Acute and Late Radiation Related
Side Effects and their Management in
Pelvic Malignancies
Dr. Kartik Kadia
Moderator : Prof Dr Rajeev K Seam
MMIMSR, Ambala

Introduction
• Radiation therapy affects both –
tumour cells and
uninvolved normal cells
• With the goal of achieving uncomplicated locoregional control of
cancer, balancing between the two is very important

Normal Tissue damage
• Most of the effects of radiation therapy on normal tissues can be
attributed to cell killing, but there are some that cannot.
• Examples include the following:
■ Nausea or vomiting that may occur a few hours after irradiation of
the abdomen.
■ Fatigue felt by patients receiving irradiation to a large volume.

• Somnolence that may develop several hours after cranial irradiation.
• Acute edema or erythema that results from radiation-induced acute
inflammation and associated vascular leakage.

Cont.
• The response to damage is governed by
(1) the inherent cellular radiosensitivity,
(2) the kinetics of the tissue, and
(3) the way cells are organized in that tissue.
• The threshold dose below which no effect is seen and the
delay between irradiation and the time at which the
damage becomes observable vary greatly among different
tissues.

Radiation Response
• Response of all normal tissues to radiation is not same
• Depending on their response tissues are either –
 Early responding – constitute fast proliferating cells such as skin,
mucosa, intestinal epithelium, colon, testis etc.
 Late responding – have large no. of cells in the resting phase e.g.
spinal cord, bladder, lung, kidneys etc.

Normal Tissue Reactions
• Radiation effects are commonly divided into two
categories, early and late, which show quite different
patterns of response to fractionation :
• Early (acute) side-effects are observed during or
shortly after a course of radiotherapy.
• Late (chronic) side-effects become clinically manifest
after latent times of months to many years.

• The cut-off time to distinguish early from late effects has arbitrarily
been set to 90 days after the onset of radiotherapy.
• Their dose-response relations are characterized by different α/β ratios.
• Late effects are more sensitive to changes in fractionation than early
effects.

Early Effects Late Effects
Cell turnover rate High Low
Progression Can repair Cant be repaired – Persistent and
progressive
Time of Manifestation 2-3 weeks Months to years
Dose per Fraction Important Very Important
a/b ratio High Low
Overall treatment time Important Not very important
Mechanism Cell depletion Combination of vascular damage
and parenchymal changes

Consequential Late Effect
• If there is depletion of 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 has been termed a consequential late effect, that is, a late
effect consequent to, or evolving out of a persistent severe early
effect
—for example, fibrosis or necrosis of skin consequent to
desquamation and acute ulceration.

History of “TOLERANCE OF NORMAL TISSUE TO THERAPEUTIC
IRRADIATION”
• Mendelsohn had discussed the lack of time-dose data related to
patterns of radiation damage in normal tissue and had noted that
“some tissues are dealt effectively, but the bulk of tissues are seldom
discussed, poorly documented and have data which are sparse and
meaningless.”
Mendelsohn, M. L. The biology of dose-limiting tissues. Conference on Time and Dose
Relationships in Radiation Biology as Applied to Radiotherapy supported by the National
Cancer Institute, National Institutes of Health; 1969: 154-160.

Cont.
• The monumental work of Rubin and Cassarett was a major step in
this direction.
• TD 5/5 (the probability of 5% complication within five years from
treatment) and
• TD 50/5 (the probability of 50% complication within five years), were
introduced
Rubin, P.; Cassarett, G. A direction for clinical radiation pathology. In: Vaeth, J.
M., et al., eds. Frontiers of radiation therapy and oncology VI. Baltimore:
University Park Press; 1972:1-16.

Tissue tolerance and sensitivity
• Concept of TD5/5, TD 50/5

Emami et al - 1991

QUANTEC
• With the development of more sophisticated three-dimensional
treatment planning systems, numerous studies in the literature
have reported associations between dosimetric parameters
and normal tissue outcomes
• The Quantitative Analysis of Normal Tissue Effects in the Clinic
(QUANTEC) article, which appeared in the International Journal
of Radiation Oncology, Biology, and Physics in 2010 summarized
the available data in a clinically useful format.

Studies
• Perez et al. described the incidence of major sequelae
in 1211 patients treated at Mallinkrodt between 1959
and 1986.
• Those patients who received a dose of less than or
equal to 80 Gy had a 2% to 3% incidence of major
rectal complications
as compared with a rate of 6% to 13% at doses greater
than 80 Gy.

