The document discusses classifications of mammalian cell sensitivity to radiation and the radiobiological basis of radiation-induced toxicities. It then focuses on the rectum as an organ at risk for pelvic irradiation, describing the acute and chronic effects of radiation proctitis. Techniques to reduce rectal toxicity during radiotherapy planning and treatment are also outlined, including emptying the rectum during simulation and using rectal spacers or balloons.

1. RADIATION INDUCED
TOXICITIES IN PELVIC
IRRADIATION
Dr KilitoliChophy
Junior Resident
Department of radiation oncology
16th March 2021

2. Casarett classification of mammalian cell
• Arranged from most sensitive (Group I) to least sensitive (Group IV).
• Group I:Vegetative Intermitotic Divides constantly with no differentiation.
Includes basal epithelial cells (skin, intestinal crypts, etc), undifferentiated hematopoietic stem cells and
germ cells.
• Group II: Differentiating Intermitotic Divides for a finite amount of cycles before differentiating into a non-
dividing cell.
• Includes all of the cells that are intermediate between stem cells and differentiated cells. For example,
myelocytes, spermatogonia, etc.
• Group III: Reverting Postmitotic : normally non-dividing cell that retains the potential to divide (“revert”).
• Includes liver, kidneys and glandular tissues such as pancreas, adrenal, thyroid and pituitary.
• Group IV: Fixed Postmitotic :A permanently non-dividing cell.
• Includes permanent cells such as nerves and muscles, as well as short-lived differentiated cells such as
neutrophils, red blood cells, and superficial epithelial cells.

3. • alpha by beta ratio :radiation dose at which the alpha
killing (lethal) is equal to beta killing (combinations of
sublethal killing leading to lethal killing)
• Early responding tissues:
α/β is large, as a consequence i.e. irreparable
damage dominates at low doses, and dose response
curve has marked initial slope & bends at higher doses.
Cells with poor repair capability (e.g. tumours) tend to
develop more lethal damage
• Late responding normal tissue:
α/β is small ,i.e. β term (repairable damage) has an
influence at low doses.
normal late responding tissue around the tumour with a
lower alpha by beta ratio tends to get damaged more.
Radiobiological basis:

4. • Therefore, adopting a dose per fraction more
than the alpha by beta ratio will kill more cells
than when dose per fraction is less than the
alpha by beta ratio for the same given total
dose.

5. • The therapeutic index (TI) defines how theTCP relates to NTCP for different doses of radiation .
• TCP and NTCP curves are sigmoid in shape
• TI = NTCP/TCP
• Usually radiosensitive tumours like seminoma have a wide therapeutic index, while those with
radioresistant tumors have a narrow therapeutic index.
• An ideal radiotherapy plan where there is 100% chance of tumor control and 0% chance of normal tissue
toxicity. Achieving an optimal balance betweenTCP and NTCP is a basic aim of any radiotherapy plan.
Therapeutic Index

6. ModifyingTherapeutic Index
1. Reducing the size of the target volume and the margins by using image guidance in radiotherapy
planning.
2. Hyperfractionation— small dose per fraction with two or three fraction delivered per day is used to
achieve a higher biologically effective dose to the tumor. Reduces the chances of long term normal
tissue complications
3. Concurrent Chemotherapy—The use of concurrent chemotherapy acts as a radiosensitizer and thereby
shifts theTCP to left.
4. RadiationSensitizers—The use of radiosensitizers helps in optimizing therapeutic index by overcoming
hypoxia
5. Extracorporeal radiotherapy
6. Radio Protectors—The radio protectors (e.g.,Amifostine) mainly act by neutralizing free radicals
generated by ionizing radiations in the normal tissue, thereby reducing normal tissue complication
rates

7.  These are normal tissues whose radiation may significantly
influence the treatment planning or prescribed dose.
 It is divided into three classes.
1. Class I-Radiation lesions are fatal or result in
severe morbidity.
2. Class II-Radiation lesion result in mild to moderate morbidity.
3. Class III-Radiation lesion are mild, transient and reversible or result
into no significant morbidity.
ICRU 62

