All the late effects are not described here

2.  Radiation therapy is an integral part of cancer
treatment
 70% of all cancer-patients need radiation therapy at
some point of the time
 With advances in treatment modalities , number of
long-term cancer survivors has significantly Increased
and they are at increased risk of developing radiation
induced late toxicities

3.  Early effects result from the death of a large number
of cells and occur within a few days or weeks of
irradiation in tissues with a rapid rate of turnover
 The time of onset of early reactions correlates with
the relatively short life span of the mature functional
cells
 Examples-
 Epidermal Layer Of The Skin
 Gastrointestinal Epithelium
 Hematopoietic System

4.  Late effects appear after a delay of months or years
 Occur predominantly in slowly proliferating tissues,
such as lung, kidney, heart, liver and central nervous
system
 The difference between the two types of lesions lies in
their progression:
 Acute damage is repaired rapidly because of the rapid
proliferation of stem cells and may be completely
reversible
 Late damage may improve but is never completely
repaired

5.  If intensive fractionation protocols deplete the stem cell
population below levels needed for tissue restoration, an
early reaction in a rapidly proliferating tissue may persist
as a chronic injury
 This is a late effect consequent to, or evolving out of a
persistent severe early effect
 The earlier damage is most often attributable to an
overlying acutely responding epithelial surface
 Example –
Fibrosis or necrosis of skin consequent to desquamation
and acute ulceration

7.  The response of a tissue or organ to radiation depends
primarily on 3 factors:
1) The inherent sensitivity of the individual cells
2) The kinetics of the tissue as a whole of which the
cells are a part
3) The way the cells are organized in that tissue

8. The inherent sensitivity of the
individual cells

9.  Two systems are typically used to classify tissue
radio sensitivity in terms of population kinetics
and tissue architecture:
 Casarett’s classification
 Michalowski’s classification

10.  Classification of mammalian cell radio sensitivity
based on histologic observation of early cell death
 Divided parenchymal cells into four major
categories, numbered I through IV

12. Hierarchical model- 3 type of cells
 Stem cells:
 Capable of unlimited proliferation and escape
senescence because of telomere shortening by the
enzyme telomerase
 Example: crypt cells in intestinal mucosa
 Functional cells:
 Fully differentiated
 Usually incapable of further division and die after a
finite life span
Example: granulocytes, villi of intestinal mucosa

13.  Maturing partially differentiated cells:
 Descendants of stem cells
 Still multiplying as they complete the process of
differentiation
Example:
Erythroblast
Granuloblast

14.  Flexible tissues (F type population) - No
compartments or no strict heirarchy
 Eg: liver, thyroid and dermis
 Rarely divide under normal conditions
 But can be triggered to divide by damage to the tissue
or organ

15.  Time dose parameters determining normal tissue
tolerance are:
 Total dose
 Overall duration of treatment
 Size of dose per fraction
 Frequency of dose fractionation
 Size of dose per fraction and fractionation frequency
determine the rate of dose accumulation
 Intensity of acute reaction depends upon rate of cell
kill & cell survival through proliferation of surviving
stem cells depends on dose accumulation

16.  Late reaction occurs in tissues with slow cellular turnover
Eg. Spinal Cord
 No depletion of cells in late reacting tissues even if full
course of RT is complete
 Hence overall Rx time as well as dose accumulation has
little role in severity of late reaction
 Instead severity of late reaction is dominated by size of
dose per fraction and interfraction interval
 As overall treatment time increases the probability of
tumor control decreases / isoeffective dose for tumor
control increases

18.  The response of normal tissues to irradiation cannot be
simply explained by the number of cells “killed”
 The spatial distribution of dose to a normal tissue is crucial
 This is often expressed in terms of tissue “architecture”
 The severity of radiation-induced normal-tissue damage
depends on the volume of tissue irradiated - “volume
effect” & dose fractionation used

19.  FSU is a concept used to model the radiation response
of normal tissue
 It is a compartment of an organ that performs part of
the organ function
 For some tissues FSUs are discrete, anatomically
delineated structures whose relationship to tissue
function is clear
 Example : Nephron in kidney, lobule in liver, acinus in
lung

