Esophageal Cancer - Management

Early Stage Resectable tumors (Tis, T1a, T1b upper esophagus N0)

• Surgical resection
• Post-operative RT is indicated for positive margins!
  

Resectable esophageal cancers (>T1bN0)

• Surgical resection
• Definitive chemoradiation (if non-surgical candidate)
• Pre-operative chemoradiation (40 Gy / 15 Fx)
  
• Pre-operative chemotherapy - controversial
  

You need to re-stage these patients with CT or PET-CT before surgery (assess response, rule out mets)

Lower GE junction cancers

• Peri-operative ECF chemotherapy (MAGIC Trial)
• Post-operative chemoradiation (MacDonald trial)
  

Palliative Esophageal Cancer

• Brachytherapy 20 Gy / 5 fractions (obstruction)
  
• External beam 30 Gy / 10 fractions (bleeding and obstruction)
  
• Stenting and/or dilatation (obstruction)
  
• Resection in very selected patients (bleeding or obstruction)
• Chemotherapy (obstruction)

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Pre-operative Chemoradiation
There is a lot of conflicting data for pre-operative chemoradiation. Even meta-analyses show conflicting results in terms of overall survival. In general, most show small, but statistically small improvements in overall survival.

Two major Phase III studies compared chemoradiation to chemoradiation followed by surgery for Squamous cell esophageal cancers. Both studies failed to show a survival benefit for the addition of surgery.

Bundenne (FFCD 9102) treated 450 patients with 2 cycles cisplatin and 5FU and 46 Gy. Patients were then randomized to either surgery or an additional 3 cycles of chemo and 20 Gy radiation. There was no overall survival benefit (40 vs 34%) and a higher treatment-related mortality for the surgery group (9 vs 1%).

Stahl treated 200 patients with 3 cycles induction 5-FU, cisplatin, etoposide and leucovorin. Patients were then randomized to either >66 Gy radiation and cisplatin/etoposide or 40 Gy and cisplatin/etoposide followed by surgery. This study demonstrated better local control for the surgery group (65 vs 40%), but ultimately there was no difference in overall survival (~25% @ 3 years).

If you are going to go this route, a recent meta-analysis by Gebski showed a significant benefit at 2 years overall survival with an absolute improvement of 13% and a hazard ratio of 0.81. When analyzed for sub-type, adenocarcinomas benefit. The two studies above were negative, but included only squamous cell cancers. Basically, this is still investigational, but it is fair to say that this may be viable treatment option and these patients should be enrolled into any active protocols.

Pre-operative Chemotherapy
Similarly, there is conflicting data for pre-operative chemotherapy. Gebski's meta-analysis also looked at pre-op chemo. There is a 2 year absolute 7% overall survival benefit for adding chemotherapy pre-surgery for adenocarcinomas.

Definitive Chemoradiation
The RTOG 8501 trial compared 64 Gy alone to 50.4 Gy and concurrent 5FU/cisplatin x 4 cycles. This trial included 260 patients with T1-3N0-1M0 esophageal cancers. This trial demonstrated superiority of chemoradiation over radiation alone. There were improvements in 5 year overall survival 27% vs 0%.

A follow-up study INT0123 looked at radiation dose escalation with concurrent chemoradiation. Essentially it was cisplatin and 5 FU combined with either 64 Gy or 50.4 Gy. This study demonstrated a lower 2 year overall survival rate for the higher-dose arm (30% vs 40% each) and equivalent local relapse rates (~50%).


Lower GE Junction Esophageal Cancer

Peri-operative Chemotherapy
The MRC randomized 500 patients to either surgery alone or to surgery and peri-operative ECF chemotherapy (3 cycles pre + 3 cycles post) in the MAGIC trial. This study demonstrated an improvement in overall survival at 5 years (36 vs 23%). As a caveat, only 15% of these patients were GE junction tumors, most were gastric cancers.

Post-operative Chemoradiation
MacDonald's trial for gastric and gastro-esophageal junction cancers compared surgery alone vs post-op chemoradiation (45 Gy in 25 fx + 5FU/LV given 1 wk pre-RT, then during wk 1 & 5 of RT, and 2 more cycles). 3-year survival was 50% vs 40% favoring chemorads. Relapse rates were also better at 50 vs 30%. This is standard treatment for post-operative GE junction cancers.

Treatment Volumes as per RTOG 0436
GTV = gross tumor
CTV = 4 cm longitudinally and 1 cm radially around primary tumor and 1cm expansion around any nodes

• Cervical esophageal cancers (10-15 cm): include the supraclavicular lymph nodes
• Middle esophageal cancers (15-30 cm): paraesophageal nodes
  
• Distal esophagus cancers (> 30 cm) : include celiac nodes
  

PTV = CTV + 1 cm

Technique:
Plan 1: Use AP/PA fields for first up to 39.6 Gy
Plan 2: Use AP and 2 posterior obliques up to 50.4 Gy
Basically want to spare the spinal cord!

Cervical esophageal cancers (cover supraclavicular LNs):
RTOG0436 recommends:
0 to 39.6 Gy: AP/PA
39.6 to 50.4 Gy: 2 anterior obliques, 1 PA field + electron boost to cover supraclavicular nodes