| Literature DB >> 35008281 |
Philippe Wind1, Zoe Ap Thomas2, Marie Laurent3,4, Thomas Aparicio5, Matthieu Siebert1, Etienne Audureau3,6, Elena Paillaud3,7, Guilhem Bousquet2,8, Frédéric Pamoukdjian8,9.
Abstract
We aimed to assess the prognostic value of the pre-operative GRADE score for long-term survival among older adults undergoing major surgery for digestive or non-breast gynaecological cancers. Between 2013 and 2019, 136 consecutive older adults with cancer were prospectively recruited from the PF-EC cohort study before major cancer surgery and underwent a geriatric assessment. The GRADE score includes weight loss, gait speed at the threshold of 0.8 m/s, cancer site and cancer extension. The primary outcome was post-operative 5-year mortality. Patients were classified as low risk (GRADE ≤ 8) or high risk (GRADE > 8) on the basis of the median score. A Cox multivariate proportional hazards regression model was performed to assess the association between pre-operative factors and 5-year mortality expressed by adjusted hazard ratio (aHR) and 95% CI. The median age was 80 years, 52% were men, 73% had colorectal cancer. The 30-day post-operative severe complication rate (Clavien-Dindo ≥ 3) was 37%. The 5-year post-operative mortality rate was 34.5%. A GRADE score ≥ 8 (aHR = 2.64 [1.34-5.21], p = 0.0002) was associated with post-operative mortality after adjustment for Body Mass Index < 21 kg/m2 and Instrumental Activities of Daily Living <3/4. By combining very simple geriatric and cancer parameters, the pre-operative GRADE score provides a discriminant prognosis and could help to choose the most suitable treatment strategy for older cancer patients, avoiding under or over-treatment.Entities:
Keywords: cancer; older adults; post-operative complications; postoperative mortality; prognostic score; surgery
Year: 2021 PMID: 35008281 PMCID: PMC8750490 DOI: 10.3390/cancers14010117
Source DB: PubMed Journal: Cancers (Basel) ISSN: 2072-6694 Impact factor: 6.639
Baseline characteristics and comparison of 136 older patients with major cancer surgery according to the GRADE score.
| Variables | Whole Cohort | GRADE ≤ 8 | GRADE > 8 | |
|---|---|---|---|---|
| Low-Risk | High-Risk | |||
| Age, y | ||||
| Mean ± SD | 80 ± 7 | 78 ± 7 | 82 ± 7 |
|
| 65–74 | 32 (23.5) | 20 (29) | 12 (18) | 0.09 |
| 75–84 | 66 (48.5) | 34 (50) | 32 (47) | |
| ≥85 | 38 (28) | 14 (21) | 24 (35) | |
| Gender (male) | 71 (52) | 42 (62) | 29 (43) |
|
| Outpatient (yes) | 108 (79) | 60 (88) | 48 (70) | 0.25 |
| Cancer site: | 0.25 | |||
| Colorectal | 99 (73) | 47 (69) | 52 (76) | |
| Others † | 37 (27) | 21 (31) | 16 (24) | |
| Local and locally-advanced cancer (yes) | 107 (79) | 62 (91) | 45 (66) |
|
| ASA scale > 2 | 60 (44) | 21 (31) | 39 (57) |
|
| ECOG > 2 | 38 (28) | 9 (13) | 29 (43) |
|
| G8-index £ 14/17 ( | 112 (84) | 50 (73) | 62 (91) |
|
| Comorbidities: | ||||
| CIRSG total ≥ 14 | 67 (49) | 29 (43) | 38 (56) | 0.12 |
| Polypharmacy (yes) | 88 (65) | 42 (62) | 46 (68) | 0.47 |
| Dependency | ||||
| ADL £ 5/6 | 45 (33) | 12 (18) | 33 (48) |
|
| IADL £ 3/4 | 76 (56) | 26 (38) | 50 (73) |
|
| Malnutrition | ||||
| BMI < 21 kg/m2 ( | 18 (13) | 8 (12) | 10 (15) | 0.56 |
| Depressed mood | ||||
| Mini-GDS ≥ 1/4 | 51 (37.5) | 22 (32) | 29 (43) | 0.21 |
| Cognition ( | ||||
| MMSE < 24/30 | 41 (45) | 19 (28) | 22 (32) |
|
| 30-day post-operative complications | ||||
| Clavien-Dindo ≥ 1 | 91 (67) | 41 (60) | 50 (73) | 0.1 |
| Clavien-Dindo ≥ 3a (severe) | 50 (37) | 19 (28) | 31 (46) |
|
* χ2 test or Fisher’s exact test for categorical variables as appropriate; Bold = significant p value (<0.05). †: gastric (n = 17); pancreas (n = 8); oesophagus (n = 3); bile-duct (n = 2); gastrointestinal and stromal tumours (n = 2); anus (n = 1); ovarian (n = 3); uterus (n = 1). ASA: American Society Anesthesiology; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; CIRSG: Cumulative Illness Rating Scale Geriatric; ADL: Activities of Daily Living; IADL: Instrumental-ADL; BMI: Body Mass Index; Mini-GDS: Mini-Geriatric Depression Scale; MMSE: Mini Mental State Examination.
