Neoadjuvant hyperfractionated accelerated radiotherapy plus concomitant 5-fluorouracil infusion in locally advanced rectal cancer: A phase II study

Table 1 Patient characteristics

Characteristic	n = 30
Sex, M/F	19/11
Age, median (range)	53 (30-70)
Tumor location, distance from anal verge
≤ 5 cm	19 (63)
> 5 cm	11 (37)
Clinical TN stage
T2N2	1 (3)
T3N0	2 (7)
T3N1	15 (50)
T3N2	12 (40)
Tumor differentiation
Well	10 (33)
Moderate	10 (33)
Poor	4 (14)
Mucinous	3 (10)
Signet ring cell	3 (10)

Unless otherwise stated, data are presented as n (%). M: Male; F: Female.

Table 2 Clinical (cT2) and pathological (ypT) tumor stages

	cT2	cT3	Total
ypT0	-	6 (20.6)	6 (20.6)
ypT1	-	3 (10.3)	3 (10.3)
ypT2	-	8 (27.5)	6 (20.6)
ypT3	1	11 (37.9)	12 (41.3)
Total	1	28	29

Data are presented as n (%).

Table 3 Surgical complications

Timing of the complication
Perioperative	6 (20.6)1
Early postoperative	4 (13.7)2
Late postoperative	2 (6.8)3

¹Bladder-urethra injury (n = 4), rectum perforation (n = 1), necrosis due to proctotectomy (n = 1);

²Acute renal failure (n = 3), perirectal abscess (n = 1);

³Colovaginal fistula (n = 1), perirectal abscess (n = 1). Data are presented as n (%).

Table 4 Studies investigating hyperfractionated accelerated radiotherapy regimen for locally advanced rectal cancer

Study	Number of patients	Design	Follow-up (mo)	Total RT dose	Intervals (wk)	Concomitant chemotherapy	pCR1	Local control	Down-staging
Coucke et al[24] 2006	250	Prospective	39 mo	41.6 Gy/1.6 Gy	1 wk	None	1.20%	91.70%	38%
Ceelen et al[22] 2007	50 vs 91	Prospective	67 mo vs 28 mo	41.6 Gy/1.6 Gy vs 45 Gy/1.8 Gy	13 d vs 6 wk	None vs 5-FU bolus chemotherapy	4% vs 18%	94% vs 95.6%	30% vs 51%
Voelter et al[23] 2006	33	Prospective	104 mo	41.6 Gy/1.6 Gy	1wk	CPT-11	NA	100%	33%
Brooks et al[42] 2006	20	Prospective	31 mo	25 Gy/1.67 Gy (CHART)	1 wk	None	NA	95%	NA
Widder et al[43] 2005	184	Prospective	43 mo	25 Gy/2.5 Gy	1 wk	None	NA	97.90%	NA
Bouzourene et al[29] 2003	104	Prospective	40 mo	41.6 Gy/1.6 Gy	1 wk	None	0%	92.30%	43%
Marsh et al[26] 2010	17	Prospective	NA	50.4-55.2 Gy/1.2 Gy	4-6 wk	Capesitabine 825 mg/m2-twice per day	18.80%	NA	81.25%
The present study	30	Prospective	60 mo	42 Gy/1.5 Gy	6-8 wk	5-FU (325 mg/m2) continuous infusion	21%	96.70%	59%

¹Pathological complete response; NA: Not available; RT: Radiotherapy; pCR: Pathological complete response.

Table 5 Biological equivalent doses[44]

	Tumor control/acute normal tissue complication probability		Late normal tissue complication probability
	Bed (Gy) (α/β = 10 Gy)		Bed (Gy) (α/β = 3 Gy)
Regimen	No time correction	With time correction
25 Gy/5 fr/5 d (d = 5 Gy)	37.5	37.5	66.7
50 Gy/25 fr/33 d (d = 2 Gy)	60.0	44.4	83.4
42 Gy/28 fr/18 d (d = 1.5 Gy)	48.3	41.7	63.0

Equation 1: Linear quadratic based isoeffect, basic formula without time correction, BED = nd (1+d/α/β), where n = number of fractions, d = dose (Gy) per fraction, α/β = the LQ quotient, Equation 2: Time-corrected LQ- formula, BED = nd (1+d/α/β)-γ/α (T- Tk), where γ/α = repair rate (set to 0.6 Gy/d), T = overall treatment time and Tk = proliferation delay (set to 7 d, or maximally T).