A Review of QUANTEC

Normal Tissue Tolerances

MaryLou DeMarco, MS,CMD

Thomas J. Dilling, MD
Moffitt Cancer Center, Tampa FL

Learning Objectives
Understand:
What increased knowledge the QUANTEC
effort provides over the 1991 Emami normal
tissue tolerance tables
New/revised QUANTEC dose constraints,
for various organs
Incorporating new information into treatment
planning

Normal Tissue Tolerance

The Emami paper (1991)
Committee of experts to review known data,
provide guidelines
Some of the constraints we use come from
the old Emami paper
Emami used some clinical data to suggest
tissue tolerance
But back then they had comparatively poor
ability to deliver and measure the dose actually
delivered

Some data made up based upon

educated guesses
Emami B, et al. Int J Radiat Oncol Biol Phys 1991; 21: 109-22.

Emami Out of Date?

Move from 2D to 3D treatment planning
IMRT, Stereotactic, higher daily doses,
new TPS technology
Higher energy beams/better penetration
Improved ability to measure dose, new
algorithms, heterogeneity corrections
Increased use of combined
chemoradiotherapy
Numerous additional studies of tissue
tolerance

QUANTEC
Quantitative Analysis of Normal
Tissue Effects in the Clinic
Large committee of experts (n=57)
Convened by ASTRO / AAPM
Updated guidelines published in Red
Journal supplement (Vol 76, No. 3,
2010)
16 organ-specific papers
Several general principle papers

16 Organ-Specific Papers & 5 Vision Papers

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.

Brain
Optic Nerve/Chiasm
Brain Stem
Spinal Cord
Ear
Parotid
Larynx/Pharynx
Lung
Heart
Esophagus
Liver
Stomach/Small Bowel
Kidney
Bladder
Rectum
Penile Bulb

1. True Dose
2. Imaging
3. Bio Markers
4. Data Sharing
5. Lessons of QUANTEC

IMPORTANT POINTS
MANY details within each paper
Explication of available data
HOW TO CONTOUR structure
Affects how/whether you meet
constraints!

These are GUIDELINES

Your MDs might use something
different (tighter or looser constraints)

Discuss with your MDs!

CNS

3D treatment planning:

Spinal Cord (QUANTEC)

Brain (QUANTEC)
Chiasm/Optic Nerves (QUANTEC)
Brainstem (QUANTEC)
Cochlea/Inner Ear (QUANTEC)
Eyes (globe) (RTOG)
Lens (RTOG)
Retina (RTOG)
Pituitary Gland (Emami)
Cauda Equina (Emami)

Stereotactic Radiosurgery:

Spinal Cord (QUANTEC)

Brain (QUANTEC)
Brainstem (QUANTEC)
Chiasm/Optic Nerves (QUANTEC)
Sacral plexus (RTOG)
Cauda Equina (RTOG)

Brain Data Summary

Brain Proposed Constraints

Emami overly conservative (standard fractionation)
Structure

Point Max

Necrosis Risk

Brain

72 Gy

5%

Brain

90 Gy

10%

Brain

< 60 Gy

< 3%

SRS:
20+% risk when >5-10 cc get >12 Gy

Children: 18 Gy WBRT ! cognitive changes

Brainstem: neuropathy or necrosis

Entire brainstem can get 54 Gy
Smaller portions (1-10cc) to 59 Gy
SRS: Max 12.5 Gy = low (<5%) risk

Spinal Cord: myelopathy

Full cord cross-section

Reirradiation: 25% of
dose forgotten at 6 mos

Cervical cord more

sensitive than thoracic
cord?

Radiation Technique

Dose

Myelopathy Risk

Standard Fractionation

50 Gy

0.2%

Standard Fractionation

60 Gy

6%

Standard Fractionation

69 Gy

50%

SBRT (single fx)

13 Gy

1%

SBRT (3 fx)

20 Gy

1%

Optic Nerves/Chiasm: Optic Neuropathy

Standard Fractionation
Max < 55 Gy

Fraction size important

Greater age ! increased risk

SRS
Max <8 Gy single fraction appears safe
(and <12 Gy = <10% optic neuropathy)

Cochlea: hearing loss

Cochlea: hearing loss

Other factors
Cisplatinum (adjuvant or concurrent)
Consider constraining to 35 Gy

Increasing patient age

Better hearing ! increased hearing loss

QUANTEC Dose recommendations:

Mean 45 Gy (< 30% hearing loss)
SRS: Limit dose to 14 Gy (<25% hearing loss)

H&N:

Parotids (QUANTEC)
Submandibular glands (QUANTEC)
Larynx (QUANTEC)
Pharyngeal Constrictors (QUANTEC)
TMJ/mandible (RTOG)
Oral Cavity (RTOG)
Esophagus (cervical) (RTOG)
Thyroid (Emami)