Figure 1Bar plot of the 30-day post-operative complications among 136 older patients with major cancer surgery.
Preoperative factors associated with 5-year mortality among 136 older patients with major cancer surgery.
| Variables | Univariate Analysis | Multivariate Analysis | ||||
|---|---|---|---|---|---|---|
| HR | (95% CI) | aHR | (95% CI) | |||
| Age (per 1 SD of more) | 1.05 | 1.01–1.10 |
| - | ||
| Gender (male) | 0.61 | 0.34–1.09 | 0.09 | - | ||
| Outpatients (yes) | 0.55 | 0.29–1.06 | 0.07 | - | ||
| GRADE score |
| |||||
| ≤8 (low risk) | 1 (reference) | – | 1 (reference) | - |
| |
| >8 (high risk) | 3.47 | 1.85–6.54 | 2.64 | (1.34–5.21) | ||
| ASA scale > 2 | 3.43 | 1.87–6.30 |
| - | ||
| ECOG-PS > 2 | 3.42 | 1.88–6.23 |
| - | ||
| G8-index £ 14/17 ( | 3.09 | 0.96–10.0 | 0.05 | - | ||
| Comorbidities: | ||||||
| CIRSG total ≥ 14 | 1.95 | 1.09–3.51 |
| - | ||
| Polypharmacy (yes) | 1.63 | 0.86–3.10 | 0.13 | - | ||
| Dependency | ||||||
| ADL £ 5/6 | 2.22 | 1.24–3.98 |
| - | ||
| IADL £ 3/4 | 4.32 | 2.13–8.73 |
| 2.95 | (1.40–6.23) |
|
| Malnutrition | ||||||
| BMI < 21 kg/m2 ( | 2.66 | 1.35–5.25 |
| 2.97 | (1.49–5.93) |
|
| Depressed mood | ||||||
| Mini-GDS ≥ 1/4 | 1.88 | 1.06–3.33 |
| - | ||
| Cognition ( | ||||||
| MMSE < 24/30 | 2.61 | 1.18–5.73 |
| - | ||
* p value for log-rank test; Bold = significant p value (<0.05); ASA: American Society Anesthesiology; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; CIRSG: Cumulative Illness Rating Scale Geriatric; ADL: Activity of Daily Living; IADL: Instrumental-ADL; BMI: Body Mass Index; Mini-GDS: Mini-Geriatric Depression Scale; MMSE: Mini Mental State Examination; NA: Non-Available.
Figure 25-year Kaplan-Meier survival according to the GRADE score for 136 older patients with major cancer surgery.
5-year risk of death according to the pre-operative GRADE score among older patients undergoing major cancer surgery.
| Risk of Death | ||||||
|---|---|---|---|---|---|---|
| GRADE | Median Survival (Months) | 12 m | 24 m | 36 m | 50 m | 62 m |
| ≤8 (low risk) | NR | 8% | 13% | 22% | 29% | 29% |
| >8 (high risk) | 34.2 (19.2–50.1) | 31% | 37% | 55% | 62% | 74% |
NR: not reached.
The GRADE and the GRADE-surgery scoring systems.
| GRADE | GRADE-Surgery |
|---|---|
| Weight loss ≥ 5% | GRADE > 8 |
| No = 0 | No = 0 |
| Yes = 1 | Yes = 3 |
| Gait speed < 0.8 m/s | IADL ≤ ¾ * |
| No = 0 | No = 0 |
| Yes = 3 | Yes = 4 |
| Cancer site | |
| Colorectal = 3 | |
| Non-breast gynaecological = 3 | |
| Digestive non-colorectal = 4 | |
| Cancer extension | |
| Local = 0 | |
| Locally-advanced = 3 | |
| Metastatic = 5 | |
| Total = 3–13 | Total = 0–7 |
| C-index (threshold of 8) = 0.76 | C-index (threshold of 4) = 0.81 |
* IADL scoring: For each item, does alone = 1; does with help = 0 (uses telephone, transports, medications, and money management).
Comparison of pre-operative scoring systems among older adults referred for a cancer-surgery.
| Scoring Systems | Study Population | Variables | Advantages | Disadvantages |
|---|---|---|---|---|
| PREOP [ | 229 patients ≥ 70 years | Total = 5 | Associated with 5-year overall survival | No external validation |
| VESPA [ | 476 patients ≥ 70 years | Total = 6 | Associated with 30-day post-operative complications | No external validation |
| GA-GYN [ | 189 patients ≥ 70 years | Total = 8 | Associated with 6-week post-operative complications (stage III/IV only) | No external validation |
| GRADE [ | 136 patients ≥ 65 years | Total = 4 | Associated with 5-year overall survival | No external validation |
ADL: Activities of Daily Living; ASA: American Society Anesthesiology; IADL: Instrumental-ADL; NRS: Nutritional Risk Screening tool; TGUG: Timed Get Up and Go test.