20.  In others FSUs have no clear anatomic demarcation
 eg: skin, mucosa, spinal cord
 Minimum number of FSUs required to maintain
tissue function is Tissue Rescue Unit

21. SERIAL ORGAN
 FSUs arranged in series in
serial organ
eg: spinal cord
 Radiation damage shows
binary response
-Threshold dose below which
there is normal function,
above there is loss of function
 Marked volume effect
PARALLEL ORGAN
 In parallel organs FSUs
are not arranged serially
eg: liver, kidney
 Threshold volume below
which no functional
damage even after high
dose radiation
 A graded response would
be expected with a lesser
effect of volume

23.  When the increase in ROS production exceeds the
antioxidant capacity of the cell, the intracellular
environment becomes strongly oxidizing
 There is persistent upregulation of transcription
factors-
 Hypoxia-inducible factor-1α (HIF-1α)
 Nuclear factor κB (NF κB)
 Cytokines-TGF-β

24.  These molecules all contribute to vascular changes,
inflammation & cell death
 Their roles in complex signalling pathways suggest that
early changes in the activity of these molecules may
also contribute to the disease process of latent injury

26.  While a causal link between chronic oxidative stress
and radiation-induced late normal tissue injury
remains to be established, there is a growing body of
evidence in support of the hypothesis that chronic
oxidative stress might serve to drive the progression of
radiation-induced late effects

27.  The irradiated tissues show a dynamic population of
different inflammatory cell types throughout the
“latency” period
 It suggests that, on a cellular level , radiation injury is
an on-going disease process

28.  Conclusion: These studies clearly demonstrate the
early and persistent elevation of cytokine production
following pulmonary irradiation
 Perpetual cascade of cytokines produced Prompt
collagen genes to turn on  cytokines persist until the
expression of late effects becomes apparent
pathologically and clinically

29.  Exposure to ionizing radiation causes damage to
endothelial cells and vascular structural elements, causing
increased vascular permeability
 This vascular dysfunction results in edema as well as
decreased perfusion  Hypoxia
 Hypoxia increase recruitment of inflammatory cells Which
produce ROS  Increase tissue hypoxia by consuming the
available oxygen
 It results in activation of HIFs (HIF-1β,VEGF etc) 
Endothelial cell damage  Increasing vascular permeability
resulting in leakage of fibrin into the extracellular matrix

30.  From a historical point of view, the first formal attempt
to address normal tissue tolerance to radiation, was
carried out by Rubin and Cassarett 1975
 They introduced TD 5/5 and TD 50/5
 TD 5/5 – The probability of 5 % complications within
five years from treatment
 TD 50/5- The probability of 50% complication within
five years

31.  Emami et.al,1991 identified 28 critical sites of normal
tissue
 They used only conventional fractionation schedule
 The most clinically important i.e., severe endpoint was
chosen
 They arbitrarily divided organs into 1/3rd ,2/3rd and
whole organ
 Only adult tissue tolerance was considered

34.  To review the available literature of the last 18 years
on volumetric/dosimetric information of normal tissue
complication
 To provide a simple set of data to be used by the busy
community practitioners of radiation oncology,
physicists, and dosimetrists
 To provide reliable predictive models on relationships
between dose-volume parameters and the normal
tissue complications to be utilized during the planning
of radiation oncology

37.  Clinical significance:
 The acute and late effects of radiotherapy on the brain
are common and represent a significant source of
morbidity
 End points :
 Radiation necrosis - Radiation necrosis of the brain
typically occurs 3 months to several years after
radiotherapy (median 1–2 years)
 Asymptomatic radiologic changes as seen on serial
magnetic resonance imaging (MRI) scans

38.  Pathology:
 Histopathologic changes that occur within the first year
are most likely to involve white matter
 Beyond 6 to 12 months, the gray matter usually shows
changes accompanied by vascular lesions such as
telangiectasia and focal hemorrhages
 A mixture of histologic characteristics is likely to be
associated with radionecrosis , which manifests from 1 to
2 years postirradiation, accompanied by cognitive defects

39.  Dose/volume/toxicity:
 For standard fractionation a dose response
relationship appears to exist
Dose
(Gy)
BED (Gy) Necrosis
%
72(60-
84)
120(100-
140)
5
90(84-
102)
150(140-
170)
10

