Script-based automatic radiotherapy planning for cervical cancer

Figures & data

Table 1. Patient population, target volumes. PTVn is a common term for LNs to 55 and 57.5 Gy, it is the total PTVn if multiple nodes are present.

		PTV_45 sizes (${\text{cm}}^3$)		PTVn sizes (${\text{cm}}^3$)
Target volumes	No. of patients	Median	Range	Median	Range
Pelvic	8	1478	(1136–1878)	NA	NA
Pelvic + pelvic LN	11	1510	(1314–1777)	43	(34-401)
Pelvic + para-aortic +/- para-aortic LN	6	2132	(2036–2177)	128	(39-217)

Figure 1. Flowchart of the script-based planning process. EUD: equivalent uniform dose.

Table 2. Dose statistics for target volumes. CTVn and PTVn are common terms for lymph nodes to 55 and 57.5 Gy. All values are normalized to prescribed dose levels (45, 55 and 57.5 Gy). $D_{\max }$ is defined as dose to 0.1 % volume and $D_{\min }$ is defined as dose to 99.9% volume. For patients with SIB, maximum doses are given in regions 10 mm outside PTVn. The $C{I}_{90\%}$ isodose was cropped to exclude isodose volumes closer than 30 mm to another target volume with an equal or higher prescribed dose. Diff. refers to the median of the pairwise differences between the automatic and clinical plans (Diff. $>$ 0 if automatic $>$ clinical). Corresponding mean values are given in Appendix B.

			Automatic		Clinical
Target	Parameter	Unit	Median	Range	Median	Range	Diff.	p-value
CTVn	$D_{98\%}$	(%)	100.3	(100.0 − 100.4)	100.7	(100.0 − 101.2)	−0.4	0.001
	$D_{50\%}$	(%)	102.6	(102.2 − 104.3)	102.7	(100.7 − 104.9)	−0.2	0.887
CTV_45	$D_{\min }$	(%)	95.1	(94.9 − 95.4)	96.9	(95.1 − 98.2)	−2.0	$<$0.001
PTVn	$D_{98\%}$	(%)	90.3	(90.1 − 90.4)	94.3	(90.1 − 96.2)	−0.7	$<$0.001
	$D_{\max }$	(%)	105.1	(103.8 − 109.9)	104.7	(102.0 − 107.7)	0.2	0.109
	$C{I}_{90\%}$	-	1.20	(1.10 − 1.27)	1.47	(1.10 − 2.47)	−0.16	0.002
PTV_45	$D_{98\%}$	(%)	95.3	(95.1 − 95.3)	96.0	(94.9 − 96.9)	−0.4	0.001
	$C{I}_{\text{43Gy}}$	-	1.03	(1.01 − 1.08)	1.12	(1.07 − 1.29)	−0.09	$<$0.001
	$C{I}_{\text{36Gy}}$	-	1.56	(1.46 − 1.77)	1.64	(1.44 − 2.00)	−0.12	$<$0.001
PTV_45 w/o SIB	$D_{\max }$	(%)	104.4	(104.2 − 105.1)	104.6	(103.6 − 105.1)	0.0	0.916
PTV_45 w SIB	$D_{\max }$	(%)	105.1	(105.1 − 105.6)	106.2	(105.1 − 113.1)	−0.9	$<$0.001

Figure 2. Average DVHs for OARs. Number of patients (n) are given for each OAR.

Table 3. Dose statistics for OARs. For patients with positive LNs, maximum doses are given in regions 15 mm outside PTVn. $D_{\max }$ is defined as dose to 0.1$\%$ of the volume, except for body where $D_{\max }$ is dose to 0.03 ${\text{cm}}^3$ of the volume. All maximum doses (%) are normalized to 45 Gy. Diff. refers to the median of the pairwise differences between the automatic and clinical plans (Diff. $>$ 0 if automatic $>$ clinical). Corresponding mean values are given in Appendix B.

