Radiation Oncology/Esophagus/Review

Esophageal Cancer Review

Epidemiology

• 2009 U.S. Data: incidence ~16,500; mortality: ~14,500 (88% death rate)
• High prevalence worldwide: Asia, southern/eastern Africa, southern France
• Risk factors: age, male gender, Plummer-Vinson, caustic injury
  • Squamous cell: smoking, tobacco; risk decreases with cessation
  • AdenoCA: GERD, Barrett's (40x), smoking, tobacco; risk does not decrease with cessation

Clinical Presentation & Work Up

• Clinical presentation: dysphagia, weight loss, hiccups (phrenic nerve), reflux (suggests EGJ tumor), satiety (suggests infiltration into stomach wall)
• EGD: distance from incisors, extent of lesion/mucosal changes
• CT scan: frequently not helpful, since Barretts shows wall thickening; miss 50% nodes
• Endoscopic ultrasound: T-stage, LN evaluation/biopsy
• PET/CT
• Bronchoscopy: if above carina, to rule out fistulas

Surgery

• Surgically resectable:
  • Cervical esophagus: typically not treated surgically for larynx preservation, need >5 cm from cricopharyngeus
  • Only 30-40% present with resectable disease, only 50% of these undergo curative (R0) resection
  • Technique: Transthoracic (Ivor Lewis) vs transhiatal
  • Lymph node dissection: based on SEER data, survival better if >10 LN removed
• Surgery alone:
  • 5-year OS 20-25%; median OS ~1.5 years
  • Local control?
• Surgery vs RT:
  • 2 older trials showed survival benefit to surgery; recent Chinese trial no difference in 5-year OS (~35%)
• Pre-op RT:
  • 6 older RCTs. No survival benefit. Meta-analysis using individual patient data showed no conclusive survival benefit for RT
• Pre-op chemo:
  • 9 RCTs. Two (MRC and Netherlands) showed significant survival benefit. Meta-analysis suggests 2-year 7% OS benefit and 5-year 4% benefit
• Pre-op chemo-RT:
  • 10 RCTs. Two (Walsh, Tepper) showed significant survival benefit. Meta-analysis showed 2-year 13% OS benefit, which persisted even after excluding Walsh trial
  • Dublin (Walsh): median OS 16 months vs 11 months (SS); 3-year OS 32% vs 6% (SS). Critique poor outcome in surgery only arm
  • CALGB 9781 (Teper): median OS 4.5 years vs 1.8 years (SS); 5-year OS 39% vs 16%. pCR 40%; Grade 3+ toxicity 40%
• Post-op chemo:
  • 3 RCTs. Meta-analysis showed no significant benefit
• Post-op chemo-RT:
  • Gastric/EGJ trial (INT 0116, MacDonald): 3-year OS benefit 41% vs 50% (SS); 3-year local relapse 29% vs 19%; Grade 4 toxicity 32%
• Pre-op chemo-RT + Surgery vs Chemo-RT alone:
  • 2 RCTs, majority squamous cell. Non-inferiority 10-15%, both trials negative for OS difference.
  • Germany (Stahl): Randomized upfront, no lower esophagus. 2-year OS 40% vs 35% (NS). 2-year local control 64% vs 41% (SS). Periop mortality 13% vs 4%
  • French FFCD-9102 (Bedenne): Only responders to CRT randomized. 2-year OS 34% vs 40% (NS). 2-year local control 66% vs 57% (SS). Periop mortality 12% vs 0%
• Concurrent chemotherapy
  • CALGB 9781: 5-FU 1000 mg/m2 + cisplatin 100 mg/m2
  • RTOG 0436 (ongoing): paclitaxel 50 mg/m2 + cisplatin 25 mg/m2 QW
  • German (Stahl): cisplatin + etoposide
• Conclusions:
  • If surgery will be done, preop chemo-RT improves 2-year survival
  • In patients with SCC at risk for surgical morbidity/mortality, primary chemo-RT may be comparable/superior
  • NCCN guidelines (v1.2010)
    • T1a: esophagectomy or EMR
    • T1b: esophagectomy for non-cervical, chemo-RT for cervical primaries
    • T2-T4N0-N1: pre-op chemo (adenoCA only), pre-op chemo-RT, or definitive chemo-RT
    • T2-T4N0-N1: if surgery done first, post-op chemo-RT (MacDonald) for distal/GEJ tumors or R1/R2 resections

Non-surgical approaches

• RT vs Chemo-RT
  • RTOG 8501 (Herskovic)
    • Concurrent chemo: cisplatin 75 mg/m2 + 5-FU 1000 mg/m2 (weeks 1, 5, 8, 11)
    • Survial benefit: 3-year OS 10% vs 40% (SS); 5-year OS 0% vs 26% (SS); median OS 9 months vs 14 months (SS)
    • Locoregional control benefit: 53% vs 38% (SS)
    • Worse toxicity: Acute Grade 4-5 2% vs 10% (including 2% deaths)

• Chemo-RT: Dose escalation
  • RTOG 9207 (Gaspar) brachytherapy boost
    • EBRT 50/25 + HDR 15/3 or LDR 20/1 with concurrent cisplatin 75 mg/m2 + 5-FU 1000 mg/m2
    • Grade 4 toxicity 24% (fistula 18%), deaths 10%
  • RTOG 9405 (Minsky) 3DCRT boost
    • EBRT 50.4 Gy vs 64.8 Gy with concurrent cisplatin 75 mg/m2 + 5-FU 1000 mg/m2
    • No difference in survival, 2-year 40% vs 31%
    • No difference in local failure: 56% vs 52%
    • Toxicity: 11 deaths in high-dose arm

• Chemo-RT: Different chemo regimens
  • RTOG 0113: Induction chemo -> chemo-RT comparing cisplatin/paclitaxel vs 5-FU/paclitaxel
    • Neither arm successful

• Local control: ~50% despite dose escalation or chemo changes
• Survival: median OS ~1.5 years, 5-year OS ~25%