RTOG 0529
A phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal (RTOG 0529)
Phase 2N = 63NCT00423293
- Population
- Patients with T2-4 N0-3 M0 carcinoma of the anal canal; of 52 evaluable patients, 54% had stage II, 25% stage IIIA and 21% stage IIIB disease
- Design
- Multi-institutional single-arm phase 2 trial of dose-painted intensity-modulated radiotherapy (DP-IMRT) with fluorouracil and mitomycin-C on days 1 and 29. The primary endpoint was a reduction of at least 15% in the combined rate of grade 2 or worse acute gastrointestinal and genitourinary adverse events compared with the conventional radiotherapy, fluorouracil and mitomycin-C arm of RTOG 9811; planned secondary endpoints were all adverse events and the investigators' ability to perform DP-IMRT. 63 patients were accrued and 52 were evaluable. Prescriptions: T2N0, 42 Gy to elective nodal and 50.4 Gy to anal tumour planning target volumes in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy (metastatic nodes up to 3 cm) or 54 Gy (more than 3 cm) and 54 Gy anal tumour volumes in 30 fractions.
- Primary endpoint
- Grade 2 or worse acute gastrointestinal or genitourinary adverse events
- Arms
- Dose-painted IMRT with fluorouracil and mitomycin-C (experimental): Dose-painted IMRT prescribed by stage (T2N0: 42 and 50.4 Gy in 28 fractions; T3-4N0-3: 45, 50.4 or 54, and 54 Gy in 30 fractions) with fluorouracil and mitomycin-C on days 1 and 29
- People
- Kachnic LA, senior author Willett CG, Radiation Therapy Oncology Group
Show the numbers
| Endpoint | Analysis | Dose-painted IMRT with fluorouracil and mitomycin-C | Control | Effect |
|---|---|---|---|---|
| Grade 2 or worse acute gastrointestinal or genitourinary adverse events52 evaluable patients of 63 accrued | primaryKachnic 2013 | 77% | — | 77% of patients had grade 2 or worse acute gastrointestinal or genitourinary adverse events, the same as the 77% in the RTOG 9811 conventional radiotherapy, fluorouracil and mitomycin arm that served as the historical comparator. The primary endpoint (a reduction of at least 15%) was not met. Different trials and grading scales (CTCAE v3.0 in RTOG 0529, CTC v2.0 in RTOG 9811 per the full text), so this is a cross-trial comparison. |
| Grade 2 or worse acute haematologic adverse events52 evaluable patients of 63 accrued | primaryKachnic 2013 | 73% | — | P=.032Compared with 85% in the RTOG 9811 conventional radiotherapy, fluorouracil and mitomycin arm (cross-trial comparison, one-sided test per the full text). |
| Grade 3 or worse acute gastrointestinal adverse events52 evaluable patients of 63 accrued | primaryKachnic 2013 | 21% | — | P=.0082Compared with 36% in the RTOG 9811 conventional radiotherapy, fluorouracil and mitomycin arm (cross-trial comparison). The full-text paragraph also gives 21% vs 37% (P = 0.0052) for combined grade 3 or worse gastrointestinal or genitourinary adverse events. |
| Grade 3 or worse acute dermatologic adverse events52 evaluable patients of 63 accrued | primaryKachnic 2013 | 23% | — | P<.0001Compared with 49% in the RTOG 9811 conventional radiotherapy, fluorouracil and mitomycin arm (cross-trial comparison). On initial pretreatment review 81% of plans required replanning; final review found normal tissue major deviations in only 3 cases. |
| DFS52 evaluable patients | long term-updatemedian follow-up 7.9 yearsKachnic 2022 | 70% at 5 y (56–81%); 62% at 8 y (47–74%) | — | 5-year and 8-year disease-free survival by the Kaplan-Meier method (95% CI in brackets); median follow-up 7.9 years (range 0.02-9.2). No control arm. |
| OS52 evaluable patients | long term-updatemedian follow-up 7.9 yearsKachnic 2022 | 76% at 5 y (61–86%); 68% at 8 y (53–79%) | — | 5-year and 8-year overall survival by the Kaplan-Meier method (95% CI in brackets). No control arm. |
| Colostomy-free survival52 evaluable patients | long term-updatemedian follow-up 7.9 yearsKachnic 2022 | 74% at 5 y (59–84%); 66% at 8 y (51–77%) | — | 5-year and 8-year colostomy-free survival by the Kaplan-Meier method (95% CI in brackets). Colostomy failure by cumulative incidence was 10% (95% CI 4%-20%) at 5 years and 12% (5%-23%) at 8 years; six patients required a colostomy (five for locoregional salvage, one temporary for anorectal dysfunction). No control arm. |
| Locoregional failure52 evaluable patientsLocal-regional failure by the cumulative incidence method. | long term-updatemedian follow-up 7.9 yearsKachnic 2022 | 16% at 5 y (7–27%); 16% at 8 y (7–27%) | — | 5-year and 8-year local-regional failure (95% CI in brackets). Eight patients had local-regional failure, five with persistent disease at 12 weeks; no isolated nodal failures occurred in the microscopic elective nodal volumes. Distant metastases: 16% (7%-27%) at 5 years and 22% (12%-34%) at 8 years. Late adverse events: grade 2 in 28 patients (55%), grade 3 in 8 (16%), grade 4 in none, grade 5 in 2 (4%; sinus bradycardia and myelodysplasia, possibly owing to chemotherapy). No control arm. |
