Background
Methods
Patients
Definition of variables
Statistical analysis
Results
Baseline prognostic factors
Baseline features | Values at diagnosis (n = 1300) | Solid cancer (n = 70) | Hematological cancer (n = 61) |
---|---|---|---|
Age at diagnosis | 54.8 ± 15.4 | † | † |
Gender (male) | 99 (7.6) | † | † |
Ethnicity (white) | 1246 (95.8) | 0.41 [0.10–1.71] | 0.99 [0.14–7.29] |
Dry mouth | 1299 (99.9) | – | – |
Dry eye | 1234 (94.9) | 0.48 [0.19–1.20] | 1.37 [0.33–5.63] |
Altered ocular tests | 1013/1156 (87.6) | 1.29 [0.47–3.58] | 5.38 [0.74–39.03] |
Altered parotid scintigraphy | 835/992 (84.2) | 0.87 [0.41–1.86] | 1.34 [0.53–3.41] |
Positive salivary gland biopsy | 497/629 (79) | 0.92 [0.35–2.44] | 1.01 [0.42–2.45] |
Anemia (Hb < 110 g/L) | 216/1297 (16.7) | 1.05 [0.59–1.86] |
2.07 [1.20–3.58]
‡
|
Leukopenia (<4000/mm3) | 227/1297 (17.5) | 1.49 [0.87–2.55] | 0.96 [0.50–1.86] |
Thrombocytopenia (<150,000/mm3) | 87/1297 (6.7) | 1.18 [0.54–2.57] | 1.17 [0.50–2.72] |
Neutropenia (<1500/mm3) | 137/1296 (10.6) | 1.41 [0.74–2.71] | 1.66 [0.83–3.32] |
Lymphopenia (<1000/mm3) | 141/1295 (10.9) | 1.80 [0.96–3.35] | 1.43 [0.71–2.86] |
Antinuclear antibodies+ | 1124/1295 (86.8) | 0.95 [0.49–1.85] | 1.05 [0.50–2.21] |
Rheumatoid factor+ | 583/1245 (46.8) | 1.13 [0.71–1.82] | 1.08 [0.65–1.80] |
Anti-Ro/SS-A+ | 981/1294 (75.8) | 1.43 [0.81–2.53] | 1.28 [0.70–2.36] |
Anti-La/SS-B+ | 626/1289 (48.6) | 0.99 [0.62–1.60] | 1.17 [0.69–1.97] |
Monoclonal gammopathy | 114/1018 (11.2) | 1.94 [0.99–3.80] |
2.13 [1.08–4.19]
|
Cryoglobulins+ | 70/929 (7.5) | 0.70 [0.25–1.94] |
4.37 [2.32–8.22]
‡
|
Low C3 levels (<0.82 g/L) | 144/1233 (11.7) | 0.59 [0.21–1.62] |
2.07 [1.06–4.03]
|
Low C4 levels (<0.11 g/L) | 163/1218 (13.4) | 1.07 [0.51–2.24] |
2.23 [1.17–4.26]
|
Systemic activity
Variables | Values at diagnosis (n = 1295)a
| Solid cancer (n = 70) | Hematological cancer (n = 61) |
---|---|---|---|
Baseline DAS | |||
Low | 707 (54.6) | REF | REF |
Moderate | 426 (32.9) | 1.17 [0.71–1.92] | 1.37 [0.73–2.58] |
High | 162 (12.5) | 0.66 [0.28–1.56] |
4.34 [2.35–8.00]
|
ESSDAI domains† | |||
Constitutional | 115 (8.9) | 1.13 [0.48–2.62] |
2.44 [1.23–4.87]
|
Lymphadenopathy | 89 (6.9) | 0.39 [0.10–1.60] |
8.03 [4.62–13.94]
‡
|
Glandular | 179 (13.8) |
0.35 [0.14–0.87]
|
3.04 [1.78–5.18]
‡
|
Articular | 498 (38.5) | 0.95 [0.58–1.56] | 1.30 [0.78–2.18] |
Cutaneous | 131 (10.1) | 1.40 [0.70–2.83] | 1.10 [0.47–2.57] |
Pulmonary | 102 (7.9) | 1.58 [0.71–3.48] | 1.07 [0.38–2.99] |
Renal | 23 (1.8) | 1.21 [0.17–8.80] | – |
Muscular | 15 (1.2) | 1.57 [0.22–11.4] | – |