8. CLASSIFICATION OF ORGANS AT
RISK
•Serial – whole organ is a continuous unit and damage at
one point will cause complete damage of the organ
(spinal cord, digestive system). So even point dose is
significant.
•Parallel – organ consists of several functional units and
if one part is damaged, the rest of the organ makes up
for the loss (lung, bladder). Dose delivered to a given
volume or average/mean dose is considered .
•Serial-parallel – kidney (glomerulus- parallel, tubules-
serial), heart (myocardium- parallel, coronary arteries-
serial). ICRU-62

9. Pelvic RT indications:
1. Ca cervix : Radical concurrent Chemoradiation, Adjuvant radiation
45-50 Gy+ brachytherapy
2. Ca Endometrium: adjuvant RT 45Gy/25# + brachytherapy
3. Ca bladder: Radical RT 64Gy/32#
4. Ca Prostate: Radical RT Radical 74Gy/37#, Hypofractionation 60Gy/20#, post op adjuvant RT
, salvage RT, (brachy alone or as boost in early prostate)
5. Ca vulva and Ca vagina : Concurrent Chemoradiation pelvis 45 to 60Gy +/- brachytherapy
6. Ca Penis : Adjuvant pelvic + inguinal RT , radical Concurrent Chemoradiation (penis +LNs)
7. Ca anal canal : Concurrent Chemoradiation 50-60 Gy
8. Ca rectum NACCRT 50.4Gy/28# , short course NART 25 Gy/5# hypofractionation.

10. Organ at risk during pelvic
radiotherapy are:
1. Bladder
2. Rectum
3. Urethra & Ureter
4. Small bowel
5. Vagina
6. Gonads

11. • Lined by simple columnar epithelium.
• TD5/5 60 Gy
• TD50/5 80 Gy
• Radiation proctitis (RP) is one of the long term complications that occurs following pelvic
radiation in Ca cervix and Ca prostate which requires relatively higher dose for local
control.
Symptoms:
•diarrhea (common)
•fecal urgency
•tenesmus
•mucous discharge
Rectum
•constipation
•fecal incontinence
•Anorectal dysfunction
•mucous discharge
•rectal bleeding

12. Time of onset
Acute (early): Up to 3 months after onset of therapy ( avg. 2 to 4
weeks).
Self limiting. Generally resolves after 4 to 6 weeks.
Does not increase the risk of chronic radiation proctitis.
Colonoscopic biopsy of the inflammatory rectal mucosa is
usually not recommended due to the increased risk of
bleeding and fistula formation
Chronic (late): Months to years later after the cessation of therapy ,
majority within 2 yrs. (avg. 8–12 months after the
completion of therapy)

13. Underlying pathologic mechanism Characteristic features
Acute Radiation
Proctitis
•Tissue Hypoplasia resulting in crypt
involution and loss of epithelial barrier
integrity
•Exposure of the lamina propria to
luminal microbes-
•Acute inflammatory response
triggered
•Superficial mucosal injury
•Acute inflammatory
infiltrate in lamina propria
•Eosinophilic and neutrophilic
crypt abscesses
Chronic Radiation
Proctitis
•Progressive vasculitis leading to
thrombosis of small arteries
•Ischemia-necrosis-ulceration-fistula
•The arteritis and submucosal fibrosis can
lead to stricturing and obstruction
•Fibrin thrombi in the
vessels
•Submucosal fibrosis
•Telangiectatic vessels –
resulting from network of
collateral small vessels,
superficial and fragile,
Susceptible to trauma

14. COLONOSCOPY
Acute Radiation Proctitis
Inflammation, edema, ulceration, and
mucosal sloughing
Chronic Radiation
Proctitis:
ProminentTELANGIECTASIA,
ERYTHEMA & FRIABILE
Mucosa
A distinct margin can be detected
between the normal rectal mucosa and
the area affected by radiation.
Should not be biopsied.
(Left) Rectal proctitis and (Right)
ulceration.

