Radical treatment for oesophageal cancer patients unfit for surgery and chemotherapy. A 10-year experience from the Norwegian Radium Hospital

Figures & data

Table I. Patient characteristics

			Divided by treatment n = 183
	Total (%*)	Curative intent n = 184	Surgery ± RT n = 81	RT > 60 Gy n=102
Sex	Males	137 (75)	66 (81)	71 (70)
	Females	47 (25)	15 (19)	31 (30)
Age	Mean	66.3	62	69
	Median	67	62	72
	(range)	(39–88)	(39–83)	(39–88)
Stage	Local	86 (47)	40 (49)	45 (44)
	Locally advanced	32 (17)	12 (14)	20 (20)
	Regional (N+)	36 (20)	22 (27)	14 (14)
	Advanced / Metastatic (T4 or M+)	19 (10)	5 (6)	14 (14)
	Not known	11 (6)	2 (3)	9 (9)
Tumor length	≤ 50 mm	79 (43)	41 (51)	37 (36)
	>50 mm ≤ 90 mm	57 (31)	22 (27)	35 (34)
	> 90 mm	34 (19)	10 (12)	24 (24)
	Not known	14 (8)	8 (10)	6 (6)
Localization	Upper	24 (13)	4 (5)	20 (20)
	Middle	59 (32)	18 (22)	41 (40)
	Lower/cardia	96 (52)	57 (70)	38 (37)
	Other	5 (3)	2 (3)	3 (3)
	Not Known	0	0	0
Histology	Squamous cell carcinoma	131 (71)	47 (58)	83 (82)
	Adenocarcinoma	51 (28)	34 (42)	17 (17)
	Small cell carcinoma	1 (<1)	0	1 (1)
	Others	1 (<1)	0	1 (1)
	Not known	0	0	0
Hist.differentiation	Undifferentiated	1 (<1)	0	1 (1)
	Low	49 (27)	23 (28)	26 (25)
	Middle	72 (39)	32 (40)	39 (38)
	High	16 (9)	7 (9)	9 (9)
	Unclassified	46 (25)	19 (24)	27 (26)
Treatment
Surgery ± radiotherapy (RT)	Preoperative RT + radical surgery	71 (39)	71 (92)	0
	Radical surgery	10 (5)	10 (8)	0
RT ± other treatment	External RT + brachytherapy	44 (24)	0	44 (43)
	External RT	58 (32)	0	58 (57)
Other	Photodynamic treatment	1 (<1)	0	0

*All percentages should be read vertically

Table II. Symptoms, performance status and use of analgesics at admission

			Divided by treatment n=183
	Total (%*)	Curative intent n=184	Surgery ± RT n = 81	RT > 60 Gy n = 102
WHO Performance status	0	92 (50)	57 (70)	35 (34)
	1	72 (39)	20 (25)	51 (50)
	2	14 (8)	1 (1)	13 (13)
	3/4	1 (<1)	0	1 (1)
	Not known	5 (3)	3 (4)	2 (2)
Weight loss (%)	≤ 5	77 (42)	46 (57)	31 (30)
	>5, ≤ 10	36 (20)	19 (24)	16 (16)
	>10	59 (32)	16 (20)	43 (42)
	Not known	11 (6)	0	12 (12)
Dysphagia before treatment	Non	14 (8)	7 (9)	7 (7)
	Solid food avoiding certain food	68 (37)	38 (47)	29 (28)
	Soft diet	46 (25)	19 (24)	27 (26)
	Fluids only	44 (24)	12 (15)	32 (31)
	Full stop	12 (6)	5 (6)	7 (7)
	Not known	0	0	0
Reflux at admission	No	110 (60)	43 (53)	67 (66)
	Yes	68 (37)	37 (46)	30 (29)
	Not known	6 (3)	1 (1)	5 (5)
Pain	Non	40 (22)	14 (17)	26 (25)
	Some	54 (29)	26 (32)	28 (27)
	Moderate	66 (35)	28 (35)	37 (37)
	A lot	16 (9)	10 (12)	6 (6)
	Not known	8 (4)	3 (4)	5 (5)
Analgesics before treatment	No analgesics	153 (83)	70 (86)	82 (80)
	Non opioids	24 (13)	8 (10)	16 (16)
	Opioids	6 (3)	3 (4)	3 (3)
	Not known	1 (<1)	0	1 (1)

*All percentages should be read vertically

Figure 1. Change in dysphagia pre and post treatment divided by treatment.

