Radiation Oncology/Esophagus/Randomized

Randomized Evidence in Esophageal Cancer

Barrett's Esophagus

• Multi-Institutional -- RFA vs. Sham procedure
  • Randomized, 2:1. 127 patients, dysplastic Barrett's esophagus. Arm 1) RFA vs. Arm 2) Sham procedure. Primary outcome 1-year rate of dysplasia/metaplasia
  • 2009 PMID 19474425 -- "Radiofrequency ablation in Barrett's esophagus with dysplasia." (Shaheen NJ, N Engl J Med. 2009 May 28;360(22):2277-88.)
    • Outcome: In low grade dysplasia patients: complete eradication RFA 90% vs. sham 23% (SS). In high grade dysplasia patients 81% vs. 19% (SS). Disease progression RFA 4% vs. sham 16% (SS), cancer development 1% vs. 9% (SS)
    • Toxicity: More chest pain, 1 patient UGI bleeding, 6% esophageal stricture
    • Conclusion: RFA associated with a high rate of complete eradication of dysplasia and intestinal metaplasia, and reduced risk of disease progression

Surgery +/- Adjuvant Radiation

• China (1986-1997)
  • Randomized. 495 patients with squamous cell treated with surgery. Arm 1) surgery alone vs. Arm 2) post-op RT (50-60 Gy).
  • 2003 PMID 12607634 — "Value of radiotherapy after radical surgery for esophageal carcinoma: a report of 495 patients" (Xiao et al. Ann Thorac Surg. 2003 Feb;75(2):331-6)
    • Outcome: 5-year OS 31.7% vs 41.3% (NS); OS benefit demonstrated for Stage III 13.1% vs 35.1% (p = 0.0027)

• Hong Kong
  • Randomized. 130 patients, squamous cell and adenoCA, treated with surgery (60 curative and 70 palliative; stratified). Arm 1) surgery alone vs. Arm 2) RT 49/14 in 3.5 Gy/fx
  • 1993 PMID 8430362 -- "Postoperative radiotherapy for carcinoma of the esophagus: a prospective, randomized controlled study." (Fok M, Surgery. 1993 Feb;113(2):138-47.)
    • Outcome: Median OS surgery 15 months vs. adjuvant RT 8 months (SS). If curative resection, no difference for LC or OS. If palliative resection, LR benefit (20% vs. 46%) but no impact on OS
    • Toxicity: stomach complications surgery 6% vs. RT 37% (SS), 5 deaths as result of bleeding
    • Conclusion: Worse survival with adjuvant RT due to RT-related deaths and early mets
  • Comment: According to authors, high dose/fx due to heavy demand on RT facilities

• France (1987-?)
  • Randomized. 221 patients with squamous cell in middle/lower third, stratified N0/N1/N2, treated with surgery. Arm 1) surgery alone vs. Arm 2) post-op RT (45-55 Gy).
  • 1991 PMID 1925862 — "Postoperative radiation therapy does not increase survival after curative resection for squamous cell carcinoma of the middle and lower esophagus as shown by a multicenter controlled trial. French University Association for Surgical Research." (Teniere P et al. Surg Gynecol Obstet. 1991 Aug;173(2):123-30.) Minimum F/U 3 years
    • Outcome: 3-year DFS 19%; No OS benefit for any subgroup. Decreased LR for RT (35% to 10%)

