Radiation Oncology/Anal canal/Review

Anal Cancer Review Epidemiology U.S. incidence: ~5,200; U.S. death rate ~700 (~13%) Risk factors: HPV 16-18 in ~75% cases, immunodeficiency, tobacco Clinical presentation: rectal bleeding, 20% asymptomatic Work-Up: DRE, inguinal evaluation, pelvic MRI/CT, chest/abdomen CT, PET not validated, GYN exam in women, consider HIV testing Anatomy: anal margin to anal verge to dentate line to anorectal sling Lymph node drainage: perirectal (N1), inguinal (N2), internal illiac (N2) LN positive ~30% (ACT II) 5-year survival Stage I: 69% Stage II: 59% Stage III: 41% Stage IV: 19% Surgery Local excision alone Not considered appropriate for any lesions in anal canal (NCCN v1.2010, ACR 2007) For T1N0 worse outcome (ACR 2007): 5-year local control ~70% (vs 80-90% with RT), 5-year OS ~50% (vs 90-100% with RT) For T1N0 well-differentiated, anal margin (NCCN v1.2010): May be considered APR 5-year OS ~50% Toxicity: permanent colostomy Surgery vs chemo-RT No randomized trials Swedish cohort data support better outcomes with chemo-RT Non-surgical approaches RT alone Control rate depends on size of primary Tumors <4 cm and cN0 have excellent 10-year local control (85-90%) and overall survival (~80%) Larger tumors have only ~60% local control rate and ~50% overall survival Chemo-RT vs RT alone 2 trials (UKCCCR, EORTC), mostly in T3-T4 or N+ patients No difference in overall survival; UKCCCR improved cancer-specific survival. 5-year OS ~55% Local control benefit: 40-50% to 65% Colostomy-free benefit: 40% to 70% Chemo-RT: chemo options RTOG 8704 (Flam) +/- Mitomycin Worse colostomy without MMC: 4-year MMC- 22% vs MMC+ 9% (SS) Worse DFS without MMC: 4-year 51% vs 73% (SS); no difference in OS RTOG 9811 (Ajani, update Gunderson) Induction/concurrent 5-FU + cisplatin vs concurrent 5-FU + Mitomycin Worse local control: cisplatin 67% vs Mitomycin 75%; colostomy rate 19% vs 10% (SS) No impact on survial on initial analysis: 5-year OS 70-75% However on update (Gunderson): DFS and OS were statistically better for RT + FU/MMC versus RT + FU/CDDP (5-year DFS, 67.8% v 57.8%; P = .006; 5-year OS, 78.3% v 70.7%; P = .026). There was a trend toward statistical significance for CFS (P = .05), LRF (P = .087), and CF (P = .074). Uncreal whether worse outcomes due to induction or due to cisplatin Chemo-RT: RT options RTOG 92-08 (Konski) split course to 59.6 Gy Worse colostomy-free survival and DFS RTOG 0529 (Kachnic) IMRT with concurrent 5-FU/mitomycin-C: 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations.