# Presentation: 301564

## 4D Radiotherapy

**4D Radiotherapy**

**Paul Keall**
**Virginia Commonwealth University**

- Adaptive 4D CT

## Outline

**Outline**

**Medical rationale**
**Basic science and technology**
**State-of-the-art**
**Future needs, directions and opportunities**
**Advice ...**

- Adaptive 4D CT

## Medical rationale

**Medical rationale**

**What is the purpose of your research?**

- Adaptive 4D CT

## What do we know?

**Where the ‘visible’ tumor is**
**To within 1 cm (on day of imaging study)**
**Where the microscopic tumor extends to**
**To within 1 cm**
**Where the patient’s skeleton is wrt the radiation beam**
**To within 1 cm**
**What the shape of the tumor is**
**To within 1 cm**
**Where the tumor is wrt the skeleton**
**To within 2 cm**

- Adaptive 4D CT

## What can we do about it?

**Reduce the uncertainties**
**Improved/functional imaging**
**Ongoing commitment to education**
**Daily 2D/3D imaging**
**Monte Carlo dose calculation/optimization**
**Intrafraction motion**
**Develop methods to account for residual uncertainties**
**Incorporate uncertainties into planning process**
**Probabilistic planning**
**Online planning**

- Adaptive 4D CT

## Why 4D?

**GI motion**

**Inter-observer **
**differences**

**Tumor growth**

**Tumor shrinkage**

**Tumor spread**

**Reoxygenation**

**Repair**

**Repopulation**

**Redistribution**

**Vascular growth**

**Weight loss**

**Cardiac motion**

**Hormone response**

**Diet**

**Bladder filling**

**Rectal filling**

**Intra-observer**
**differences**

**Skeletal motion**

**Respiratory motion**

**Weight gain**

**Respiratory motion**

**Why 4D?**

- Adaptive 4D CT

## Respiratory motion affects:

**All tumor sites in the thorax and abdomen**
**Lung cancer alone:**
**173 770 new cases in 2004 (ACS)**
**160 440 deaths (28% of cancer deaths)**
**15% five-year survival**
**Evidence of tumor dose response 50%/30 month LPFS at 85 Gy (Martel *****et al*****)**
**Strong evidence of lung dose response (many 100+ patient studies)**

- Adaptive 4D CT

## Problems of respiratory motion in radiotherapy

- Adaptive 4D CT

## The tumor moves with time 

**The tumor moves with time **

- Adaptive 4D CT

**Notes:**
Shown is a fluoroscopy video of a lung tumor. The patient was undergoing quiet respiration, though the tumor, visible just above the diaphragm, is moving 2 cm during inhale and exhale.  

3D methods do not account for this motion, which causes errors and inaccuracies during the imaging, planning and delivery of radiation.  

Thus, 4D methods are required.

## Distorted images, incorrect anatomical positions, volumes or shapes 

- Conventional	       With gated imaging

**Distorted images, incorrect anatomical positions, volumes or shapes**** **

- Keall *et al* Aust Phys
- Eng Sci Med 2002

- Adaptive 4D CT

**Notes:**
One of the problems with applying 3D techniques in the presence of respiratory motion occurs during imaging

This slide shows a conventional CT scan image on the left, and a gated CT scan image of the same patient on the right.  The tumor is seen above the diaphragm in the right lung.

In the conventional scan, because of respiration motion the tumor, lung and liver are interspersed, making tumor definition very difficult.

In the gated scan, the tumor is clearly seen, and boundaries can be confidently  drawn. 

## Treatment Planning: Large margins are added to the clinical target volume

**Treatment Planning: Large margins are added to the clinical target volume**

**Increases normal tissue dose and limits target dose**

**CTV**

-     Conventional       		With gating

**CTV**

- Adaptive 4D CT

**Notes:**
A second limitation of applying 3D techniques in the presence of respiratory motion occurs during planning

Because of the motion of the tumor during radiotherapy, if we do not account for this motion (we don’t during conventional radiotherapy)  we need larger radiation beams to cover the extent of the motion than if we used methods that explicitly accounted for this tumor motion during treatment.  