15. RTOG/EORTC Late Radiation Morbidity Scoring
Grade 1 Grade 2 Grade 3 Grade 4
Bowel movement up
to 5 times daily,
Mild diarrhoea,
Mild cramping
Slight rectal discharge
or bleeding
Bowel movement >5
times daily,
Moderate diarrhoea and
colic
Excessive rectal mucus or
intermittent bleeding
Obstruction or
bleeding
requiring surgery
Necrosis/
Perforation
Fistula

16. CTCAE 4
Grade 1 Grade 2 Grade 3 Grade 4
Diarrhea
Rectal
mucositis
Increase of <4 stools
per day over baseline;
Mild increase in
ostomy output
compared to
Baseline
Asymptomatic or
mild symptoms;
intervention not
indicated
Increase of 4 - 6 stools
per day over baseline;
Moderate increase in
ostomy output
compared to baseline
Symptomatic;
medical intervention
indicated; limiting
instrumentalADL
Increase of ≥7 stools
per day over baseline;
incontinence;
hospitalization
indicated; severe
increase in ostomy
output compared to
baseline; limiting self
care ADL
Severe symptoms;
limiting self
careADL
Life-threatening
consequences;
urgent intervention
indicated
Life-threatening
consequences;
urgent
operative
intervention
indicated
Rectal
Haemorr
hage
Mild; intervention not
indicated
Moderate symptoms;
medical intervention
or minor cauterization
indicated
Transfusion,
radiologic,
endoscopic, or
elective
operative intervention
indicated
Life-threatening
consequences;
urgent
Operative
intervention
indicated

17. CTCAE contd.
Grade 1 Grade 2 Grade 3 Grade 4
Rectal
obstruction
Asymptomatic
; clinical or
diagnostic
observations
only;
intervention
not indicated
Symptomatic;
altered GI
function;
limiting
instrumental
ADL
Hospitalizatio n
indicated;
elective
operative
intervention
indicated;
limiting self
care
ADL; disabling
Life-
threatening
consequences;
urgent
operative
intervention
indicated

18. Techniques to reduce rectal
toxicity:
1. Rectal protocol:
Ideally the rectum should be
empty during simulation as the
rectum volume decreases during
treatment particularly in small
tumors prone to motion.(1)
1 . National rectal cancer intensity-modulated radiotherapy (IMRT)
guidance (rcr.ac.uk)

19. Effect of rectal distension and movements
in treatment

20. 2. Rectal spacers:
Rectal spacers are used to limit dose to the
anterior rectal wall in high dose external beam
radiation therapy of the prostate and have
been shown to reduce radiation induced
toxicity.
Rectum-spacer related acute toxicity – endoscopy results of 403 prostate cancer patients after implantation of gel
or balloon spacers | Radiation Oncology | FullText (biomedcentral.com)

21. 3. Rectal balloon:
• The use of a rectal balloon
during intensity-modulated
radiotherapy significantly
reduces prostate motion.
• Prostate immobilization
thus allows a safer and
smaller planning target
volume margin. It has also
helps spare the anterior
rectal wall and reduced
the rectal volume that
received high-dose
radiation
The use of rectal balloon during the delivery of intensity modulated
radiotherapy (IMRT) for prostate cancer: more than just a prostate
gland immobilization device? - PubMed (nih.gov)

22. 4.Radiation techniques
IGRT :
• Imaging the tumor before and
during treatment. By comparing
these images to the reference
images taken during simulation,
the patient's position and/or the
radiation beams may be
adjusted to more precisely
target the radiation dose to the
tumor.
Adaptive RT:
• Incorporates changes in
anatomy and/or deviations in
planned delivered dose due to
patient setup deviations or
machine delivery deviations to
estimate the actual delivered
dose to a patient as the
treatment progresses.

23. 5. Radioprotectors
Amifostine rectal suspension
 A thiol derivative, acts as a free radical scavenger and radioprotector
Simone et al. 2008
2 g vs. 1 g of amifostine given in a rectal suspension to patients receiving radiotherapy for Prostate cancer
placed 30–45 min before each radiation treatment.
Reduced RTOG ≥ Grade 2 toxicity & improved acute and late bowel quality of life scores compared to patients
who received 1 g of amifostine.

