cervical carcinoma- everything for residents in oncology

1. CARCINOMA OF CERVIX
By-
Dr. Saadvik Raghuram.Y
MD Radiotherapy

2. • carcinoma cervix is the most common genital
cancer encountered in clinical practise in India.
• ca cervix accounts to 15% of all the cancers in the
female.

3. ETIOLOGY, EPIDEMIOLOGY AND
PRE DISPOSING FACTORS
• Average age 35-45 years
• coitus before the age of 18 years.
• multiple sexual partners.
• Delivery of the first baby before the age of 20
years.
• multiparity with poor birth spacing between
pregnancies.

4. • poor personal hygiene.
• poor socioeconomic status.
• women with-
• HIV
• HSV 2 infection
• HPV (16,18,31,33)
• condylomata , have an increased
risk.

5. • women with pre invasive lesion
• immunocompromised women(following transplant).
• women on combined oral contraceptives and
progesterone have doubled the risk of
ADENOCARCINOMA ENDOCERVIX
• 5% of women who received diethylstilbestrol in
utero developed cancer of vagina and cervix.
withdrawal of this hormone has reduced the
incidence.

7. CERVICAL INTRAEPITHELIAL
NEOPLASIA
• CIN refers to histopathological description in which a part or the full
thickness of the stratified squamous epithelium is replaced by cells
showing varying degree of dysplasia,but the BASEMENT
MEMBRANE IS INTACT.
• These pre invasive lesions end up as invasive lesions over a period
of time.
• 4% - at the end of first year
• 11%- by the end of 3 years
• 22%- by 5 years
• 30%- by 10 years

8. DYSPLASIA
• Dysplasia in term literally means disordered growth.It is
characterised by a constellation of changes that include a loss of
uniformity of the individual cells as well as a loss in their
architectural orientation.
• dysplasia is graded as
• mild (CIN I)
• moderate (CIN II)
• severe (CIN III)
• tadpole cells as seen in invasive cancer

9. • MILD DYSPLASIA(CIN I)- undifferentiated cells are
confined to lower third of epithelium.
• aka low grade squamous intraepithelial
neoplasia(LSIL)[Bethseda classification].
• MODERATE DYSPLASIA(CIN II)- undifferentiated cells
occupy lower 50-75% of thickness.
• SEVERE DYSPLASIA(CIN III)- entire thickness of
epithelium is filled with abnormal cells. basement
membrane is still intact.
• CIN II and CIN III are together considered as high grade
squamous intra-epithelial lesion HSIL.

11. • Mild dysplasias are usually seen with inflammatory
conditions or infections with trichomoniasis and HPV
and reversible following treatment.
• Severe varieties progress to invasive cancer in about
10-30% cases in 5-10 years.
• ICMR reports the incidence of dysplasia to be
15:1000 women cytologically screened.
• AHUJA from hyderabad reports an incidence of
dysplasia progressing into invasive cancer to be 0.5%
in mild dysplasia and 9.6% in severe dysplasia.

12. DIAGNOSIS
• Is based mainly on the cytological screening of the population.
• mostly are asymptomatic, few present with
• postcoital bleeding or
• discharge or
• post menopausal bleeding.
• on inspection- cervix appears normal or with an erosion which
bleeds on touch.
• All women who are above 21 years and sexually active for past
3 years should be routinely screened.

13. • American College of Obstetrics and Gynecology recently updated
their guidelines for cervical cancer screening.“ACOG Practice Bulletin no. 109: Cervical cytology
screening. Obstet Gynecol 2009;114:1409.”
• Screening is recommended every 2 years to begin at age 21
years.
• After age 30 years, the screening interval can be extended to 3
years for women who have no history of
• CIN 2 or CIN 3,
• who are not HIV-infected or otherwise immunocompromised, and
• who were not exposed to diethylstilbestrol (DES) in utero.
• Women who have had a total hysterectomy for benign conditions
and who have no history of high-grade CIN may discontinue
routine screening.

14. • It is also reasonable to discontinue screening for
women older than 65 to 70 years who have three
or more consecutive negative studies and have
had no abnormal test results in the past 10 years.
• Women previously treated for high-grade CIN or
for cancer should continue to have annual
screening for at least 20 years and periodic
screening indefinitely.

15. • PAP smear- is done routinely to screen patients.
• interpretation of pap smear is as follows-

16. • usefullness of the pap smear-
• it has helped detect CIN and treat it
adequately therefore reducing
incidence of invasive cancer by 80%
and mortality by about 60% in
developed nations.
• there is a latent period of approx 10-15
years for CIN to progress to invasive
cancer therefore adequate treatment is
given and invasive cancer can be
prevented.