			Automatic		Clinical
	Parameter	Unit	Median	Range	Median	Range	Diff.	p-value
Bowel	$D_{\max }$	(%)	104.2	(101.8 − 104.4)	104.0	(99.3 − 108.9)	0.0	0.573
	$V_{\text{40Gy}}$	(${\text{cm}}^3$)	227.9	(75.9 − 420.0)	268.0	(78.6 − 471.7)	−29.2	$<$0.001
	$V_{\text{30Gy}}$	(${\text{cm}}^3$)	407.9	(101.0 − 702.3)	506.9	(111.7 − 900.5)	−61.4	$<$0.001
	$D_{\text{mean}}$	(Gy)	23.5	(10.0 − 30.3)	25.3	(11.6 − 34.2)	−1.9	$<$0.001
Rectum	$D_{\max }$	(%)	104.0	(102.2 − 104.4)	103.3	(100.4 − 106.2)	0.5	0.075
	$V_{\text{40Gy}}$	(%)	69.1	(49.2 − 97.0)	72.5	(52.5 − 96.6)	−0.7	0.113
	$V_{\text{30Gy}}$	(%)	84.9	(65.5 − 100.0)	90.1	(69.3 − 100.0)	−1.1	0.005
	$D_{\text{mean}}$	(Gy)	38.7	(31.9 − 43.1)	40.1	(33.2 − 43.4)	−0.7	$<$0.001
Bladder	$D_{\max }$	(%)	104.2	(102.9 − 104.4)	104.0	(100 − 107.6)	0.4	0.916
	$V_{\text{40Gy}}$	(%)	61.9	(43.4 − 100.0)	64.9	(44.8 − 100.0)	−1.9	0.003
	$V_{\text{30Gy}}$	(%)	74.6	(54.9 − 100.0)	85.3	(60.7 − 100.0)	−2.9	$<$0.001
	$D_{\text{mean}}$	(Gy)	37.1	(30.7 − 43.6)	39.4	(33.5 − 44.3)	−1.1	$<$0.001
Sigmoid	$D_{\max }$	(%)	103.5	(98.7 − 104.4)	103.4	(101.3 − 107.6)	−0.7	0.173
	$D_{\text{mean}}$	(Gy)	40.8	(35.1 − 45.2)	42.5	(39.3 − 48.9)	−1.1	0.002
Kidney_L	$D_{\text{mean}}$	(Gy)	5.1	(0.8 − 7.2)	3.9	(0.8 − 8.8)	1.0	0.463
Kidney_R	$D_{\text{mean}}$	(Gy)	4.3	(1.3 − 7.4)	3.3	(1.5 − 8.7)	0.6	0.237
SpinalCord	$D_{\max }$	(Gy)	40.9	(33.9 − 41.1)	40.6	(31.0 − 47.0)	−1.3	0.688
FemoralHead_L	$D_{\max }$	(Gy)	40.8	(30.6 − 45.3)	43.1	(31.9 − 49.3)	−2.0	$<$0.001
FemoralHead_R	$D_{\max }$	(Gy)	41.8	(30.4 − 48.4)	43.8	(35.4 − 51.1)	−2.1	$<$0.001
Body	$D_{\max }$	(%)	105.8	(104.7 − 106.7)	106.7	(104.0 − 118.9)	−0.7	$<$0.001
	$D_{\text{mean}}$	(Gy)	13.7	(8.7 − 19.1)	14.5	(9.4 − 19.9)	−0.6	$<$0.001

Figure 3. Preferred plans in the blinded comparison between the automatic and clinical plans for all 25 patients. The number of LNs and dose prescriptions level for each patient are reported.

Figure 4. Automatic vs. clinical plans for two different representative patients in (a), (b) and (c), (d). Isodose lines are dark yellow for 55 Gy, dark green for 49.5 Gy, orange for 47.3 Gy, yellow for 45 Gy, green for 42.75 Gy, white for 27.5 Gy, and sea green for 16.5 Gy. PTV is outlined in blue, CTV in pink and GTV in red. The bowel is dark green, the sigmoid is orange, and the rectum is brown.

Table 4. Number of MU, gamma passing rate (3%/3 mm) with 20%–500% local dose, and maximum gamma-index.

