Esophageal cancer management controversies: Radiation oncology point of view

Table 1 Important randomized trials for preoperative chemoradiation n (%)

Ref.	n	Histology	Treatment	R0	pCR	Op mortality	MS	3 YS	Locoregional failure
Nygaard et al[10], 1992		Sq	S	37%	-	5 (3.4)	Approximately 0.6 yr	Approximately 9%	-
			CB → S	41%		6 (4.0)	Approximately 0.7 yr	Approximately 2%
			R → S	40%		4 (2.7)	Approximately 0.9 yr	Approximately 20%
			CB + R → S	55% (Gp 4 vs 1, P = 0.08)		8 (5.4)	Approximately 0.7 yr	Approximately 18%
Walsh et al[11], 1996	113	A	CF + R → S	-	25%	5 (10.4)	16	32%	-
			S	-	0%	2 (3.7)	11 mo	6%	-
							P = 0.01	P = 0.01
Bosset et al[12], 1997	282	Sq	C + R → S	-	26%	17 (12.3)	18.6 mo	36%	-
			S	-	0%	5 (3.6)	18.6 mo	34%	-
								See text
Urba et al[13], 2001	100	75% A	CFV + R → S	90%	28%	1 (2.1)	16.9 mo	30%	19%
		25% Sq	S	90%	0%	2 (4)	17.6 mo NS	16%	42%
									P = 0.02
Burmeister et al[14], 2005	256	37% Sq	CF + R → S	80%	16%	5 (4.8)	22.2 mo	35%	15%
		62% A	S	59%	0%	6 (5.5)	19.3 mo	30%	19%
		1% mixed/other						See text
Tepper et al[15], 2008	56	25% Sq	CF + R → S	-	33%	0 (0)	4.5 yr	39%	13%
		75% A	S		0%	1 (3.8)	1.8 yr	16%	15%
							P = 0.002	5 YS
Cao et al[9], 2009	366	Sq	CFM → S	87%	1.7%	0%	Approximately 42 mo	Approximately 69%	-
			R → S	98%	15%	0%	Approximately 42 mo	69%
			CFM + R → S	98%	22%	0%	Approximately 60 mo	74%
			S	73%	0%	0%	Approximately 42 mo	53%
								P = 0.013
van Hagen et al[16], 2012	366	23% Sq	JT + R → S	92%	29%	6 (4)	49.4 mo	58%	-
	T1-3	75% A	S	69%	0%	8 (4)	24 mo	44%
	N0-1	2% other						P = 0.03
	M0

-: Not reported; A: Adenocarcinoma; B: Bleomycin; C: Cisplatin; F: 5-flurouracil; Gp: Group; J: Carboplatin; M: Mitomycin; MS: Median survival; NS: Non-significant; Op: Operative mortality using number of patients actually operated as denominator; pCR: Pathological complete response; R: RT; R0: No residual tumor; S: Surgery; Sq: Squamous cell carcinoma; T: Paclitaxel; V: Vinblastine; YS: Year survival.

Table 2 Pros and cons of pre-operative therapy for esophageal cancer

Pre-op therapy	Pros	Intact vascular supply allowing for potential improved oxygenation for radiotherapy
		Smaller radiotherapy volume
		Potential tumor downstaging
		Sterilization of tumor bed in preparation for surgery
		Improve resectability
	Cons	Treatment decision based on clinical stage, may over-treat patients
		Narrow window for surgical resection post CRT, may increase surgical complications with pre-op CRT
		Dysphagia and issue of nutrition support due to tumor and treatment

CRT: Chemoradiation therapy.

Table 3 Pros and cons of post-operative therapy for esophageal cancer

Post-op therapy	Pros	Treatment decision based on true pathologic stage, avoid CRT in patient who may not require it
		Accurate assessment of disease extent to allow delineation of disease involvement
		Immediate relief of dysphagia due to tumor
	Cons	Difficulty to delineate RT target volume
		Large RT therapy volume and difficulty in RT planning
		Potential decrease in oxygenation to tumor bed due to postoperative tissue alteration in vascular supply
		Inability to assess RT or chemo tumor response
		May preclude the use of postoperative CRT for those patients with reduced functional status postoperatively

CRT: Chemoradiation therapy; RT: Radiotherapy.

Table 4 Randomized trials for definitive chemoradiation therapy

Ref.	n	Histology	Treatment	MS	2 yr OS	Locoregional failure
Herskovic et al[50], 1992	121	88% Sq	CF + R 50 Gy	12.5 m	38%	43%
		12% A	R 64 Gy	8.9 m	10%	64%
					P < 0.001	local recurrence + persistent primary
Minsky et al[44], 2002	218	86% Sq	CF + R 50.4 Gy	18 m	40%	52%
		14% A	CF + R 64.8 Gy	13 m	31% (NS)	56%

A: Adenocarcinoma; C: Cisplatin; F: 5-flurouracil; MS: Median survival; NS: Non-significant; R: RT; Sq: Squamous cell carcinoma.

Table 5 Complications of radiotherapy to esophagus and their management

Acute complications

Skin erythema: 0.5% hydrocortisone, flamazine cream

Hair loss: no treatment

Mucositis, odynophagia, loss of appetite, fatigue, generalized weakness, dysphagia, dehydration, malnutrition, intestinal obstruction: intravenous hydration, xylocaine viscus, feeding tube

Pneumonitis: prednisone, oxygen

Spinal cord L'hermitte sign: no treatment

Larynx hoarseness: prednisone

Fistula/erosion of great vessels, esophageal perforation: consult thoracic surgeons

Chronic complications

Fibrosis/hyperpigmentation of skin: no treatment

Lung fibrosis: oxygen

Esophageal stricture: begins at 3-4 mo. Incidence: 50 Gy 0.8%, 60 Gy 0.6%; 60 Gy + chemo 12%. Treat by dilatation and/or stent

Peptic ulcer: proton pump inhibitor

Chronic enteritis: anti-diarrhoeal, aminosalicylates, pentoxifylline and tocopherol, cholestyramine, antibiotics, corticosteroids, hyperbaric oxygen

Spinal cord myelopathy: hyperbaric oxygen, anticoagulation