24. Treatment

25. Acute Proctitis: Self-limiting
• Cessation of therapy is usually the definitive treatment and surgical
interventions are rarely needed.
• Sitz baths
• Stool softeners,
• Antimotility agents
• Ethamsylate/Tranexamic acid
• Adequate oral hydration
• Probiotics:
Modulate the pro-inflammatory pathways and prevent transcription of the
dependent pro-inflammatory genes by intestinal epithelial cells

26. • steroid or 5-aminosalicylate enemas
• Sucralfate:
 It mechanically protects the gastrointestinal mucosa by forming a
protective coating on inner surface of the bowel and stimulate healing by
increasing angiogenesis.
 Administration of sucralfate enema given as 2gm/day bd.
• Hyperbaric oxygen (HBO)—HBO is also an effective modality in
management of RP, especially in patients not responding to conservative
management. A

27. Formalin
• scleroses and seals fragile neovasculature in radiation damaged
tissues to prevent further bleeding through chemical
cauterization
• its success is entirely dependent on accurate localization.
• rectal instillation of 4% formalin solution or direct topical
application of a 10% formalin solution. Topical formalin is
generally applied through a rigid proctoscope, flexible
endoscope, or by direct application with formalin soaked gauze
Contact with formalin for 2-3 minutes (until slight blanching of
the mucosa is achieved) is allowed.

28. Endoscopic Laser Coagulation
• based on the delivery of thermal coagulation
• should be reserved for patients with significant hemorrhagic proctitis
APC (Argon Beam Plasma Coagulation)
• Argon plasma coagulation modality utilizes a jet of sprayed argon gas, which is ionized by a high
voltage spark into plasma, once ionized, it produces coagulation and hemostasis in bleeding mucosa.
• Very limited tissue penetration
• Sustained responses in 83– 100% of patients with approximately 2–3 sessions of treatment with
minimal complications
Neodymium yttrium- argon-garnet (Nd:YAG) laser coagulation
• YAG lasers have the same theoretical benefit as argon plasma coagulation with a limited depth of
penetration with precise application

29. Surgery
Reserved for severe, complicated cases refractory to other options.
• The most frequent indications for surgery are fistulas and strictures causing
obstruction
• Fistulas- often require a diverting colostomy before
definitive resection or in high risk surgical candidates.
• Rectal strictures may also be relieved by dilators and stent
• Other indications are perforation or refractory bleeding- may be treated by a variety
of surgical techniques including combinations of excision, diversion, and
reconstruction

30.  The urinary bladder and ureters are covered by urothelium—
transitional epithelium.
•
Bladder
TD5/5 TD50/5
2/3rd 65 80
1/3 rd 80 85

31. Urothelium
Nuclear irregularity
Cellular oedema
Increased cytoplasmic elements
Disruption of tight junctions & polysaccharide layer
Vasculature
Vascular endothelial cell oedema
Endothelial cell proliferation
Perivascular fibrosis
Muscle
Smooth muscle oedema
Replacement of smooth muscle with fibroblasts
Increased collagen deposition
Vascular ischaemia of bladder wall
Mechanism of radiation damage

32. Symptoms of radiation induced cystitis:
• Acute side effects include urinary frequency, urgency, and dysuria.
• Late effects include hematuria, fistula, obstruction, ulceration, contracted
bladder, vesicovaginal fistula, necrosis, spasm, reduced flow, and
incontinence.
• Median onset of late complications after radiation is 13–20 months.

