Grade, Resection status, Age, Symptom; CI, confidence interval; ENSAT, European Network for the Study of Adrenal Tumour; HPF, high powered field; R0, complete resection; RX, uncertain resection; R1, microscopic incomplete resection; R2, macroscopic incomplete resection.
a mS-GRAS components: ENSAT stage (S), modified grading (modified G), resection status (R), age (A), and tumor- or hormone-related symptoms (S);
b Patients subjected to mS-GRAS analysis who underwent adrenalectomy and had data for all variables included in mS-GRAS scores;
c P values comparing Harrell’s C-index of the variable with that of the mS-GRAS score;
d P values comparing Harrell’s C-index of the variable with that of the S-GRAS groups;
e Significant results (P<0.05).
Variable | Available | Value |
---|---|---|
Women | 114 (100.0) | 67 (58.8) |
Age at diagnosis, yr | 114 (100.0) | 51.0 (41.0–62.0) |
≥50 | 114 (100.0) | 61 (53.5) |
BMI, kg/m2 | 105 (92.1) | 23.6 (22.0–25.9) |
Size, cm | 111 (97.4) | 7.9 (5.5–11.0) |
Symptom | 111 (97.4) | 55 (48.2) |
ENSAT stage | 114 (100.0) | |
1 | 13 (11.4) | |
2 | 54 (47.4) | |
3 | 17 (14.9) | |
4 | 30 (26.3) | |
Ki67 index or mitotic count | ||
Ki67 index | 79 (69.3) | 10.0 (4.0–18.5) |
Mitotic counts/50 HPF | 96 (84.2) | 20.0 (5.0–46.5) |
Additional treatment |
114 (100.0) | 61 (53.5) |
Adjuvant mitotane | 114 (100.0) | 35 (30.7) |
Mitotane dose, mg | 32 (94.1) | 2,000 (1,500–3,000) |
Mitotane level, mg/L | 9 (26.5) | 11.8 (7.1–13.5) |
Mitotane blood level >14 mg/L | 9 (26.5) | 6 (66.7) |
Resection status | 114 (100.0) | |
R0 | 70 (61.4) | |
RX | 7 (6.1) | |
R1 | 7 (6.1) | |
R2 | 30 (26.3) |
Scores | Variable | No. (%) | No. of relapse (%) | HR (95% CI) | P value | Harrell’s C-index (95% CI) | P value |
P value |
---|---|---|---|---|---|---|---|---|
S | ENSAT stage | 114 (100.0) | 70 (61.4) | 0.782 (0.716‒0.833) |
0.037 |
0.115 | ||
0 | 1‒2 | 67 (58.8) | 33 (49.3) | Ref | ||||
1 | 3 | 17 (14.9) | 7 (41.2) | 1.12 (0.49–2.56) | 0.786 | |||
2 | 4 | 30 (26.3) | 30 (100.0) | NA | 0.994 | |||
Modified G | Ki67 index (%) or mitotic count, mitoses/50 HPF | 114 (100.0) | 70 (61.4) | 0.644 (0.558‒0.715) |
<0.001 |
<0.001 |
||
0 | 0‒9 or ≤5 | 44 (38.6) | 21 (47.7) | Ref | ||||
1 | 10‒19 or 6‒20 | 33 (28.9) | 21 (63.6) | 1.67 (0.91–3.07) | 0.097 | |||
2 | ≥20 or >20 | 37 (32.5) | 28 (75.7) | 2.99 (1.67–5.35) |
<0.001 |
|||
R | Resection status | 114 (100.0) | 70 (61.4) | 0.814 (0.755‒0.867) |
0.333 | 0.832 | ||
0 | R0 | 70 (61.4) | 30 (42.9) | Ref | ||||
1 | RX | 7 (6.1) | 6 (85.7) | 3.29 (1.35–8.03) |
0.009 |
|||
2 | R1 | 7 (6.1) | 4 (57.1) | 2.15 (0.76–6.14) | 0.151 | |||
3 | R2 | 30 (26.4) | 30 (100.0) | NA | 0.995 | |||
A | Age, yr | 114 (100.0) | 70 (61.4) | 0.526 (0.480‒0.583) | <0.001 |
<0.001 |
||
0 | <50 | 54 (47.4) | 35 (64.8) | Ref | ||||
1 | ≥50 | 60 (52.6) | 35 (58.3) | 0.89 (055–1.42) | 0.614 | |||
S | Symptom | 114 (100.0) | 70 (61.4) | 0.628 (0.563‒0.691) |
<0.001 |
<0.001 |
||
0 | No | 60 (52.6) | 28 (46.7) | Ref | ||||
1 | Yes | 54 (47.4) | 42 (77.8) | 2.26 (1.40–3.65) |
0.001 |
|||
mS-GRAS | 114 (100.0) | 70 (61.4) | 1.90 (1.65–2.18) |
<0.001 |
0.829 (0.759‒0.880) |
Ref | ||
mS-GRAS group | 114 (100.0) | 70 (61.4) | 0.815 (0.751‒0.864) |
Ref | ||||
0–1 | 28 (24.6) | 10 (35.7) | Ref | |||||
2–3 | 43 (37.7) | 22 (51.2) | 1.84 (0.87–3.90) | 0.109 | ||||
4–5 | 11 (9.6) | 7 (63.6) | 3.18 (1.19–8.48) |
0.021 |
||||
6–9 | 32 (28.1) | 31 (96.9) | 69.51 (25.99–185.86) |
<0.001 |
Scores | Variable | No. (%) | No. of death (%) | HR (95% CI) | P value | Harrell’s C-index (95% CI) | P value |
