Anal

Question 1

What is the clinical relevance of RTOG 8704?

Answer 1

This trial showed that outcomes for anal cancer are inferior with RT + 5FU when compared to RT + 5FU + MMC (i.e. the MMC is necessary for anal cancer).

Question 2

What was the patient population studied in RTOG 8704?

Answer 2

291 pts; any stage anal SCCa

Question 3

What was the regimen studied in RTOG 8704?

Answer 3

RT (45Gy) + 5FU +/- MMC

Question 4

What were the results of RTOG 8704?

Answer 4

Improved with MMC:<div>4 yr colostomy free survival (91% vs 78%)<div>DFS (73% vs 51%)</div><div><br></br></div><div>No differencein OS (76% vs 67%)</div></div><div><br></br></div><div>Worse toxicity with MMC (heme)</div>

Question 5

“<span><span>What is the clinical relevance of EORTC 22861?</span></span>”

Answer 5

Showed that adding 5FU and MMC to RT improves outcomes for anal cancer

Question 6

“What was the population studied in<span><span>EORTC 22861?</span></span>”

Answer 6

103 pts; T3 or T4 or N+

Question 7

“What were the results of<span><span>EORTC 22861?</span></span>”

Answer 7

Improved with addition of 5FU/MMC:<div>CR rate (80% vs 54%)</div><div>5 yr LC (68% vs 50%)</div><div>Colostomy free survival (72% vs 40%)</div><div><br></br></div><div>No difference in OS (65% vs 72%)</div>

Question 8

“What was the regimen studied in<span><span>EORTC 22861?</span></span>”

Answer 8

RT (45Gy + 15-20Gy boost) +/- 5FU and MMC

Question 9

What is the clinical relevance of ACT I?

Answer 9

Showed that adding 5FU and MMC to RT improves outcomes for patients with anal SCCa

Question 10

What population was studied in ACT I?

Answer 10

577 pts; Stage II-IV anal SCCa

Question 11

What regimen was studied in ACT I?

Answer 11

RT (45Gy + 15Gy boost) +/- 5FU and MMC

Question 12

What were the results of ACT I?

Answer 12

Improved with addition of 5FU/MMC:<div>3 yr LC (66% vs 41%)</div><div>Cancer specific survival</div><div>Colostomy free survival</div><div><br></br></div><div>No difference in OS</div>

Question 13

Did ACT I show that adding chemotherapy to RT in anal cancer caused increased non-cancer related deaths?

Answer 13

At 5 years, yes (9.1% increase). However, this difference disappeared at 10 years.

Question 14

What is the clinical relevance of ACT II?

Answer 14

Showed that RT + concurrent 5FU/MMC was equivalent to RT + concurrent 5FU/Cisplatin. Since Cisplatin is harder to administer, MMC remains standard of care.

Question 15

What population was studied in ACT II?

Answer 15

940 pts; anal SCCa; all stages

Question 16

What regimen was studied in ACT II?

Answer 16

RT (50.4 Gy) + concurrent 5FU with either MMC (1 cycle) or Cisplatin (60mg/m2)<div><br></br></div><div>*Also studied adjuvant 5FU/Cis vs no CHT but there was no benefit to this</div>

Question 17

What were the results of ACT II?

Answer 17

No difference in outcomes among arms<div>3 yr CR: ~90%</div><div>3 yr CFS: ~75%</div><div>3 yr PFS: ~75%</div><div><br></br></div><div>Also no benefit to adding adjuvant CHT</div>

Question 18

What is the clinical relevance of RTOG 9811?

Answer 18

Showed that RT + concurrent 5FU/MMC is superior to induction 5FU/Cisplatin followed by RT + concurrent 5FU/Cisplatin.<div><br></br></div><div>(essentially showed that induction is not helpful and 5FU/MMC is at least as good as 5FU/Cisplatin if not better)</div>

Question 19

What population was studied in RTOG 9811?

Answer 19

644 pts; T2-T4 tumors with any N; anal SCCa

Question 20

What was the regimen studied in RTOG 9811?

Answer 20

Arm 1: RT (45-59Gy) + concurrent 5FU/MMC<div><br></br><div>Arm 2: Neoadjuvant 5FU/Cisplatin –> RT (45-59Gy) + concurrent 5FU/Cisplatin</div></div>

Question 21

What were the results of RTOG 9811?

Answer 21

Significantly better OS, DFS, and CFS with 5FU/MMC arm:<div>5 yr OS 78% vs 71%</div><div>5 yr DFS 68% vs 58%</div><div>5 yr CFS 72% vs 65% (p=0.05)</div><div><br></br></div><div>Also showed induction not helpful</div>

Question 22

What two trials compared RT + 5FU/MMC with RT + 5FU/Cisplatin? And what are the key differences?

Answer 22

ACT II and RTOG 9811<div><br></br></div><div>ACT II: also analyzed adjuvant CHT, MMC was only 1 cycle</div><div><br></br></div><div>RTOG 9811: also analzed neoadjuvant CHT, MMC was 2 cycles</div>

Question 23

What is the key message of RTOG 9811 and ACT II?

Answer 23

5FU/MMC is preferred over 5FU/Cisplatin for concurrent treatment with RT for anal SCCa

Question 24

What is the clinical relevance of RTOG 0529?

Answer 24

Showed the benefit of IMRT for anal SCCa

Question 25

What population was studied in RTOG 0529?

Answer 25

63 pts; T2-4N0-3; anal SCCa

Question 26

What was the RT dosing paradigm established by RTOG 0529?

Answer 26

“<div><span>Gross Disease:</span></div><span>T2: 50.4Gy</span><div><span>T3/4: 54Gy</span></div><div>Node <3cm: 50.4 Gy</div><div>Node >3cm: 54 Gy</div><div><br></br></div><div>Elective Nodes:</div><div>T2 Primary: 42 Gy</div><div>T3/4 Primary: 45 Gy</div>”

Question 27

What was the treatment paradigm in RTOG 0529?

Answer 27

RT + concurrent 5FU/MMC utilizing IMRT

Question 28

What were the key outcomes of RTOG 0529? What trial did they compare their results to?

Answer 28

“Compared to RTOG 9811, this trial showed lower Grade 3+ skin and GI, and lower Grade 2+ heme toxicities.<div><br></br></div><div><span>RTOG 0529 vs. 9811:</span><br></br><span>grade 2+ heme: 73% vs. 85%</span><br></br><span>grade 3+ skin 23% vs. 49%</span><br></br><span>grade 3+ GI: 21% vs. 36%</span><br></br></div><div><br></br></div>”

Question 29

What are the key dose constraints that came from RTOG 0529?

Answer 29

“<div>Small bowel (V45<20cc)</div><div>Femoral heads (V44<5%)</div><div><br></br></div><img></img>”