Variations in adjuvant chemotherapy and survival in women with epithelial ovarian cancer – a population-based study

Figures & data

Figure 1. Flowchart showing inclusions and exclusions for women with ovarian cancer included in the study analysis (N = 351).

Table I. Characteristics of women included in the analyses compared with those excluded due to missing chemotherapy dose data.

Characteristic	Included N = 351 n (%)	No dose data N = 94 n (%)	p-Value^a
Age (Mean in years)	57.7	57.4	0.78
		n (%)
Comorbidity score^b
0	290 (83)	72 (79)	0.31
1	29 (8)	6 (7)
2	24 (7)	9 (10)
≥ 3	6 (2)	4 (4)
Missing	2	3
FIGO stage
Early (I & II)	96 (28)	23 (25)	0.70
Advanced (III & IV)	253 (72)	71 (75)
Missing	2	0
Histological subtype
Serous	234 (67)	63 (67)	0.17
Mucinous	7 (2)	3 (3)
Endometroid	30 (8)	14 (15)
Clear cell	49 (14)	8 (9)
Carcinosarcoma	6 (2)	3 (3)
Other epithelial	25 (7)	3 (3)
Residual disease (cm)
0	143 (45)	34 (45)	0.97
> 0	173 (55)	41 (55)
Missing	35	19

^ap-Value based on t-test for age and χ² statistic for other variables; ^bweighted score based on the Charlson Comorbidity Index.

Figure 2. Kaplan-Meier survival curves for ovarian cancer by relative dose intensity (RDI %) of carboplatin and paclitaxel among women with advanced disease (N = 253).

Table II. Hazard ratios for the association between survival and relative dose intensity (RDI), total chemotherapy dose, chemotherapy delays amongst women diagnosed with invasive epithelial ovarian cancer in Australia in 2005.

Variable		Unadjusted HR (95% CI)	Adjusted HR (95% CI)^a		Unadjusted HR (95% CI)	Adjusted HR (95% CI)^a
	N	All women N = 351		N	Women with advanced disease N = 253
Total RDI%
> 100^b	13	1.65 (0.80–3.42)	1.50 (0.73–3.12)	13	1.14 (0.64–2.77)	1.07 (0.51–2.23)
91–100	175	Ref	Ref	120	Ref	Ref
81–90	84	1.04 (0.71–1.51)	1.00 (0.68–1.45)	62	1.03 (0.70–1.54)	1.00 (0.67–1.48)
71–80	28	1.18 (0.64–2.16)	1.18 (0.64–2.16)	22	1.22 (0.64–2.19)	1.16 (0.63–2.13)
≤ 70	51	1.85 (1.23–2.78)	1.62 (1.05–2.49)	36	2.08 (1.35–3.19)	1.90 (1.22–2.96)
Per 5% decrease in RDI^c
		1.08 (1.01–1.16)	1.05 (0.98–1.13)		1.09 (1.02–1.18)	1.08 (1.00–1.16)
% planned combined dose of carboplatin and paclitaxel
> 100^d	25	1.64 (0.97–2.78)	1.46 (0.86–2.48)	24	1.19 (0.70–2.01)	1.11 (0.65–1.88)
91–100	230	Ref	Ref	162	Ref	Ref
81–90	44	1.24 (0.79–1.95)	1.16 (0.74–1.83)	34	1.24 (0.78–1.96)	1.21 (0.76–1.92)
71–80	17	1.12 (0.55–2.30)	1.05 (0.51–2.16)	12	1.20 (0.56–2.58)	1.10 (0.51–2.32)
≤ 70	35	1.31 (0.79–2.16)	1.06 (0.61–1.83)	21	1.80 (1.06–3.06)	1.57 (0.91–2.73)
Per 5% decrease in % planned combined dose of carboplatin and paclitaxel^c
		1.04 (0.96–1.12)	1.00 (0.92–1.09)		1.09 (1.00–1.18)	1.06 (0.97–1.16)
Duration of delay during the course of chemotherapy (days)
	327^e			244^e
0–3	175	Ref	Ref	122	Ref	Ref
4–21	113	0.97 (0.69–1.38)	0.96 (0.68–1.36)	85	0.91 (0.63–1.30)	0.89 (0.62– 1.28)
22–42	26	1.91 (1.18–3.08)	1.75 (1.08–2.85)	25	1.26 (0.77–2.07)	1.18 (0.71 –1.97)
> 42	13	2.07 (1.04–4.12)	1.94 (0.97–3.86)	12	1.50 (0.75–2.99)	1.44 (0.72 – 2.89)
Per week of delay during the course of chemotherapy
		1.14 (1.04–1.25)	1.12 (1.03–1.23)		1.07 (0.98–1.18)	1.06 (0.97–1.16)

^aadjusted for age, comorbidity; ^bThose in this category had RDI of 101–110 except one woman with RDI of 116%; ^cMeasures above 100% were excluded from this calculation; ^dThose in this category had a % planned dose of 101–110 except one woman with a dose of 116%; ^eOnly those who had at least 6 cycles of chemotherapy were included. All the bold values were significant at P> 0.05

Table III. Hazard ratios for the association between time interval (TI) between surgery and initiation of chemotherapy and survival amongst women diagnosed with invasive epithelial ovarian cancer in Australia in 2005.