Peripheral nervous system | 54 (4.2) | 0.59 [0.14–2.45] | – |
Central nervous system | 41 (3.2) | – | 0.44 [0.06–3.22] |
Hematological | 447 (34.5) | 1.31 [0.81–2.10] | 1.36 [0.81–2.26] |
Biological | 681 (52.6) | 1.32 [0.81–2.15] |
2.12 [1.19–3.76]
|
Prognostic factors for hematological cancer subtypes
Variables | B-cell MALT (n = 27) | B-cell non-MALT (n = 19) | Non-B-cell neoplasms (n = 15) |
---|---|---|---|
Dry eye | – | 0.90 [0.12–6.83] | 0.76 [0.10–5.94] |
Altered ocular tests | – | 1.33 [0.17–10.17] | – |
Altered parotid scintigraphy | – | 1.10 [0.25–4.86] | 0.49 [0.13–1.87] |
Positive salivary gland biopsy | 1.84 [0.42–8.04] | 0.37 [0.07–2.12] | 0.83 [0.17–3.98] |
Anemia (Hb < 110 g/L) | 0.89 [0.31–2.61] |
2.58 [1.01–6.58]
|
4.02 [1.42–11.38]
|
Leukopenia (<4000/mm3) | 0.51 [0.15–1.69] | 0.84 [0.24–2.89] | 2.54 [0.86–7.52] |
Thrombocytopenia (<150000/mm3) | 0.47 [0.06–3.48] | – |
4.85 [1.64–14.34]
|
Neutropenia (<1500/mm3) | 1.24 [0.42–3.63] | 0.51 [0.07–3.92] |
5.86 [1.89–18.14]
|
Lymphopenia (<1000/mm3) | 2.12 [0.79–5.68] | 0.32 [0.04–2.48] | 2.14 [0.65–7.02] |
Antinuclear antibodies+ | 1.15 [0.35–3.84] | 0.86 [0.25–2.97] | 1.14 [0.26–5.10] |
Rheumatoid factor+ | 0.94 [0.43–2.03] | 1.16 [0.47–2.86] | 1.28 [0.46–3.53] |
Anti-Ro/SS-A+ | 1.07 [0.42–2.71] | 1.63 [0.53–5.03] | 1.26 [0.39–4.09] |
Anti-La/SS-B+ | 0.66 [0.30–1.46] | 2.35 [0.88–6.32] | 1.34 [0.47–3.83] |
Monoclonal gammopathy | 1.30 [0.38–4.43] |
3.34 [1.14–9.83]
| 2.16 [0.58–8.04] |
Cryoglobulins+ |
6.32 [2.47–16.15]
|
3.31 [1.06–10.36]
|
4.36 [1.12–16.99]
|
Low C3 levels (<0.82 g/L) |
3.25 [1.33–7.93]
| 1.14 [0.26–5.06] | 1.43 [0.31–6.48] |
Low C4 levels (<0.11 g/L) | 1.76 [0.65–4.78] |
3.83 [1.31–11.21]
| 1.36 [0.30–6.11] |
Baseline ESSDAI |
1.07 [1.03–1.11]
| 1.04 [0.98–1.09] |
1.08 [1.03–1.13]
|
Baseline DAS (REF = low) | |||
Moderate | 0.91 [0.33–2.51] | 1.20 [0.42–3.47] | 3.37 [0.84–13.52] |
High |
4.80 [1.99–11.62]
| 2.60 [0.84–8.07] |
8.29 [2.05–33.55]
|
ESSDAI domains† | |||
Constitutional | 1.31 [0.39–4.44] | 1.62 [0.37–7.12] |
7.20 [2.43–21.32]
|
Lymphadenopathy |
9.39 [4.20–21.02]
|
8.99 [3.35–24.14]
|
4.74 [1.32–17.02]
|
Glandular |
7.35 [3.36–16.10]
| 1.34 [0.44–4.13] | 1.38 [0.38–5.04] |
Articular | 1.09 [0.50–2.39] | 2.07 [0.82–5.18] | 1.00 [0.34–3.00] |
Cutaneous | 1.16 [0.35–3.87] | 1.28 [0.29–5.56] | 0.78 [0.10–6.00] |
Pulmonary | – | – |
4.98 [1.50–16.59]
|
Central nervous System | 1.12 [0.15–8.29] | – | – |
Hematological | 1.10 [0.50–2.42] | 0.61 [0.22–1.69] |
4.99 [1.58–15.76]
|
Biological | 1.35 [0.60–3.06] |
6.57 [1.51–28.55]