• Lanciano and colleagues in the Patterns of Care
Study reported a crude complication rate of 9.8%
with 3- and 5-year actuarial rates of 10% and 14%,
respectively, in 1558 patients treated only with
radiation for all stages of disease at a large number
of institutions in the United States.
• Of all complications, -
61% occurred in the large and small bowel,
21% in the bladder, and
10% in the vagina.
• Of these complications, 64% required surgical
correction,and 9% were fatal (total of 0.8% fatal
complication rate).

Classification systems
• The absence of a uniform classification system for reporting treatment
morbidity had resulted in a considerable inconsistency in the reporting of
treatment complications in cervical cancer patients.
Nowadays the classifications most used are the:
• RTOG/EORTC
• LENT/SOMA
• European
• WHO
• French/Italian
• AADK
• Common Toxicity Criteria (CTC).

Tissue Tolerance
Tissue Tolerance – The ability of tissue/organs to endure
the effect of radiation without adverse effect
Tolerance Doses :
• Uterus - 300 Gy
• Cervix - 250 Gy
• Upper third of the vagina - 120 Gy to 140 Gy,
• The lower two thirds - 80 Gy to 85 Gy.
Most institutions do not exceed:-
• 75 Gy to 80 Gy (combined EBRT and LDR intracavitary
dose)

Acute Reactions

Acute Toxicity
• In cervical cancers, the use of concurrent CRT has clearly shown to
increase in acute toxicities
• Especially with respect to –
hematologic and
gastrointestinal function
as compared with RT alone

Radiation Complications
• Acute complications : (cell loss in rapidly dividing tissue)
• Acute radiation enteritis
• Acute radiation proctitis
• Skin reaction
• Nausea
• Anorexia
• Fatigue,Weakness
• Acute Genito-urinary symptoms: Dysuria, frequency

Late Reactions

• Chronic complications :
• GI: ulceration ,hemorrhage ,stricture ,small bowel obstruction, malabsorption
• Bladder: Mucosal thinning, telangiectasia and fibrotic contracture in bladder.
• Skin: thinning ,loss of appendage, telangiectasia,subcut fibrosis.
• Cervix and vagina: obliteration of os, shortening of vagina ,fistula
• Ovary: early menopause

Late Toxicities
• The incidence of major late sequelae of radiation therapy for –
 stage I and IIA carcinomas of the cervix ranges from 3% to 5%
 stages IIB and III between 10% and 15%
• The severe complications occur in the first 3 years to 5 years
after completion of radiotherapy, but there still remains a
small but continuous added risk thereafter

• Injury –
 gastrointestinal tract usually appears within the first
2 years after radiation therapy
 urinary tract are seen more frequently 3 to 5 years
after treatment
Late Toxicities

• Smoking during RT has been associated with a significantly higher risk
of late complications.
• Most reports of late morbidity have focused on severe gastrointestinal
and genitourinary toxicities; only recently have rigorous efforts been
made to monitor for less severe sequelae.
Late Toxicities

Late toxicities
Late effects, which are now recognized as important consequences-
• Pelvic insufficiency fracture
• Vaginal stenosis
• Lymphedema
• Neuropathy

Contin.
• Perez et al. quantitated the effect of total doses of
irradiation
dose rate
ratio of doses
to bladder and rectum and point A on sequelae in 1,456 patients. (EBRT plus
two LDR 70 to 90 Gy to point A; Median follow-up was 11 years)

Cont.
The most frequent grade 2 urinary/rectal sequelae were
I. cystitis and
II. proctitis (0.7% to 3%)
The most common grade 3 sequelae were-
I. vesicovaginal fistula (0.6% to 2% in patients with stage I to III tumors)
II. rectovaginal fistula (0.8% to 3%), and
III. intestinal obstruction (0.8% to 4%).

Late toxicities (cont.)
• In the bladder, doses <80 Gy correlated with a <3% incidence of morbidity,
which was 5% with higher doses (P = .31).
• In the rectosigmoid, the incidence of significant morbidity was <4% with
doses <75 Gy and increased to 9% with higher doses.
• For the small intestine, the incidence of morbidity was
I. <1% with 50 Gy or less,
II. 2% with 50 to 60 Gy, and
III. 5% with higher doses to the lateral pelvic wall

Skin Reactions

Patient-related and treatment-related factors for
Dermatologic toxicity
• Risk of skin toxicity as well as its onset, severity, and
duration are strongly affected by clinical and
treatment related factors:
• Vascular disease, smoking, and poor nutrition may
impair acute and long-term recovery of the dermis
and subcutaneous tissues.
• Radiation-induced skin reaction may occur in a
patient with a high body mass index because of the
presence of skin folds and may be compounded by
parallel fungal or bacterial infection.

