Intensified intensity-modulated radiotherapy in anal cancer with prevalent HPV p16 positivity

Table 1 Constraints for normal tissue

Organ	Constraints
Bladder	Median < 30 Gy	V45 < 35%
Bowel bag	Median < 20 Gy	V40 < 30%	V45 < 195 mL
Femoral heads	V35 < 15%	V20 < 55%
Pelvic bones	V10 < 90%	V20 < 75%	V30 < 50%	V40 < 37%
External genitalia	Median < 15 Gy

Table 2 Patients characteristics n (%)

Age (yr)
median	63
range	32-84
Gender
Male	3 (7.3)
Female	38 (92.7)
Tumor stage
T1	3 (7.3)
T2	19 (46.3)
T3	10 (24.4)
T4	9 (22)
Nodal stage
N0	16 (39)
N1	18 (44)
N2	6 (14.6)
N3	1 (2.4)
Staging
I	2 (4.8)
II	13 (31.8)
IIIA	12 (29.3)
IIIB	14 (34.1)
Smoke
Yes	18 (44)
No	7 (17)
Unknown	16 (39)
Histology
SCC	41 (100)
Chemotherapy
MMC + 5-FU	33 (80.7)
MMC + Capecitabine	4 (9.7)
Capecitabine	2 (4.8)
None	2 (4.8)

SCC: Squamous cell cancer; MMC: Mitomycin–C; 5-FU: 5-fluorouracil.

Table 3 Acute toxicity (41 patients analyzed) n (%)

	G0	G1	G2	G3	G4	G5
Gu	26 (63.4)	11 (26.8)	4 (9.8)	/	/	/
Skin	0 (0)	10 (24.4)	29 (70.7)	2 (4.9)	/	/
Gi	10 (24.4)	17 (41.5)	11 (26.8)	3 (7.3)	/	/
Pain	7 (17)	22 (53.6)	12 (29.4)	/	/	/
Hematological	31 (75.6)	4 (9.8)	3 (7.3)	2 (4.9)	/	1 (2.4)

GU: Genitourinary; GI: Gastrointestinal.

Table 4 Late toxicity (40 patients analyzed) n (%)

	G0	G1	G2	G3
GU (dysuria)	38	0	1 (3.8)	1 (3.8)
GI (incontinence)	29	6 (23)	4 (15.4)	1
Female genital tract (atrophy of vaginal mucosa)	37	3 (11.5)	0	0

GU: Genitourinary; GI: Gastrointestinal.

Table 5 Comparison with acute toxicity data reported in the literature

Ref.	No. pts	SIB	d/fx	CHT	Gastrointestinal		Genitourinary		Skin		Hematologic
					G2	G3	G2	G3	G2	G3	G2	G3	G4
Pepek et al[26], 2010	29	No	1.8	89%	76%	10%	45%	3%	100%	0	45%	24%
Bazan et al[24], 2010	29	Yes	1.6-1.8	86%	\	7%	\	\	\	21%	\	21%
Vieillot et al[28], 2012	72	No	1.8-2.0	85%	14%	4%	4%	2%	16%	16%	4%	5%	4%
DeFoe et al[11], 2012	78	No	1.8	98%	60%	27.7%	18.5%	0	91.3%	29%	51.4%	42.9%	12.9%
Kachnic et al[5], 2012	43	Yes	1.5-1.8	100%	42%	7%	5%	5%	63%	5%	21%	49%	12%
Kachnic et al[13], 2012	52	Yes	1.5-1.8	100%	52%	21%	13.4%	1.9%	52%	21%	15.4%	30%	27%
Chuong et al[29], 2013	52	Yes	1.8-2.0	100%	39.5%	9.6%	26.9%	0	57.7%	11.5%	37.8%	28.8%
Koerber et al[30], 2014	68	Yes	1.8-2.2	\	47.1%		19.1%		63.2%		\	\	\
Current study	41	Yes	1.8-2.2	95%	26.8%	7.3%	9.8%	0	70.7%	4.9%	7.3%	4.9%	\

No. pts: Patients number; d/fx: Dose per fraction; CHT: Chemotherapy; SIB: Simultaneous integrated boost.

Table 6 Comparison with outcome data reported in the literature

	Bazan et al[24]	Chuong et al[29]	Dasgupta et al[31]	Koerber et al[30]	Mitchell et al[32]	Pepek et al[26]	Janssen et al[23]	Tozzi et al[22]	Current study
No. pz	29 pz	52 pz	45 pz	68 pz	65 pz	47 pz	25 pz	36 pz	41 pz
LC	92%2	91.3%2	87%1	75.3%2	90%1	90%1	92%1	78.1%3	92%1
OS	88%2	91.1%2	93%1	82.9%2	96%1	85%1	88%1		93%1

¹Two years;

²Three years;

³Five years. LC: Local control; OS: Overall survival.