RECTUM AND ANAL CANAL CARCINOMA-TARGET VOLUME DELINEATION

Basic dimensions and boundaries

• The anal canal is about 4 cm in length.
• It extends from the anorectal ring proximally (palpable border of the anal sphincter and puborectalis muscle) to the anal verge distally.

Anal verge and epithelial transitions

• The anal verge is the junction of the nonkeratinized squamous epithelium of the distal anal canal and the keratinized hair-bearing perianal skin.
• Embryologically, the dentate (pectinate) line is formed by the junction of endoderm proximally and ectoderm distally.
• This embryologic transition leads to important differences in both histology and lymphatic drainage.
• The dentate line demarcates the transition from the columnar epithelium of the proximal anal canal to the squamous epithelium of the distal anal canal.

Oncologic implications

• Squamous cell carcinomas arising proximal to the anal verge are managed as anal canal cancers.
• Squamous cell carcinomas arising distal to the anal verge are managed as perianal skin cancers.

Primary draining lymphatics

• The primary draining lymphatics of the anal canal include:
  • Perirectal lymph nodes
  • Internal iliac (hypogastric) lymph nodes
  • Superficial inguinal lymph nodes
• The pattern of lymphatic drainage depends on the location of the primary tumor within the anal canal.

Lymphatic drainage of the anal canal and distal rectum

Location of primary tumor	Draining lymphatics
Distal anal canal, perianal skin, and anal verge	Superficial inguinal Femoral External iliac
Anal canal just proximal to dentate line	Internal pudendal Hypogastric Obturator Inferior and middle hemorrhoidal
Proximal anal canal and distal rectum	Perirectal Superior hemorrhoidal

Clinical assessment

• Physical examination is a critical part of staging and planning.
• Assessment should include detailed characterization of the primary tumor:
  • Size of the lesion
  • Location relative to the anal verge
  • Anal sphincter function
  • Invasion of adjacent structures on pelvic examination
• Examine and palpate inguinal lymph nodes carefully.

Evaluation of suspicious lymph nodes

• Inguinal lymph nodes that are suspicious for metastatic involvement but borderline in size should be biopsied to confirm metastasis.
• Nearly 50% of suspicious nodes may represent reactive hyperplasia rather than true metastasis.

Imaging

• PET/CT is recommended both for staging and for treatment planning to assist in delineating the extent of gross disease.
• Areas of low uptake on PET should not supersede findings on physical examination or abnormalities seen on CT or MRI.

Patient positioning and immobilization

• Simulate the patient supine with arms on chest in a body mold.
• Prone positioning with a belly board may be used to allow anterior displacement of bowel, but:
  • It is less reproducible.
  • It complicates bolus placement.
• Place a radiopaque marker at the anal verge to aid in localization.

CT simulation and imaging fusion

• Perform CT simulation with:
  • Intravenous contrast.
  • Slice thickness of ≤3 mm.
• Goal: delineate pelvic blood vessels and the gross tumor volume (GTV).
• If available, perform PET/CT fusion to aid in target volume delineation.
• MRI may also be useful for soft-tissue definition.

Bladder and rectal management

• Consider bladder filling/emptying strategies:
  • A full bladder may keep bowel from migrating into the pelvis.
  • An empty bladder may be more reproducible from day to day.

Image-guided radiotherapy (IGRT)

• Use image guidance with daily orthogonal kilovoltage imaging.
• Use weekly cone-beam CT (CBCT) scans to assess soft tissue and verify alignment during treatment.
• CBCT may be done more frequently if there is significant variation in bladder and/or rectal filling.

Role of IMRT and importance of accurate delineation

• RTOG 0529 has established the feasibility of IMRT for anal canal cancers in a multi-institutional setting.
• IMRT demonstrated:
  • Lower rates of grade 2 or higher hematologic toxicity.
  • Lower rates of grade 3 or higher gastrointestinal or dermatologic toxicity.
  • These improvements were observed when compared with historical controls in RTOG 9811, which utilized 3D conformal radiotherapy.
• However, accurate target volume delineation is critical.
• Non-compliance with consensus contouring guidelines is associated with an increased risk of disease recurrence.

Planning techniques

• Conventional 3D conformal radiotherapy for anal canal cancers is complex due to the need to irradiate both the pelvis and inguinal lymph nodes.
• The historical “thunderbird” technique was the most common 3D method used to treat anal cancer.
• IMRT allows better conformality compared with thunderbird-style fields while still covering:
  • Primary tumor and anal canal.
  • Pelvic nodes (perirectal, internal iliac, obturator, etc.).
  • Inguinal nodal regions, when indicated.

Practical contouring reminders

• Base the GTV on all available information: physical examination, endoscopy, CT/MRI, and PET/CT.
• Ensure coverage of nodal basins according to the tumor’s location and the lymphatic drainage patterns summarized earlier.
• Follow published consensus atlases for:
  • Pelvic nodal CTVs.
  • Inguinal nodal volumes.
• Carefully document any intentional deviations from consensus guidelines and the reason (e.g., prior radiation, anatomic variants, or patient-specific constraints).