Surgery +/- Adjuvant Chemo-RT

• Country Unknown
  • Intergroup - INT 0116 (1991-98)
    • Randomized. 556 patients. Completely resected (negative margins) adenocarcinoma of the stomach or GE junction. Stage IB to IV(M0) [1988 staging; IB=T1N1 or T2N0]. Stratified by T stage and number of nodes. Arm 1) Surgery alone vs. Arm 2) chemo -> concurrent chemo-RT. Bolus 5-FU (425 mg/m2/d) + LV (20mg/m2/d) x 5 days, followed by RT one month later. Chemotherapy given on first 4 and last 3 days of RT (dose 5-FU 425; LV 20). Adjuvant chemo one month following RT with two 5-day cycles of 5-FU/LV given one month apart. A D2 lymph node dissection was recommended, but most (54%) had a less than D1 dissection or a D1 dissection (31%).
    • RT technique: 45 Gy to tumor bed, regional nodes, 2 cm beyond proximal and distal margins of resection. Defined tumor bed by pre-op CT. Lymph nodes included were: perigastric, celiac, local para-aortic, splenic, hepatoduodenal or hepatic-portal, and pancreaticoduodenal. Exclusion of the splenic nodes was allowed in patients with antral lesions if it was necessary to spare the left kidney. For tumors of GE junction, included paracardial and paraesophageal lymph nodes.
  • 2001 PMID 11547741 — "Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction." MacDonald JS et al. N Engl J Med. 2001 Sep 6;345(10):725-30.
    • Outcome: median OS surgery 2.2 years vs. surgery+CRT 3.0 years (SS). 3-year OS 41% vs. 50%; 3-year RFS 31% vs 48%, median OS 1.6 years vs 2.5 years (SS); LR 29% vs 19%, regional relapse 72% vs 65% (largely abdominal carcinomatosis), DM higher 18% vs 33%. Regional failure included peritoneal spread or liver mets. Only 64% in chemo/RT arm completed therapy as planned.
    • Toxicity: Grade 3 or higher, hematologic 54%, GI 33%. 17% stopped treatment due to toxic effects. 32% of pts in chemo/RT group experience grade 4 toxic effects; 1% had treatment-related deaths.
    • Conclusion: Adjuvant CRT beneficial in GEJ tumors (T2N0, T1N1 and higher) after curative resection
• Dutch
  • PMID: 26254683 (2004-2008 )
    • CROSS (Chemoradiotherapy for Oesophageal Cancer followed by Surgery Study:
    • 366 out of 368 patients were analyzed from a randomized study comparing neoadjuvant chemoradiotherapy versus surgery alone. Histologically confirmed, potentially curable squamous-cell carcinoma, adenocarcinoma, or large-cell undifferentiated carcinoma of the esophagus or esophagogastric junction were included. Neoadjuvant chemotherapy was given with weekly Paclitaxel and Carbopltin. Radiotherapy dose was 41.4Gy in 23 fractions as per conventional dose fractionation schedule. Overall survival was significantly better in the chemoradiotherapy–surgery group (49.4 months versus 24 months favoring neoadjuvant chemoradiation)

Surgery +/- Neoadjuvant Radiation

• 2nd Scandinavian trial (1983-1988)
  • 1992 PMID 1455880 -- "Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer." (Nygaard K, World J Surg. 1992 Nov-Dec;16(6):1104-9; discussion 1110.)
  • Randomized. 186 patients with squamous cell, 2x2 design: Arm 1) surgery alone, Arm 2) neoadjuvant cisplatin/bleomycin, Arm 3) neoadjuvant RT 35 Gy, and Arm 4) neoadjuvant chemotherapy and RT
  • Outcome: 3-year OS significantly higher if receiving RT vs. no RT. No difference if receiving chemo vs. no chemo; Females significantly better survival
  • Conclusion: neoadjuvant RT has benefit, neoadjuvant chemotherapy does not

• Scotland (1979-1983)
  • Randomized. 176 patients, operable squamous cell or adenoCA of middle/lower third. Arm 1) preoperative RT 20/10 AP/PA vs. Arm 2) surgery alone.
  • 1992 PMID 1496141 -- "Low dose preoperative radiotherapy for carcinoma of the oesophagus: results of a randomized clinical trial." (Arnott SJ, Radiother Oncol. 1992 Jun;24(2):108-13.)
    • Toxicity: None significant; no impact on operative complications
    • Outcome: median OS no difference; 5-year OS preop RT 9% vs. surgery 17% (NS)
    • Prognostic factors: LN+, high grade, male sex
  • Conclusion: Low dose pre-op RT offers no advantage

• Beijing (1977-1985)
  • 1989 PMID 2646253 -- "Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of esophageal carcinoma: report on 206 patients." (Wang M, Int J Radiat Oncol Biol Phys. 1989 Feb;16(2):325-7.)
  • Randomized. 206 patients, tumor <8cm, patients <65. Arm 1) preop RT AP/PA 40 Gy whole mediastinum and left gastroepiploic lymphatics
  • Op stats: resection RT 93% vs. surgery alone 85%, mortality 5% vs. 6%, LN mets 27% vs. 35%
  • Outcome: 5-year OS RT 35% vs. surgery alone 30%; patients with Grade III esophagitis survival 50%; LN failure 41% vs. 34%
  • Conclusion: no difference

