# Radiation Oncology/Prostate/IMRT

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## Ongoing Trials

* RTOG 01-26 -- A Phase III Randomized Study of High Dose 3D-CRT/IMRT vs. Standard Dose 3D-CRT/IMRT in Patients Treated for Localized Prostate Cance

## Outcomes - Toxicity

Toxicity appears to be comparable or better to 3D-CRT, at higher doses
* MSKCC PMID 18164858 -- Ultra-High Dose (86.4 Gy) IMRT for Localized Prostate Cancer: Toxicity and Biochemical Outcomes. (2008 Cahlon O, Int J Radiat Oncol Biol Phys. 2008 Jun 1;71(2):330-7.)
** 478 pts (50 as part of dose-escalation trial), retrospective. 86.4 Gy / 48 fx / 180 cGy. Planning: prescribed dose 86.4 Gy to PTV covers 87% of PTV; 95% of PTV covered by 83.1 Gy (96%); Dmax 110% of prescription dose. PTV = P + SV + 1 cm (0.6 cm at prostate-rectum interface). Rectum max dose limited to 99%=85.5 Gy. No image guidance used (weekly port films only).
** Median f/u 53 mo. Acute GU toxicity: 59% Gr 1, 22% Gr 2, <1% Gr 3. Acute GI toxicity: 34% Gr 1, 8% Gr 2, no Gr 3+. Late GU: 16% Gr 1, 13% Gr 2, <3% Gr 3. Late GI: 13% Gr 1, 3% Gr 2, 0.4% Gr 3.
** 5-yr PSA relapse free survival: 99% low risk, 79% int risk, 72% high risk - original ASTRO definition (vs 98%,85%,70% for Phoenix def)
** Conclusion: ultra-high dose RT for prostate cancer is well-tolerated
* William Beaumont PMID 15667959 -- A dose-escalation trial with the adaptive radiotherapy process as a delivery system in localized prostate cancer: analysis of chronic toxicity. (2005 Brabbins D, Int J Radiat Oncol Biol Phys.)
** 3 dose groups: 70.2-72 Gy, >72-75.6 Gy, and >75.6-79.2 Gy
** Constraints: <5% of the rectal wall has a dose >82 Gy, <30% of the rectal wall has a dose >75.6 Gy, <50% of the bladder volume has a dose >75.6 Gy, and the maximum bladder dose is 85 Gy.
** 280 patients, mean follow-up 29 months
** Toxicity at the high dose level was not different from toxicity at the intermediate or lower dose levels. No significant difference was observed in any of the individual toxicity categories.
* MDACC PMID 15990025 -- The calculated risk of fatal secondary malignancies from intensity-modulated radiation therapy. (2005 Kry SF, Int J Radiat Oncol Biol Phys.)
** IMRT required 3.5-4.9 times as many monitor units as did the conventional treatment
** Maximum risk of fatal second malignancy was 1.7% for conventional radiation, 2.1% for IMRT using 10-MV X-rays, and 5.1% for IMRT using 18-MV X-rays.
* Centre Alexis-Vautrin PMID 15679257 -- Preliminary results of the assessment of intensity modulated radiotherapy (IMRT) for prostatic and head and neck tumors (STIC 2001) (2004 Marchal C, Cancer Radiother.)
** 88 patients (39 3D-CRT and 49 IMRT) with a mean dose of 78 Gy at the ICRU point at 2 Gy/fx; mean follow-up 11.5 months
** Clinical study: Acute reactions do not show any difference between groups, but we want to point out the short follow-up and the relatively high dose delivered to cancers of the prostate.
** Physics study: IMRT is technically feasible in good clinical conditions with high quality assurance, a good reproducibility and precision.
** Cost study: The direct costs of "routine" treatments for the prostatic cancers were 4911 euros for IMRT versus 2357 for 3D-CRT.
* Ghent University Hospital PMID 15465194 -- Intensity-modulated radiotherapy as primary treatment for prostate cancer: acute toxicity in 114 patients. (2004 De Meerleer G, Int J Radiat Oncol Biol Phys.)
** 114 patients, follow-up unclear
** GI toxicity: None 34%, Grade 1 39%, Grade 2 27%, no Grade 3
** GU toxicity: None 10%, Grade 1 47%, Grade 2 36%, Grade 3 7%
** Conclusion: Anatomy-based IMRT to treat prostate cancer is incorporated into our daily routine without any problem. Acute toxicity is very low. Most of the recorded symptoms decrease over time, except for GI urgency and incontinence.
* Val-d'Aurelle-Paul-Lamarque PMID 15063872 -- Pilot study of conformal intensity modulated radiation therapy for localized prostate cancer (2004 Ailleres N, Cancer Radiother.)
** 16 patients treated to 78Gy, follow-up unclear
** 95% of PTV1 received 5 Gy more using IMRT (compared to theoretical 3D-CRT) with protection of the bladder and the rectum walls.
** GI toxicity: Grade 2 25%, no Grade 3
** GU toxicity: Grade 2 31%, no Grade 3
** Conclusion: "Dose escalation with IMRT is feasible with no grade 3 or higher acute GI or GU toxicity. Examination of a larger cohort and longer-term follow-up are warranted in the future."
* MSKCC PMID 12128109 -- High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients. (2002 Zelefsky MJ, Int J Radiat Oncol Biol Phys.)
** 772 patients with clinically localized prostate cancer treated with IMRT (698 patients (90%) treated to 81.0 Gy, and 74 patients (10%) treated to 86.4 Gy); median follow-up 24 months
** 3-year actuarial rectal Grade 2+ toxicity: 4%
** 3-year actuarial urinary Grade 2+ toxicity: 15%
** 3-year actuarial PSA FFS: 92% favorable, 86% intermediate, 81% unfavorable
** Conclusion: "These data demonstrate the feasibility of high-dose IMRT in a large number of patients. Acute and late rectal toxicities seem to be significantly reduced compared with what has been observed with conventional three-dimensional conformal radiotherapy techniques. Short-term PSA control rates seem to be at least comparable to those achieved with three-dimensional conformal radiotherapy at similar dose levels. Based on this favorable risk:benefit ratio, IMRT has become the standard mode of conformal treatment delivery for localized prostate cancer at our institution."
* MSKCC PMID 10869739 -- Clinical experience with intensity modulated radiation therapy (IMRT) in prostate cancer. (2000 Zelefsky MJ, Radiother Oncol.)
** 132 patients with T1c- T3 (61 with 3D-CRT and 171 with IMRT) treated to a prescribed dose of 81 Gy
** IMRT improved the coverage of the clinical target volume (CTV) by the prescription dose and reduced the volumes of the rectal and bladder walls carried to high dose levels (P<0.01)
** 2-year actuarial risk of grade 2 rectal bleeding was 2% for IMRT and 10% for conventional 3D-CRT (P<0.001)
** Conclusion: "The data demonstrate the feasibility and safety of high-dose IMRT for patients with localized prostate cancer and provide a proof-of-principle that this method improves dose conformality relative to tumor coverage and exposure to normal tissues."