		Automatic		Clinical
Parameter	Unit	Mean	STD	Mean	STD	p-value
MU	MU	547.4	52.6	470.9	71.3	$<$0.001
Gamma passing rate (3%/3 mm)	(%)	99.8	0.3	99.6	0.4	0.094
Max gamma-index	-	1.16	0.22	1.14	0.25	0.626

Table A1. Dose constraints used in this study. Adapted from national guidelines and the EMBRACE II study [32, 34]. CTVn/PTVn is a common term for lymph nodes to 55 and 57.5 Gy. All values are normalized to the prescribed dose level (45, 55, and 57.5 Gy). $D_{\max }$= dose to 0.1$\%$ of the volume, except for body where $D_{\max }$= dose to 0.03 ${\text{cm}}^3$ of the volume. All maximum doses to OARs (%) are normalized to 45 Gy.

	Hard dose constraints	Soft dose constraints
Target volumes
PTV_45	$D_{98\%}>$ 95%
	$D_{\max }<$ 107%^a
CTVn	$D_{98\%}>$ 100% of prescribed dose	$D_{50\%}>$ 102% of prescribed dose
	$D_{\max }<$ 107% of prescribed dose
PTVn	$D_{98\%}>$ 90% of prescribed dose
	$D_{\max }<$ 107% of prescribed dose
OARs
Bowel	$D_{\max }<$ 105%^b	No para-aortal irradiation:
		$V_{40\mathrm{Gy}}<$ 250 ${\text{cm}}^3$
		$V_{30\mathrm{Gy}}<$ 500 ${\text{cm}}^3$
		Para-aortal irradiation:
		$V_{40\mathrm{Gy}}<$ 300 ${\text{cm}}^3$
		$V_{30\mathrm{Gy}}<$ 650 ${\text{cm}}^3$
Sigmoid	$D_{\max }<$ 105%^b
Bladder	$D_{\max }<$ 105%^b	$V_{40\mathrm{Gy}}<$ 60%
		$V_{30\mathrm{Gy}}<$ 80%
Rectum	$D_{\max }<$ 105%^b	$V_{40\mathrm{Gy}}<$ 60%
		$V_{30\mathrm{Gy}}<$ 95%
Spinal cord	$D_{\max }<$ 48 Gy
Femoral head	$D_{\max }<$ 50 Gy
Kidney	$D_{\text{mean}}<$ 15 Gy	$D_{\text{mean}}<$ 10 Gy
Body	$D_{\max }<$ 107% ^b
$C{I}_{\text{43Gy}}$		1.10
$C{I}_{\text{36Gy}}$		1.55

^aFor patients with involved lymph nodes; in regions 10 mm outside PTVn.

^bFor patients with involved lymph nodes; in regions 15 mm outside PTVn.

Table B1. Dose statistics for target volumes. CTVn/PTVn is a common term for lymph nodes to 55 and 57.5 Gy. All values are normalized to prescribed dose levels (45, 55, and 57.5 Gy). $D_{\max }$ is defined as dose to 0.03 ${\text{cm}}^3$ volume and $D_{\min }$ is defined as dose to 99.9% volume. The $C{I}_{90\%}$ isodose was cropped to exclude isodose volumes closer than 30 mm to another target volume with an equal or higher prescribed dose. Diff. refers to the mean pairwise differences between the automatic and clinical plans (Diff. $>$ 0 if automatic $>$ clinical).