41.  In SRS of brain lesions, normal tissue toxicity appears
to be a function of -
 Dose
 Volume
 Location in the brain

42.  RTOG 90-05
 Goal- To determine maximum tolerated dose as a
function of maximum diameter of the lesion
Max
tolerated
dose (Gy)
Diameter
(cm)
Late
unacceptabl
e toxicities
(%)
≥24 ≤2 10
18 2.1-3 14
15 3.1-4 20

43.  The results of dose–volume studies of the
development of “radionecrosis” following single-
fraction radiosurgery shows that the crude rate of
radionecrosis is a function of volume irradiated
 These results suggest that the rate of complications
increases rapidly as the V12 increases beyond 5 to 10
cm3

44.  The location of the lesion is important as the severity
of expressed damage is greater in the more eloquent
parts of the brain
 For a V12 of 10 cm3 complication rate *was:
<5% >20%
Frontal
Temporal
Parietal
Brainstem
Thalamus
Basal ganglia
*Flickinger et al.

45.  Factors affecting risk:
 Younger age is associated with a higher risk of
neurocognitive decline
 Female gender
 Neurofibromatosis-1 (NF1) mutation
 Extent of surgical resection
 Hydrocephalus
 Concomitant chemotherapy (especially methotrexate)
 Location
 Volume of brain irradiated

46.  Recommended dose volume limit
Volume
Segmente
d
Irradiatio
n Type
Endpoint Dose Or Dose
Volume
Parameters
Rate %
Whole
organ
3DCRT Symptom
atic
Necrosis
Dmax <60 <3
Whole
organ
3DCRT Symptom
atic
Necrosis
Dmax 72 5
Whole
organ
3DCRT Symptom
atic
Necrosis
Dmax 90 10
Whole
organ
SRS Symptom
atic
Necrosis
V12 <5-
10ml
<20

47.  Clinical Significance:
 Irradiation of the brain, base of the skull, and the neck
can deliver a significant dose to the brainstem, which
is frequently the dose-limiting structure
 End Points:
 Specific cranial neuropathies
 Focal motor, sensory, or balance deficits
 Mild to life-threatening Global dysfunction

48. Volume
Segmented
Irradiation
Type
Endpoint Dose Or Dose
Volume
Parameters
Rate %
Whole organ 3DCRT Permanent
cranial
neuropathy or
necrosis
D max <54 <5
Whole organ 3DCRT Permanent
cranial
neuropathy or
necrosis
D1-
10ml
≤59 <5
Whole organ 3DCRT Permanent
cranial
neuropathy or
necrosis
Dmax <64 <5
Whole organ SRS Permanent
cranial
neuropathy or
necrosis
Dmax <12.5 <5

49.  Clinical Significance:
 The optic nerves and chiasm frequently receive a
substantial dose during therapeutic irradiation of
the brain, base of the skull, and head and neck
targets
 End Points:
 The primary end point for radiation-induced optic
neuropathy (RION) is visual impairment

50.  Dose/volume/toxicity:
 The risk of RION appears to rise steeply past 60 Gy
 Most proton series have reported a very low incidence
of RION, and a threshold dose in the range of 55 to 60
CGE has been observed
 The risk of RION appears to be related to the fraction
size *
*Parsons et al.
DOSE FRACTION
SIZE
OPTIC
NEUROPATHY
≥60 Gy <1.9 Gy 11 %
≥1.9Gy 47 %

51.  Factors Affecting Risk:
 There appears to be an increased risk of RION with
increasing age
 Special situations:
 RION may occur at lower doses in patients with pituitary
tumors as low as 46 Gy at 1.8 Gy/fraction*
 The average latency was 10.5 in pituitary targets and 31
months (range 5 to 168 months) in nonpituitary targets
*Mackley et al., van den Bergh et al

52.  The estimate by Emami et al of a 5% risk of blindness
within 5 years of treatment for a dose of 50 Gy
appears inaccurate
 The QUANTEC review suggests that the incidence of
RION was unusual (<2%) for Dmax < 55 Gy
Whole organ 3DCRT OPTIC
NEUROPATHY
Dmax <55 <2%
Whole organ 3DCRT OPTIC
NEUROPATHY
Dmax 55-60 3-7%
Whole organ 3DCRT OPTIC
NEUROPATHY
Dmax >60 >7-20%
Whole organ SRS OPTIC
NEUROPATHY
Dmax <12 <10 %