• EORTC (1976-1982)
  • Randomized. 208 patients. Squamous cell only. Arm 1) preop RT 33/10 fractions, interval to surgery <8 days vs. Arm 2) surgery alone.
  • 1987 PMID 3630187 (No abstract) — "The value of preoperative radiotherapy in esophageal cancer: results of a study of the EORTC." Gignoux M et al. World J Surg. 1987 Aug;11(4):426-32.
    • Op stats: Operability equal (RT 95%, no RT 100%); Resectability similar (RT 77%, no RT 82%), operative mortality slightly favoring surgery alone (RT 25%, no RT 18%),
    • Outcome: 5 year OS preop RT 10% vs. surgery 9% (NS). Survival for resected patients favored RT arm (RT 16% versus no RT 10%). Local failure preop RT 46% vs. surgery alone 67%
  • Conclusion: No benefit for preop RT

• France (1973-1976)
  • Randomized. 124 patients, squamous cell. Arm 1) 40 Gy Co-60 in 8 days (@ 5 Gy/fx?) vs. Arm 2) surgery alone
  • 1981 PMID 6794167 -- "Preoperative radiotherapy for carcinoma of the esophagus." (Launois B, Surg Gynecol Obstet. 1981 Nov;153(5):690-2.)
    • Resection rate: RT 70% vs. surgery alone 58% (NS), operative mortality 23% both arms (NS)
    • Outcome: 5-year OS: RT 9% vs. surgery alone 11% (NS)
  • Conclusion: No benefit for preop RT

Surgery +/- Neoadjuvant Chemotherapy

• MRC Trial (1992-1998)
  • 2002 PMID 12049861 -- "Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial." (MRC Oesophageal CWG, Lancet. 2002 May 18;359(9319):1727-33.)
  • Randomized. 802 patients, any cell type, resectable. Arms 1) cisplatin 80 mg/m2 + 5-FU 1000 mg/m2 x2 cycles followed by surgery vs. 2) surgery alone. Preop RT could be given at discretion regardless of randomization.
    • Outcome: median OS chemo-S 17 months vs. S alone 13 months (SS); R0 in 60% vs. 54% (SS)
    • Toxicity: no difference
    • Conclusion: 2 cycles of neoadjuvant cisplatin/5-FU improve survival
  • Comment: different outcome from US INT-0113 trial, despite similar design

• RTOG 89-11 (INT-0113) (1990 - 1995)
  • Randomized. 443 patients with Stage I-III, excluding cervical esophagus and SCV LN+. Randomized to chemo then surgery vs surgery alone. Chemo consisted of 3 cycles of cisplatin/5-FU then 2 additional cycles. Post-op RT allowed for R1 or R2 resection
  • 9-years; 2007 PMID 17704421 -- "Long-Term Results of RTOG Trial 8911 (USA Intergroup 113): A Random Assignment Trial Comparison of Chemotherapy Followed by Surgery Compared With Surgery Alone for Esophageal Cancer." (Kelsen DP, J Clin Oncol. 2007 Aug 20;25(24):3719-25.) Median F/U 8.8 years
    • Outcome: Median OS 1.3 years both arms (NS), 5-year OS not given but both <25%
    • By resection: median OS R0 2.2 years vs. R1 1.0 years vs. R2 0.6 years vs. not resected 0.2 years (SS); 5-year OS R0 32% vs. R1 5%
    • Conclusion: Neoadjuvant chemo no benefit. Need R0 resection for reasonable survival. For R1 resection, only CRT offers possibility of long-term DFS

Surgery +/- Neoadjuvant Chemo-RT

• CALGB 9781 / RTOG 97-16 (1997-2000)
  • Closed early due to non-accrual. Randomized. 56 pts (target 500). Stage I-III. Randomized to: concurrent RT 50.4/28 + 5-FU 1000 mg/m2 + cisplatin 100 mg/m2 followed by surgery vs surgery alone.
  • 2008 PMID 18309943 — "Phase III Trial of Trimodality Therapy With Cisplatin, Fluorouracil, Radiotherapy, and Surgery Compared With Surgery Alone for Esophageal Cancer: CALGB 9781." (Tepper J et al. J Clin Oncol. 2008 Mar 1;26(7):1086-92.) Median F/U 6 years

Cisplatin 100 mg/m2 and Fluorouracil 1,000 mg/m2/d for 4 days on weeks 1 and 5 concurrent with radiation therapy (50.4 Gy total: 1.8 Gy/fraction over 5.6 weeks)