| Endpoint | Analysis | Dose-painted IMRT with fluorouracil and mitomycin-C | Control | Effect |
|---|---|---|---|---|
| Grade 2 or worse acute gastrointestinal or genitourinary adverse events52 evaluable patients of 63 accrued | primaryKachnic 2013 | 77% | — | 77% of patients had grade 2 or worse acute gastrointestinal or genitourinary adverse events, the same as the 77% in the RTOG 9811 conventional radiotherapy, fluorouracil and mitomycin arm that served as the historical comparator. The primary endpoint (a reduction of at least 15%) was not met. Different trials and grading scales (CTCAE v3.0 in RTOG 0529, CTC v2.0 in RTOG 9811 per the full text), so this is a cross-trial comparison. |
| Grade 2 or worse acute haematologic adverse events52 evaluable patients of 63 accrued | primaryKachnic 2013 | 73% | — | P=.032Compared with 85% in the RTOG 9811 conventional radiotherapy, fluorouracil and mitomycin arm (cross-trial comparison, one-sided test per the full text). |
| Grade 3 or worse acute gastrointestinal adverse events52 evaluable patients of 63 accrued | primaryKachnic 2013 | 21% | — | P=.0082Compared with 36% in the RTOG 9811 conventional radiotherapy, fluorouracil and mitomycin arm (cross-trial comparison). The full-text paragraph also gives 21% vs 37% (P = 0.0052) for combined grade 3 or worse gastrointestinal or genitourinary adverse events. |
| Grade 3 or worse acute dermatologic adverse events52 evaluable patients of 63 accrued | primaryKachnic 2013 | 23% | — | P<.0001Compared with 49% in the RTOG 9811 conventional radiotherapy, fluorouracil and mitomycin arm (cross-trial comparison). On initial pretreatment review 81% of plans required replanning; final review found normal tissue major deviations in only 3 cases. |
| DFS52 evaluable patients | long term-updatemedian follow-up 7.9 yearsKachnic 2022 | 70% at 5 y (56–81%); 62% at 8 y (47–74%) | — | 5-year and 8-year disease-free survival by the Kaplan-Meier method (95% CI in brackets); median follow-up 7.9 years (range 0.02-9.2). No control arm. |
| OS52 evaluable patients | long term-updatemedian follow-up 7.9 yearsKachnic 2022 | 76% at 5 y (61–86%); 68% at 8 y (53–79%) | — | 5-year and 8-year overall survival by the Kaplan-Meier method (95% CI in brackets). No control arm. |
| Colostomy-free survival52 evaluable patients | long term-updatemedian follow-up 7.9 yearsKachnic 2022 | 74% at 5 y (59–84%); 66% at 8 y (51–77%) | — | 5-year and 8-year colostomy-free survival by the Kaplan-Meier method (95% CI in brackets). Colostomy failure by cumulative incidence was 10% (95% CI 4%-20%) at 5 years and 12% (5%-23%) at 8 years; six patients required a colostomy (five for locoregional salvage, one temporary for anorectal dysfunction). No control arm. |
| Locoregional failure52 evaluable patientsLocal-regional failure by the cumulative incidence method. | long term-updatemedian follow-up 7.9 yearsKachnic 2022 | 16% at 5 y (7–27%); 16% at 8 y (7–27%) | — | 5-year and 8-year local-regional failure (95% CI in brackets). Eight patients had local-regional failure, five with persistent disease at 12 weeks; no isolated nodal failures occurred in the microscopic elective nodal volumes. Distant metastases: 16% (7%-27%) at 5 years and 22% (12%-34%) at 8 years. Late adverse events: grade 2 in 28 patients (55%), grade 3 in 8 (16%), grade 4 in none, grade 5 in 2 (4%; sinus bradycardia and myelodysplasia, possibly owing to chemotherapy). No control arm. |
- Dose-painted IMRT with fluorouracil and mitomycin-C (experimental)
Data table (modelled values)
| Months | Dose-painted IMRT with fluorouracil and mitomycin-C |
|---|---|
| 0 | 100.0% |
| 26 | 86.1% |
| 52 | 73.2% |
| 78 | 65.4% |
| 104 | 62.0% |
- Dose-painted IMRT with fluorouracil and mitomycin-C (experimental)
Data table (modelled values)
| Months | Dose-painted IMRT with fluorouracil and mitomycin-C |
|---|---|
| 0 | 100.0% |
| 26 | 89.0% |
| 52 | 78.7% |
| 78 | 71.6% |
| 104 | 68.0% |
Appears in
Sources
Kachnic LA, Winter K, Myerson RJ, Goodyear MD, Willins J, Esthappan J, et al. RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 2013;86(1):27-33.
Kachnic LA, Winter KA, Myerson RJ, Goodyear MD, Abitbol AA, Streeter OE, et al. Long-Term Outcomes of NRG Oncology/RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity Modulated Radiation Therapy in Combination With 5-Fluorouracil and Mitomycin-C for the Reduction of Acute Morbidity in Anal Canal Cancer. Int J Radiat Oncol Biol Phys. 2022;112(1):146-157.