Fig. 14.1
AP and lateral films for 3D conformal radiation planning. AP and lateral films demonstrating appropriate borders based on bony landmarks for radiation therapy. Colors: red gross tumor volume, pink mesorectum, magenta lymph nodes, dark blue vessels, green rectum, light green small bowel, yellow bladder
For postoperative low anterior resection (LAR) patients, fields are the same, and the dose is typically 50.4 Gy.
For postoperative abdominoperineal resection (APR) patients, fields are the same. The perineal scar is wired at the time of simulation and included in the field (perineal scar inferior to the sacrum). At treatment, bolus may be used on the scar every other day, typically with a 0.5 cm bolus. The dose is 50.4 Gy or 55.8 Gy for gross disease.
In the Dutch Rectal Trial [5], the superior border was at the level of L5/S1 (sacral promontory). In a follow-up study evaluating the local recurrences in those enrolled on the Dutch Rectal Trial, most cranial recurrences were located a few centimeters caudal of the promontory regardless of RT treatment or not. For patients without primary nodal involvement, the most cranial recurrences were located at the level of S2–S3. These results suggest that the cranial border of the pelvic field may be able to be lowered in early rectal cancers [6].
In the Swedish Rectal Trial [7], the superior border was at the mid-L4. In a follow-up study examining the local recurrences among patients enrolled on the Swedish Rectal Trial treated both with and without radiation, all recurrences were located below the S1–S2 interspace [8].
14.4.2 Intensity-Modulated Radiation Therapy (IMRT)
IMRT allows for increased conformality around target and at-risk structures.
IMRT “conforms” radiation delivery to the shape of the tumor using concave/convex isodose lines (Fig. 14.2).
Fig. 14.2
IMRT plan for rectal cancer. IMRT allows for highly conformal dose distributions, as demonstrated on the axial, coronal, and sagittal slices. The GTV is outlined in red
This modality allows for a reduction of high doses to organs at risk, without compromising target coverage.
The small bowel is radiosensitive, as acute radiation enteritis occurs in many patients undergoing RT for rectal cancer (Fig. 14.3).
IMRT has been previously demonstrated to reduce bowel irradiation in prostate, cervical, and endometrial cancers.
Fig. 14.3
Acute radiation enteritis. CT scan of a patient with acute radiation enteritis after undergoing chemoradiation for rectal cancer. Enteritis is identified by the diffusely thickened small bowel present on the scan
Dosimetric analysis in rectal cancer patients, simulated prone with a full bladder, found that the use of inverse planning IMRT was associated with a 64 % reduction in the percentage of bowel volume irradiated to 45–50 Gy compared with 3DCRT [11].
Unclear how this translates clinically
NRG Oncology RTOG 0822 [12] sought to determine whether IMRT could decrease the rate of GI toxicity in combination with multiagent neoadjuvant chemoradiation in locally advanced rectal cancer. Neoadjuvant chemotherapy consisted of capecitabine and oxaliplatin.
RTOG 0822 was based on RTOG 0247 [13], a phase II randomized trial comparing capecitabine and oxaliplatin with 3DCRT versus capecitabine and irinotecan with 3DCRT.
There was an unexpectedly high rate of grade 3–4 GI toxicity in both arms.
RTOG 0822 included radiation delivery using inverse-planned IMRT to the rectum and lymphatics at risk to 45 Gy (1.8 Gy fractions) followed by a 3D chemoradiation boost to the gross disease with a 2-cm margin including all of the presacral space to 5.4 Gy (1.8 Gy fractions). Patients were simulated either supine or prone.
T3 tumors: Clinical target volume (CTV) included all gross diseases as well as internal iliac lymph nodes and the mesorectum (i.e., perirectal fat and presacral space).
T4 tumors: CTV included same structures as well as the external iliac lymph nodes.
Unified CTV included: rectal gross tumor volume (GTV) expanded 1.5 cm radially and 2.5 cm craniocaudally, nodal GTV expanded 1.5 cm symmetrically, uninvolved internal (and external if T4 disease) iliac vessels expanded 1 cm symmetrically, presacral space defined as the 8 mm of soft tissue anterior to the sacrum from mid-S1 to S5, and the mesorectum/perirectal lymphatics.
Planning tumor volume (PTV): 0.5 symmetric expansion of the unified CTV.
Treatment plan had to cover ≥98 % of the PTV with ≥93 % of the prescription (≤10 % of the PTV could receive ≥105 % of the prescribed dose, and ≤5 % of the PTV could receive ≥110 % of the prescribed dose).