33. Grading: RadiationTherapy Oncology Group for radiation cystitis

34. Prevention
• Maintaining the bladder dose within tolerable limit and minimizing volume
irradiated .

35. In early reactions
 Symptomatic frequency and urgency are best treated with anticholinergic agents. These
agents act primarily by inhibiting involuntary detrusor muscle contractions.
 Oxybutynin chloride is an antispasmodic that relaxes the bladder smooth muscle and
relieve the symptoms of frequency and urgency.
 Detrol has a greater inhibitory effect on bladder contraction and it has fewer side effects
as compare to oxybutynin (eg, dryness of mouth), usual adult dose is 2 mg bd till
symptomatic relief is obtained.
 Saline bladder irrigation: Continuous bladder irrigation and clot removal , removes
urokinase, preventing bleeding
 Bladder irrigation with Alum (1%) irrigation: Acts by protein precipitation leading to
vasoconstriction and reduction in edema and inflammation.
Management

36.  Phenazopyridine (Pyridium) can be used to provide symptomatic relief in dysuria.
It is a azo dye, it acts directly on urinary tract mucosa to produce local analgesic
effect.
 The usual adult dose of pyridium is 100 to200 mg tds for 5 to 7 days.
If dysuria associated with UTI, then antibiotics should be added.

37. Botulinum toxin-
 Detrusor injections of botulinum toxin are approved by the FDA for the treatment
of adults with over active bladder who do not adequately respond to
anticholinergic medication.
 Acts by inhibition of the release of acetylcholine from the presynaptic nerve
terminal, which prevents stimulation of the detrusor muscle.
 Recommended total dose is 100 Units injection across 20 sites into the detrusor
muscles by cystoscope in every 12 weeks.

38. Hematuria:
• The primary treatment modality for hematuria is bladder irrigation. Intravesical
treatments with silver nitrate, prostaglandins or formalin have also been used.
• In severe hematuria other treatment involves the injection of a sclerosing agent (1%
ethoxysclerol) into the bleeding areas to control the
• other interventions can include embolization of the hypogastric arteries or urinary
diversion and cystectomy.
Contracted bladder:
• Treated by reconstruction of bladder with a segment of small or large bowel (sigmoid
colon).
• Cystectomy- This procedure is used as a last resort for contracted bladder and involves
removing the bladder and surgically constructing a replacement or an stoma on the
skin.

39.  Urethral injury usually consists of stricture formation and Incontinence.
 classical teaching is that a ureteral stricture represents recurrent carcinoma until proven
otherwise, and so needs evaluation with CT or MRI.
Management:
• endoscopic procedures, such as dilation or stent placement
• May require ureteral reimplantation or ileal ureteral substitution.
Ureter and urethra
TD5/5 70 5–10 cm
length
TD50/5 100

40. Small bowel
• The small intestine is at risk during abdominal-pelvic irradiation. The risk is increased when the
intestinal loops occupy the place of removed organ(s) after abdominal-pelvic organ resection.
This is particularly the case after total hysterectomy for cancer or after proctectomy for rectal
cancer, where the intestinal loops fall down into the pelvic cavity.
• Acute radiotoxicity corresponds to mucosal injury. The normal villous epithelium of the
intestine is renewed by non-functional cells, which leads to the loss of the barrier effect ,and
consequently to abdominal pain and accelerated intestinal transit.
• Conversely, late radiotoxic effects consist of a combination of submucosal fibrosis and vascular
degeneration
TD5/5 TD50/5
Whole 40 55
1/3 rd or ½ 50 60

41. Clinical features:
Acute radiation enteritis
• occurring within the three months
following irradiation, with maximal
prevalence between the 4th and 5th week.
• associated intestinal functional disorders
such as diarrhea, abdominal pain, and
weight loss. In case of associated
radiation proctitis, bleeding per anum,
rectal pain and episodes of anal
incontinence.
Acute radiation enteritis manifests as diffuse thickening,
hyperemia, and hyper‐enhancement (red arrows) of the
small bowel wall in the pelvis on computerized
tomography imaging.

43. Chronic radiation enteritis
• majority of symptoms occur with in 3 years of post radiation.
• Present persistent diarrhea, obstruction, ulceration, perforation and bleedin

44. Management:
 Dietary modifications- A low-residue diet and a diet low in fats and lactose
free diet.
 Drugs-Antispasmodics, anticholinergics and opiates can improve symptoms
of pain and diarrhoea by reducing motility. Oral antibiotics may improve
diarrhoea in associated bacterial colonization.
 Total parenteral nutrition-Bowel rest and total parenteral nutrition (TPN)
may be used for severe symptomatic disease and for enterocutaneous
fistulas
 Surgical management- Indications for surgery include bowel obstruction,
perforation, abscess, intractable bleeding or diarrhoea, and occasionally
malabsorption.