P value |
---|---|---|---|---|---|---|---|---|
S | ENSAT stage | 114 (100.0) | 55 (48.2) | 0.700 (0.627‒0.754) |
0.047 |
0.050 |
||
0 | 1‒2 | 67 (58.2) | 22 (32.8) | Ref | ||||
1 | 3 | 17 (14.9) | 8 (47.1) | 2.36 (0.62–8.94) | 0.205 | |||
2 | 4 | 30 (26.3) | 25 (83.3) | 8.23 (2.47–27.50) |
0.001 |
|||
Modified G | Ki67 index (%) or mitotic count, mitoses/50 HPF | 114 (100.0) | 55 (48.2) | 0.634 (0.553‒0.694) |
0.001 |
0.004 |
||
0 | 0‒9 or ≤5 | 44 (38.6) | 14 (31.8) | Ref | ||||
1 | 10‒19 or 6‒20 | 33 (28.9) | 14 (42.4) | 1.41 (0.67–2.96) | 0.365 | |||
2 | ≥20 or >20 | 37 (32.5) | 27 (73.0) | 3.44 (1.79–6.58) |
<0.001 |
|||
R | Resection status | 114 (100.0) | 55 (48.2) | 0.713 (0.636‒0.769) |
0.148 | 0.141 | ||
0 | R0 | 70 (61.4) | 21 (30.0) | Ref | ||||
1 | RX | 7 (6.1) | 5 (71.4) | 2.91 (1.09–7.75) |
0.033 |
|||
2 | R1 | 7 (6.1) | 4 (57.1) | 2.39 (0.82–6.96) | 0.112 | |||
3 | R2 | 30 (26.4) | 25 (83.3) | 6.33 (3.48–11.50) |
<0.001 |
|||
A | Age, yr | 114 (100.0) | 55 (48.2) | 0.545 (0.490‒0.612) | <0.001 |
<0.001 |
||
0 | <50 | 54 (47.4) | 22 (40.7) | Ref | ||||
1 | ≥50 | 60 (52.6) | 33 (55.0) | 1.56 (0.91–2.69) | 0.106 | |||
S | Symptom | 114 (100.0) | 55 (48.2) | 0.551 (0.484‒0.613) | <0.001 |
<0.001 |
||
0 | No | 60 (52.6) | 27 (45.0) | Ref | ||||
1 | Yes | 54 (47.4) | 28 (51.9) | 1.32 (0.78–2.25) | 0.298 | |||
mS-GRAS | 114 (100.0) | 55 (48.2) | 1.37 (1.25–1.50) |
<0.001 |
0.747 (0.684‒0.805) |
Ref | ||
mS-GRAS group | 114 (100.0) | 55 (48.2) | 0.746 (0.673‒0.795) |
Ref | ||||
0–1 | 28 (24.6) | 5 (17.9) | Ref | |||||
2–3 | 43 (37.7) | 17 (39.5) | 2.32 (0.85–6.28) | 0.099 | ||||
4–5 | 11 (9.6) | 5 (45.5) | 3.22 (0.93–11.15) | 0.065 | ||||
6–9 | 32 (28.1) | 28 (87.5) | 13.14 (5.01–34.50) |
<0.001 |
Values are expressed as number (%) or median (interquartile range). ACC, adrenocortical carcinoma; mS-GRAS, modified Stage, Grade, Resection status, Age, Symptom; BMI, body mass index; ENSAT, European Network for the Study of Adrenal Tumour; HPF, high powered
field. mS-GRAS components: ENSAT stage (S), modified grading (mG), resection status (R), age (A), and tumor- or hormone-related symptoms (S); Additional treatment included the adjuvant treatment with mitotane, additional operation, and other chemotherapy/radiation.
PFS, progression-free survival; HR, hazard ratio; mS-GRAS, modified Stage, Grade, Resection status, Age, Symptom; CI, confidence interval; ENSAT, European Network for the Study of Adrenal Tumour; HPF, high powered field; R0, complete resection; RX, uncertain resection; R1, microscopic incomplete resection; R2, macroscopic incomplete resection. mS-GRAS components: ENSAT stage (S), modified grading (modified G), resection status (R), age (A), and tumor- or hormone-related symptoms (S); Patients subjected to mS-GRAS analysis who underwent adrenalectomy and had data for all variables included in modified S-GRAS scores; Significant results (
OS, overall survival; HR, hazard ratio; mS-GRAS, modified Stage, Grade, Resection status, Age, Symptom; CI, confidence interval; ENSAT, European Network for the Study of Adrenal Tumour; HPF, high powered field; R0, complete resection; RX, uncertain resection; R1, microscopic incomplete resection; R2, macroscopic incomplete resection. mS-GRAS components: ENSAT stage (S), modified grading (modified G), resection status (R), age (A), and tumor- or hormone-related symptoms (S); Patients subjected to mS-GRAS analysis who underwent adrenalectomy and had data for all variables included in mS-GRAS scores; Significant results (