17. • Due to the 15-30% false negative reporting,its
prudent to repeat the pap smear for 3 consecutive
years if negative.
• If continues to remain negative then is repeated 3-
5 yrs unto the age of 50 yrs. After the age of 50
yrs the incidence of CIN drops by to 1%.
• Sensitivity of pap smear for HSIL is 70-75% and
specificity is 95-98%.

18. • Pap smear in a postmenopausal women is often negative and
inaccurate on account of in drawing of the squamocolumnar
junction and dry vagina and poor exfoliation of cells.
• This can however be improved by oestrogen cream daily for 10
days or 400 mcg misoprostol.
• To reduce the number of false negatives the following can be
added to pap test-
• endocervical scrape cytology with endocervical brush/currettage.
• incorporating HPV testing by hybridization/PCR.
• Liquid based cytology.
• visual inspection of acetowhite areas( VIA).

19. Findings from a randomized, controlled trial conducted
among 150,000 women in Mumbai slums over a 15-year
period show that biennial screening for cervical cancer by
trained nonmedical personnel using acetic acid reduced
cervical cancer mortality by 31% .Clinical trial information:
NCT00632047.
If implemented in developing countries that have little or
no access to Pap screening, this easy-to-use procedure
could ultimately prevent 22,000 deaths from cervical
cancer in India and 72,000 deaths in low-resource
countries worldwide each year, according to Plenary
Session Presenter Surendra S. Shastri, MD, of the Tata
Memorial Hospital, India.
VIA

21. SUAL INSPECTION AFTER APPLICATION OF LUGALS IODINE

23. • COLPOSCOPY-
• to study cervix when pap smear shows
abnormal cells.
• to locate the extent of the lesion
• to take biopsies from abnormal areas.
• to manage by conservative surgeries.
• to follow up the conservative surgery
cases.

25. • CONE BIOPSY-
• It is both therapeutic and diagnostic.
• when the area of abnormality is
large or
• the squamocolumnar junction has
receded inwards into the canal.
• there is a discrepancy between
cytology and colposcopy findings
then the procedure can be applied.

26. • complications-
• bleeding
• infection
• cervical stenosis
• incompetent os

27. • HPV testing-
• it when combined with cytological screening increases the
positive predictive value.
• SITES-
• cells in liquid based cytology
• cells in endocervical secretion
• vaginal swab
• Combined HPV testing and pap smear yield sensitivity of
90% as compared to 60-70% with pap smear alone

31. • CRITERIA FOR CONSERVATIVE
PROCEDURE
• The entire area must be visible within the
squamocolumnar junction.
• No evidence of macro or micro metastasis as
proven by histopathological study.
• No evidence of endocervical involvement.
• Young women desirous of child bearing.

32. • Hysterectomy is desirable in-
• old and parous women,
• when a women cannot comply with
followup.
• if uterus is associated with
fibroids/DUB/prolapse.
• if micro invasion exists.
• if recurrence occurs following conservative
therapy or persistence of lesion.

33. • PROPHYLAXIS-
• Given before exposure to virus( before sexual
activity) in adolescents. 70% protection can be
expected.
• vaccines-
• bivalent vaccine (cervarix) HPV 16,18
• quadrivalent (gardisil) HPV 6,11,16,18.

36. • First dose given before exposure - 0.5ml
• second dose given 2 months after first dose
• Third dose given 6 months after first dose
• vaccines are contraindicated in pregnancy
• side effects- fever, local pain, erythema.
• other vaccines may be given simultaneously at different
sites.
• nasal and oral vaccines are under trial.

37. INVASIVE
CARCINOMA CERVIX

38. • EPIDEMIOLOGY-
• Cervical cancer is the 4th most common cancer in
women.
• Estimated 528,000 cases are diagnosed
worldwide with 266,000 deaths in 2012.
• In India- 123,000 cases detected with 67,000
deaths in 2012.

39. Estimated cervical cancer incidence worldwide in 2012

41. Government of India-World Health Organization Collaborative
Programme (2004-2005)

42. • NATURAL HISTORY AND PATTERN OF
SPREAD
• Most cervical carcinomas arise at the junction
between the primarily columnar epithelium of the
endocervix and the squamous epithelium of the
ectocervix.
• This junction is a site of continuous metaplastic
change, which is greatest
• in utero,
• at puberty, and
• during first pregnancy, and declines after
menopause.