45. Techniques to reduce toxicity:
1. Immobilization in prone position
with belly board for anterior
displacement of bowel loops.
2. Simulate and treat with full bladder
to displace small bowel.
1 h before the planning CT scan, ask
patient to first empty bladder
completely, then drink 750 ml of water
in the space of 10–15 min and then wait
without emptying their bladder for 40–
60 min.

46.  The testis is one of the most radiosensitive tissues in the body with a
radiation dose as low as 15 cGy causing a significant depression in the
sperm count.
 Direct testicular irradiation of 24 Gy results in ablation of the germinal
epithelium which is responsible for sperm development and Leydig cell
function (production of testosterone).
 Leydig cell function is usually preserved up to 20 Gy in prepubertal boys
and 30 Gy in sexually mature men.
 Leydig cell function can be monitored by both testosterone and LH serum
levels. Normal testosterone value and elevated LH levels are indicative of
Leydig cell damage.
Testes

47. Cell Radiation dose Toxicity Recovery
Spermatogonia ≤1 Gy Oligospermia 9–18 months
Spermatocytes 1–3 Gy Azoospermia 10–30 months
Spermatids >3 Gy Azoospermia >60 months
Sensitivity of gonadal tissues following single dose irradiation and time to recovery
• Permanent azoospermia occurs after about 6 to 8 Gy in 2-Gy fractions

48.  When testes present directly in the
irradiation field, it cannot be
protected.
 The dose from scattered
irradiation from nearby beams,
can be reduced by moving the
gonad away from or by applying
thick shielding cups directly over
the scrotum.
Clamshell shield has aV cut for inserting the
testis and to hold in position,wax coating is done
on the inner surface of the shields. It makes the
inner surface smooth and avoid back-scattered
electron dose from the shield.
Prevention:

49. Features of hypogonadism:
 Loss of libido
 Erectile dysfunction
 Fatigue
 Decreased muscle mass
 Body and facial hair loss
 Difficulty in concentrating
 Depression
 Irritability
 Low sense of well-being

50. Management:
 Androgen replacement therapy to enable normal pubertal
development and future sexual function for patients with deficient
testosterone production.
 Inj testesterone 200 mg (I.M.) in every 2 weeks till regression of
symptoms occurs.
 Pre treatment sperm banking for fertitlity preservation

51. Effect on Pelvic Bones:
irreversible physiologic changes including narrowing of the vascular
channels (endarteritis)
blood flow↓
loss of osteocytes, osteoblasts
limited re-modelling of bone and limited healing .
Resulting injuries include atraumatic femoral neck fracture, and
osteonecrosis of the femoral head or of the acetabulum.
• Pathophysiology

52. Avascular necrosis of the femoral head
Right femoral head/acetabulum pathologic fracture identified on (Left) x‐ray and (Right) computed
tomography.

53.  The tolerance doses for the femoral head
 TD 5/5 is 52Gy , TD 50/5 is 65 Gy
 Prevetion: Femoral head sparing using conformal radiotherapy
 Treatment for bone fractures following radiation
1. calcium supplements
2. pain management with analgesics
3. surgical fixation.

54. Dermatological effects
• Sequential events of skin reactions of radiation
RT dose Gross change
> 5 Gy Transient erythema Due to capillary dilatation
mediated by histamine like
substances.
~ 20 Gy Epilation
20 – 40 Gy Dusky
pigmentation
Initially punctuated and then
coalesced – skin warm and
edematous.
~45 Gy
50 – 60 Gy
Dry desquamation
Moist
desquamation
Due to depletion of basal layer.
Epidermal slough and serous
discharge.

55. TD 5/5 55 Gy 100 cm2
50/5 65 Gy
TD 5/5 70 Gy 10 cm2
5/5 60 Gy 30 cm2
• most commonly observed in the
vulva, perineum, and the inguinal
and gluteal folds.

