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Emami Out of Date?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. Brain 1. True Dose
2. Optic Nerve/Chiasm
2. Imaging
3. Brain Stem
4. Spinal Cord 3. Bio Markers
5. Ear 4. Data Sharing
6. Parotid 5. Lessons of QUANTEC
7. Larynx/Pharynx
8. Lung
9. Heart
10. Esophagus
11. Liver
12. Stomach/Small Bowel
13. Kidney
14. Bladder
15. Rectum
16. Penile Bulb
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 < 50 Gy < 20% Symptomatic
Constrictors dysphagia/
Mean aspiration
CNS/H&N Guidelines
CNS (200cGy/day):
Spinal Cord Max 5000 QUANTEC
Brain Max 7200 (partial) QUANTEC
Chiasm/optic nerve Max 5500 QUANTEC
Brainstem Max?<5400 (entire), V59 < 1-10cc QUANTEC
Cochlea/Inner Ear Mean 4500 QUANTEC
Parotid Glands Mean <2500 (both), mean >2000(1) QUANTEC
Submandibular Mean <3500 QUANTEC
Larynx Mean 4400, V50 27%, max 63-6600 QUANTEC
Pharyngeal Con Mean <5000 QUANTEC
Esophagus
Esophagus(cervical) V45<33%, Mean <3000 RTOG 0920 & 1106
Eyes(globe) Mean <3500, Max 5400 RTOG 0225 & 0615
TMJ/mandible Max 7000 or V75 <1cc, Max 6600 RTOG 0615 & 1106
Oral Cavity(non) Mean<3000, max 6000 RTOG 0920 & 1106
Oral Cavity(cancer) Mean <5000,V55<1cc,Max 6500 RTOG 0920
Lens Max 700 RTOG 0539
Retina Max 5000 RTOG 0539
Pituitary Gland Max 4500 Emami
Cauda Equina Max 6000 Emami
Thyroid 4500 T5/5
Trachea ?
CNS (Single Fraction)
Spinal Cord Max 1300 (3fx=2000) QUANTEC
Brain V12 < 5-10cc QUANTEC
Brainstem Max 1250 QUANTEC
Chiasm/optic nerves Max 1000 QUANTEC
Sacral plexus V18 < 0.035cc V14.4 < 5cc RTOG 0631
Cauda Equina V16< 0.035ccm V14<5cc 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 Max 5000 QUANTEC
Total Lung Mean < 2000-2300, V20<30-35% QUANTEC
Single Lung V5<60%, V20<-10%,Mean <800 QUANTEC
Bronchial Tree Max 8000 QUANTEC
Heart (breast Ca tx) V25 < 10% QUANTEC
Heart (lung Ca tx) V45<67%, V60<33% NCCN (2010)
Esophagus V60 < 33% Emami
Brachial Plexus V60<5% RTOG 0619
Ipsi Lung (breast tx) V25 <10% 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 V50 <5% RTOG GU consensus
Testis V3 < 50% 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: Compute model-based

Single-point: e.g. V20 NTCP estimates
Global: e.g. mean dose
Lessons from QUANTEC