# Presentation: 204664

## Measuring Normal Tissue Effectsof Radionuclide Therapy

***Ruby Meredith, M.D., Ph.D.***
***Department of Radiation Oncology***
- University of Alabama at Birmingham

## What is the Tolerance of Normal Organs to Radiation ? 

**What is the Tolerance of Normal Organs to Radiation ?**** **

**Usually more tolerance for radionuclides than external beam - but not well studied**

## Organ Tolerance Data Comparison

_***External Beam***_*** ******	******	******	***_***Radionuclide***_
- TD5/5, TD 50/5			any toxicity
- Severe Late complications 	acute + late
- # patients reported			usually < 50
- +/- surgery				failed multiple 							therapies

## Organ Tolerance Data Comparison

_***External Beam***_***	******	******	***_***Radionulcide***_	2Gy/d x 5/week			single dose_>_1 MeV					lower energyHigh dose rate				low dose rateWhole/partial organ			mostly whole

## Normal Organ Tolerance to Radiation (cGy)

## Normal Organ Tolerance to Radiation (cGy)

## Normal Organ Tolerance to Radiation (cGy)

**Normal Organ Tolerance to Radiation (cGy)**

## How Accurate are Radionuclide DoseEstimates and Comparison Between Studies?

- 1.	Radionuclide dosimetry is less accurate 	than external beam.
- 2.	How accurate are tracer studies?
- 3.	Calculated dose is  biologic dose.
- 4.	How accurate are comparisons 	of radionuclide dose estimates?

## Radionuclide Dosimetry Is Less Accurate Than External Beam

- Radionuclide = less precise. e.g. parenchymal lung tumor difference in attenuation between lung vs. more dense tissue,										 *immediate full dose

## How Accurate Are Tracer Studies?

**Comparison of tracer-predicted vs. therapeutic radiation doses measured**

## 	Calculated Dose Is  Biologic Dose

_**Physical/biologic interaction factors**_heterogeneous distribution 	dose rate effectseffective range of radiation RBE, other characteristics

## Biologic Factors Affecting Tolerance 

- age, prior therapies, time since prior Rx,
- disease status-e.g. anemia,				marrow replacement; 			genetic factors and/or physiologic 		conditions - hypoxia that affect 				radio-sensitivity & repair

## Slide 13

##  Biologic Effectiveness ofRadionuclide Therapy 

- Agents/factors not contributing to radiation dose estimates.  Chemotherapy, other biologic response modifiers
- 																	
- Radiosensitizers,       Cytokines      Growth Factor    								Inhibitors
- 	BuDR	 		IL-1, IL-2	anti-EGFr

## 90Y-ChL6 Therapy ofBreast Cancer Xenografts 

**DeNardo et al., PNAS 1997**

## 	How Accurate are Comparisons of 		   Radionuclide Dose Estimates?	

**	****How Accurate are Comparisons of ****	****	****   Radionuclide Dose Estimates?****	**

**Variance in Dosimetry Methods  Include:  **
- a)	Measured organ volume as used in myeloablative 		studies (U. Washington) vs Phantom MIRD model 			b) 	Do calculations use computer programs- 			 MIRDOSE 2 or MIRDOSE 3

## 	How Accurate are Comparisons of 		   Radionuclide Dose Estimates?	

**	****How Accurate are Comparisons of ****	****	****   Radionuclide Dose Estimates?****	**

**Variance in Dosimetry Methods:****  **
- c)	Was attenuation correction applied for imaged ROI 	or a transmission scan technique used
- d)	Was background subtraction correction performed
- e)	What was  the frequency & appropriateness of data 	collection, if peak concentration missed  			lower dose estimate

## How Accurate are Doses Reported - 

**Wessels: marrow  +/-700% in 1980’s, **
**	****200% in 1990’s, now ~30%**
**reports of 7 institutions vs. his ****	****recalculation****	****of their data******** -35% - +6% **
**AAPM-Sgouros method,  0.19 blood in marrow ******** ~ 200 cGy vs. report whole blood had marrow dose ~600 cGy**

## When Does Imaging/Dosimetry Potential Have Great Impact ?

**When Does Imaging/Dosimetry Potential Have Great Impact ?**

**Good correlation of data with organ toxicity and/or anti-tumor effects.****	****	****	****	**
**When normal organ that can be “accurately” assessed is dose limiting. e.g.–myeloablative, lung, liver**

## Slide 20

## Slide 21

## When Does Imaging/Dosimetry Potential Have Great Impact ?

**When Does Imaging/Dosimetry Potential Have Great Impact ?**

**Tumor adjacent critical organ**
**Distribution – highly variable -****	**** ****131****I-anti-CEA**** >2x  faster T1/2 colorectal**
**Unknown distribution**

## Loculation, Then Resolved

**Loculation, Then Resolved**

## Catheter Eroded into Bowel

**Catheter Eroded into Bowel**

## RIT + External Beam RT

**RIT + External Beam RT**

- Hepatoma: 2100cGy + concurrent
- Adr/alternating  5-Fu + Flagyl,
- 2 months  dose chemo.
- 93-157mCi 131I-anti-ferritin
- 	400-1000cGy to nl liver (Order)

## Myeloablative  RIT + XRT

**Myeloablative  RIT + XRT**

**Leukemia: ( U. Washington)****	****	****	**** 76-612 mCi ****131****I-anti-CD45****	****	****	****CY + 1200cGy TBI, MTD liver 1050cGy**
**Breast, Prostate Ca ****131****I-anti-TAG-72****	****CY + 1320cGy TBI +/- Thiotepa, ****131****I-Ab ******** 142-990cGy to liver, ******** LFT also chemo only regimens (UAB)**

##          Tissue Tolerance 			to Re-Irradiation

**Acutely Responding Tolerate ****	****Full 2****nd**** Course (Months)**
**Late Responding Vary-****     No Recovery:  Heart, Bladder, Kidney.**
**Partial Recovery:  Skin, Mucous, Lung, ****	****	****Spinal Cord**
***Sem Rad Onc *****10(3): 200-209; 2000**

## Tolerance for 2nd Radiation Course - May be Close to that of Initial for Some Tissues

## Radionuclide Re-treatment

**Radionuclide Re-treatment**

- 89Sr > 5x, > 6 wk
- 90Y2B8 40mCi(3 pt.) unfavorable factors
- 131I-LYM-1,177Lu-CC49, 131I-CC49
- Trend = longer recovery,		 	mildly increased toxicity with			 re-treatment at short interval

## Summary & Conclusions

**More radionuclide data needed to improve dose/toxicity relationships.**
**improved data collection/processing methods will increase accuracy of dose estimates.**

## Summary & Conclusions

**Modifiers ******** chemotherapy- ****	****	****	****other radiosensitizing agents**
** ****prior Rx, disease status  affect toxicity & tumor response without changing dose estimates**