Anal canal

Anatomy
Perianal skin/Anal margin: 5cm radius around anal verge
Anal verge: End of hair bearing skin, marks beginning of anal canal
Dentate line: transition from squamous to glandular mucosa; about 2cm inferior to anorectal ring
  Regions from the dentate line and inferiorly drain to superficial inguinal nodes
  Above the dentate line drain to perirectal and inferior mesenteric nodes
Most commonly involved nodes in anal canal cancers are the perirectal nodes (~50%); pelvic 30%, groin 30%; remember that groin nodes are considered N2 disease

Epidemiology
4600 cases per year
Incidence is rising
60% occur in women

Risk factors
HIV
HPV
Other STD's
Cervical/vulvar/vaginal cancers
Immune suppression
Smoking
Anal intercourse

Pathology
80% squamous cell
10% adeno...treated like rectal cancer (CRT then surgery not definitive CRT)
5% melanoma
5% other (sarcoma, lymphoma, etc)

Prognostic factors
T/N/M stage
Anemia
Poorly controlled HIV

Therapy
Early T1 tumors can be excised if wide enough margins for sphincter preservation
Otherwise definitive CRT is used

Nigro regimen
First trial to establish CRT as a viable organ preserving option
5-FU/MMC/30Gy in 15 fx
90% of patients cleared disease at six week biopsy

UKCCCR
RT only vs. RT/FU/MMC
CRT was superior in: local control (59 vs 36%)
Trend to improved OS (65 vs 58%) and improved CSS (72 vs 61%)
CRT increased acute toxicity (particularly hematologic); no change in late effects

EORTC
RT only vs. RT/FU/MMC
CRT associated with: higher complete response rates (80 vs 54%), higher LC at 5 years (68 vs 50%), 5-year colostomy free survival (72 vs 40%)
OS was identical in the two groups at 58% at 5 years

Intergroup
RT/FU/MMC vs. RT/FU only
Adding MMC was associated with: lower rates of + biopsy after treatment (8 vs. 15%); better colostomy free survival at 4 years (91 vs. 77%), better 4-year DFS (73 vs 51%)
MMC did not affect overall survival
Acute toxicity was also worse in the MMC arm

RTOG 9811 (PMID 23150707)
RT/FU/cisplatin vs. RT/FU/MMC
MMC group had better 5-year DFS (56 vs 48%) and better colostomy free survival (90 vs. 80% at 5 years) but worse acute toxicity

Fields:
T2N0
 -Initial AP, to 30.6Gy: Superior = L5/S1, Inferior = 2cm below anus, Lateral to cover inguinals
 -Initial PA, to 30.6Gy: Same sup/inf borders, Don't include inguinals

 -Field reduction #1: Drop the top border to the SI joint...Continue treating the groins to 36Gy

 -Field reduction #2: Block groin nodes, treat pelvic and perirectal nodes as well as tumor, to 45Gy

 -Field reduction #3: Boost gross disease (Can skip boost if CR @ 45Gy?)


RT dosing
PTV1 = perineum, anus, b/l groins, whole pelvis: 30.6Gy
PTV2 = perineum, anus, b/l groin, whole pelvis: 36Gy for clinically negative nodes; 45Gy for + nodes
PTV3 = any gross disease (primary or lymph nodes): 55 - 59Gy (go higher for larger primaries)