Time interval (days)	N	Unadjusted HR (95% CI)	Adjusted HR^a (95% CI)
All women N = 351
	351
≤ 7	50	1.21 (0.77–1.89)	0.89 (0.55–1.43)
8–14	95	Ref	Ref
15–21	60	0.86 (0.54–1.37)	0.95 (0.57–1.59)
22–28	51	0.82 (0.50–1.35)	0.80 (0.48–1.35)
29–35	24	0.95 (0.51–1.79)	0.93 (0.42–2.11)
> 35	71	0.75 (0.48–1.19)	1.02 (1.00–1.04)
Per week increase in TI
		0.98 (0.93–1.03)	1.00 (0.94–1.06)
Women with residual disease N = 173
	173
≤ 7	36	0.84 (0.50–1.42)	0.77 (0.44–1.35)
8–14	49	Ref	Ref
15–21	30	1.14 (0.68–1.92)	1.06 (0.59–1.93)
22–28	26	0.68 (0.36–1.27)	0.71 (0.37–1.36)
29–35	11	2.10 (1.03–4.29)	1.30 (0.47–3.58)
> 35	21	0.84 (0.45–1.57)	0.81 (0.40–1.64)
Women without residual disease N = 143
	143
≤ 7	11	1.39 (0.48–4.01)	2.10 (0.68–6.51)
8–14	37	Ref	Ref
15–21	24	0.24 (0.05–1.10)	0.49 (0.10–2.33)
22–28	24	1.05 (0.43–2.63)	0.61 (0.21–1.74)
29–35	12	0.47 (0.10–2.13)	0.62 (0.07–5.53)
> 35	35	1.09 (0.47–2.51)	2.36 (0.90–6.18)
Women with advanced disease N = 253
	253
≤ 7	75	0.96 (0.61–1.53)	0.83 (0.50–1.35)
8–14	44	Ref	Ref
15–21	38	1.11 (0.70–1.78)	1.02 (0.61–1.73)
22–28	37	0.68 (0.39–1.17)	0.67 (0.38–1.18)
29–35	15	1.37 (0.71–2.64)	1.11 (0.49–2.55)
> 35	44	0.88 (0.55–1.41)	1.03 (0.61–1.75)

^aadjusted for age, comorbidity, stage, grade, subtype, residual disease, extent of surgery, surgical complications.

Table IV. Summary of recent studies on the association of time interval (TI) between surgery and initiation of chemotherapy with survival in epithelial ovarian cancer.

Study, year (place)	Years of diagnosis	Number of women	FIGO Stage	Chemotherapy	Median TI (days)	Hazard ratio for TI	Adjustment factors
Hofstetter, 2013 [10] (Germany/Belgium/ Austria)	2005	191	III– IV (serous subtype)	carboplatin/taxane	28	HR = 1.73 (1.08–2.78) for > 28 days vs. ≤ 28 days Any residual disease HR = 2.24 (1.08– 4.66)	Age, FIGO stage, residual disease, extent of surgery, and treatment centre
Mahner, 2013 [23] (Germany/France)	1995–2002 (three RCTs)	3326	IIB–IV	platinum/ paclitaxel (+/- study drug)	19	Overall no significant association No residual disease HR = 1.087 (1.005–1.176) per additional week TI	Age, FIGO stage, residual disease, grade and ascites
Lydiksen, 2014 [24] (Denmark)	2005–2006	650	I–IV	carboplatin/taxane	32	HR = 1.13 (0.92–1.39) > 32 days vs. ≤ 32 days	Residual disease, FIGO stage

Hofstetter G, Concin N, Braicu I, Chekerov R, Sehouli J, Cadron I, et al. The time interval from surgery to start of chemotherapy significantly impacts prognosis in patients with advanced serous ovarian carcinoma – analysis of patient data in the prospective OVCAD study. Gynecol Oncol 2013;131:15–20.

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Mahner S, Eulenburg C, Staehle A, Wegscheider K, Reuss A, Pujade-Lauraine E, et al. Prognostic impact of the time interval between surgery and chemotherapy in advanced ovarian cancer: Analysis of prospective randomised phase III trials. Eur J Cancer 2013;49:142–9.

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Lydiksen L, Jensen-Fangel S, Blaakaer J. Is it possible to define an optimal time for chemotherapy after surgery for ovarian cancer? Gynecol Oncol 2014;133:454–9.

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