CTV Boundaries

• Inguinal region margins:
  • 1 cm radial margin around femoral vessels.
  • 1 cm around saphenous-femoral junction.
  • 3 cm medial/lateral margin along lower inguinal ligament.
• Inferior border: level of anal margin.

Dose Prescription Examples (from RTOG 9811)

• T2N0: PTV-LR 40 Gy (1.6 Gy/fx), PTV-HR 45 Gy (1.8 Gy/fx), PTV-P → 50.4 Gy.
• T3N1a: PTV-LR 40 Gy, PTV-HR 45 Gy, PTV-P/PTV-N → 54 Gy.
• Postop T1: PTV-HR/PTV-P 45 Gy, boost → 55.8 Gy.

Contouring Atlases

• RTOG atlas:
  • CTV-A: perirectal, presacral, internal iliac
  • CTV-B: external iliac
  • CTV-C: inguinal

  The AGITG atlas defines 7 regions:

  • Mesorectum
  • Presacral space
  • Internal iliac nodes
  • Ischiorectal fossa
  • Obturator nodes
  • External iliac nodes
  • Inguinal nodes

Inguinal Node Contouring — Areas of Disagreement

• Variations exist across major guidelines: RTOG, AGITG, BNG.
• Recent data show 10–29% of involved inguinal nodes are located outside recommended nodal borders.
• To cover the entire chain adequately, a 2 cm radial margin is suggested around the inguinal vessels.

Target volumes	Definition and description
Gross tumor volumes (GTV-P, GTV-N)	GTV-P (primary): all gross disease on physical exam and imaging. GTV-N (regional): all nodes ≥1.5 cm, PET-positive and/or biopsy-proven. Include any lymph node in doubt as GTV-N if biopsy not performed. Nodes ≤3 cm may be designated GTV-Na; nodes >3 cm, GTV-Nb.
Clinical target volumes for gross disease (CTV-P, CTV-N)	CTV-P = GTV-P + 1.5–2.5 cm margin, excluding uninvolved bone, muscle, or air. CTV-N = GTV-N + 1.0–1.5 cm margin, excluding uninvolved bone, muscle, or air.
High-risk clinical target volume (CTV-HR)	Should cover: CTV-P and CTV-N Entire mesorectum and perirectal lymph nodes Bilateral internal iliac lymph nodes inferior to the inferior border of sacroiliac joint If inguinal or external iliac nodes are involved, include them in CTV-HR. If upper internal iliac nodes are involved, include them as well. Margins around vessels: Internal iliac: 0.7 cm margin around vessels (trimmed off uninvolved muscle & bone). External iliac: additional 1 cm anterolateral margin around vessels. Inguinal: entire inguinal compartment contoured, including small vessels and adjacent nodes. Obturator nodes: 1.8-cm wide volume between external and internal iliac vessels. Anteriorly, add 1–1.5 cm into bladder to account for bladder/rectal filling changes.
Low-risk clinical target volume (CTV-LR)	Includes uninvolved internal iliac nodes superior to inferior sacroiliac joint and uninvolved external iliac & inguinal nodes. Margins similar to CTV-HR: 0.7 cm around internal iliac vessels. Additional 1 cm anterolateral around external iliac vessels. Entire inguinal compartment including small vessels & adjacent lymph nodes.
Planning target volumes (PTV)	Each CTV expanded by approximately 0.5–1 cm. Exact margin depends on setup accuracy, imaging frequency, and IGRT capabilities.

Clinical target volume	Key highlights
CTV-A (Perirectal, presacral, internal iliac)	Lower pelvis: inferior border 2 cm below gross disease, including entire mesorectum. Volume need not extend more than a few mm beyond levator muscles unless tumor extends into ischiorectal fossa. Mid pelvis: includes rectum, mesorectum, internal iliac nodes and 1 cm margin into bladder for daily variation in filling. Posteriorly, extend to pelvic sidewall muscles or bone; at minimum include posterior portion of internal obturator vessels. Draw 7–8 mm margin in soft tissue around internal iliac vessels; trim from uninvolved muscle & bone. Upper pelvis: superior extent at bifurcation of common iliac into external/internal iliacs (approx sacral promontory). Again, 7–8 mm soft-tissue margin around vessels, at least 1 cm anteriorly if vessels or small nodes seen, trimmed off uninvolved structures.
CTV-B (External iliac region)	Border between inguinal and external iliac regions somewhat arbitrary. Consensus: set border at level of inferior extent of internal obturator vessels (bony landmark: upper edge of superior pubic rami). Recommend 7–8 mm soft-tissue margin around external iliac vessels, at least 1 cm anteriorly if vessels/nodes present. CTV trimmed off uninvolved muscle and bone.
CTV-C (Inguinal region)	Most inferior extent 2 cm below saphenous–femoral junction. Border between CTV-B and CTV-C approximates upper border of superior pubic rami. Entire inguinal compartment should be contoured, including small vessels and lymph nodes. CTV should be trimmed off uninvolved muscle and bone.

