Rectal Cancer Trials

Meta-analysis

The Colorectal Cancer Collaborative Group Meta-analysis

• (Lancet 2001) ^[1]

Method

• 22 randomized trials of pre-operative RT

Results

Arms	Any Recurrence at 10 years	isolated local recurrence at 5 years	isolated local recurrence at 10 years
Pre-op RT	45.9%	12.5%	16.7%
Surgery Alone	52.9%	22.2%	25.8%
p-value	<.01	<.01	<.01

• Overall Surival: Pre-op RT with BED > 30 Gy improved rectal cancer deaths 45%(RT + S) vs 50%(S)
• But this was largely cancelled by an increase early (< 1 year from treatment) non-rectal cancer related deaths 8% vs 4%

Dutch Total Mesorectal Trial

NEJM 2001^[3]
Eligibility

• All stages

Treatment and Results

Groups	2-Local Recurrence	2-OS
5 Gy x 5 + TME	2.4%	82%
TME Alone	8.2%	71.8%
p-value	< .01	N.S.

• Univariate analysis showed no improvement for tumors 10.1 - 15 cm from anal verge
• Tumors 0 - 10 cm did have a local control benefit with radiation

Swedish Rectal Cancer trial

• (NEJM 1997)^[2]

Patient Characteristics

• 1100 patients

Technique

• pre-op XRT (5 Gy x 5)

Result

• the only single modality adjuvant trial to show both OS and LRC improvement.
• (OS 48 vs 58%, LRC 28% vs 11%).

NSABP B-01

Patient Characteristics

• T3 or T4 with N0 (Duke B)
• any T with N1 or N2 (Duke C)

Treatment Technique

• Radiation Therapy: 46-47 Gy in 26-27 fractions with boost to 51-53 Gy
• Chemotherapy: 5FU: Semustine, Vincristine

Results

Trial Arms	Local Failure	DFS-5	OS-5
Surgery Alone[S]	25%	30%	43%
S + adj. Chemo Alone	21%	42%	53%
S + adj. RT Alone	16%
p-value	.06 (S vs RT)	.006	.05

• Adjuvant chemotherapy improves DFS-5 and OS-5
• Ajuvant Radiation improves local control but not DFS-5 or OS-5

NSABP R03

• Pre-operative chemoradiation has improved OS, DFS, PFS
• Not significant for sphincter preservation (35% pre vs 39% post)
• Not significant for local control (9% pre vs 5% post)

Intergroup 0144

• Different chemo delivery had no effect on outcome (OS or RFS)
• RT dose 50.4 to 54 Gy.

Pre-op vs. Post-Op

German Rectal Cancer Study Group (NEJM 2004)

Other Names

• Also called (CAO/ARO/AIO 94)

Treatment

• 5040 in 180 QD (3-field or 4-field). Post-op patients received 540 boost in addition.
• 5-FU 120 hour continuous infusion at 1000 mg per square meter per day during 1st and 5th week.

Results

Treatment Arms	Local Failure	DFS	OS	Sphincter Preservation	Grade 3/4 toxicity
Pre-op RT	6%	59%	78%	19%	27%
Post-op RT	13%	55%	73%	39%	40%
p-value	0.006	0.23	0.38

• Improved local control with pre-operative radiation
• no difference in DFS or OS
• more sphincter preservation with pre-op arm

Criticism

• many in the post-operative arm did not get the full dose of chemotherapy treatment

Swedish Trial (Pahlman and Glimelius)

Treatment

• 2750cgy pre-op (5.5 Gy x 5) vs. 6000cgy postoperatively

Results

• Local fialure 13% vs 22% favors pre-op
• No difference in survival.

Bibliography

1. Colorectal Cancer Collaborative Group: Adjuvant radiotherapy for recal cancer: a systematic overview of 8507 patients from 22 randomized trials. Lancet 385 (October 20):1291-1304, 2001.

2. Swedish Rectal Cancer Trial: Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 336: 980-987, 1997.

3. Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001 Aug 30;345(9):638-46. Summary for patients in: Can J Surg. 2003 Feb;46(1):54-6. Med J Aust. 2002 Nov 18;177(10):563-4. PMID: 11547717