Organs at risk included the small bowel, i.e., peritoneal space containing the small bowel (V35Gy<180 cc, V40Gy<100 cc, V45Gy<65 cc, max point <50 Gy), femoral heads, and bladder.
Primary endpoint was to determine the rate of grade ≥2 GI toxicity with the goal of identifying 12 % reduction in adverse effects compared to what was seen in RTOG 0247.
The study showed a 51.5 % rate of grade ≥2 GI toxicity, which exceeded the observed rate of 40 % in RTOG 0247.
Both trials assessed toxicity in setting of multiagent chemotherapy; however, it is unlikely that oxaliplatin will be employed with neoadjuvant chemoRT in rectal cancer given its lack of benefit in phase III studies [14, 15].
Volume of the bowel receiving low-dose RT (e.g., 15 Gy) may be more important when using multiagent chemotherapy, suggesting that low-dose constraints may need to be more stringent.
RTOG contouring guidelines have been published to define targets and elective tissue coverage with IMRT planning. Target volumes for rectal cancer differ substantially from genitourinary or gynecological cancers, as the rectum and its associated mesentery represent first-echelon drainage from the rectum and are thus part of target coverage, as opposed to avoidance structures [16].
The role of IMRT in rectal cancer remains to be determined. It may be more beneficial in situations where there is more volume of the bowel within a 3DCRT field, in patients with T4 tumors requiring external iliac coverage, or in the postoperative setting.
14.4.3 Proton Beam Therapy
Proton therapy uses charged particles and takes advantage of the Bragg peak to deposit dose in the tumor with sharp falloff to avoid most normal structures (Fig. 14.4).
A dosimetric analysis from the University of Florida [17] comparing 3DCRT, IMRT, and conformal proton therapy with eight patients showed that all three modalities covered the target volume and met normal tissue metrics.
Bladder V40Gy was significantly lower with IMRT and proton beam therapy compared to 3DCRT, though no difference was seen between IMRT and protons (29 % IMRT, 31 % proton, 41 % 3DCRT, p = 0.016). Small bowel V40Gy was also significantly lower in the IMRT and proton therapy plans compared to 3DCRT, but this metric was again comparable between IMRT and protons (19 % IMRT, 22 % proton, 27 % IMRT). The only small bowel metric that was improved with protons compared to IMRT was V10Gy (45 % from 90 %, p = 0.015) and V20Gy (39 % from 56 %, p = 0.015).
At all dose levels evaluated, proton plans offered significantly reduced pelvic bone marrow exposure over 3DCRT and IMRT.
This could be of substantial benefit in 30 % of patients who may recur distantly at 10 years (per German Rectal Trial updated report [18]) and will require myelosuppressive systemic therapy.
It remains to be seen how proton beam therapy for rectal cancer translates clinically; it is unknown whether the reduction of normal tissue exposure leads to differences in acute and late toxicities.
Proton beam limitations/uncertainties:
Range or depth of a proton beam is dependent on coulombic interactions with electrons in constituent atoms of different tissue.
Proton range is significantly greater in air than in tissue; changes in rectal gas may affect the beam range, leading to potential undercoverage of the target or overdose of normal tissue structures.
Fig. 14.4
Proton radiation plan for rectal cancer. Proton radiotherapy takes advantage of the Bragg peak to deliver dose to the target (outlined in red) and avoid normal structures
14.4.4 Stereotactic Body Radiation Therapy (SBRT)
SBRT has recently emerged as a potentially effective therapy for pelvic cancers, particularly pelvic recurrences of rectal cancer, in the reirradiation setting.
The technique allows for smaller expansion margins and greater conformality, maximally avoiding normal structures.
A study from the Beth Israel Deaconess Medical Center in Boston, MA, using CyberKnife-based SBRT reported on outcomes of 18 patients with 22 pelvic recurrences [19]. Fiducial markers were placed percutaneously within or near the tumor. Patients underwent CT simulation with body immobilization.
Five fractions were used when the tumor was adjacent to dose-limiting structures; three fractions were used for all others.
Total dose ranged from 24 to 40 Gy (median, 25 Gy).
1-year, 2-year, and 3-year local control rates were 100, 94, and 86 %, respectively. Median local progression-free survival was 39 months.
Toxicities included fatigue for most patients. One patient developed a small bowel perforation requiring surgery; two patients treated for pelvic sidewall recurrence had symptomatic neuropathy; one patient developed ureteral fibrosis and resulting hydronephrosis requiring a stent.Related posts:
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