Table III. Overall survival, tumor status at death or three years after start of treatment and causes of death

		Divided by treatment n=183
Total (%*)	Curative intent n = 184	Surgery ± RT n = 81	RT > 60 Gy n = 102
Overall survival (months)
Median	9	20	7
Tumor status* n (%)
Tumor free without relapse	37 (20)	23 (28)	10 (10)
Treated for relapse	12 (7)	4 (5)	9 (9)
Untreated relapse	14 (7)	7 (9)	7 (7)
Treated for metastases	20 (11)	21 (26)	1 (1)
Untreated metastases	18 (10)	11 (14)	8 (8)
Never tumor free	67 (36)	8 (10)	59(58)
Unknown	16 (9)	7 (9)	8 (8)
Status at 3 years observation n (%)
Alive	31 (17)	23 (28)	8 (8)
Dead index tumor	120 (65)	42 (52)	78 (77)
Dead complications	12 (7)	10 (12)	1 (1)
Dead other cancer	1 (<1)	0	1 (1)
Dead other disease	11 (6)	3 (4)	7 (7)
Dead unknown reason	9 (5)	3 (4)	7 (7)

* At death or three years after start of treatment

Figure 2. Overall survival for patients divided by treatment (n = 183). Overall survival for patients treated with surgery with or without preoperative radiotherapy (dotted line), a total of 17 patients were censored. Overall survival for patients treated with radical radiotherapy (RT) (continuous line), a total of four patients were censored.

Table IV. Association between clinical factors and survival (Univariate analyses)

		Curative intent n = 184
Survival	Total number of patients	Median (months)	95% confidence interval	Number of censored patients	p - value
Overall	184	9	7–11	29
Clinical stage					0.007
Local	86	11	8–14	13
Loc. advanced / regional	68	9	6–12	7
Advanced / metastatic	19	5	3–7	1
Treatment					< 0.001
Surgery ± RT	81	20	15–25	17
Radiotherapy	102	7	6–8	4
Performance status					0.001
0	92	14	9–19	16
1	72	8	7–10	4
2–4	15	6	4–9	0
Weight loss%					0.001
≤ 5	77	14	3–25	15
> 5, ≤ 10	36	10	2–18	3
> 10	59	8	6–10	3
Tumor length					< 0.001
≤ 50	79	14	8–20	17
51–90	57	8	7–9	1
≥ 91	34	6	4–8	2

Table V. Comparison of results between radical radiotherapy at the Norwegian Radium Hospital and results from other radical radiotherapy trials