43. • Once tumor has broken through the basement membrane, it may
penetrate the cervical stroma directly or through vascular
channels.
• Invasive tumours may develop as exophytic growths protruding
from the cervix into the vagina or as endocervical lesions that can
cause massive expansion of the cervix despite a relatively normal-
appearing ectocervix.
• From the cervix, tumor may extend
• superiorly -to the lower uterine segment,
• inferiorly -to the vagina,
• laterally- to the broad ligaments (where it may cause ureteral
obstruction),
• posterolaterally -to the uterosacral ligaments.

44. • Extensive bladder involvement is uncommon, occurring in fewer than
5% of cases.
• LYMPHATIC DRAINAGE-
• The upper branches-which originate in the anterior and lateral cervix,
follow the uterine artery, are sometimes interrupted by a node as they
cross the ureter, and terminate in the uppermost hypogastric nodes.
• The middle branches drain to deeper hypogastric (obturator) nodes.
• The lowest branches follow a posterior course to the inferior and
superior gluteal, common iliac, presacral, and subaortic nodes.

45. • Additional posterior lymphatic channels-
• arising from the posterior cervical wall may
drain to superior rectal nodes or may
continue upward in the retrorectal space to
the subaortic nodes overlying the sacral
promontory.
• Anterior collecting trunks-
• pass between the cervix and bladder along
the superior vesical artery and terminate in
the internal iliac nodes.

47. • Cervical cancer usually follows a relatively orderly
pattern of metastatic progression, initially to primary-
echelon nodes in the pelvis and then to para-aortic
nodes and distant sites.
• Even patients with locoregionally advanced disease
rarely have detectable hematogenous metastases at
initial diagnosis of cervical cancer.
• The most frequent sites of distant recurrence are
• lung,
• extrapelvic nodes,
• liver, and
• bone.

48. PATHOLOGY
• ADENOCARCINOMA IN SITU
• MICROINVASIVE CARCINOMA
• INVASIVE SQUAMOUS CELL CARCINOMA
• ADENOCARCINOMA
• ANAPLASTIC SMALL CELL/ NEUROENDOCRINE
CARCINOMA
• OTHERS

49. • ADENOCARCINOMA IN SITU-
• Is diagnosed when normal endocervical gland cells
are replaced by tall, irregular columnar cells with
stratified, hyperchromatic nuclei and increased
mitotic activity but the normal branching pattern of
the endocervical glands is maintained and there is
no obvious stromal invasion.
• Adenocarcinoma in situ is frequently multifocal,
cone biopsy margins are unreliable.

50. • MICROINVASIVE CARCINOMA-
• Microinvasive carcinoma is defined by International
Federation of Gynecology and Obstetrics (FIGO) as
“invasive carcinoma which can be diagnosed only by
microscopy, with deepest invasion ≤5 mm and largest
extension ≥7 mm”
• Following the advent of cytologic screening, the
proportion of invasive carcinomas that invade less than 5
mm increased more than tenfold to about 20% in the
United States.
• Lesions that have invaded less than 3 mm (FIGO stage
IA1) are rarely associated with metastases; 5% to 10% of
tumors that have invaded 3 to 5 mm (FIGO stage IA2) are
associated with positive pelvic lymph nodes.

51. • INVASIVE SQUAMOUS CELL CARCINOMA-
• 80% to 90% of cervical carcinomas are squamous cell
carcinomas.
• Although squamous neoplasms are often subclassified as
• large cell keratinizing,
• large cell nonkeratinizing, or
• small cell carcinomas, these designations do not
correlate well with prognosis.
• However most authorities believe that small cell
carcinoma has somewhat poorer prognosis than large cell
neoplasms with or without keratin“Robert ME, Fu YS. Squamous cell carcinoma of the
uterine cervix: a review with emphasis on prognostic factors and unusual variants. Semin Diagn Pathol 1990;7:173.”

52. • Papillary variants of squamous carcinoma may be well
differentiated (occasionally confused with immature
condylomata) or very poorly differentiated (resembling
high-grade transitional carcinoma).
• Verrucous carcinoma is a very rare warty-appearing
variant of squamous carcinoma that may be difficult to
differentiate from benign condyloma without multiple
biopsies or hysterectomy.
• Sarcomatoid squamous carcinoma is another very rare
variant, demonstrating areas of spindle-cell
carcinomatous tumor confluent with poorly differentiated
squamous cell carcinoma.
• Immunohistochemistry demonstrates expression of
cytokeratin as well as vimentin.