## Dosimetry

* PMID 15922172 -- IMRT versus conventional 3DCRT on prostate and normal tissue dosimetry using an endorectal balloon for prostate immobilization. (Vlachaki MT, Med Dosim. 2005)
** Insignificant differences in tumor control probability (TCP) values between IMRT and 3DCRT were calculated for prostate (p = 0.320) and seminal vesicles (p = 0.289).
** Compared to 3DCRT, IMRT resulted in significantly reduced normal tissue complication probability (NTCP) only for upper rectum (p = 0.025) and femurs (p = 0.021).
** Conclusion: "IMRT achieves superior normal tissue avoidance, especially for rectum and femurs compared to 3DCRT, with comparable target dose escalation."
* MSKCC - PMID 15913914 -- Whole pelvic radiotherapy for prostate cancer using 3D conformal and intensity modulated radiotherapy. (Ashman JB, Int J Radiat Oncol Biol Phys. 2005)
** Sequential IMRT plans: 45 Gy to pelvic LN, then boost to prostate / SVs (75.6-81 Gy).
** Bowel: 3D-CRT resulted in 40% relative reduction ( p < 0.001) in the volume of bowel receiving 45 Gy compared with 2D, and IMRT provided a further 60% reduction relative to 3D-CRT (p < 0.001).
** Rectum: IMRT reduced the volume of rectum receiving 45 Gy by 90% (p < 0.001) compared with either 2D or 3D-CRT
** Conclusion: "Compared to conventional 2D planning, conformal planning for WPRT resulted in significant reductions in the doses delivered to the bowel, rectum, and bladder. IMRT was superior to 3D-CRT in limiting the volume of bowel and rectum within high-dose regions. These dosimetric findings correlated with low rates of acute and late GI morbidity."
* PMID 15010385 -- Sparing of the penile bulb and proximal penile structures with intensity-modulated radiation therapy for prostate cancer. (Kao J, Br J Radiol. 2004)
** 10 consecutive patients with clinically organ confined prostate cancer were planned with IMRT to dose of 74 Gy without specifically constraining the plans to spare the penile bulb.
** IMRT reduced the mean penile bulb doses compared with 3D-CRT (33.2 Gy vs 48.9 Gy, p<0.001), the percentage of penile bulb receiving over 40 Gy (37.7% vs 67.2%, p<0.001) and the dose received by >95% of penile bulb (5.3 Gy vs 11.7 Gy, p=0.003). Maximum penile bulb doses were higher with IMRT (81.2 Gy vs 73.1 Gy, p<0.001) although the volume of this high dose region was small.
** Conclusion: "IMRT may potentially reduce long term sexual morbidity by reducing the dose to the majority of the penile bulb."