Salivary Gland:
Long-term salivary function < 25%
Much data re: parotid gland sparing
Some data re: submandibular gland sparing
Sparing 1 parotid eliminates xerostomia (mean
dose < 20 Gy)
Mean dose both glands < 25 Gy

Sparing 1 submandibular gland reduces

xerostomia
Structure

Dose

Risk

Parotid (both)

Mean < 25 Gy

< 20%

Parotid (both)

Mean < 39 Gy

< 50%

Parotid (one)

Mean < 20 Gy

< 20%

Submandibular

Mean < 35 Gy

Larynx: Vocal dysfunction, aspiration, edema

Pharynx: symptomatic dysphagia & aspiration
QUANTEC Recommendations
Structure

Constraint

Risk

Symptom

Larynx Max

< 66 Gy

< 20%

Vocal Dysfunction

Larynx Mean

< 50 Gy

< 30%

Aspiration

Larynx Mean

< 44 Gy

< 20%

Edema

Larynx V50

< 27%

< 20%

Edema

Pharyngeal
Constrictors
Mean

< 50 Gy

< 20%

Symptomatic
dysphagia/
aspiration

CNS/H&N Guidelines

CNS (200cGy/day):
Spinal Cord
Brain
Chiasm/optic nerve
Brainstem
Cochlea/Inner Ear
Parotid Glands
Submandibular
Larynx
Pharyngeal Con
Esophagus
Esophagus(cervical)
Eyes(globe)
TMJ/mandible
Oral Cavity(non)
Oral Cavity(cancer)
Lens
Retina
Pituitary Gland
Cauda Equina
Thyroid
Trachea
CNS (Single Fraction)
Spinal Cord
Brain
Brainstem
Chiasm/optic nerves
Sacral plexus
Cauda Equina

Max 5000
Max 7200 (partial)
Max 5500
Max?<5400 (entire), V59 < 1-10cc
Mean 4500
Mean <2500 (both), mean >2000(1)
Mean <3500
Mean 4400, V50 27%, max 63-6600
Mean <5000

QUANTEC
QUANTEC
QUANTEC
QUANTEC
QUANTEC
QUANTEC
QUANTEC
QUANTEC
QUANTEC

V45<33%, Mean <3000

Mean <3500, Max 5400
Max 7000 or V75 <1cc, Max 6600
Mean<3000, max 6000
Mean <5000,V55<1cc,Max 6500
Max 700
Max 5000
Max 4500
Max 6000

RTOG 0920 & 1106

RTOG 0225 & 0615
RTOG 0615 & 1106
RTOG 0920 & 1106
RTOG 0920
RTOG 0539
RTOG 0539
Emami
Emami
4500 T5/5
?

Max 1300 (3fx=2000)

V12 < 5-10cc
Max 1250
Max 1000
V18 < 0.035cc V14.4 < 5cc
V16< 0.035ccm V14<5cc

QUANTEC
QUANTEC
QUANTEC
QUANTEC
RTOG 0631
RTOG 0631

Lung

Lung: Symptomatic Pneumonitis

Factors impacting on side effects
Current smoking is protective (anecdotal)
Chemotherapy increases risk

General QUANTEC Guidelines:

Limit V20 30 35%

Limit MLD 20 23 Gy
Limit central airways < 80 Gy (stenosis)
Mesothelioma:
V5 < 50%; V20 < 4-10%; MLD < 8 Gy

Recommend LENT-SOMA scoring of symptoms

Structure

Dose

Pneumonitis

Lung Mean

7 Gy

5% Risk

Lung Mean

13 Gy

10% Risk

Lung Mean

20 Gy

20% Risk

Lung Mean

24 Gy

30% Risk

Lung Mean

27 Gy

40% Risk

Heart: pericarditis & long-term cardiac mortality

Mostly breast/lymphoma data (high cure rate/long survival)

Whole heart to 3000 cGy ok without chemo (old lymphoma data)
Other factors:

Whole heart to 1500 cGy with Adriamycin

Age
Gender
Diabetes Mellitus
Smoking
High Blood Pressure
Cholesterol
Parental history of early MI

Pericarditis: Mean pericardium dose <2600 cGy, V30 <46%

Heart: QUANTEC guidelines

Mean < 26 (<15% pericarditis)
V30 < 46% (<15% pericarditis)
Breast Cancer:
V25 heart < 10% (<1% risk cadiac
mortality @15 years)

Lymphoma
Whole Heart < 15 Gy seems
prudent

Esophagus
Various metrics used in publications

Mean esophageal dose

V20
V35
Max dose
Esophageal length receiving full circumference dose
Length with 7000 Gy to 75% circumference
Not possible to identify single best threshold
volumetric parameter

Esophagus
Record V60 (Emami = V60<33%)
Minimize hot spots
Use CTCAE criteria to log toxicity
Esophagus