53. • ADENOCARCINOMA-
• Invasive adenocarcinoma may be pure or mixed
with squamous cell carcinoma (adenosquamous
carcinoma).
• About 80% of cervical adenocarcinomas are
endocervical-type adenocarcinomas.
• Endocervical-type adenocarcinomas are
frequently referred to as mucinous.
• Minimal-deviation adenocarcinoma (adenoma
malignum) is a rare, extremely well-differentiated
adenocarcinoma that is sometimes associated
with Peutz-Jeghers syndrome.

54. • Due to the branching glandular pattern strongly resembles
normal endocervical glands and the mucin-rich cells can be
deceptively benign-appearing, minimal-deviation
adenocarcinoma may not be recognized as malignant in small
biopsy specimens.
• Glassy cell carcinoma is a variant of poorly differentiated
adenosquamous carcinoma characterized by cells with
abundant eosinophilic, granular, ground-glass cytoplasm with
large round to oval nuclei and prominent nucleoli.
• Adenoid basal carcinoma is a well-differentiated tumor that
histologically resembles basal cell carcinoma of the skin and
tends to have a favorable prognosis.
• Adenoid cystic carcinoma consists of basaloid cells in a
cribriform or cylindromatous pattern; metastases are frequent,
although the natural history of these tumors may be long.

55. • ANAPLASTIC SMALL CELL/
NEUROENDOCRINE CARCINOMA-
• Anaplastic small cell carcinomas resemble oat cell
carcinomas of the lung and are made up of small tumor
cells that have scanty cytoplasm, small round to oval nuclei,
and high mitotic activity.
• Anaplastic small cell carcinomas behave more aggressively
than poorly differentiated small cell squamous carcinomas.
• Most investigators report survival rates of less than 50%
even for patients with early stage I disease.
• Widespread hematogenous metastases are frequent, but
brain metastases are rare unless preceded by pulmonary
involvement.

56. CLINICAL
MANIFESTATIONS-
• Early invasive disease may not be associated with any
symptoms and is also usually detected during screening
examinations.
• The earliest symptom of invasive cervical cancer is
usually abnormal vaginal bleeding, often following coitus
or vaginal douching.
• This may be associated with a clear or foul-smelling
vaginal discharge.
• Pelvic pain may result from locoregionally invasive
disease or from coexistent pelvic inflammatory disease.

57. • Flank pain may be a symptom of hydronephrosis,
often complicated by pyelonephritis.
• Patients with very advanced tumors may have
hematuria or incontinence from a vesicovaginal
fistula caused by direct extension of tumor to the
bladder.
• External compression of the rectum by a massive
primary tumor may cause constipation, but the
rectal mucosa is rarely involved at initial
diagnosis.

58. CLINICAL EVALUATION-
• All patients with invasive cervical cancer should
be evaluated with a detailed history and physical
examination, with particular attention paid to
inspection and palpation of the pelvic organs with
bimanual and rectovaginal examinations.
• All patients should have chest radiography to rule
out lung metastases; additional imaging of the
abdomen and pelvis should be performed for all
patients who have stage IB2 or greater disease.

61. • Cystoscopy and either a proctoscopy or a barium
enema study should be considered in patients
with bulky tumors, particularly for those with
computed tomography (CT) or magnetic
resonance imaging (MRI) findings suggestive of
organ involvement.
• The results of CT or MRI scans to evaluate
regional lymph nodes, have suboptimal accuracy
because they fail to detect small metastases and
because patients with bulky necrotic tumors often
have enlarged reactive lymph nodes that may be
free of metastasis.

62. • In a large Gynecologic Oncology Group (GOG)
study that compared the results of radiographic
studies with subsequent histologic findings, Heller
et al.56 found that the sensitivity of CT in the
detection of positive para-aortic nodes was only
34%.
• Positron emission tomography appears to be a
more sensitive, noninvasive method of evaluating
the regional nodes of patients with cervical cancer
and a useful method for following response to
treatment.
• MRI provides more accurate information than CT
about the distribution of tumor in the cervix and
paracervical tissues .

63. CLINICAL STAGING
• The FIGO staging system is the most widely accepted
staging system for carcinomas of the cervix.
• FIGO stage is based primarily on careful clinical
examination.
• The use of diagnostic imaging techniques to assess tumor
size and local extent is encouraged but not mandatory in
the 2009 staging system.
• FIGO still does not incorporate evidence of lymph node
metastasis gained by surgical staging or advanced imaging
studies in the 2009 staging system.

64. • Stage should be assigned before any definitive
therapy is administered.
• The clinical stage should never be changed on the
basis of subsequent findings.
• When the stage to which a particular case should
be allotted is in doubt, the case should be
assigned to the earlier stage.