53.  Clinical significance:
 Portions of the spinal cord and canal are often
included in radiotherapy fields during treatment of
malignancies involving the neck, thorax, abdomen,
and pelvis
 End points:
 Diagnosis of myelopathy is based on the appearance
of signs/symptoms of
- Sensory or motor deficits
- Loss of function
- Pain
 Radiation myelopathy rarely occurs <6 months after
completion of radiotherapy and, in most cases,
appears within 3 years

54.  Dose/Volume/Toxicity
Data:
 Rate of myelopathy
appears very low below
total doses of 50 Gy at 2
Gy/#

55.  Of the 1,400 cases of spinal radiosurgery
presented in the published literature, there are
only 12 reported instances of radiation-induced
myelopathy, equalling a crude rate of 0.8%
 Factors Affecting Risk:
 Immature cord is more susceptible to radiation-
induced complications and the time to
manifestation of damage is shorter

56.  Special Situations:
 The need to re-irradiate previously treated cord is often
encountered in the setting of recurrent spine metastases
 The re-irradiation tolerance model* estimates a recovery of
34 Gy (76%) - 1year
38 Gy (85%) - 2 years
45 Gy(101%) - 3years
* Ang Kk et.al., Extent and kinetics of recovery of occult spinal
cord injury.

57.  Recommended Dose–Volume Limits:
Volume
Segmented
Irradiation
Type
Endpoint Dose Or Dose
Volume
Parameters
Rate %
Partial organ 3DCRT myelopathy Dmax 50 0.2
Partial organ 3DCRT myelopathy Dmax 60 6
Partial organ 3DCRT myelopathy Dmax 69 50
Partial organ SRS (SF) myelopathy Dmax 13 1
Partial organ SRS(hypo-
fractionation)
myelopathy Dmax 20 1

58.  Clinical Significance:
 In radiotherapy of head and neck tumors, the parotid,
submandibular, and minor salivary glands often receive
substantial doses of radiation
 End Points:
 Xerostomia (dry mouth secondary to inadequate saliva
production)
 Recommended Dose–Volume Limits:
 Severe xerostomia (long-term salivary function <25% of
baseline) can be avoided if Dmean of one parotid gland <
20 Gy or if both glands Dmean < 25Gy
 Dose to the submandibular glands <35 Gy may reduce
the severity of xerostomia

59.  End Points:
 Laryngeal edema
 Vocal dysfunction
 Dysphagia, resulting from laryngeal and/or
pharyngeal dysfunction
 Factors Affecting Risk:
 The addition of concurrent chemotherapy to high-
dose RT appears to at least double the risk of
laryngeal edema and dysfunction

60.  Recommended Dose–Volume Limits:
Larynx
Volume
Segmented
Irradiation
Type
Endpoint Dose Or Dose
Volume
Parameters
Rate %
Whole organ 3DCRT VOCAL
DYSFUNCTION
Dmax <66 <20
Whole organ 3DCRT ASPIRATION Dmea
n
<50 <30
Whole organ 3DCRT EDEMA Dmea
n
<44 <20
Whole organ 3DCRT EDEMA V 50 <27% <20
Pharyngeal
constrictors
3DCRT Dysphagia and
aspiration
Dmea
n
<50 <20
Pharynx

61.  Clinical Significance :
 The lung’s primary function is the exchange of oxygen for
carbon dioxide
 End points:
 Two distinct clinical stages are recognized in radiation-
induced lung disease:
-Early-radiation pneumonitis
-Chronic radiation fibrosis
 Radiation pneumonitis usually occurs about 4–12 weeks
after completion of radiation therapy
 Fibrous changes take 6–24 months to evolve but usually
remain stable after 2 years

62. RADIATION
TYPE 1 pneumocytes
destroyed
Production of cytokines, protease,
and growth factors
Acute pneumonitis
Increased ROS/RNS production
Increases TGF Beta production
Continuing
inflammation
Radiation induced lung
fibrosis
Destruction of
endothelium
Neovascularization
Starts at 2
weeks
2- 4weeks
6-8weeks