Region	Key borders & anatomical limits (summarised)
Mesorectum	Cranial: rectosigmoid junction / sacral promontory. Caudal: anorectal junction / levator ani insertion. Anterior: mesorectal fascia anterior to rectum; in males includes seminal vesicles & prostate; in females cervix/vagina. Posterior: presacral space and sacral fascia. Lateral: mesorectal fascia and pelvic sidewall muscles.
Presacral space	Cranial: S1/S2 level. Caudal: inferior border of sacrum / coccyx. Anterior: mesorectal fascia / posterior rectal wall. Posterior: anterior sacral surface & periosteum. Lateral: sacro-iliac joints and medial iliac vessels.
Internal iliac region	Follows internal iliac vessels from bifurcation to pelvic floor. Medial: pelvic viscera (rectum, bladder, uterus/prostate). Lateral: pelvic sidewall / obturator internus muscle. Anterior: posterior bladder/uterus surfaces. Posterior: presacral space.
Ischiorectal fossa	Fat-filled space inferior to levator ani around anal canal. Medial: external anal sphincter & levator ani. Lateral: obturator internus & ischial tuberosity. Includes space where perianal disease and low anal canal extension may track.
Obturator region	Between internal and external iliac vessels around obturator canal. Anterior: pelvic sidewall muscles. Posterior: obturator internus muscle. Inferior: level of obturator foramen.
External iliac region	Extends along external iliac vessels from common iliac bifurcation to inguinal ligament. Medial: psoas / iliopsoas muscle. Lateral: iliacus muscle / pelvic sidewall. Anterior: peritoneal surface.
Inguinal region	From saphenous–femoral junction superiorly to at least 2 cm inferior. Anterior: subcutaneous tissue and skin. Posterior: femoral vessels and pectineus muscle. Includes superficial and deep inguinal nodes around femoral vessels.

Target volume	RTOG 9811	RTOG 0529 / Trans-Australian
PTV-P (primary gross disease)	T1N0: 45–50.4 Gy at 1.8 Gy/fraction. T2N0: 50.4 Gy at 1.8 Gy/fraction. N+ or T3–T4: 54–59.4 Gy at 1.8 Gy/fraction.	T1N0: not specifically included on RTOG 0529. T2N0: 50.4 Gy at 1.8 Gy/fraction. N+ or T3–T4: 54 Gy at 1.8 Gy/fraction.
PTV-N (gross nodal disease)	54–59.4 Gy at 1.8 Gy/fraction.	50.4 Gy at 1.68 Gy/fx if node ≤3 cm. 54 Gy at 1.8 Gy/fx if node >3 cm.
PTV-HR (high-risk subclinical)	45 Gy at 1.8 Gy/fraction.	T2N0: 42 Gy at 1.5 Gy/fraction. N+ or T3–T4: 45 Gy at 1.5 Gy/fraction.
PTV-LR (low-risk subclinical)	30.6–36 Gy at 1.8 Gy/fraction. Alternatively 40 Gy at 1.6 Gy/fraction (SIB may be used).	A discrete low-risk PTV was not used in RTOG 0529.

Organ-at-risk	Constraints
Small bowel	QUANTEC: V15Gy < 120 cc (individual loops) V45Gy < 195 cc (entire potential space within peritoneal cavity) RTOG 0529: V30Gy < 200 cc V35Gy < 150 cc V45Gy < 20 cc Dmax < 50 Gy
Large bowel	RTOG 0529: V30Gy < 200 cc V35Gy < 150 cc V45Gy < 20 cc
Bladder	QUANTEC: Dmax < 65 Gy V65Gy < 50% RTOG 0529: V35Gy < 50% V40Gy < 35% V50Gy < 5%
Femoral heads	RTOG 0529: V30Gy < 50% V40Gy < 35% V44Gy < 5%
Iliac crest	RTOG 0529: V30Gy < 50% V40Gy < 35% V50Gy < 5%
External genitalia	RTOG 0529: V20Gy < 50% V30Gy < 35% V40Gy < 5%

Target coverage

• Ideally, at least 95% of each PTV should receive 100% of the prescription dose.
• Maximum dose within each PTV should generally not exceed about 110% of prescription.

Evaluation of sequential boosts

• For plans with sequential boosts to gross disease, each phase should be independently reviewed before summing plans.
• Check for hot spots and under-coverage in each individual PTV.

Organs at risk

• Key OARs: small bowel, large bowel, bladder, femoral heads, iliac crests, external genitalia, and pelvic bone marrow.
• Use RTOG consensus guidelines for contouring bowel, bladder, and femoral heads.
• Apply dose constraints from QUANTEC and RTOG 0529 (see OAR accordion above).

Pelvic bone marrow considerations

• Recognised as an important OAR to minimise acute hematologic toxicity during concurrent chemoradiation.
• Potential constraints:
  • Mean pelvic bone marrow dose < 28 Gy.
  • V10 < 90%.
  • V20 < 75%.
• These are suggested goals rather than absolute limits and should not supersede PTV coverage.