| 1.68 [0.57–4.95] |
Standardized incidence ratios (SIRs) for cancer
Cancer categories | Total (n = 1239)a
| Women (n = 1145) | Men (n = 94) | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Obs‡ | Exp | SIR | LCI | UCI | Obs | Exp | SIR | LCI | UCI | Obs | Exp | SIR | LCI | UCI | |
All cancers† | 121 | 63.77 | 1.9 | 1.59 | 2.27 | 105 | 56.77 | 1.85 | 1.53 | 2.24 | 16 | 7 | 2.29 | 1.4 | 3.73 |
Solid cancers§ | 60 | 53.1 | 1.13 | 0.88 | 1.46 | 55 | 47.42 | 1.16 | 0.89 | 1.51 | 5 | 5.68 | 0.88 | 0.37 | 2.12 |
Thyroid | 4 | 0.79 | 5.05 | 1.89 | 13.45 | 4 | 0.77 | 5.17 | 1.94 | 13.79 | 0 | 0.02 | 0 | – | – |
Lip, oral cavity | 4 | 0.99 | 4.05 | 1.52 | 10.8 | 4 | 0.83 | 4.81 | 1.81 | 12.83 | 0 | 0.16 | 0 | – | – |
Stomach | 5 | 2.24 | 2.23 | 0.93 | 5.36 | 5 | 1.98 | 2.53 | 1.05 | 6.07 | 0 | 0.26 | 0 | – | – |
Kidney | 3 | 1.67 | 1.8 | 0.58 | 5.57 | 2 | 1.44 | 1.39 | 0.35 | 5.55 | 1 | 0.23 | 4.39 | 0.62 | 31.14 |
Brain, nervous system | 2 | 1.17 | 1.72 | 0.43 | 6.86 | 2 | 1.07 | 1.87 | 0.47 | 7.48 | 0 | 0.1 | 0 | – | – |
Gallbladder | 1 | 0.77 | 1.3 | 0.18 | 9.2 | 1 | 0.72 | 1.39 | 0.2 | 9.83 | 0 | 0.05 | 0 | – | – |
Lung | 6 | 4.66 | 1.29 | 0.58 | 2.87 | 4 | 3.43 | 1.17 | 0.44 | 3.11 | 2 | 1.23 | 1.63 | 0.41 | 6.5 |
Prostate | 2 | 1.66 | 1.2 | 0.3 | 4.81 | 2 | 1.66 | 1.2 | 0.3 | 4.81 | |||||
Melanoma of skin | 2 | 1.73 | 1.16 | 0.29 | 4.62 | 2 | 1.63 | 1.23 | 0.31 | 4.92 | 0 | 0.1 | 0 | – | – |
Bladder | 2 | 2.1 | 0.95 | 0.24 | 3.8 | 2 | 1.48 | 1.35 | 0.34 | 5.42 | 0 | 0.63 | 0 | – | – |
Colorectal | 9 | 10.08 | 0.89 | 0.46 | 1.72 | 9 | 9.02 | 1 | 0.52 | 1.92 | 0 | 1.06 | 0 | – | – |
Breast | 14 | 15.68 | 0.89 | 0.53 | 1.51 | 14 | 15.68 | 0.89 | 0.53 | 1.51 | |||||
Pancreas | 2 | 2.29 | 0.87 | 0.22 | 3.5 | 2 | 2.1 | 0.95 | 0.24 | 3.8 | 0 | 0.18 | 0 | – | – |
Cervix uteri | 1 | 1.39 | 0.72 | 0.1 | 5.1 | 1 | 1.39 | 0.72 | 0.1 | 5.1 | |||||
Corpus uteri | 2 | 3.72 | 0.54 | 0.13 | 2.15 | 2 | 3.72 | 0.54 | 0.13 | 2.15 | |||||
Ovary | 1 | 2.16 | 0.46 | 0.07 | 3.28 | 1 | 2.16 | 0.46 | 0.07 | 3.28 | |||||
Hematologicalb
| 50 | 4.54 | 11.02 | 8.35 | 14.54 | 42 | 4.14 | 10.14 | 7.49 | 13.72 | 8 | 0.39 | 20.34 | 10.17 | 40.67 |
Leukemia | 3 | 1.49 | 2.02 | 0.65 | 6.26 | 2 | 1.34 | 1.49 | 0.37 | 5.95 | 1 | 0.14 | 7.02 | 0.99 | 49.8 |
MM/ID and lymphoma | 47 | 3.05 | 15.41 | 11.58 | 20.51 | 40 | 2.80 | 14.29 | 10.48 | 19.48 | 7 | 0.25 | 27.91 | 13.31 | 58.54 |
Hodgkin lymphoma | 4 | 0.21 | 19.41 | 7.29 | 51.72 | 3 | 0.19 | 15.87 | 5.12 | 49.21 | 1 | 0.02 | 58.64 | 8.26 | 416.27 |
