Association of body composition with toxicity to first-line chemotherapy and three-year survival in women with ovarian adenocarcinoma

Figures & data

Figure 1. Flowchart for patient selection in the study.

Figure 2. Chemotherapy protocol drugs with potential severe drug-drug interaction with regular and support medications waived at Institution during the treatment of patients. SOURCE: Drugs.com Statistics (2020) [42].

Table 1. Clinical, pathological, and treatment-related characteristics of women with ovarian adenocarcinoma (n = 239).

Variables	Overall n (%)	Skeletal muscle index (cm²/m²)		p*	Skeletal muscle density (HU)		p*
		<38.9 n (%)	≥38.9 n (%)		<p50 n (%)	≥p50 n (%)
Clinical-pathological characteristics
Age (years)
<65	181 (75.7)	57 (67.9)	124 (80.0)	.04	73 (61.3)	108 (90.0)	.01
≥65	58 (24.3)	27 (32.1)	31 (20.0)		46 (38.7)	12 (10.0)
Histological subtype (n = 186)
Serous	137 (73.7)	47 (77.0)	90 (72.0)	.39	66 (78.6)	71 (69.6)	.16
Endometrioid	15 (8.1)	5 (8.2)	10 (8.0)		6 (7.1)	9 (8.8)
Mucinous	17 (9.1)	7 (11.5)	10 (8.0)		9 (10.7)	8 (7.8)
Clear cells	9 (4.8)	1 (1.6)	8 (6.4)		1 (1.2)	8 (7.8)
Mixed	8 (4.3)	1 (1.6)	7 (5.6)		2 (2.4)	6(5.9)
Tumor staging (n = 214)
Stage I-II	28 (13.1)	7 (10.0)	21 (14.6)	.40	13 (12.1)	15 (14.0)	.84
Stage III-IV	186 (86.9)	63 (90.0)	123 (85.4)		94 (87.9)	92 (86.0)
Tumor grade (n = 159)
Grade I-II	40 (25.2)	15 (26.8)	25 (24.3)	.85	12 (16.0)	28 (33.3)	.02
Grade III	119 (74.8)	41 (73.2)	78 (75.7)		63 (84.0)	56 (66.7)
Performance status (n = 235)
0–1	159 (67.7)	48 (57.1)	111 (73.5)	.01	76 (65.0)	83 (70.3)	.41
2–3	76 (32.3)	36 (42.9)	40 (26.5)		41 (35.0)	35 (29.7)
Charlson's comorbidity index^a
0 point	110 (46.0)	44 (52.4)	66 (42.6)	.50	43 (36.1)	67 (55.8)	.02
1 point	98 (41.0)	31 (36.9)	67 (43.2)		56 (47.1)	42 (35.0)
2 points	26 (10.9)	9 (9.5)	22 (11.6)		16 (13.4)	10 (8.3)
3 points	5 (2.1)	1 (1.2)	4 (2.6)		4 (3.4)	1 (0.8)
Glomerular filtration rate
<60 ml/min/1.73m²	25 (10.5)	9 (10.7)	16 (10.3)	1.00	20 (16.8)	5 (4.2)	.01
≥60 ml/min/1.73m²	214 (89.5)	75 (89.3)	139 (89.7)		99 (83.2)	115 (95.8)
Treatment characteristics
Platinum sensitivity (n = 208)^b
Platinum sensitive	90 (43.3)	21 (31.3)	69 (48.9)	.05	42 (42.0)	48 (44.4)	.03
Platinum partially sensitive	22 (10.6)	11 (16.4)	11 (7.8)		17 (17.0)	5 (4.6)
Platinum resistant	62 (29.8)	21 (31.3)	41 (29.1)		26 (26.0)	36 (33.3)
Platinum refractory	34 (16.3)	14 (20.9)	20 (14.2)		15 (15.0)	19 (17.6)
Number of cycles
<6	52 (21.8)	23 (27.4)	29 (18.7)	.14	24 (20.2)	28 (23.3)	.64
≥6	187 (78.2)	61 (72.6)	126 (81.3)		95 (79.8)	92 (76.7)
First cycle dose reduction^c
No	206 (86.2)	68 (81.0)	138 (89.0)	.12	98 (82.4)	108 (90.0)	.10
Yes	33 (13.8)	16 (19.0)	17 (11.0)		21 (17.6)	12 (10.0)
First cycle monotherapy^d
No	201 (84.1)	69 (82.1)	132 (85.2)	.58	92 (77.3)	109 (90.8)	.01
Yes	38 (15.9)	15 (17.9)	23 (14.8)		27 (22.7)	11 (9.2)
Potential severe drug-drug interaction
No	124 (51.9)	42 (50.0)	82 (52.9)	.69	56 (47.1)	68 (56.7)	.16
Yes	115 (48.1)	42 (50.0)	73 (47.1)		63 (52.9)	52 (43.3)
Treatment-related complications
Overall dose reduction^e	33 (13.8)	–	–	–	–	–	–
Carboplatin reduction
No	214 (89.5)	77 (91.7)	137 (88.4)	.51	102 (85.7)	112 (93.3)	.06
Yes	25 (10.5)	7 (8.3)	18 (11.6)		17 (14.3)	8 (6.7)
Paclitaxel reduction
No	228 (95.4)	78 (92.9)	150 (96.8)	.20	110 (92.4)	118 (98.3)	.03
Yes	11 (4.6)	6 (7.1)	5 (3.2)		9 (7.6)	2 (1.7)
Delay^f
No	187 (78.2)	71 (84.5)	116 (74.8)	.10	89 (74.8)	98 (81.7)	.21
Yes	52 (21.8)	13 (15.5)	39 (25.2)		30 (25.2)	22 (18.3)
Monotherapy^g
No	229 (95.8)	78 (92.9)	151 (97.4)	.10	113 (95.0)	116 (96.7)	.54
Yes	10 (4.2)	6 (7.1)	4 (2.6)		6 (5.0)	4 (3.3)
Interruption^h
No	227 (95.0)	79 (94.0)	148 (95.5)	.76	110 (92.4)	117 (97.5)	.08
Yes	12 (5.0)	5 (6.0)	7 (4.5)		9 (7.6)	3 (2.5)
Adverse events ≥grade 3^i
No	116 (48.5)	39 (46.4)	77 (49.7)	.69	50 (42.0)	66 (55.0)	.05
Yes	123 (51.3)	45 (53.6)	78 (50.3)		69 (58.0)	54 (45.0)
Number of adverse events ≥grade 3
0	116 (48.5)	39 (46.4)	77 (49.7)	.88	50 (42.0)	66 (55.0)	.13
1–2	94 (39.3)	34 (40.5)	60 (38.7)		53 (44.5)	41 (34.2)
≥3	29 (12.1)	11 (13.1)	18 (11.6)		16 (13.4)	13 (10.8)
Toxicity-induced modification of treatment^j
No	161 (67.4)	59 (70.2)	102 (65.8)	.56	71 (59.7)	90 (75.0)	.01
Yes	78 (32.6)	25 (29.8)	53 (34.2)		48 (40.3)	30 (25.0)