Constraint

Mean

< 34 Gy

V35

< 50%

V50

< 40%

V70

< 20%

Brachial Plexus
No QUANTEC data
RTOG 0619 =
Max 6600
V60 < 5%

Thoracic Guidelines in cGy

Spinal Cord
Total Lung
Single Lung
Bronchial Tree
Heart (breast Ca tx)
Heart (lung Ca tx)
Esophagus
Brachial Plexus
Ipsi Lung (breast tx)

Max 5000
Mean < 2000-2300, V20<30-35%
V5<60%, V20<-10%,Mean <800
Max 8000
V25 < 10%
V45<67%, V60<33%
V60 < 33%
V60<5%
V25 <10%

QUANTEC
QUANTEC
QUANTEC
QUANTEC
QUANTEC
NCCN (2010)
Emami
RTOG 0619
JHH

Liver
Patients (and livers) vary:
Healthy vs. unhealthy liver
Primary HCC vs. metastases

Hepatitis
Portal vein thrombosis
Prior arterial chemoembolization
Concurrent chemo
Tumor stage
Male/Female
Child-Pugh score (bilirubin, albumin, ascites)
QUANTEC Whole Liver
Mean 28-32 Gy (2 Gy fx)

Liver - SBRT
Primary Hepatocellular Carcinoma
Mean < 13 Gy (3 fx), <18 Gy (6 fx)

Mets
Mean < 15 Gy (3 fx), <20 Gy (6 fx)

Other guidelines:
Dmax < 15 Gy (< 5% classic RILD)
Mean < 6 Gy for primary, child-Pugh B, in
4-6 Gy fx s
15 Gy to 700 mL normal liver (3-5 fx)

Kidney
Long latency period:
Toxicity under-reported?

Acute toxicity subclinical

Kidney Recommendations
Kidney (bilateral):
V28 < 20%
V23 < 30%
V20 < 32%
V12 < 55%
Mean < 18 Gy
If mean kidney dose to 1 kidney is > 18 Gy, then
constrain remaining kidney to V6 < 30%

Stomach/Small Bowel
How to contour small bowel
(individual loops vs one large
region in peritoneum)?
Stomach/Small Bowel move day to
day

Stomach/Small Bowel
QUANTEC dose guidelines
Stomach
D100 (whole stomach) < 45 Gy ! 5-7% risk ulceration
SBRT: V22.5 <4% (or 5cc)
SBRT: Dmax <3000 Gy (3 fx)

Small Bowel:
V15 Gy <120 cc (contouring individual bowel
loops)
V45 Gy <195 cc (contour peritoneal space)
Single-Fx SBRT: V12.5 <30 cc (avoid
circumferential dose)
SBRT Max <3000 Gy (3-5 fx)

GI Constraints (Conventional Fx)

Structure

Constraint

Liver (healthy)

Mean < 3200 cGy

Liver (hepatocellular carcinoma)

Mean < 2800 cGy

Kidney (bilateral)

Mean < 1800 cGy

Whole Stomach

< 4500 cGy

Small Bowel

V45 < 195 cc

Colon

Max 5500 (Emami)

Bladder
Poor data re: partial volume XRT
(bladder motion not accounted for)
Confounding factors
Pre-RT GU toxicity
Smoking history, obesity, black race
Age, DM, HTN, PID not correlative
Structure

Constraint

Whole Bladder

V80 < 15%

Whole Bladder

V75 < 25%

Whole Bladder

V70 < 35%

Whole Bladder

V65 < 50%

Penile Bulb
Prudent to keep mean dose to 95% of
volume to <50 Gy
Difficult to define anatomically
QUANTEC Recommendations
Mean dose to 95% of PB < 50 Gy
D90 < 50 Gy
D70 < 70 Gy
No hot spots

Rectum
QUANTEC dose guidelines:
V50 < 50%
V60 < 35%
V65 < 25%
V70 < 20%
V75 < 15%

GU Guidelines:
Femoral Heads
Testis

V50 <5%
V3 < 50%

RTOG GU consensus
RTOG 0630

Rectum: (QUANTEC)
V75 < 15%
V70 < 20%
V65 < 25%
V60 < 35%
V50 < 50%
Bladder: (QUANTEC)
V80 < 15%
V75 < 25%
V70 < 35%
V65 < 50%
Penile Bulb: (QUANTEC)
Mean < 50 Gy
D90 < 50
D60 < 70
No hot spots more than prescribed dose

Lessons from QUANTEC

Need a peer-reviewed central
repository of
Dose-volume constraints
Contouring standards
Atlases
Contouring standards
Toxicity grading schemas
Endpoint definitions
Toxicity data/rates
From TPS, directly calculate risks of
toxicity for individual patient

Lessons from QUANTEC

Discard
spatial,
anatomical,
physiological
data

3D dose distribution

Extract unambiguous data:

Single-point: e.g. V20
Global: e.g. mean dose

Compute model-based
NTCP estimates

Lessons from QUANTEC