Neoadjuvant radiotherapy for rectal cancer management

Table 1 Impact of radiotherapy on local recurrence and survival

Study	n	Interventions	Local recurrence	Overall survival	5-yr disease free survival
Swedish Rectal Cancer Trial, NEJM, 1997[24]	1168	25 Gy in 5 fractions in one week surgery	27% 11% (P ≤ 0.001)	58% 48% (P = 0.004)	74% 65% (after nine years) (P = 0.002)
Dutch Rectal Cancer Trial, NEJM, 2001[25]	1861	25 Gy in one week TME surgery	2.4% 8.2% (P ≤ 0.001)	82% 81.8% (P = 0.2)	N/A
MRC CR-07, Lancet, 2009[26]	1350	25 Gy in one week TME surgery and adjuvant therapy	27 (674) = 4% 72 (676) = 10.7%	70.3% 67.9% (P = 0.4)	73.6% 66.7% (P = 0.013)
Sauer et al[27], NEJM, 2004	850	50.4 Gy over 5 wk with 5-FU TME surgery	6% 13%	76% 74%	68% 65%
Fryckholm et al[28], 2001	70	40 Gy and 5-FU 40 Gy	4% 35% (P = 0.02)	66% 38% (P = 0.03)	29% 18% (P = 0.3)
Stockholm III trial, 2017[33]	840	Short course Short course w/ delay Long course w/ delay	2.24% 2.8% 5.5%	73% 76% 78%	65% 64% 65%
Bujko et al[88], 2016	515	5 × 5 Gy and FOLFOX 50.4 Gy in 28 fractions w/ 5-FU	22% 21% (P = 0.82)	73% 64.5% (P = 0.055)	53% 52% (P = 0.74)
Trans-Tasman Oncology Group, 2012[89]	326	5 × 5 Gy in 1 wk 50.4 Gy in 5 wk	7.5% 4.4% (P = 0.24)	74% 70% (P = 0.62)	N/A
Wawok et al[90], 2018	51	5 × 5 Gy 50.4 Gy w/5-FU	35% 5% (P = 0.036)	47% 86% (P = 0.009)	N/A
German CAO/ARO/AIO-04 study, 2012[91]	1236	50.4 Gy w/ 5-FU (Control) 50.4 Gy w/5-FU and Oxaliplatin	4.6% 2.9%	88% 88.7%	71.2% 75.9%

TME: Total mesorectal excision; FU: Fluorouracil; FOLFOX: Folinic Acid, Fluorouracil, Oxaliplatin; 5-FU: 5-Fluorouracil.

Table 2 RTOG/EORTC radiation toxicity grading system for lower gastrointestinal tract

	Grade 1	Grade 2	Grade 3	Grade 4
Early radiation toxicity (< 6 mo post radiotherapy)	Increased frequency of bowel movements not requiring medical therapy	Increased frequency of bowel movements requiring medication or causing abdominal pain	Diarrhoea requiring IV treatment, mucous or bloody discharge PR, abdominal distention	Acute/subacute bowel obstruction, fistula formation, GI bleed requiring transfusion, abdominal pain requiring tube decompression
Late radiation toxicity (> 6 mo post radiotherapy)	Bowel movements of 5 per day, mild abdominal cramping, mild PR bleeding	Bowel movements > 5 per day, increased mucous PR, intermittent PR bleeding	Obstruction or bleeding requiring operative management	Necrosis, perforation, fistula formation

PR: Per rectum; IV: Intravenous; GI: Gastrointestinal.

Table 3 Studies on watch and wait outcomes, n (%)

Study	n	NA regime	Recurrence	Salvage therapy	Survival post salvage therapy	Survival
Habr-Gama et al[57], 2004	71	Long-course radiotherapy w/ 5-FU	Local:2 Distant: 3	2 (100)	100%	OS: 100% DFS: 92%
Habr-Gama et al[92], 2014	90	Long course radiotherapy w/ 5-FU	Local: 28 (31%)	26 (92.8)	OS: 94%	OS: 91% DFS: 68%
OnCore Project, 2016[59]	129	45 Gy w/ 5-FU	Local: 44 (34%)	36 (88)	N/A	OS: 96% at 3 yr DFS: 88% at 3 yr
IWWD Consortium, 2015[58]	880	Chemoradiotherapy: 91%	Local: 25.2%	141 (69)	OS: 75.4% DFS: 84%	OS: 85% DFS: 94%
Appelt et al[93], 2015	40	Chemoradiotherapy	Local: 25.9% at 2 yr	9	OS: 100% at 2 yr DFS: 100% at 2 yr	OS: 100% at 2 years DFS: 70% at 2 years
Smith et al[94], 2012	32	Long-course chemoradiotherapy	Local: 6 (18.75)	6 (100)	OS: 100% at 17 mo	OS: 96% DFS: 88% all at 17 mo
Smith et al[95], 2019	113		Local: 22 (19.5)	22 (100)	DFS: 91%	OS: 73% DFS: 75%
Martens et al[96], 2016	100	Long-Course: 95% Short Course: 5%	Local: 15% Distant: 5%	13	OS: 92.3%	OS: 96.6% DFS: 80.6% all after 3 yr
Lai et al[97], 2016	18	Chemoradiotherapy	Local: 2	2	100%	OS: 100%
Rijkmans et al[98], 2017	38	External beam radiotherapy and brachytherapy (iridium)				DFS: 42% OS: 63%
Vuong et al[99], 2007	100	External beam radiotherapy with brachytherapy (iridium)	Local recurrence at 5 yr: 5%			DFS: 65% OS: 70%
Gerard et al[100], 2019	74	Contact X-ray brachytherapy	10% at 3 yr	2		DFS: 88%
Sun Myint et al[101], 2018	83	Contact X-ray brachytherapy	13.2% after 2.5 yr (n = 7)	6		DFS: 83.1%
Ortholan et al[63], 2012	45	External beam radiotherapy with contact X-ray boost				DFS: 53% OS: 55%

DFS: Disease-free survival; OS: Overall survival.

Table 4 Outcomes in transanal endoscopic microsurgery

Study	n	Post-op complications	Local recurrence	Survival
Lee et al[71], 2017	247	11%	7%	DFS: 80%
CARTS study, Stijns et al[68], 2019	47	N/A	7.7%	DFS: 81.6% OS: 82.8%
O’Neill et al[67], 2017	92	10.9%	6.7%	DFS: 98.6% OS: 89.4% (after 3 yr)
Jeong et al[102], 2009	45	0	15.5%	DFS: 88.5% OS: 96.2%
Stipa et al[103], 2012	86 (T1 patients)	N/A	11.6% (for T1 tumours)	OS: 92% (for T1 patients)
Baatrup et al[104],2009	143	N/A	18%	DFS: 87% OS: 66%
Van Den Eynde, 2019[105]	53	40%	N/A	N/A

DFS: Disease-free survival; OS: Overall survival.

Table 5 Transanal minimally invasive surgery studies

Study	Pt numbers (n)	Average distance from Anal Verge (cm)	Positive margins	Local recurrence	Average length of follow-up
Atallah et al[70], 2010	6	9.3	0	N/A	N/A
Albert et al[73], 2013	50	8.1	6%	2 (4%)	N/A
Keller et al[74], 2016	75 17 (malignant) 58 (benign)	10	5
Garcia-Florez et al[106], 2017	32	5.6	1	10.3%	26 mo
Van den Eynde et al[105], 2019	68	6	12%	N/A	30 d
Melin et al[107], 2016	29	6.79	3	1	Retrospective study