			Automatic		Clinical
Target	Param.	Unit	Mean	STD	Mean	STD	Diff.	p-value
CTVn	$D_{98\%}$	(%)	100.3	0.1	100.6	0.3	−0.3	$<$ 0.001
	$D_{50\%}$	(%)	102.7	0.5	102.7	0.9	−0.1	0.445
CTV_45	$D_{\min }$	(%)	95.1	0.2	96.9	0.8	−1.7	$<$ 0.001
PTVn	$D_{98\%}$	(%)	90.3	0.1	93.2	2.3	−3.0	$<$ 0.001
	$D_{\max }$	(%)	105.5	1.4	104.7	1.5	0.8	0.109
	$C{I}_{90\%}$	-	1.2	0.1	1.5	0.3	−0.3	$<$ 0.001
PTV_45	$D_{98\%}$	(%)	42.9	0.1	43.2	0.2	−0.3	$<$ 0.001
	$C{I}_{\text{43Gy}}$	-	1.04	0.02	1.13	0.06	−0.1	$<$ 0.001
	$C{I}_{\text{36Gy}}$	-	1.55	0.06	1.68	0.14	−0.1	$<$ 0.001
PTV_45 w/o SIB	$D_{\max }$	(%)	104.4	0.3	104.5	0.5	0.0	0.105
PTV_45 w/ SIB	$D_{\max }$	(%)	105.2	0.2	107.2	2.2	−1.9	$<$ 0.001

Table B2. Dose statistics for OARs. For patients with positive LNs, maximum doses are given in regions 15 mm outside PTVn. $D_{\max }$ is defined as dose to 0.1$\%$ of the volume, except for body where $D_{\max }$ is dose to 0.03 ${\text{cm}}^3$ of the volume. All maximum doses (%) are normalized to 45 Gy. Diff. refers to the mean pairwise differences between the automatic and clinical plans (Diff. $>$ 0 if automatic $>$ clinical).

			Automatic		Clinical
OAR	Parameter	Unit	Mean	STD	Mean	STD	Diff.	p-value
Bowel	$D_{\max }$	(%)	104.1	0.5	104.0	1.8	0.0	0.616
	$V_{40\mathrm{Gy}}$	(${\text{cm}}^3$)	254.9	89.7	291.7	101.4	−36.8	$<$0.001
	$V_{30\mathrm{Gy}}$	(${\text{cm}}^3$)	432.2	139.0	512.9	172.5	−80.7	$<$0.001
	$D_{\text{mean}}$	(Gy)	23.5	4.8	25.5	5.5	−2.1	$<$0.001
Rectum	$D_{\max }$	(%)	103.7	0.6	103.3	1.3	0.4	0.072
	$V_{40\mathrm{Gy}}$	(%)	72.2	14.3	73.6	12.6	−1.4	0.113
	$V_{30\mathrm{Gy}}$	(%)	85.3	11.0	87.8	9.5	−2.5	0.005
	$D_{\text{mean}}$	(Gy)	38.6	3.3	39.4	2.9	−0.8	$<$0.001
Bladder	$D_{\max }$	(%)	104.1	0.4	104.0	1.9	0.2	0.937
	$V_{40\mathrm{Gy}}$	(%)	67.6	16.2	69.3	15.5	−1.7	0.003
	$V_{30\mathrm{Gy}}$	(%)	79.5	14.6	83.6	12.4	−4.2	$<$0.001
	$D_{\text{mean}}$	(Gy)	37.9	4.1	39.5	3.2	−1.6	$<$0.001
Sigmoid	$D_{\max }$	(%)	99.0	15.1	99.7	15.2	−0.7	0.173
	$D_{\text{mean}}$	(Gy)	41.0	2.7	42.7	2.5	−1.7	0.002
Kidney_L	$D_{\text{mean}}$	(Gy)	4.7	2.7	4.3	2.8	0.4	0.463
Kidney_R	$D_{\text{mean}}$	(Gy)	4.4	2.4	3.8	2.3	0.6	0.237
SpinalCord	$D_{\max }$	(Gy)	39.0	3.3	40.3	5.9	−1.3	0.688
FemoralHead_L	$D_{\max }$	(Gy)	41.9	3.9	44.1	3.3	−2.2	$<$0.001
FemoralHead_R	$D_{\max }$	(Gy)	40.4	3.0	42.5	3.1	−2.1	$<$0.001
Body	$D_{\max }$	(%)	105.7	0.6	108.5	4.2	−2.8	$<$0.001
	$D_{\text{mean}}$	(Gy)	13.8	2.6	14.4	2.6	−0.5	$<$0.001

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Data availability statement

Raw data were generated at St Olavs Hospital, Norway. Derived data supporting the findings of this study are available from the corresponding author MF on request.