Acute skin reactions
• Grade 1 and 2 skin reactions are most common in
Radiotherapy, with an incidence of 10%.
• At a dose of 40 Gy, grade 2 reactions are typically
observed

• Grade 3 skin reactions are associated with exceed 50 to 60 Gy with
bolus placement.
• Grade 4 skin reactions are associated with even more higher doses.
Acute skin reactions

Acute skin reactions
• Severe skin reactions are rare (range, 1%-5%) in the treatment of
cervical cancer
• Acute skin reactions typically peak within 1 or 2 weeks after
treatment, with a relatively rapid healing time of 3 to 4 weeks

Treatment of acute skin toxicity
• An acute skin reaction is generally apparent
after 2 or 3 weeks of pelvic EBRT with
conventional dose fractionation
• Mild skin reactions, such as erythema, may
be treated with topical moisturizers without
added perfumes or metals like zinc or silver,
which can irritate the skin or enhance the
reaction.

Late Dermatologic Effects
• May include –
• hyperpigmentation or hypopigmentation,
• Telangiectasia
• textural changes (xerosis and hyperkeratosis),
• thinning of the skin because of atrophy
xerosis
telangiectasia hyperkeratosis

Cont.
• In the months after RT, folliculitis is common
because of regrowth of occluded hair
follicles, sweat glands, and sebaceous glands
and may be relieved with warm compresses
or occasionally may require antibiotics
• Subcutaneous fibrosis with associated woody
thickening of the skin may also be observed
Folliculities

• Physicians use –
 Kojic Acid cream for hyperpigmentation
 Laser therapies
 Sclerotherapy
 Surgical excisions for treatment of chronic skin
reactions like xerosis and telangiectasia

Gastro-intestinal System

Patient-related and treatment-related factors
associated with GI toxicity
• Prior abdominal or pelvic surgery has increased risk
of developing small bowel obstructions in patients
who receive > 50 Gy of RT to the pelvis and can lead
to adhesions, which limit intestinal displacement.

Cont.
coexisting comorbidities including –
prior pelvic inflammatory disease,
vascular disease because of diabetes or arteriosclerosis,
collagen vascular disease,
smoking history
inflammatory bowel disease
may be at greater risk for developing acute and long-term radiation induced GI side effects.

Contin..
• Overall, for patients treated with radiation for
carcinoma of the uterine cervix, the crude incidence
of small bowel obstruction was –
2% to 3% in the Perez report
4% in the Patterns of Care Study
4% in the pelvic radiation therapy–alone arm of the
RTOG para-aortic study
• Incidence increases to 17% in patients treated who
had a prior history of abdominal surgery.
• Studies that have pushed the dose to 60 Gy have
resulted in severe GI complication rates of as high as
57%.

Mechanism of GI injury
• Both early and late complications are observed in the gastrointestinal
tract.
• Acute mucositis frequently occurs, with symptoms such as -
diarrhea or
gastritis
• depending on the treatment field.

Acute GI injury mechanism
• In the small intestine, stem cells are
located toward the bottom of the
crypts of Lieberkühn
• Atrophy of the villus occurs about 2
to 4 days postirradiation.

• Epithelial denudation is responsible for the acute gut reactions.
• A regenerative response appears rapidly, and within 2 to 4 days,
microcolonies and macrocolonies are detectable.
• The surviving crypts have at least the same radiosensitivity to
reirradiation as the unirradiated crypts
Acute GI injury mechanism

Late GI mechanism
• Long-term late sequelae, which may develop either from
persistent severe early reactions (consequential late effects) or
independently of acute damage in the submucosal, muscular, or
serosal layers.
• Late bowel reactions involve all tissue layers and are caused by
atrophy of the mucosa caused by vascular injury, with
subsequent breakdown resulting from mechanical irritation and
bacterial infection, which leads to an acute inflammatory
response.