63.  The QUANTEC publication reviewed >70 published
articles looking at both mean lung doses and Vx
parameters
 It demonstrated no clear threshold dose for
symptomatic Radiation pneumonitis
 20% risk of RP for a MLD 20 Gy
 In addition, multiple Vx values have been
investigated for predicting RP but the data are not
as consistent as the data for mean lung doses
 V20 is most useful parameter for predicting the
risk of RP , V20 ≤ 30%

64.  The risk of RT-associated lung injury was <10% to
15% after lung SBRT with a MLD of the combined
lungs <8 Gy and (V20) <10% -15%
 Incidence of Bronchial stenosis was more when
compared to conventional fractionation
Zhao et al.

65. • Long term
corticosteroid
therapy
• Azithromycin 250
mg daily/ 500 mg
alternate days
• Chest percussion
• Postural
drainage
• Inhaled
mannitol
• Inhaled 4-7%
• hypertonic
• saline
• Regular exercise
• Pneumococcal
vaccine
• Influenza
vaccine
General
supportive
care
Mobilisation
of airway
secretions
Anti-
inflammatory
therapy
Acute
exacerbations
Management

66.  Clinical Significance:
 The heart is a muscular organ typically located in the left hemi thorax
 Survivors of breast cancer and Hodgkin Disease (HD) are at a greater
risk of RIHD as they have a relatively longer cancer specific survival
 Symptomatic cardiac disease after radiation occurs in approximately
10% of the patients
 End Points :
 Radiation-induced cardiac injury includes:
-Pericarditis (Most Common)
-CHF
-Restrictive cardiomyopathy
-Valvular insufficiency
-CAD, ischemia & infarction
 Long term follow up is essential as the incidence of radiation induced
heart disease begins to increase 10 years after radiation

68.  Factors Affecting Risk:
 Anthracycline chemotherapy can exacerbate
radiation-elated cardiac toxicity
 Interaction with topoisomerase 2a (an enzyme
which regulates DNA winding during cell
proliferation) is the molecular basis of
anthracycline induced cardio toxicity

69. Volume
Segmented
Irradiation
Type
Endpoint Dose Or Dose
Volume
Parameters
Rate
%
Pericardium 3DCRT Pericarditis Mean
dose
<26 <15
Pericardium 3DCRT Pericarditis V30 <46% <15
Pericardium 3DCRT Pericarditis V30 <30% <5
Whole
organ
3DCRT Long term
cardiac
mortality
V25 <10% <1

70.  The treatment is also in the same lines as the treatment of
these diseases in non-irradiated patients, but the prognosis
may be slightly worse in irradiated patients

71.  Clinical Significance :
 The liver is a vital organ, involved in the
metabolism of ingested nutrients
 There is no effective treatment to reverse the
process of radiation-induced liver disease (RILD)
therefore, prophylaxis and prevention are best

72.  Classical RILD (patients
without underlying liver
disease):
 Fatigue
 Abdominal Pain
 Increased abdominal girth
 Hepatomegaly
 Anicteric ascites
 Isolated elevation of ALP
out of proportion to other
liver enzymes
 Non-classical(patients
with underlying liver
disease) RILD:
 Jaundice
 Markedly elevated serum
transaminase

73.  Pathology:
 Liver biopsy of a patient with RILD may show
endothelium swelling
 Terminal hepatic venule narrowing
 Sinusoidal congestion
 Parenchymal atrophy of zone
 Proliferation of collagen
 Treatment :
 No therapy has been shown to prevent or to modify
the natural course of the disease
 Treatment is mainly directed at control of symptoms