• • • Outcome: median OS trimodality 4.5 years vs. surgery 1.8 years (SS). 5-year OS: 39% vs. 16%; pCR 40%
    • Toxicity: Grade 3+ esophagitis/dysphagia 42%; infection 34% (1 death); pain 24%; hematologic toxicity 57%
    • Conclusion: Long-term OS significantly better with trimodality

• TROG/AGITG (1994 - 2000)
  • Randomized. 256 patients, 62% adeno, 37% squamous. Resectable disease, T1-3, N0-1. Randomized to preoperative chemoradiotherapy vs surgery alone. One cycle cisplatin 80 mg/m2 + 5-FU 800 mg/m2/d. RT AP/PA 35/15 @ 2.33 Gy/fx, margins 5cm sup/inf and 2cm radial. Trimodality arm 18% didn't get surgery
  • 2005 PMID 16129366 — "Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial." Burmeister BH et al. Lancet Oncol. 2005 Sep;6(9):659-68. Median F/U 5.4 years
    • Outcome: no difference in OS or PFS. Median OS 22 months vs. 19 months (NS). More R0 resections (80% vs. 59%), fewer N+ (43% vs. 67%). Better PFS for squamous cell (SS)
    • Toxicity: Grade 3-4 16% esophagitis, 5% nausea/vomiting
    • Conclusion: No difference, further assessment in squamous cell

• Ireland (1990-1995)
  • Randomized. 113 patients with adenocarcinoma. Concurrent cisplatin and 5-FU with RT 40/15 @2.67 Gy/fx, followed by another chemo cycle. RT fields: 5cm margins longitudinally, 2-3 cm laterally. Surgery on Week 9.
  • 1996 PMID 8672151 -- "A comparison of multimodal therapy and surgery for esophageal adenocarcinoma." (Walsh TN, N Engl J Med. 1996 Aug 15;335(7):462-7.)
    • Outcome: Median OS trimodality 16 months vs surgery 11 months (SS). 3-yr OS 32% vs 6% (SS). pCR in 13/58 pts in combined arm.
    • Conclusion: Multimodality superior to surgery alone
  • Comment: Criticized for short follow-up (median 10 months; 7.5m for dead vs 18 months for alive). 11 pts withdrew from combined therapy arm, versus only 1 for surgery arm. Also criticized for poor outcome on surgery alone arm (10-20% less than expected compared to Urba or EORTC).

• EORTC (1989-1995)
  • Randomized. 282 patients with squamous cell of thoracic esophagus, excluded T3N1 (>3cm diameter and N+) and T4N0. Randomized to surgery vs pre-op chemo/RT. RT: Split course, two one-week courses two weeks apart, 18.5/5 @ 3.7 Gy/fx to macroscopic tumor/enlarged LNs, 5cm sup/inf and 2cm radial margin. Chemo: cisplatin 80mg/m2
  • 1997 - PMID 9219702 — "Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus." Bosset JF et al. N Engl J Med. 1997 Jul 17;337(3):161-7. Median F/U 4.6 years
  • Outcome: no difference in overall survival (median OS 19 months), improved DFS (17% vs. 21%, SS), improved cancer-related deaths (SS), improved LC. However, more post-op deaths in trimodality therapy. pCR 26%
  • Conclusion: No difference in OS, but improvement in DFS and LC
  • Comments: Authors speculated that RT too toxic (given in 3.7 Gy/fx)

• Michigan (1989-94)
  • Randomized. 100 patients with squamous or adeno, any stage without distant mets. Randomized to surgery alone vs preop chemo/RT followed by surgery. Chemo: cisplatin 20 mg/m2 C.I. + 5-FU 300 mg/m2 C.I. + vinblastine. Required inpatient stay. RT: 45/30 @1.5 BID to tumor and involved nodes only; no elective nodal irradiation. Surgery after a 3 week rest, in 94% of pre-op pts.
  • 2001 - PMID 11208820 — "Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma." (Urba SG et al. J Clin Oncol. 2001 Jan 15;19(2):305-13.). Median F/U 8 years
    • Outcome: median OS surgery 18 months vs. trimodality 17 months (NS); 3-year OS 16% vs. 30% (NS, p=0.15) but powered only to detect increase from 1 year to 2.2 years
    • Prognosis: pCR in 28%: these pts have a MS of 49 months vs. 12 months; 3-year OS 64% vs. 19%. Worse prognosis for squamous cell histology.
    • Conclusion: No difference in OS, DFS, or cause-specific survival. Improved survival for those with pCR after chemo/RT.
  • Comment: Intensive preop therapy can be given, with 94% undergoing surgery