• In addition, overgrowth of the fibromuscular tissue with stenosis and
serosal breakdown and adhesion formation may occur, which may be
predisposed to by previous surgery and is related to inflammatory
mediators.
• Fibrosis and ischemia are typical late effects.
Late GI mechanism

Tolerance Dose
• Tolerance dose is about 50 Gy for the small intestine
and slightly higher for the large intestine.
• Rectal tolerance dose is about 70 Gy.

Acute Radiation Enteritis
• Enteritis is inflammation of the small intestine
• Symptoms:
 diarrhea
 nausea and vomiting
 loss of appetite
 abdominal cramps and pain

• The management of acute radiation enteritis is mainly supportive
• Patients may be treated with fiber products and probiotics
• Frequent use of antidiarrheal agents, such as loperamide or diphenoxylate
and atropine, starting with 1 tablet a day before the development of
diarrhea and increasing as needed, may be indicated.
Acute Radiation Enteritis

• Fluid status and electrolytes also should be monitored carefully
• Intravenous hydration may also be required if patients are unable to
adequately maintain fluid intake.
• Aggressive management during treatment is important to reduce the
risk of chronic enteropathy.
Acute Radiation Enteritis

Acute Radiation Proctitis
• Proctitis is a condition in which the lining tissue of the
inner rectum becomes inflamed
• Symptoms :
A frequent or continuous feeling that patient needs to have
a bowel movement
Pain on the left side abdomen.
A feeling of fullness in the rectum.
Pain with bowel movements.
Rectal pain
Rectal bleeding

• Numerous anti-inflammatory agents, intestinal protectants, intestinal
antimotility agents, and probiotics have been studied as preventative
strategies
• However till date, none of these agents have demonstrated the
ability to definitively mitigate radiation toxicity.
Acute Radiation Proctitis

• The treatment of acute radiation proctitis can
mainly be considered supportive and includes
antidiarrheal agents and intravenous hydration
as needed.
• Several studies have also suggested a potential
benefit with short-chain fatty acid butyrate
enemas, which may aid in accelerating the
healing process of acute radiation damage
Acute Radiation Proctitis

Chronic Radiation Enteritis
• Symptoms –
 diarrhea.
 nausea and vomiting.
 loss of appetite.
 abdominal cramps and pain.
 pain, bleeding, or mucus-like discharge from the
rectum.
 fever
 Malabsorption

• Cholestyramine may be useful in treating bile
salt malabsorption.
• Surgical resection may be required in up to 30%
of patients because of persistent ileus,
intestinal fistulization, or adhesions
Chronic Radiation Enteritis

Late Radiation Proctitis
• Proctitis is inflammation of the lining of the
rectum
• Symptoms:
Tenesmus (A feeling of fullness in rectum)
Rectal bleeding.
Rectal pain.
Diarrhea.
Pain with bowel movements.

• If rectal bleeding does not cause symptoms, then treatment is not
always necessary, because most cases will resolve spontaneously.
• Stool softeners may aid in minimizing damage to friable rectal tissue
with the passage of stool.
• Treatment with a 4-week course of metronidazole also has been
effective, possibly because of the treatment of anaerobic bacteria,
which may contribute to hypoxia or immunomodulatory effects
Late Radiation Proctitis

Contin..
• Severe Rectal bleeding that is refractory to
medical management, patients may be
referred for consideration of endoscopic
therapy with argon-plasma coagulation
• In cases of chronic rectal bleeding,
hyperbaric oxygen has been effective in
reducing chronic pelvic radiation toxicities

Genito-Urinary System

Patient-related and treatment-related risk factors
for Genito-Urinary toxicity
• Treatment-related factors that influence the risk of
GU toxicity include –
cumulative radiation dose
treatment volume
radiation modality (EBRT, brachytherapy, or both),
prior pelvic surgery.

Cont.
• Patients who undergo radical hysterectomy, adjuvant radiation may
cause higher rates of –
 bladder dysfunction
 hydroureteronephrosis
 stress incontinence
 radiation cystitis.

Mechanism of Bladder injury
• Cell renewal rate of Bladder is low, the superficial cells
having a life span of several months.
• Because of this long life span, proliferation following
irradiation does not begin for months.
• Senescence of the differentiated functional cells then
reveals latent damage in the basal layer.