Larger radiation beams mean that more healthy lung is irradiated, increasing the chance of radiation-induced pneumonitis and limiting the tumor dose.

## IMRT Delivery: Interplay between anatomy and MLC leaf motion leads to motion artifacts

- Dose

- Position

- Adaptive 4D CT

**Notes:**
Problems also occur during radiation delivery.  

If we plan to deliver a smooth dose distribution to the tumor, as shown on the right, due to the interplay between the multileaf collimator used to shape the radiation beam and the tumor motion, the delivered dose has hot and cold spots.

Hot spots in the tumor can cause necrosis, and the presence of cold spots significantly lowers the chance of killing the tumor. 

## Basic science and technology

**Basic science and technology**

**What is the underlying scientific/technological basis of your research?**

- Adaptive 4D CT

##    “The explicit inclusion of the temporal changes in anatomy during the imaging, planning and delivery of radiotherapy” 

- 4D Radiotherapy Panel
- ASTRO 2003

**What is 4D radiotherapy?**

- Adaptive 4D CT

## The 4D radiotherapy process

**4D Radiotherapy**

**4D CT Imaging**

**4D Treatment Planning**

**4D Treatment Delivery**

- Acquisition of a sequence of CT image sets over consecutive phases of a breathing cycle

- The explicit inclusion of the temporal changes in anatomy during the imaging, planning and delivery of radiotherapy

- Designing treatment plans on CT image sets obtained for each phase of the breathing cycle

- Continuous delivery of the 4D treatment plans throughout the breathing cycle

**The 4D radiotherapy process**

- Adaptive 4D CT

## 4D Radiotherapy I:4D CT Imaging

- Adaptive 4D CT

## 4D CT imaging

- Adaptive 4D CT

## 4D CT images

- Vedam *et al* PMB
- 2003 48:45-62

- 8 respiratory phases
-   Peak inhale
-   Early inhale
-   Mid inhale
-   End inhale
-   Peak exhale
-   Early exhale
-   Mid exhale
-   Late exhale

**4D CT images**

- Adaptive 4D CT

## Slide 19

- Adaptive 4D CT

## 4D Radiotherapy II:4D Planning

- Adaptive 4D CT

## 4D Planning Flow Chart

**4D Planning Flow Chart**

- Adaptive 4D CT

## 4D PTVs

**4D PTVs**

- Adaptive 4D CT

## BEVs

**3D BEV**

**4D BEV**

**BEVs**

- Adaptive 4D CT

## 3D (solid) vs 4D (dashed) DVHs

- Adaptive 4D CT

## 4D Radiotherapy III:4D Delivery

- Adaptive 4D CT

## 4D radiotherapy delivery

- Adaptive 4D CT

## MLC leaf motion 

**3D ****	****	**** ****	****	****4D**

- Keall *et al* PMB
- 2001 46:1-10

- Adaptive 4D CT

**Notes:**
Shown in this slide are beam views of the multileaf collimator, used to shape the radiation beam before it hits the patient. 

If tumor motion is not explicitly accounted for, as shown on the left, the beam will need to be bigger to cover the tumor as it moves during the  radiation delivery.  Bigger beam equals more lung toxicity

4D methods, as shown on the right track the tumor during radiation delivery

## MLC leaf motion 

**3D IMRT****	****	**** ****	****	****4D IMRT**

- Adaptive 4D CT

**Notes:**
These 4D principles are directly applied to IMRT fields as well, where the beam is again tracking the tumor as the tumor moves up and down during respiration.  

## Tracking motion perpendicular and parallel to the MLC 

- Adaptive 4D CT

**Notes:**
Hot off the press are preliminary results showing the the ability to track tumor motion both parallel and perpendicular to the MLC leaf motion.