74. Volume
Segmented
Irradiatio
n Type
Endpoint Dose Or Dose Volume
Parameters
Rate
%
WHOLE
LIVER-GTV
3DCRT CLASSIC RILD Mean dose <30-32 <5 EXCLUDING
HCC OR PRE
EXISTING
LIVER DISEASE
WHOLE
LIVER-GTV
3DCRT CLASSIC RILD Mean dose <42 <50
WHOLE
LIVER-GTV
3DCRT CLASSIC RILD Mean dose <28 <5 IN PTS WITH
HCC OR PRE
EXISTING
LIVER DISEAES
WHOLE
LIVER-GTV
3DCRT CLASSIC RILD Mean dose <36 <50
WHOLE
LIVER-GTV
SBRT CLASSIC RILD Mean dose <13 <5 3# FOR
PRIMARY
LIVER CANCER
WHOLE
LIVER-GTV
SBRT CLASSIC RILD Mean dose <15 <5 3# FOR
PRIMARY
LIVER METS>700ml
Liver
SBRT CLASSIC RILD

75.  End Points:
 Acute radiation nephropathy
 Chronic radiation nephropathy
 Benign hypertension
 Malignant hypertension
 Hyper reninemic hypertension
Volume
Segmented
Irradiation
Type
Endpoint Dose Or Dose Volume
Parameters
Rate
%
B/L whole
kidney
3DCRT RENAL
DYSFUNCTION
Mean dose <15-18 <5
B/L whole
kidney
3DCRT RENAL
DYSFUNCTION
V12
V20
<55%
<32%
<5

76.  End Points :
- Dysphagia
- Stricture
- Dysmotility
- Necrosis or fistula
 Factors Affecting Risk :
 Greater rates of acute esophagitis seen with
Hyperfractionation
Concurrent chemotherapy
Increasing age
 Acute esophageal toxicity was the greatest predictor of late
toxicity
 Recommended Dose–Volume Limits :
 Given the available data, there are no strict dose–volume
limits for the esophagus
 Intergroup trial, RTOG 0617, has recommended Dmean <34
Gy

77.  END POINTS:
 Late radiation-induced toxicity to the stomach can
include dyspepsia and ulceration
 Ulceration and segmental enteritis that can lead
to stenosis of the bowel lumen, with varying
degrees of obstruction during the chronic period
 Factors affecting risk :
 Total dose (>40 - 50 Gy)
 Fractional dose
 Prior abdominal surgery
 concurrent chemotherapy

78.  Pathology:
 Late bowel reactions involve all tissue layers and
are caused by atrophy of the mucosa caused by
vascular injury
 Overgrowth of the fibromuscular tissue with
stenosis and serosal breakdown and adhesion
formation may occur
 Fibrosis and ischemia are typical late
manifestations

79.  Recommended dose volume limits
Volume
Segmented
Irradiation
Type
Endpoint Dose Or Dose
Volume Parameters
Rate %
STOMACH
WHOLE
ORGAN
3DCRT ULCERATIO
N
D Max <45 <7
SMALL BOWEL
INDIVIDUAL
BOWEL
LOOPS
3DCRT ≥ Grade 3 V15 <120ml <10
BOWEL BAG SBRT ≥ Grade 3 V45 <195ml <10

80.  End Points: Late effects
Global injury
 Dysuria
 Frequency
 Urgency
 Contracture
 Spasm
 Reduced
Flow
 Incontinence
Focal injury
 Haematuria
 Fistula
 Obstruction
 Ulceration
 Necrosis

81.  Factors Affecting Risk:
 Prior pelvic surgery can result in increased risk of bladder
toxicity as a direct result of bladder or urethral trauma
and/or denervation of the bladder
 SBRT:
 In study by *King et.al., in Ca Prostate patients after SBRT
(7.25 Gy × 5)
 Grade 1 to 2 genitourinary toxicity occurred in 28%
 Grade 3 toxicity was reported in 3%
 Urinary incontinence , complete obstruction, or persistent
hematuria was not observed
*King CR, et al. Long-term outcomes from a prospective trial of stereotactic body
radiotherapy for low-risk prostate cancer

83.  There is no preventive modality to decrease the
incidence of radiation-induced hemorrhagic
cystitis except dose modification
 Prevention of radiation-induced hemorrhagic
cystitis has been investigated using various oral
agents (steroids, vitamin E, trypsin and Orgotein),
but efficacy has not been clearly demonstrated

84.  End Points:
 Bleeding (MC)
 Rectal ulceration
 Fistula
 Stricture and decreased rectal compliance
 Factors Affecting Risk:
 Diabetes
 Vascular disease
 Inflammatory disease
 Age
 Prior abdominal surgery