					Survival
Author [ref]	Year	Study treatment	(n)	Stage	Median(months)	2y%	3y%	5y%	Conclusion
Radiotherapy only
Amdal [Present paper]	2009	Retrospective AH split-course RT (63 Gy) + BRC (6–8 Gy)	102 64	All Local	7 9	12 16	8 11	– –
Churn [18]	2002	Retrospective: CF RT (45–55 Gy) + BRC (8.5–10Gy)	32	T1–T3 NxM0	9	16	16		External RT and BRC well tolerated and good symptom relief
Hishikawa [19]	1991	CF RT(60 Gy) + BRC (12 Gy)	66 82	Stage I–II Stage III–IV		37 7		18	BRC boost after external RT is safe and effective
Nishimura [11]	1994	Prospective CF RT versus AH RT	88	Stage I–III	Local 1-y control AH: 47% CF: 22%				AH shortened the treatment time with two weeks. Trend of better cause-specific survival
Shi [20]	1999	Prospective randomized: Late course AF RT (LCAF) (1.8 Gy × 1 × 23) + 1.5 Gy × 2 × 9 total: 68.4 Gyversus CF (1.8 Gy × 1 × 38) total: 68.4 Gy	85	No distant metastases	LCAF: 29 CF: 11			3415	AH RT is superior to CF RT to the cost of more acute radiation induced bronchitis and oesophagitis
Zhao [21]	2004	Prospective study : LCAF	201	All		73	34	26	Similar results on survival as the chemoradiation arm in the study by Herskovic et al.
Wang [22]	2002	Prospective randomized: continuous AF RT (CAHF) vs LCAF	101	Stage I–III	CAHF LCAF	51 57	37 41		Similar results for survival and local control. More acute complications after CAHF
Combined treatment (radiotherapy and chemotherapy)
Herskovic [23] Al-Sarraf [25]	1992 1997	Prospective randomizedCiFu + CF (50 Gy) versus CF (64 Gy)	129	Stage I–III	CiFu (50 Gy) 14.1 CiFu (64 Gy) 8.9	38 10	30 -	27	Chemoradiation is superior to radical RT alone
Minsky [24]	2002	Prospective randomizedCiFu + CF, 50 Gy versus 64 Gy	218	T1–T4 N0–N1M0	CiFu+50 Gy: 18 CiFu+64 Gy: 13	40 31			High-dose RT no benefit on survival, more toxicity

Abbreviations: Radiotherapy (RT), Conventional fractionation (CF), Hyperfractionated accelerated (AH), Brachytherapy (BRC)

Churn M, Jones B, Myint AS. Radical radiotherapy incorporating a brachytherapy boost for the treatment of carcinoma of the thoracic oesophagus: Results from a cohort of patients and review of the literature. Clin Oncol (R Coll Radiol) 2002;14:117–22.

 PubMedGoogle Scholar

Hishikawa Y, Kurisu K, Taniguchi M, Kamikonya N, Miura T. High-dose-rate intraluminal brachytherapy for esophageal cancer: 10 years experience in Hyogo College of Medicine. Radiother Oncol 1991;21:107–14. Review.

 PubMed Web of Science ®Google Scholar

Nishimura Y, Ono K, Tsutsui K, Oya N, Okajima K, Hiraoka M, . Esophageal cancer treated with radiotherapy: Impact of total treatment time and fractionation. Int J Radiat Oncol Biol Phys 1994;30:1099–105.

 PubMed Web of Science ®Google Scholar

Shi XH, Yao W, Liu T. Late course accelerated fractionation in radiotherapy of esophageal carcinoma. Radiother Oncol 1999;51:21–6.

 PubMed Web of Science ®Google Scholar

Zhao KL, Shi XH, Jiang GL, Wang Y. Late-course accelerated hyperfractionated radiotherapy for localized esophageal carcinoma. Int J Radiat Oncol Biol Phys 2004;60:123–9.

 PubMedGoogle Scholar

Wang Y, Shi XH, He SQ, Yao WQ, Wang Y, Guo XM, . Comparison between continuous accelerated hyperfractionated and late-course accelerated hyperfractionated radiotherapy for esophageal carcinoma. Int J Radiat Oncol Biol Phys 2002;54:131–6.

 PubMedGoogle Scholar

Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, . Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 1992;326:1593–8.

 PubMed Web of Science ®Google Scholar

Al-Sarraf M, Martz K, Herskovic A, Leichman L, Brindle JS, Vaitkevicius VK, . Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: An intergroup study. J Clin Oncol 1997;15:277–84.

 PubMed Web of Science ®Google Scholar

Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Ritsuko K, . INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: High-dose versus standard-dose radiation therapy. J Clin Oncol 2002;20:1151–3.

 PubMedGoogle Scholar