• Thailand (1986-1992)
  • Randomized. 69 patients with squamous cell. Chemo (cisplatin + 5-FU), RT, surgery vs. surgery alone. 75% completed trimodality arm. pCR 20%
  • 1994 PMID 7959579 -- "A prospective study of combined therapy in esophageal cancer." (Apinop C, Hepatogastroenterology. 1994 Aug;41(4):391-3.)
    • Outcome: no difference in survival or complications at 1 and 5 years. Median OS 10 months

• France
  • 1994 PMID 8137201 -- "A randomized study of chemotherapy, radiation therapy, and surgery versus surgery for localized squamous cell carcinoma of the esophagus." (Le Prise E, Cancer. 1994 Apr 1;73(7):1779-84.)
  • Randomized. 86 patients with squamous cell. Chemo: cisplatin 100 mg/m2 + 5-FU 600 mg/m2. RT 20 Gy
    • Outcome: No difference in survival; median OS 10 months; 1-year OS 47% both groups
    • Toxicity: operative mortality 8.5% and 7%
    • Conclusion: No difference

• Scandinavian (1983-88)
  • Randomized. 187 patients with squamous cell only, stage T1-2 NX. Four arm randomization: 1) surgery alone, 2) pre-op chemo then surgery, 3) pre-op RT 35 Gy then surgery, and 4) pre-op chemo+RT then surgery. Chemo: cisplatin + bleomycin x 2 cycles. RT: 35/20, included whole esophagus + mediastinum. No nodal irradiation.
  • 1992 PMID 1455880 — "Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer." (Nygaard K et al. World J Surg. 1992 Nov-Dec;16(6):1104-9)
    • Outcome: Pooled analysis for pre-RT groups showed survival benefit. No benefit for pooled analysis of pre-op chemo groups

Primary Chemo-RT vs. Chemo-RT -> Surgery

• French FFCD 9102 (1993-2000)
  • Randomized. 444 enrolled patients, but only 259 randomized after initial therapy, remainder no improvement/contraindication/refusal/death. Operable T3N0-1 thoracic esophageal CA, squamous (90%) or adenoCA. Everyone treated with neoadjuvant 5-FU/cisplatin x2 cycles + RT (given either conventional 46/23 Gy or split course 15/5 + 15/5 with 2 week rest(became disallowed during study after this trial)). If response (clinical and esophagogram), randomized to surgery vs. further CRT (5-FU/cisplatin x3 cycles + RT (conventional 20/10 or split course 15/5). Total RT dose in primary CRT was 66 Gy. Margin 3-cm sup/inf and 2-cm radial.
  • 2007 PMID 17401004 -- "Chemoradiation Followed by Surgery Compared With Chemoradiation Alone in Squamous Cancer of the Esophagus: FFCD 9102" (Bedenne L, J Clin Oncol. 2007 Apr 1;25(10):1160-1168. Median F/U 4 years
    • Survival: Median OS trimodality 18 months vs. chemo-RT 19 months (NS) vs. unassigned patients 11 months, overall 16 months; 2-year OS: no difference (surgery 34% vs. CRT 40%). 3-month mortality: surgery 9.3% vs. CRT 0.8% (SS). 80% recurrences within 2 years
    • 2-year LC: trimodality 65% vs. CRT 57% (SS); stents required: surgery 5% vs. CRT 32% (SS). High grade dysphagia prevented in 46% chemo-RT vs. 63% trimodality. No difference in DM. Majority of recurrences in first year (60%) or first 2 years (80%)
    • Toxicity: QoL higher in chemo-RT at 6 months, no difference thereafter.
    • Conclusion: in advanced thoracic esophageal CA patients who respond to neoadjuvant CRT, no benefit to surgery compared with continued CRT. CRT fewer early deaths, but more LR relapses
    • Editorial PMID 17401002: clinical staging only, no surgical QC, some split-course RT. Surgery should be selective, given morbidity/mortality. Systemic agents needed