^aNonmalignant comorbidities, points attributed to systemic arterial hypertension (n = 107), diabetes mellitus (n = 30), congestive heart failure (n = 11), peripheral vascular disease (n = 13), chronic pulmonary disease (n = 10), and mild liver disease (n = 3). ^bPlatinum sensitivity: refractory (relapse <1 month), resistant (relapse 1–6 months), partially sensitive (relapse 6–12 months) or sensitive (relapse > 12 months); ^cFirst cycle dose reduction: reduction of carboplatin (area under the curve four or less) and/or paclitaxel (20% less) due to comorbidities or poor performance status; ^dFirst cycle monotherapy: carboplatin or paclitaxel suspension due to comorbidities or poor performance status; ^eDose reduction: temporary or permanent administration of a lower carboplatin dose than the target AUC at the beginning of treatment or a 20% reduction in paclitaxel from the starting dose; ^fDelay: at least 7-days delay reported in medical charts due to toxicity; ^gMonotherapy: discontinuation of any given drug, carboplatin or paclitaxel; ^hInterruption: permanent discontinuation of treatment due to toxicity; ⁱAlopecia not considered; ^jToxicity-induced modification of treatment: any toxicity that resulted in delayed treatment, dose reduction, discontinuation of any given chemotherapy and/or permanent discontinuation due to toxicity.

* Chi-square or Fisher’s exact test.

Table 2. Regression models for adverse events ≥ grade 3 and toxicity-induced modification of treatment.

Models	Number of adverse events ≥ grade 3^a		Toxicity-induced modification of treatment^b
	RR	CI (95%)	OR	CI (95%)
Model 1 – SMI
SMI < 38.9 cm²/m²	1.14	0.87–1.51	0.64	0.34–1.22
SATI < 61.76 cm²/m²	1.42	1.08–1.87	2.21	1.18–4.15
Potential severe drug-drug interaction	1.59	1.21–2.08	2.16	1.20–3.89
Age (each year increase)	0.98	0.97–1.00	1.00	0.97–1.03
Performance status ≥2	1.27	0.95–1.70	1.68	0.91–3.12
Comorbidity (vs. no)	1.02	0.77–1.36	1.95	1.02–3.74
Model 2 – SMD
SMD < 21.24 HU	1.67	1.25–2.25	2.25	1.17–4.31
SATI < 61.76 cm²/m²	1.53	1.16–2.00	2.18	1.18–4.05
Potential severe drug-drug interaction	1.50	1.14–1.97	1.95	1.08–3.53
Age (each year increase)	0.98	0.96–0.99	0.98	0.95–1.01
Performance status ≥2	1.24	0.93–1.66	1.61	0.86–2.99
Comorbidity (vs. no)	0.98	0.74–1.30	2.01	1.05–3.87

CI: Confidence interval; HU: Hounsfield unit; OR: Odds ratio; RR: Relative Risk; SATI: Subcutaneous adipose tissue index; SMD: Skeletal muscle radiodensity; SMI: Skeletal muscle index. ^aMultivariable Mixed Effects Poisson Regression Models, additionally adjusted for first cycle dose reduction and first cycle monotherapy. ^bMultivariable Logistic Regression.

Table 3. Multivariable Cox regression models for three-year overall survival.

Models	HR	CI (95%)
Model 1 – SMI
SMI < 38.9 cm²/m²	1.20	0.77–1.87
SATI < 61.76 cm²/m²	0.81	0.53–1.23
Platinum resistant/refractory	6.20	3.93–9.77
Age (each year increase)	1.02	1.00–1.04
Tumor staging	1.66	1.21–2.27
Performance status ≥2	1.99	1.29–3.05
Model 2 – SMD
SMD < 21.24 HU	2.66	1.68–4.20
SATI < 61.76 cm²/m²	0.88	0.58–1.34
Platinum resistant/refractory	7.58	4.72–12.18
Age (each year increase)	1.00	0.98–1.02
Tumor staging	1.49	1.09–2.05
Performance status ≥2	2.27	1.47–3.51

CI: Confidence interval; HR: Hazard ratio; HU: Hounsfield unit; SATI: Subcutaneous adipose tissue index; SMD: Skeletal muscle radiodensity; SMI: Skeletal muscle index.

Drugs.com. Drug Interaction Checker; c1996-2018; 2020. [cited 2020 Dec 1]. Available from: https://www.drugs.com/drug_interactions.html

 Google Scholar