85. RECTUM BLADDER
V50 <50 (1/2)
V60 <35 (1/3)
V65 <25 (1/4) 1/2
V70 <20 (1/5) 1/3
V75 <15 (1/6) 1/4
V80 --- 1/5
DMax <65

86.  Treatment:
 Non-invasive treatment-
 NSAIDs
 Anti-oxidants
 Sucralfate
 Short chain fatty acids
 Hyperbaric oxygen
 Invasive treatment :
 Ablative procedures like formalin application
 Endoscopic YAG laser coagulation or argon plasma
coagulation
 Surgery

87.  Urinary Morbidity
And Bladder D2cc:
 For doses > 80Gy
EQD2 to D2cc
bladder there is a
clinically significant
increase in ≥G2
morbidity
*Tanderup K. et al. 2014

88.  Rectal Bleeding And Rectum D2cc :
 Rectal bleeding correlated significantly with dose
 The dose response was shallow below 70Gy
 For doses above 70-75Gy there is a steep increase in
risk of rectal bleeding

89.  Chronic radiation dermatitis is often permanent,
progressive, and potentially irreversible with substantial
impact on quality of life

91.  At present after surviving from a primary
malignancy, 17%–19% patients develop second
malignancy
 Reasons:
 Continued lifestyle
 Genetic susceptibility
 Treatment modality
 RT contributes to only about 5% of the total
treatment related second malignancies

92.  Contributing factors:
 Radiation exposure during childhood significantly increases
the risk of second malignancy as compared to older
population
 Gender - Females have a greater propensity to develop RISM
 Radiation technique &Type of radiation
 Screening and prevention:
 In many countries, recommendations on screening for second
malignancies (especially breast cancer) have been developed
based on consensus rather than evidence based
 Effective screening is only possible with better understanding
of the pathogenesis of treatment-related secondary cancers
and Currently such knowledge is lacking

93.  The two large organizations that initiate & coordinate
multicenter clinical trials in Europe & North America
1. European Organization for Research and Treatment
of Cancer (EORTC)
2. Radiation Therapy Oncology Group (RTOG)
 To update their system for assessing late injury to
normal tissues

94.  This led to the Late Effects of Normal Tissue (LENT)
conference in 1992
 This conference led to the introduction of the SOMA
classification for late toxicity
 SOMA is acronym for subjective, objective,
management criteria with analytic laboratory and
imaging procedures

95.  Subjective : injury recorded from subject’s point of
view, as perceived by the patient
-Interviews, questionnaire and diary
 Objective : By clinician during clinical examination,
able to detect sign of dysfunction still below TD
 Management : Active steps to ameliorate symptoms

96.  Analytic : tools by which tissue function can be
assessed even more objectively or with biological
insight than by simple clinical examination
 There is no grade 0,because 0 indicate no effect
 No grade5 ,because it indicates loss of an organ

100.  Development of a test to
predict those likely to suffer
side effects should enable
individualized radiation dose
prescription to increase
cancer cure while reducing
the number of survivors
suffering with the
consequences of treatment

101.  With the rapid reduction in cost of genotyping, there is
increasing interest in carrying out GWASs to identify new
genes associated with toxicity
 In a *study of African-American patients with prostate
cancer, 27 pts who developed erectile dysfunction after
radiotherapy were compared with 52 controls
 The SNP rs2268363 in the follicle-stimulating hormone
receptor gene (FSHR; involved in testes development and
spermatogenesis) was associated with erectile
dysfunction with a P-value that reached genome-wide
significance (P = 5.5 × 10-8) and an odds ratio of 7.0 (95%
confidence interval 3.4 to 12.7)
* Kerns et al

102.  Late reacting normal tissues constitute a heterogenous group
and should be taken into account individually with respect to
their constraints
 They constitute the back bone of fractionction and altered
fractionation schedules and they should be considered
accordingly
 The goal of ideal cancer therapy irrespective of therapeutic
modality is the eradication of cancer & preservation of the
structural & functional integrity of the organ of origin &
surrounding structures
 For the radiation oncologist the goal is to achieve a truly selective
effect & advantageous therapeutic ratio

103. THANK YOU