56. • Prevention:
1. Positioning: Frog leg position (supine with legs
abducted ) to reduce perineal skin reactions (in ca
vagina )
2. IMRT may decrease the risk of vulvar skin toxicity,
and one series reported no grade 3 groin skin
desquamation(1)
3. s
Beriwal S, Shukla G, Shinde A, et al. Preoperative intensity modulated radiation therapy and chemotherapy
for locally advanced vulvar carcinoma: analysis of pattern of relapse. Int J Radiat Oncol Biol
Phys. 2013;85:1269‐1274.

57. Management:
• Gentle cleaning with a mild, unperfumed soap is advised for folliculitis.
• moisturizing treated skin using hydrophilic moisturizer
• preventing mechanical or chemical irritation of treated skin (such as resulting from tight clothing
or perfumes) encouraged to wear loose‐fitting and cotton clothing and to avoid temperature
extremes
• adequate pain management
• Daily use of a sitz bath with the addition of sodium bicarbonate, Epsom salts, for symptomatic
relief.
• For patients with desquamation, the application of silver clear nylon, nonadherent or hydrogel
dressings,, creates a moist environment that stimulates wound healing. Vaseline gauze
impregnated with antibiotics may also provide topical relief and prevent secondary infection.

58.  Radiation to the ovaries can damage oocytes and result in premature menopause as a
result of ovarian failure
 Oocytes undergo meiosis and are relatively radioresistant (single dose LD50 is 4Gy)
however, proliferating granulosa cells are radiosensitive.
 a total dose of 24 Gy leads to ablation of ovaries due to the loss of granulosa cells.
 Immediate ovarian failure will be produced by 16.5 Gy in females of 20 years, and 14
Gy in 30-year-olds or in elderly group.
Ovaries
TD5/5 2-3 Whole ovary
(age
dependent )
TD50/5 6-12

59. Symptoms of ovarian irradiation includes-
 Amenorrhea
 Hot flashes
 Night sweats
 Vaginal dryness
 Irritability
 Difficulty in concentrating
 Loss of libido
 Infertility

60.  Hormonal therapy-Estrogen therapy can help prevent
osteoporosis and relieve hot flashes and other symptoms of
estrogen deficiency. Estrogens can be administered orally or
transdermally.
 The usual adult dose for transdermal estradiol is 100-150 mcg and
oral estradiol 2 to 4 mg.
 Progestins should be administered cyclically, 10-14 days in each
month, to prevent endometrial hyperplasia.
 The recommended regimens include medroxyprogesterone 10
mg daily for 10-12 days in each month.
 Preservation of fertility by egg storage (oocyte) is a useful
technique prior to treatment.
Management:

61.  Lined by stratified squamous epithelium
 early vaginal injury is marked by acute epithelial denudation with
endothelial injury that lead to thrombosis,edema,and smooth muscle
necrosis.
Vagina
TD5/5 90
TD50/5 100

62.  Delayed injury involves severe fibrosis that may obliterate
portions of the muscle and vasculature potentially resulting in
vaginal stenosis and ulceration.
 complications :
1. mucosal necrosis
2. fistula formation.
3. vaginal stenosis or shortening
4. formation of telangiectasia (which can lead to bleeding)
5. thinning of the vaginal mucosa
6. Vaginal dryness.

63.  soft tissue necrosis :
symptomatic management with antibiotics, debridement,
gentle irrigation of local area
 prevention of vaginal stenosis or shortening
encourage sexual intercourse
use of vaginal dilators.
 Estrogen cream or systemic estrogen may aid in the rejuvenation of cells and
increase the elasticity of the vagina.
 Vaginal douches: Twice daily use of a 1:10 diluted hydrogen peroxide douche can
prevent the formation of necrotic tissue, particularly in previously irradiated patients
Management

64. Bone marrow Suppression
• stem cells are particularly radiosensitive
• dose as low as 0.3 Gy leads to a reduction
in the number of lymphocytes. After
larger doses, lymphopenia is followed by
granulopenia, then thrombopenia, and
finally anemia.
• Hematologic toxicity predisposes patients
to infection, hospitalization, and
requirements for transfusions and growth
factors and lead to delayed or missed
chemotherapy cycles and treatment
breaks, which potentially may
compromise disease control.

