# Presentation: 137163

## Workshop on Advanced Technologies in Radiation Oncology

- Howard Sandler

## Prostate Cancer

- Model for use of advanced technologies
- Common, long follow-up, simple geometric relationship to critical structures

## Dose Limiting Toxicity

- _Rectal toxicity_
- What about bladder?

## Garg, et al. IJROBP

- 66:1294,2006

## Late Morbidity from Early Proton Study – median FU 13 yrs

- Gardner, et al. MGH J Urol167:123,2002

- GI Morbidity

## Shipley, et al. IJROBP 32:3,1995

- 50.4 photon + 25.2 CGE proton

- 50.4 photon + 16.8 photon

## RTOG 9406?

## Slide 8

## RTOG 9406

- 1084 patients from 34 institutions
- 36% had neoadjuvant hormonal rx
- By dose level, 5 yr OS is 89%, 87%, 88%, 89%, [95%*]

- * 3-yr OS

## RTOG 9406 – Biochemical Results

| Dose
level | Study  Group | n | 3-Year Rate
ASTRO | 5-Year Rate
ASTRO | 3-Year Rate
Nadir + 2 | 5-Year Rate
Nadir + 2 |
| --- | --- | --- | --- | --- | --- | --- |
| I
68.4 Gy | 1 | 73 | 68% | 58% | 86% | 69% |
|  | 2 | 34 | 65% | 55% | 85% | 67% |
| II
73.8 Gy | 1 | 95 | 82% | 67% | 90% | 78% |
|  | 2 | 112 | 48% | 38% | 78% | 60% |
|  | 3 | 94 | 52% | 47% | 78% | 64% |
| III
79.2 Gy | 1 | 102 | 73% | 59% | 91% | 70% |
|  | 2 | 68 | 61% | 52% | 85% | 73% |
| IV
74 Gy | 1 | 115 | 79% | 72% | 93% | 83% |
|  | 2 | 142 | 65% | 61% | 74% | 65% |
| V
78 Gy | 1 | 119 | 83% | - | 84% | - |
|  | 2 | 101 | 74% | - | 78% | - |

## RTOG 9406 – Toxicity

## RTOG 9406 – Toxicity

- Grade 3+
- By dose level
- 4%, 4%, 5%, 7%, 10%

## Slide 13

## DVH

**DVH**

**Dose-**
**Volume**
**Histogram**

## Grade ≥2 Rectal Morbidity at 70 Gy

- Grade ≥2 Rectal Morbidity at 70 Gy

- Huang, et al MD Anderson IJROBP 54:1314,2002

## Rectal Bleeding Requiring Laser Treatment or Transfusion

- (3DCRT)

- Peeters et al. IJROBP 61:1019, 2005

## Peeters et al. IJROBP 64:1151, 2006

## LKB Modelling of Dutch Study – Uses Entire DVH

- n = 0.13, TD50 81 Gy, m = 0.14, p=0.025

- Peeters et al. IJROBP 66:11, 2006

## Rectal Constraint

| Institution | Rectal Constraint |
| --- | --- |
| UM | <20% over 70, <50% over 50 |
| FCCC | <17% over 65, <35% over 40 |
| Wash U | <17% over 65, <35% over 40 |
| Wisconsin | <15% over 70 |
| Duke | <20% over 70 |
| Jefferson | <20% over 65, <40% over 50 |
| ROC | <20% over 65, <45% over 40 |
| UCSF | DVH-based |
| Mayo | <15% over 70, <30% over 60, <50% over 50 |

## 64 Gy

- 3 field
- Conv – open
- Conf – 16 mm
-   GTV-block margin
-   90% coverage
- HD vol reduced
-   by 40%
- Bladder toxicity NS

## Slide 21

## Modelling Data from Marsden Trial

- Dose-surface histograms
- 79 pts available
- Physical dose converted using α/β=3
- 1000 points per contour (= points per slice)

- Fenwick, et al IJROBP 49:473–480, 2001

## Slide 23

## Slide 24

## Randomized Trials

- Of higher dose vs. lower dose?

## Trial design
No hormonal therapy

***No hormonal therapy***

**PROG 9509**

**T1b-2b prostate cancer**
**PSA **_**<**_**15ng/ml**

**Proton boost **
**19.8 GyE**

**Proton boost **
**28.8GyE**

**3-D conformal photons **
**50.4 Gy**

**3-D conformal photons **
**50.4 Gy**

**Total prostate dose **
**70.2 GyE**

**Total prostate dose **
**79.2 GyE**

*r a n d o m i z a t i o n*

## Zietman, et al. JAMA2005;294:1233-1239

- Zietman, et al. JAMA2005;294:1233-1239

## Morbidity?

- Zietman, et al. JAMA2005;294:1233-1239

## Peeters et al. JCO 24:1990,2006 

- _Dutch Study Points_
- ASTRO no backdating
- 21% had hormonal rx
- 0 mm post PTV marginfrom 68-78 Gy
- Dose prescribed toisocenter

- Peeters et al. JCO 24:1990,2006

## Slide 30

## Randomized Trials

- Of altered fractionation vs. standard fractionation?

## Hypofractionation

## Hypofractionated Randomized Trial

- 16 Canadian regional centres
- 66 Gy in 33 fx vs. 52.5 Gy in 20 fx (2.62)
- Simple conformal rx
- Non-inferiority design with abs diff 7.5%

- Lukka, et al. JCO 23:6132,2005

## 7% worse in short arm

## RTOG 0415 Schema

- GS <7
- PSA <10

- 73.8 Gy/41 Fx

- 70 Gy/28 Fx

**RTOG 0415 Schema**

- n=800
- Endpoint is 5 Year BFFF
- Non-inferiority margin 7% (Control 85%, Exp 78%)

## Other Hypofractionation Randomized Trials

- CHHIP (Conv or Hypo High Dose IMRT)
- N=2200
- 3 arm study
- Standard vs. 2 hypofractionated arms

## Randomized Trials

- Particle vs. photon?
- No PSA era trials
- MGH proton, RTOG neutron

## Particle Therapy

- Protons
- Bragg peak
- Concerns
- ‘Wide’ penumbra due to scattering
- Neutron dose unless proton IMRT (scanned beam) is used (from p,n reaction)

## Carbon Ion

- Higher LET - ?Better for more “resistant” tumors
- ?Fewer fractions needed
- “The promising results obtained with carbon radiotherapy need confirmation in controlled clinical trials with large patient numbers comparing carbon ion RT with photon IMRT and proton RT taking also into account toxicity and quality of life.”
*Schulz-Ertner, et al Radiation Therapy With Charged Particles Semin Radiat Oncol 16:249,2006*

## Future Technologies/Areas for Study

- Particle therapy
- Carbon vs. Proton vs. Photon IMRT
- Hypofractionation
- Can the low α/β model for prostate be verified?
- NTCP modelling
- Randomized trials can help
- Target motion
- Issue for all externally delivered, highly conformal dose approaches