## Pelvic nodal IMRT

* See below: Ashman et al. 2005
* Surrey, UK, 2000 - PMID 11020560 — "Reduction of small and large bowel irradiation using an optimized intensity-modulated pelvic radiotherapy technique in patients with prostate cancer." Nutting CM et al. Int J Radiat Oncol Biol Phys. 2000 Oct 1;48(3):649-56.
** 10 pts. CTV included prostate and pelvic nodes (obturator, hypogastric, internal & external iliac, presciatic, and presacral nodes to S2).
** Planning goals: LN + prostate 50 Gy, bowel 35 Gy (max 45 Gy), bladder and rectum 40 Gy (max 50 Gy)

## Treatment Planning

* PMID 15214533 -- Automatic beam angle selection in IMRT planning using genetic algorithm. (Li Y, Phys Med Biol. 2004)
** The results show that ABAS (automatic beam angle selection algorithm) is valid and efficient and can improve the dose distributions within a clinically acceptable computation time.

## Field Size

* PMID 14740973 -- Predictors of extracapsular extension and its radial distance in prostate cancer: implications for prostate IMRT, brachytherapy, and surgery. (Teh BS, Cancer J. 2003)
** 712 RP specimens
** Measurable ECE in 26% (median 2.00mm, range 0.5-12.00 mm)
** Conclusion: "This is the largest series in the literature thus far that quantitatively assesses radial extracapsular extension. Coverage of subclinical disease must be addressed carefully before successful implementation of intensity-modulated radiation therapy, brachytherapy, or prostatectomy in order to avoid geographical miss."

## Hypofractionation

* PMID 15890583 -- Individualized planning target volumes for intrafraction motion during hypofractionated intensity-modulated radiotherapy boost for prostate cancer. (Cheung P, Int J Radiat Oncol Biol Phys. 2005)
** Conclusion: PTV margins can be reduced significantly with daily online correction of prostate position. "Delivering a hypofractionated boost with this high-precision IMRT technique resulted in acceptable acute toxicity."

## Dose Constraints

* RTOG 0126
| Volume | Constraint |
| GTV (Prostate) | 100% to 79.2 Gy |
| PTV2 (GTV + 0.5 cm) | 98% to 79.2 Gy |
| CTV (Prostate/SV) | 100% to 50.4 Gy |
| PTV1 (CTV + 0.5 cm) | 98% to 50.4 Gy |
| Rectum | <50% to 60 Gy |
| Rectum | <35% to 65 Gy |
| Rectum | <25% to 70 Gy |
| Rectum | <15% to 75 Gy |
| Rectum | Dmax 84.7 Gy |
| Bladder | <50% to 65 Gy |
| Bladder | <35% to 70 Gy |
| Bladder | <25% to 75 Gy |
| Bladder | <15% to 80 Gy |
| Bladder | Dmax 84.7 Gy |
| Femoral head | Dmax 50 Gy |
| Penile bulb | Mean <52.5 Gy |
* Rectum = from the anus (at the level of the ischial tuberosities) for a length of 15 cm or to the rectosigmoid flexure. This generally is below the bottom of the sacroiliac joints.
* Bladder = contoured from its base to the dome