MM/ID | 31 | 0.86 | 36.17 | 25.44 | 51.43 | 28 | 0.79 | 35.59 | 24.58 | 51.55 | 3 | 0.07 | 42.58 | 13.73 | 132.03 |
Non-Hodgkin lymphoma | 12 | 1.99 | 6.04 | 3.43 | 10.64 | 9 | 1.82 | 4.94 | 2.57 | 9.49 | 3 | 0.16 | 18.37 | 5.93 | 56.96 |
Discussion
Author | Year | Country | Setting | Primary SjS patients (n) | Mean folow-up (yrs/pat-years) | Population cancer registry/classif | Hemat neoplasia classif | Cancer (n) | All-cancer SIR (95% CI) | Specific solid cancer SIR | Hemat cancers (n) | NHL (n) | MALT (n) | DLBC (n) | MZ (n) | Myel (n) | Other B-cell | Non-B-cell | NHL SIR (95% CI) | MM SIR (95% CI) |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Theander | 2006 | Sweden | Hosp | 286 | jul-64 | Swedish Cancer Reg/ICD7 | WHO 2001 | 33 | 1.42 (0.98–2.00) | NA | 12 | 11 | 1 | 7 | 0 | 2 | 1 | T-cell (1) | 15.6 (7.8–27.8) | 3.27 (0.1–18.2) |
Baimpa | 2009 | Greece | Hosp | 536 | 2.6/ND | NA | ND | ND | NA | NA | 40 | 38 | 21 | 7 | 5 | 0 | 5 | HD (1), T-cell (1) | NA | ND |
Zhang | 2010 | China | Hosp | 1320 | 4.4/ND | Shangai Reg/ICD10 | WHO 2001 | 29 | 3.25 (2.12–4.52) | NA | 10 | 8 | 2 | 2 | 0 | 0 | 3 | T-cell (1) | 48.1 (20.7–94.8) | 37.9 (4.58–136.7) |
Weng | 2012 | Taiwan | Pop | 7852 | ND/27246 | NHI/ICD9 | ICD9 | 227 | 1.01 (0.74–1.35) | Colon 0.22 (0.05–0.6); Thyroid 2.56 (1.4–4.3) | 31 | 23 | ND | ND | ND | ND | ND | ND | 7.1 (4.2–10.3) | 6.1 (2.0–14.2) |
Baldini | 2012 | Italy | Hosp | 563 | 6/ND | NA | WHO 2001 | NA | NA | NA | NA | 12 | 8 | 3 | 1 | 0 | 0 | ND | NA | ND |
Hemminki | 2012 | Sweden | Pop | 1516 | ND/16700 | Swedish Cancer Reg/ICD | NA | NA | NA | Breast 0.46 (0.26–0.75) | NA | NA | ND | ND | ND | ND | ND | ND | NA | ND |
Johnsen | 2013 | Norway | Pop | 443 | ND/3813 | Norway Reg/ICD10 | ICD10 | NA | NA | NA | NA | 7 | 6 | 0 | 1 | 0 | 0 | ND | 9.0 (7.1–26.3) | ND |
Risselada | 2013 | Netherl | Hosp | 195 | 7.7/ND | NA | WHO 2001 | NA | NA | NA | NA | 21 | 10 | 8 | 3 | 0 | 0 | ND | NA | ND |
Quartuccio | 2014 | Italy | Hosp | 661 | ND | NA | ND | NA | NA | NA | NA | 40 | ND | ND | ND | ND | ND | ND | NA | ND |
Papageorgiou | 2015 | Greece | Hosp | ND | ND | ND | WHO | ND | ND | ND | ND | 77 | 51 | 12 | 8 | 0 | 6 | ND | ||
Nocturne | 2016 | France | Hosp | ND | ND | ND | WHO | ND | ND | ND | ND | 99 | 58 | 17 | 18 | 0 | 6 | HD (1), T-cell (1) | ND | ND |
Present study | 2016 | Spain | Hosp | 1300 | 7.6/ND | GLOBOCAN/ICD10 | WHO 2016 | 122 | 1.91 (1.6–2.28) | Thyroid 5.17 (1.94–13.79); Lip/oral 4.81 (1.81–12.83); Stomach 2.53 (1.05–6.07) | 61 | 12 | 27 | 7 | 4 | 2 | 6 | HD (4), T-cell (3), myeloid/leuk (8) | 6.04 (3.43–10.64) | 36.17 (25.44–51.43) |