• Germany (1994-2002)
  • Randomized. 172 patients with squamous cell only, upper/mid esophagus only, T3-4N0-1 staged by EUS. Randomized to induction chemo followed by chemo-RT to 40 Gy followed by surgery vs same regimen to 65 Gy without surgery. Induction chemo was FLEP (5-FU, leucovorin, etoposide, cisplatin); concurrent chemo was PE (cisplatin, etoposide). In the chemo-RT alone arm, RT was 50/25 followed by a 1.5 Gy BID for 65 Gy for T4 or obstructive T3 tumors; or 60 Gy followed by HDR brachytherapy 4 Gy @ 0.5cm x 2 for non-obstructed T3 tumors. Margins 3.5 cm sup/inf and 1.5 cm radial. 34% patients didn't undergo surgery (refused after neoadjuvant response or developed mets); R0 resection in 82%
  • 2005 PMID 15800321 — "Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus." (Stahl M et al. J Clin Oncol. 2005 Apr 1;23(10):2310-7.) Median F/U 6 years
    • Outcome: Median OS surgery 16 months vs. CRT 15 months (NS); 3-year OS 31% vs. 24% (NS); PFS surgery 64% vs. CRT 41% (SS). 75% of failures in-field. Only prognostic factor was response to neoadjuvant therapy
    • Toxicity: surgery 70% at least one severe complication; treatment mortality surgery 13% vs. CRT 4% (SS)
    • Conclusion: Surgery improves LC but not OS, significantly more complications. Authors recommend primary chemo-RT for patients that respond to initial neoadjuvant CRT, while offering surgery to poor responders

Primary CRT: Dose Escalation

• INT 0123 / RTOG 94-05 (1995-99)
  • Stopped early. Randomized. 236 patients with T1-4 N0-1, squamous (85%) or adenoCA (15%). Concurrent chemo cisplatin 75 mg/m2 + 5-FU 1000 mg/m2. Arm 1: standard RT (50.4/28) with 5cm sup/inf and 2cm radial margin to primary + regional LNs, included SCV LN for cervical primary vs. Arm 2: high-dose RT 64.8/36, initial fields 50.4/28 + 14.4/8 boost to primary only with 2cm margin)
  • 2002 PMID 11870157 — "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." (Minsky BD et al. J Clin Oncol. 2002 Mar 1;20(5):1167-74.) Median F/U 1.3 years
    • Toxicity: 11 treatment related deaths in high dose arm, although 7/11 died at less than 50.4 Gy.
    • Outcome: No difference. Median OS high-dose 13 months vs. standard-dose 18 months (NS), 2-year OS (31% vs. 40%), LRF (56% vs. 52%, NS) or persistence of disease.
    • Conclusion: Standard is 50.4 Gy with concurrent 5-FU/cisplatin.
  • Comment: Unclear why significantly more on-treatment deaths at <50.4 Gy in high dose arm, but no difference in outcome after correcting for it. Significant prolongation of treatment time in high-dose arm due to treatment breaks, significantly lower dose (65%) of target 5-FU delivered. Outcomes in standard-arm comparable to RTOG-85-01

Primary CRT: Induction Chemotherapy

• RTOG 01-13 (E0113), 2008 - Compares two induction chemotherapy regimens
  • Phase II. 84 pts. Induction chemotherapy x 2 cycles -> concurrent chemo/RT.
    • Arm A - Induction 5-FU + Taxol; 50.4 Gy + concurrent 5-FU (96-hr C.I.) + weekly Taxol. With G-CSF. (Based on MDACC regimen.)
    • Arm B - Induction Cisplatin + Taxol; 50.4 Gy + concurrent Taxol (96-hr C.I.) + weekly Cisplatin. (Based on MSKCC regimen.)
  • 2008 - PMID 18574157 — Phase II Randomized Trial of Two Nonoperative Regimens of Induction Chemotherapy Followed by Chemoradiation in Patients With Localized Carcinoma of the Esophagus: RTOG 0113 (Ajani JA, J Clin Oncol. 2008 Oct 1;26(28):4551-6.).
    • MS 28.7 mo (Arm A) vs 14.9 mo (Arm B). 2-yr OS 56% vs 37%. 1-yr OS 75.7% for Arm A. High rate of toxicity: Grade 3/4 in 54%/27% vs 43%/40%. Treatment related death in 3% and 6%.
  • Conclusion: Both arms of RTOG 0113 were associated with high morbidity, and the study did not meet its 1-year survival end point.