65. Prevention:
1 . Sparing functional BM subregions:
Integration of functional imaging to identify
active BM subregions .
PET, single positron emission CT (SPECT),
and/or specialized MRI sequences
2. Bone marrow sparing IMRT

66. Management
1. Weekly blood counts are routinely obtained.
Chemotherapy is withheld when the neutrophil count decreases below 1500/μL., Platelet counts
fall below 100,000/ μL.
Transfusions to maintain a hemoglobin level above 10 mg/dL.
RT is withheld when the neutrophil count approaches 500/μL to 1000/μL.
2. Antibiotics in event of infections

67. Erectile dysfunction
 Critical erectile function and that receive a
substantial radiation dose include
neurovascular bundles (NVBs), internal
pudendal arteries (IPAs), accessory pudendal
arteries, corpora cavernosa and the penile bulb.
 The incidence of ED progressively
increases after RT in Ca prostate (1).
 Prevention:
IMRT technique with sparing of penile bulb
(1).Pinkawa M, Gagel B, Piroth MD, Fischedick K, Asadpour B, Kehl M, Klotz J, Eble MJ. Erectile
dysfunction after external beam radiotherapy for prostate cancer. Eur Urol. 2009 Jan;55(1):227-34. doi:
10.1016/j.eururo.2008.03.026. Epub 2008 Mar 24. PMID: 18375048.
(2). Sparing of the penile bulb and proximal penile structures with intensity-modulated radiation therapy for
prostate cancer, J Kao, J Turian, A Meyers, R J Hamilton, B Smith, S Vijayakumar, and A B Jani
The British Journal of Radiology 2004 77:914, 129-136

68. (1) Incrocci L. Radiotherapy for prostate cancer and sexual health. Transl Androl Urol. 2015
Apr;4(2):124-30. doi: 10.3978/j.issn.2223-4683.2014.12.08. PMID: 26813740; PMCID:
PMC4708125.
 Management:
Patients and their partner need to be counselled
Phosphodiesterase type 5 inhibitors (PDE5-I) sildenafil and tadalafil
have been shown to be effective to treat post-radiation ED in about half
of the patients in randomized trials. (1)

69. Secondary malignancy
I. Secondary Bladder Cancer: Radiation for rectal cancer found to be associated with an
increased risk of secondary bladder cancer (1)
II. Secondary Leukemia: pelvic radiation found to be associated with an increased risk of
secondary leukemia, risk is greatest 5 to 10 years after treatment and remains elevated
for up to 15 years after radiotherapy. The association is strongest for acute myeloid
leukemia, with an increased risk of acute lymphocytic leukemia and chronic myeloid
leukemia. (2)
1. Frontiers | Risk and Prognosis of Secondary Bladder Cancer After RadiationTherapy for Rectal Cancer: A Large
Population-Based Cohort Study | Oncology (frontiersin.org)
2. Pelvic radiotherapy and the risk of secondary leukemia and multiple myeloma -Wright - 2010 - Cancer -Wiley
Online Library

70. References:
 Eric J. Hall, Amato J. Giaccia - Radiobiology for the Radiologist-LWW (2018)
 ICRU 50 and ICRU 62
 Optimal organ-sparing intensity-modulated radiation therapy (IMRT) regimen for the treatment of
locally advanced anal canal carcinoma: a comparison of conventional and IMRT plans (nih.gov)
 Complications of pelvic radiation in patients treated for gynecologic malignancies -Viswanathan -
2014 - Cancer -Wiley Online Library
 Basic clinical radiobiology / edited by Michael C.Joiner and Albert J.Van der Kogel. Description: Fifth
edition
 Supriya Mallick • Goura K. Rath Rony Benson Editors Practical Radiation Oncology

71. THANK YOU