Anal cancer nodal drainage is initally to the pre-rectal nodes. For this reason, the rectum and mesorectum are prime sites of inital spread and must be included in treatment volumes. Inguinal nodes, pre-sacral and lower pelvic nodes are significant paths of progression and must be covered by radiation fields. The NRG/RTOG, motivated by a deficiency in the treatment planning reviews of RTOG 0529 have published a collaborative radiotherapy atlases for use in defining treatment volumes for anal cancer. These two atlases are available from the RTOG directly (RTOG Anorectal Contouring Atlas and Target Volumes for Anal Cancer) and are the product of a consensus group.
The RTOG groups initially published GTV, CTV and nodal CTV volumes, and later refined this into GTV, CTVA (internal iliac, pre-sacral, peri-rectal) CTVB (external iliac) CTVC (inguinal) regions.
The internal iliac nodes begin at the bifurcation of the common iliacs, generally at the sacral promontory. The elective target volume should extend ≥ 2 cm around the anal verge or areas of peri-anal skin involvement or 2 cm distal to the most distal extent of palpable disease. RTOG 0529 required 2.5 cm margin. The volume should not extend beyond a few mm into the levator ani muscles. If the cancer does invade the levators or into the ischiorectal fossa, (very advanced tumors) add 1-2 cm margin to bone. In this situation, PET/CT or MRI are recommended for planning purposes. RTOG 0529 recommends the volume extend superiorly to the bifurcation of the common iliac vessels into the internal and external iliac vessels, which is approximately at the level of the sacral promontory.
The lateral borders in the mid-pelvic region extend to the pelvic sidewall musculature or bone. The anterior border is about 1 cm into the posterior aspect of the bladder to account for day-to-day bladder position variation. The posterior portion of the internal obturator vessels between the internal and external iliac vessels should be included. The higher lateral borders should cover the internal and external iliac nodes plus about a 2 cm margin laterally.
Coverage of external iliac nodes and inguinal nodes should be routine for anal cancers. The inferior most extent of the target volume should be 2 cm distal to the femoral artery split (roughly the inferior level of the bottom of the obturator foramen or the upper edge of the superior pubic rami). The upper limits of the inguinal nodes is found approximately at the upper edge of the superior pubic ramus. The vessels are surrogates for the lymphatic chains and a 7-10 mm margin should be added.
Organs at risk include the femoral heads, bladder and small bowel. If the small bowel falls within a CTV, the CTV should not be modified and the small bowel should not be subtracted from the DVH. When assessing small bowel doses the volume of small bowel will vary, therefore, consistent bowel volumes are difficult to predict. The RTOG recommends using absolute bowel volumes rather than volume percents and that the bowel be specifically contoured as loops, rather than as a bowel bag. The RTOG panel felt that the motion of the bowel, in the aggregate was reflective of small bowel dose.
There are several schemes used to treat anal cancers. The RTOG 9811 study with MMC/5FU used a large APPA field with 18 MV AP and 6 MV PA energies to treat to 30.6 Gy at 1.8 Gy/fraction. The PA field was narrower, and the inguinal nodes were supplemented with anterior direct electron fields matched to the exit dose of the narrower PA fields.
After 30.6 Gy was delivered with this technique, a first field reduction bringing the upper APPA border from the L5/S1 to inferior border of the SI Joints, and an additional 14.4 Gy was delivered at 1.8 Gy/fraction bringing the total dose to 45 Gy. If the disease was N0 the inguinal nodes were stopped at 36 Gy.
A second field reduction was made to treat the GTV/PTV for T3/T4 N+ and T2 lesions with residual disease after 45 Gy with an additional boost. This boost treated the original tumor plus a 2.5 cm margin an additional 10-14 Gy at 2 Gy/fraction, bringing the total dose to 55-59 Gy. Involved inguinal nodes were also carried to this dose.
The primary CTV consists of the GTV with 3 cm margins including the peri-rectal nodes along the anal canal. The target volumes include the primary tumor, enlarged lymph nodes, internal and external iliac chains, and inguinal lymph nodes. All treatments were sequential with successive field size reductions during boost portions of the treatment.
Node negative patients: PTV1 is the anal area, inguinal lymphatics and pelvic nodes extending from L5/S1 to 3 cm inferior to the tumor, making sure to include the anal verge. This is treated to 36 Gy at 1.8 Gy/fraction. A second PTV is boosted with an additional 19.8 Gy at 1.8 Gy/fraction bringing the total dose delivered to 55.8 Gy. Treatment is delivered sequentially.
Node POSITVE patients n <1.5 cm are treated with the same PTV as node negative patients for PTV1. PTV2 is modifed to account for positive nodes. The primary tumor and positive nodes (< 1.5 cm) are carried to an additoinal 9 Gy at 1.8 Gy/fraction to a total dose of 45 Gy. A third PTV, PTV3 encompases the primary tumor which is boosted to 10.8 Gy at 1.8 Gy/fraction with a final dose of 55.8 Gy.
Node POSITIVE patients n > 1.5 cm are treated with PTV1 as above, PTV2 (primary tumor and LN > 1.5 cm) are boosted with an additional 19.8 Gy to a total dose of 55.8 Gy at 1.8 Gy/fraction.
The RTOG uses simultaneous integrated boost technique rather than reduced field size consecutive boosts in RTOG 0529, and used a standard contouring atlas. For T2 N0, the PTV-A (primary tumor) was treated to 50.4 Gy in 28 fractions at 1.8 Gy/fraction. A second PTV-42 included all nodal regions and recieved 42 Gy in 28 fractions at 1.5 Gy.
For T3/T4 N0 disease the PTVA was treated to 54 Gy at 1.8 Gy/fraction. A PTV 45 Gy covered the lymphatics to 45 Gy simultaneously at 1.5 Gy/fraction.
For Node POSITIVE patients the PTVA was treated to 54 Gy at 1.8 Gy/fraction in 30 fractions, PTV45 (uninvolved LN) was treated to 45 Gy at 1.5 Gy/fraction. A PTV50 was constructed covering lymph nodes ≤ 3 cm, which was treated to 50.4 Gy at 1.8 Gy/fraction. A third PTV54 was constructed covering all lymph nodes > 3 cm and treated to 54 Gy (same as primary PTV) at 1.8 Gy/fraction.
The NCCN guidelines are increasingly being used to enhance clinical decision making. On review of the radiotherapy dose/fraction schemes recommended by the NCCN, a minimum dose of 45 Gy to the tumor is recommended. For T2 lesions with residual disease after 45 Gy a boost to 50.4 Gy is recommended, with concurrent mitomycin C and i-5FU. The primary tumor, pelvic and inguinal lymphatics should be included. If there is residual disease after 45 Gy, T2 and T3/4 or Node positive disease, a boost to of 9-14 Gy (54 - 59 Gy) should be delivered.
OAR constraints are: