RTOG 9501
Phase III Intergroup Trial of Surgery Followed by (1) Radiotherapy vs. (2) Radiochemotherapy For Resectable High Risk Squamous Cell Carcinoma of the Head and Neck
Phase 3N = 459NCT00002670
- Population
- High-risk resected squamous-cell carcinoma of the head and neck
- Design
- Intergroup randomised trial. Between September 1995 and April 2000, 459 patients with high-risk resected squamous-cell carcinoma of the head and neck were enrolled after total resection of all visible and palpable disease: 231 were assigned to radiotherapy alone (60 to 66 Gy in 30 to 33 fractions over 6 to 6.6 weeks) and 228 to identical radiotherapy plus concurrent cisplatin 100 mg per square metre on days 1, 22 and 43. Long-term follow-up analysed 410 patients.
- Primary endpoint
- Locoregional control
- Arms
- Postoperative radiotherapy alone (control, n = 231): 60 to 66 Gy in 30 to 33 fractions over 6 to 6.6 weeks
- Postoperative radiotherapy plus cisplatin (experimental, n = 228): Identical radiotherapy plus cisplatin 100 mg per square metre on days 1, 22 and 43
- People
- Cooper JS, Radiation Therapy Oncology Group 9501/Intergroup
Locoregional controlHR 0.61 (95% CI 0.41–0.91)Δ 24-month Locoregional control+10 pointsDFSHR 0.78 (95% CI 0.61–0.99)OSHR 0.84 (95% CI 0.65–1.09)Δ Severe adverse events (grade 3 or higher)+43 pointsΔ 120-month Locoregional failure−6.5 points
Show the numbers
| Endpoint | Analysis | Postoperative radiotherapy plus cisplatin | Postoperative radiotherapy alone | Effect |
|---|---|---|---|---|
| Locoregional controlRandomised patients (231 and 228); analysis population not stated in the abstract | primarymedian follow-up 45.9 monthsCooper 2004 | 82% at 2 y | 72% at 2 y | HR 0.61 (95% CI 0.41–0.91)P=0.01Hazard ratio is for local or regional recurrence. |
| DFSRandomised patients (231 and 228); analysis population not stated in the abstract | primarymedian follow-up 45.9 monthsCooper 2004 | — | — | HR 0.78 (95% CI 0.61–0.99)P=0.04 |
| OSRandomised patients (231 and 228); analysis population not stated in the abstract | primarymedian follow-up 45.9 monthsCooper 2004 | — | — | HR 0.84 (95% CI 0.65–1.09)P=0.19 |
| Severe adverse events (grade 3 or higher)Randomised patients; acute adverse effects | primarymedian follow-up 45.9 monthsCooper 2004 | 77% | 34% | P<0.001Four patients who received combined therapy died as a direct result of the treatment (abstract). |
| Locoregional failure410 analysable patients | long term-updatemedian follow-up 9.4 yearsCooper 2012 | 22.3% at 10 y | 28.8% at 10 y | P=0.10Median follow-up among surviving patients was 9.4 years. |
| DFS410 analysable patients | long term-updatemedian follow-up 9.4 yearsCooper 2012 | 20.1% at 10 y | 19.1% at 10 y | P=0.25 |
| OS410 analysable patients | long term-updatemedian follow-up 9.4 yearsCooper 2012 | 29.1% at 10 y | 27% at 10 y | P=0.31 |
| Locoregional failureUnplanned subset with microscopically involved resection margins and/or extracapsular spread | exploratorymedian follow-up 9.4 yearsCooper 2012 | 21% at 10 y | 33.1% at 10 y | P=0.02Unplanned subset analysis; subset sizes are not given in the abstract. |
| DFSUnplanned subset with microscopically involved resection margins and/or extracapsular spread | exploratorymedian follow-up 9.4 yearsCooper 2012 | 18.4% at 10 y | 12.3% at 10 y | P=0.05Unplanned subset analysis; subset sizes are not given in the abstract. |
| OSUnplanned subset with microscopically involved resection margins and/or extracapsular spread | exploratorymedian follow-up 9.4 yearsCooper 2012 | 27.1% at 10 y | 19.6% at 10 y | P=0.07Unplanned subset analysis; subset sizes are not given in the abstract. |
| Endpoint | Analysis | Postoperative radiotherapy plus cisplatin | Postoperative radiotherapy alone | Effect |
|---|---|---|---|---|
| Locoregional controlRandomised patients (231 and 228); analysis population not stated in the abstract | primarymedian follow-up 45.9 monthsCooper 2004 | 82% at 2 y | 72% at 2 y | HR 0.61 (95% CI 0.41–0.91)P=0.01Hazard ratio is for local or regional recurrence. |
| DFSRandomised patients (231 and 228); analysis population not stated in the abstract | primarymedian follow-up 45.9 monthsCooper 2004 | — | — | HR 0.78 (95% CI 0.61–0.99)P=0.04 |
| OSRandomised patients (231 and 228); analysis population not stated in the abstract | primarymedian follow-up 45.9 monthsCooper 2004 | — | — | HR 0.84 (95% CI 0.65–1.09)P=0.19 |
| Severe adverse events (grade 3 or higher)Randomised patients; acute adverse effects | primarymedian follow-up 45.9 monthsCooper 2004 | 77% | 34% | P<0.001Four patients who received combined therapy died as a direct result of the treatment (abstract). |
| Locoregional failure410 analysable patients | long term-updatemedian follow-up 9.4 yearsCooper 2012 | 22.3% at 10 y | 28.8% at 10 y | P=0.10Median follow-up among surviving patients was 9.4 years. |
| DFS410 analysable patients | long term-updatemedian follow-up 9.4 yearsCooper 2012 | 20.1% at 10 y | 19.1% at 10 y | P=0.25 |
| OS410 analysable patients | long term-updatemedian follow-up 9.4 yearsCooper 2012 | 29.1% at 10 y | 27% at 10 y | P=0.31 |
| Locoregional failureUnplanned subset with microscopically involved resection margins and/or extracapsular spread | exploratorymedian follow-up 9.4 yearsCooper 2012 | 21% at 10 y | 33.1% at 10 y | P=0.02Unplanned subset analysis; subset sizes are not given in the abstract. |
| DFSUnplanned subset with microscopically involved resection margins and/or extracapsular spread | exploratorymedian follow-up 9.4 yearsCooper 2012 | 18.4% at 10 y | 12.3% at 10 y | P=0.05Unplanned subset analysis; subset sizes are not given in the abstract. |
| OSUnplanned subset with microscopically involved resection margins and/or extracapsular spread | exploratorymedian follow-up 9.4 yearsCooper 2012 | 27.1% at 10 y | 19.6% at 10 y | P=0.07Unplanned subset analysis; subset sizes are not given in the abstract. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| Locoregional control | 0.61 | 0.41–0.91 |
| DFS | 0.78 | 0.61–0.99 |
| OS | 0.84 | 0.65–1.09 |
Appears in
Sources
Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004;350(19):1937-44.
Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, et al. Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2012;84(5):1198-205.