Clinical efficacy and toxicity of radio-chemotherapy and magnetic resonance imaging-guided brachytherapy for locally advanced cervical cancer patients: A mono-institutional experience

Figures & data

Table I. Patient and tumor characteristics.

Number of patients	85
Follow-up, months, mean (range)	36 (6–94)
Age, years, median (range)	50 (26–78)
Co-morbidities/past medical history (%)
Previous abdominal surgery	36 (42.4)
Hypertension	10 (11.8)
Diabetes	4 (4.7)
Smoking	39 (45.9)
Pre-treatment hemoglobin, mean (range)	12.5 (8.1–17.4)
FIGO (%)
IB	19 (22.3)
IIA	15 (17.6)
IIB	34 (40.0)
IIIA	2 (2.4)
IIIB	13 (15.3)
IVA	2 (2.4)
Tumor size at diagnosis, cm, mean, (range)	5 (1–8.3)
≥ 5 cm (%)	46 (54.1)
< 5 cm (%)	39 (45.9)
Histology (%)
Squamous cell	73 (85.9)
Adenocarcinoma	6 (7.1)
Adeno-squamous	6 (7.1)
Nodes
Negative	40 (47.1)
Positive	45 (52.9)
Pelvic nodes (cN+)	40 (47.1)
Paraaortic nodes (cN+)	18 (21.2)
LND	66 (77.6)
Pelvic LND	23 (27.1)
Pelvic pN+	17 (70.8)
Paraaortic LND	59 (69.4)
Paraaortic pN+	8 (13.3)

cN+, clinically positive nodes; LND, lymph node dissection; pN+, pathologically positive nodes.

Table II. Treatment characteristics.

EBRT target (%)
Pelvis	62 (72.9)
Pelvis and paraaortic region	21 (24.7)
Pelvis and inguinal regions	2 (2.4)
EBRT technique (%)
3D conformal	61 (71.8)
IMRT	24 (28.2)
Pelvis EBRT dose and fractionation (%)
45 Gy/25 fx	2 (2.4)
50.4 Gy/28 fx	65 (76.5)
50.4 Gy/28 fx + 10 Gy/5 fx to primary disease	18 (21.2)
Nodal boost (%)	36 (42.4)
SeqB^a, 10 Gy/5 fx	28 (77)
SIB^b, 58 Gy/28 fx	8 (23)
Total BT dose (%)
≤ 25 Gy	17 (20)
30 Gy	35 (41.2)
35 Gy	33 (38.8)
BT technique (%)
Ir192 (PDR), IC	75 (88.3)
Ir192 (PDR), IC/IS	10 (11.7)
Chemotherapy
Concomitant	85 (100)
Number of completed cycles, median (range)	6 (1–8)
Overall treatment time, days, median (range)	49 (40–81)

^asequential boost; ^bsimultaneously integrated boost. IC, intracavitary; IC/IS, combined intracavitary and interstitial BT.

Table III. Dose-volume parameters in EQD2.

	Total
	Mean	SD
HR-CTV volume, cm^3	38.1	27.6
Dose-parameters, Gy
HR-CTV
D90	84.4	9
IR-CTV
D90	69.1	4.3
Rectum
D0.1cm^3	73.7	10.9
D2cm^3	65	6.8
ICRU point	68.7	11.1
Bladder
D0.1cm^3	95.8	23.8
D2cm^3	77.3	10.5
ICRU point	80.1	16.1
Sigmoid
D0.1cm^3	70	11.4
D2cm^3	63	7.9
Bowel
D0.1cm^3	72.1	14.9
D2cm^3	64	9.1

D0.1cm³, minimum dose to highest 0.1cm³ of the organ at risk volume; D2cm³, minimum dose to highest 2cm³ of the organ at risk volume; D90 HR-CTV, minimum dose to 90% of the HR-CTV volume; SD, standard deviation.

Figure 1. D90 HR-CTV shown as a function of HR-CTV volume. Black spots and star show locally failed patients with FIGO stage and initial tumor size. Dotted black line represents the actual planning aim of 85 Gy for the D90 HR-CTV.

Figure 2. Outcome: (a) Local control (PFSlocal), cancer specific survival (CSS) and overall survival (OS) for all 85 patients. (b) Overall survival for patients with or without lymph node metastasis.

Table IV. Disease control with IGABT.

	Liège	Vienna[4]	Aarhus[13]	Leiden[15]	Pittsburgh[16]	Utrecht[14]
Number of cases	85	156	140	83	126	46
Age, mean/median	50	58	56^a	55^a	52	50
Number of patient ≥ 2B, %	60	84	85.7	65	75	69
Initial tumor size, cm, %	≥ 5cm: 54	> 5cm: 66	6^a	≥ 4 cm: 74	5^b	5^b
Node positive patients, %	53	48	50	34.6	43	43.5
Tumor response (%)
Complete remission	97.6	97	95	98.8	NR	95.7
Actuarial rates, 3 years %
PFSlocal/local control	94	95	91	NR	91.6	93
PFSpelvic/pelvic control	90	91	85	93	NR	NR
PFSoverall	74	75	NR	83	76.6	71
CSS	85	74	87	NR	85.4	74
OS	81	68	79	86	80	65

^amean value; ^bmedian value.

Table V. Severe late adverse events (AEs) with IGABT.

	Liège	Vienna[4]	Aarhus[13]	Leiden[15]	Pittsburgh[16]	Utrecht[14]
Number of cases	85	156	140	82	126	42
Crude ≥ Grade 3 AEs, N (%)
Gastrointestinal	5 (5.8)	5 (3.2)	NR	4 (4.9)	1 (0.8)	4 (9.5)
Urological	5 (5.8)	3 (1.9)	NR	0	2 (1.6)	2 (2.4)
Vaginal	5 (5.8)	3 (1.9)	NR	0	0	1 (4.8)
Actuarial ≥ Grade 3 AEs at 3 years, % (N)
Gastrointestinal	8 (5)	2	3	8.4^†	0.9^a	NR
Urological	5 (3)	4	1		0.9^a
Vaginal	8 (5)	1	4		0

^a2-year actuarial. ^†for all side effects.

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