• Frequency of urination increases in parallel with bladder damage and
loss of surface cells.
• The absence of these surface cells explains the irritation by urine of the
deeper cellular layers, leading to stimulation of cellular proliferation.
• Subsequent late effects are related to fibrosis and reduction in bladder
capacity.
Mechanism of Bladder injury

Cont.
• Acute side effects (Focal) from incidental bladder irradiation are
common and include urinary frequency, urgency, and dysuria
(symptoms that may also reflect acute urethral toxicity).
• Late effects (Global) include dysuria, frequency, urgency, contracture,
spasm, reduced flow, and incontinence.
• In contrast, late effects arising from focal injury include hematuria,
fistula, obstruction, ulceration, and necrosis.

Acute Genito-Urinary toxicity
• Pelvic radiation for gynaecologic malignancies may
result in both upper and lower tract genitourinary
(GU) complications, which are dose-dependent and
related to RT modalities

• Low-grade (grade 1-2) acute GU toxicity is relatively common during
EBRT, with an incidence of 17% to 40% in the definitive treatment of
cervical cancer with concurrent chemoradiotherapy
• Severe urinary tract toxicity is relatively rare during treatment (range,
2%- 5%).
Acute Genito-Urinary toxicity

Cystitis
• Cystitis is an inflammation of the bladder
• Symptoms:
pain, burning or stinging while micturition
Increased urgency for micturition than normal.
urine that's dark, cloudy or strong-smelling.
pain in lower abdomen
feeling generally unwell, sick and tired.

Cystitis
Treatment
• Antibiotics if infectious source;
• Pyridium/NSAID’s if non-infectious;
• Urinary urgency is effectively managed with
anticholinergics like oxybutynin.
• Tolderodine, Trospium have similar efficacy but
lower rates of confusion, dry eyes, dry mouth,
and constipation compared with oxybutynin.

Late Genito-Urinary effects
• The reported rates of major urologic
complications (grades 3-4) after RT
for cervical cancer range from -
1.3% to 14.5% at 3 years and most
commonly include ureteral stricture
and hemorrhagic cystitis
• Hemorrhagic cystitis may be treated
with laser fulguration of ectatic
vessels, intravesical alum or formalin,
or hyperbaric oxygen

Ureteral Strictures
• Ureteral strictures – Narrowing of Ureter.
• Symptoms –
oSide or back pain.
oFeeling of fullness.
oBlood in the urine.
oUrinary tract infections.
oPain that worse with increased fluids

have been noted in –
 5% of patients after preoperative RT and
 2.5% of patients after definitive RT alone for cervical cancer
Ureteral Strictures

• Strictures of the ureter may be managed by
endoscopic procedures, such as –
dilation or stent placement, but they often require
ureteral reimplantation or
ileal ureteral substitution
• Ureteral strictures may represent recurrent cancer
until proven otherwise
Ureteral Strictures

Vaginal Complications

Vaginal stenosis
• Risk factors include –
higher radiation dose
age older than 50 years,
lack of compliance to treatment
• Radiation doses >80 Gy have been associated with a
10% to 15% increased risk of grade 2 vaginal
toxicities, including Vaginal Stenosis

Vaginal adhesions
• Vaginal adhesions is shortening of vagina – leading
to labial adhesions, and potentially total
agglutination of the vagina.
• Small adhesions form quickly in the irradiated patient,
which can make coitus and pelvic examinations quite
painful.
• May be prevented by use of Vaginal Dilators

Vaginal dryness
• Dryness of the irradiated vagina is a common
side effect, because of a combination of direct
radiation effect.
• Vaginal lubricants and topical estrogen creams
are beneficial in partially relieving these
symptoms.

Vaginal Complications
• Other effects of irradiation of the vagina
includes –
Erythema
moist desquamation
confluent mucositis - leading to the loss of
vaginal epithelium that may persist for 3 to 6
months.

• Gross abnormalities in the vagina may include pale color, a thin atrophic
mucosa, inflammation, and tissue necrosis with ulceration leading to a
fistula.
• Tolerance doses, however, are high –
90 Gy for ulceration and
100 Gy for the development of a fistula
Vaginal Complications

Vaginal necrosis
• Vaginal necrosis may result from high doses of radiation,
especially in patients who have undergone reirradiation
• Patients who receive HDR, may be at greater risk for
vaginal necrosis
• Hydrogen peroxide douching with a dilution of at least
1:10 with saline, oral metronidazole, and hyperbaric
oxygen may be considered.