## Finite response time- need motion prediction

- Adaptive 4D CT

## Respiratory motion causes problems during the imaging, planning and treatment stages of radiotherapy
Several methods have been proposed to address respiratory motion
4D radiotherapy has some advantages over existing methods
There are still many unanswered questions ...

**Several methods have been proposed to address respiratory motion**
**4D radiotherapy has some advantages over existing methods**
**There are still many unanswered questions ...**

**4D radiotherapy summary**

- Adaptive 4D CT

## State-of-the-art

**State-of-the-art**

**How does your research fit into the overall scheme of medical research?**

- Adaptive 4D CT

## Respiratory motion solutions

**Breath-hold techniques (ABC/DIBH)**
**Uncomfortable for patients, limited applicability (MSKCC:  7/13 patients)**
**Increases treatment time (MSKCC:  17 to 33 minutes for conventional RT)**
**Respiratory gating**
**Residual motion within **
**    ****gating window**
**Increases treatment time**
**Baseline shift**
**4D Radiotherapy**
**Hardware/Software **
**   ****complexity**

- Adaptive 4D CT

**Notes:**
There are two existing methods that explicitly account for respiratory motion during radiotherapy. These are breathhold techniques and gating techniques, and have been successfully applied clinically.

However, both of these methods increase the treatment time, that causes accuracy as well as patient throughput problems. Breathhold techniques require patients to have adequate lung function and thus has limited applicability. Gating has other limitations explained in detail in the application. 

4D IMRT can potentially overcome these problems, though this solution is more complex.  

## Future needs, directions and opportunities

**Future needs, directions and opportunities**

**What is currently limiting your research or what change in****direction do you anticipate in the future?**

- Adaptive 4D CT

## Limitations

**Ethics/IRB**
**Length of grant review cycles**
**Industry support**
**We need them unless resource and time unlimited**
**Why isn’t my project the highest priority?**
**Distractions**

- Adaptive 4D CT

## Directions

**Incorporate recent scientific and technical developments **
**Greater scope**
**More general**
**More scientifically rigorous**
**Integrate with concurrent internal and external programs**

- Adaptive 4D CT

## Opportunities

**Many problems to solve**
**Many different ways to solve problems **

- Adaptive 4D CT

## NCI Roadmap

**A focus on the following initiatives will move the work of NCI through the process of discovery, development, and delivery toward the goal of eliminating suffering and death from cancer by 2015 ... **

- Adaptive 4D CT

## Advice

**Advice**

- Adaptive 4D CT

## 1999 $4500 VCU faculty grant-in-aid
2001 $20 000 ACS Inst. Research Grant
2002 $1.5 million NCI grant
2003 $400 000 industrial grant
2003 Co-I $1 million NCI grant
2004 Consultant $1 million NCI grant
2004 Co-I STTR
...

**2001 $20 000 ACS Inst. Research Grant**
**2002 $1.5 million NCI grant**
**2003 $400 000 industrial grant**
**2003 Co-I $1 million NCI grant**
**2004 Consultant $1 million NCI grant**
**2004 Co-I STTR**
**...**

**How did you get started?**

- Adaptive 4D CT

## Why get a grant?

**Promotion**
**Tenure**
**Independence**
**Invitations**
**Staff**
**Resources**
**Travel**
**Intangibles**

- Adaptive 4D CT

## What advice can you give?

**Write early**
**Write often**
**Work hard**
**Work smart**
**Think broadly**
**Good luck**

- Adaptive 4D CT

## And get a great team!

**And get a great team!**

**Ted Chung **
**Rohini George**
**Sarang Joshi**
**Vijay Kini**
**Radhe Mohan**
**Jeffrey Siebers**
**Sastry Vedam**
**Krishni  Wijesooriya**
**Jeffrey Williamson**

**ACS**
**NIH**
**MDACC**
**MGH**
**Philips Medical Systems**
**Standard Imaging**
**UNC**
**Varian Medical Systems**

- Adaptive 4D CT

## Another great team!

- Adaptive 4D CT