Vesicovaginal Fistula
• Patients who have bladder involvement at diagnosis
are at risk of developing a vesicovaginal fistula after
definitive RT.
• Fistulae should first undergo biopsy to rule out
recurrence of malignancy.

Fistula
• Small vesicovaginal fistulae may be managed with –
 simple fulguration and catheter drainage
 but they may require open surgical repair and, occasionally
 urinary diversion
• Uretero-arterial fistulae are rarely encountered and have a acute mortality
rate.
• They should be treated with endovascular stent placement or, if this fails,
open surgical repair.

Other Complications
• Most common gynecologic complications of pelvic radiation are
ovarian failure in premenopausal patients and
vaginal stenosis (VS) in any female patient who receive pelvic
radiation (Incidence ranges from 20% to 88% of patients)

Contin..
• Patients who receive radiation to the pelvis for locally advanced cervical
cancer will have their ovaries irradiated and, thus, may undergo
menopause, typically within the first 6 months after treatment.
• Vaginal Stenosis is most likely to occur within the first year of treatment but
has been observed in as short a time as 26 days and as far out as 5.5 years
from definitive therapy.
• The distal vaginal mucosa has less radiation tolerance than the mucosa in
the upper region, and vaginal shortening may begin during the course of RT.

Haematological

Hematological toxicity
• Includes - Anemia, Neutropenia, Thrombocytopenia
• Large prospective studies have demonstrated that the
rate of grade 3 hematologic toxicity with cisplatin-
based pelvic chemoradiotherapy is approximately
20% to 25%.
• Extended-field RT leads to the irradiation of a larger
proportion of the total Bone Marrow and a
correspondingly higher rate of hematologic toxicity.

Haematological toxicities
• Weekly blood counts should be routinely taken into
consideration
• Chemotherapy is typically held when the neutrophil
count decreases below 1500/mcL
• Radiotherapy is typically held when the neutrophil
count approaches 500/mcL to 1000/mcL

Osteogenic Toxicities

Bone Complications
• Important sequelae of radiation to bone, such as
pathologic fractures
osteoradionecrosis
second malignancies
are associated with a decrease in quality of life and
increase in mortality.

• Factors that influence bone toxicity include –
• radiation dose (>50 Gy)
• as well as patient factors, such as
 age,
 menopausal status,
 presence of underlying bone weakness (such as osteopenia or
osteoporosis),
 cigarette smoking,
 vascular integrity.
Bone Complications

• Fractures of the humeral and femoral head are observed if the
dose - in conventional fractions is high
 TD5/5 is 52 Gy and
 TD50/5 is 65 Gy.
Bone Complications

• The 5-year cumulative rate of PIF (pelvic insufficiency
fracture) ranges from 5.1 to 45%.
• A 4-level instability classification system is followed
Bone Complications

• The classification recommends –
• nonoperative treatment for stable type I fractures,
• nonoperative or minimally invasive surgical fixation for type 2 fractures
• surgical stabilization for type 3 and 4 fracture patterns.
Bone Complications

• Nonoperative treatment measures usually consist of a combination of –
 nonsteroidal antiinflammatory and
 pain medication
• And slow progression from bed rest to full mobilization with full weight-
bearing on the affected side.
Bone Complications

Neurologic Toxicity
• Extremely rare, lumbosacral plexopathy has been
occasionally reported in patients treated for pelvic
tumors with doses of 60 to 67.5 Gy.
• Lower extremity paralysis secondary to lumbosacral
plexopathy
• The neurologic deficit is irreversible, and no effective
therapy other than supportive care has been found.

Second Malignancy
• The risk of second malignancies rises over time after
radiation for carcinoma of the cervix,
although the exact increase over the rate expected in
the general population is difficult to assess.

• The Risk rate of developing a second tumor after pelvic irradiation is greater than 2.5
for the development of –
 vulva or vagina carcinoma (5.6)
 anal carcinoma (4.6)
 Laryngeal carcinoma (3.3)
 lung cancer(3.0)
 bladder carcinoma (2.7)
 bone cancer(2.7)
Second Malignancy
*Perez & Brady’s Principles of Radiation Oncology – 7th Edition

• However, the presence of shared causal factors, such as –
 HPV in anal, vulvar, and cervical malignancies, or
 excess smoking in the population of cervical carcinoma patients
makes it unclear that the treatment contributes to this excess risk of
second malignancy
Second Malignancy

Thank You