66. TNM STAGING

71. PROGNOSIS FACTORS
• Tumour size,
• dept of stromal invasion
and
• lymph node metastasis
are considered important
prognostic factors.

73. • Lymph node metastasis is one of the most
important predictors of prognosis.
• Survival rates for patients treated with radical
hysterectomy with or without postoperative
radiotherapy for stage IB disease were usually
reported as 85% to 95% for patients with negative
nodes and 45% to 55% for those with lymph node
metastases.
• {“Averette HE, Lichtinger M, Sevin BU, et al. Pelvic exenteration: a 150-year experience in a general hospital. Am J
Obstet Gynecol 1970;150:179.
• Delgado G, Bundy B, Zaino R, et al. Prospective surgical-pathological study of disease-free interval in patients with stage IB
squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol 1990;38:352”}

74. • Roman et al reported a correlation between the
percentage of histopathologic sections containing
LVSI and the incidence of lymph node
metastases.
• Uterine-body involvement has been associated
with an increased rate of distant metastases[Noguchi H,
Shiozawa I, Kitahara T, et al. Uterine body invasion of carcinoma of the uterine cervix as seen from surgical
specimens. Gynecol Oncol 1988;30:173.]
• Most investigators have concluded that
adenocarcinomas confer a poorer prognosis [Shingleton
HM, Bell MC, Fremgen A, et al. Is there really a difference in survival of women with squamous cell carcinoma,
adenocarcinoma, and adenosquamous cell carcinoma of the cervix? Cancer 1995;76:1948.]

75. TREATMENT OF
INVASIVE CARCINOMA
CERVIX
BY -Dr.SAADVIK.R.Y
JR-1
MD (RADIATION ONCOLOGY)

76. • The treatment is based on the stage of the
disease.
• STAGE 1A-
• The standard treatment for patients with
stage IA1 disease is cervical conization or
total (type I) hysterectomy.
• The risk of pelvic lymph node metastases
from these minimally invasive tumors is
less than 1%,pelvic lymphadenectomy is
not usually recommended.Kolstad P. Follow-up study of 232
patients with stage Ia1 and 411 patients with stage Ia2 squamous cell carcinoma of the
cervix (microinvasive carcinoma). Gynecol Oncol 1989;33:265.”

77. • Patients who have FIGO stage IA1 disease without
LVSI and who wish to maintain fertility may be
adequately treated with a therapeutic cervical
conization if the margins of the cone are negative.
• Although reports suggest that recurrences are
infrequent,patients who have this conservative
treatment must be followed very closely with
• periodic cytologic evaluation,
• colposcopy, and
• endocervical curettage.
• Diakomanolis E, Haidopoulos D, Rodolakis A, et al. Laser CO(2) conization: a safe mode of treating conservatively
microinvasive carcinoma of the uterine cervix. Eur J Obstet Gynecol Reprod Biol 2004;113:229.

78. • As accurate assessment of the maximum depth of invasion is
critical, the entire specimen must be sectioned and carefully
handled to maintain its original orientation for microscopic
assessment.
• Complications occur in 2% to 12% of patients, are related to the
depth of the cone, and include
• hemorrhage,
• sepsis,
• infertility,
• stenosis, and
• cervical incompetence.

79. • STAGE 1A2-
• Whose tumors invade 3 to 5 mm into the stroma (FIGO stage IA2), the risk of
nodal metastases is approximately 5%.
• Therefore, in such patients, bilateral pelvic lymphadenectomy should be
performed in conjunction with modified radical (type II) hysterectomy.
• The uterus,
• cervix,
• upper vagina, and
• paracervical tissues are removed after careful dissection of the
ureters to the point of their entry to the bladder.
• The medial halves of the cardinal ligament and the uterosacral
ligaments are also removed.

80. The pelvic ligaments and spaces. Dotted lines indicate the tissues
removed with a modified radical (type II) or radical (type III)

81. STAGE 1B AND IIA
• Early-stage IB cervical carcinomas can be treated effectively with
combined external-beam irradiation and brachytherapy or with
radical hysterectomy and bilateral pelvic lymphadenectomy.
• Disease-specific survival rates for patients with stage IB cervical
cancer treated with surgery or radiation usually range between
80% and 90%, suggesting that the two treatments are equally
effective.
• “Alvarez RD, Potter ME, Soong SJ, et al. Rationale for using pathologic tumor dimensions and nodal status to subclassify surgically treated stage IB cervical
cancer patients. Gynecol Oncol 1991;43:108.
• Eifel PJ, Morris M, Wharton JT, et al. The influence of tumor size and morphology on the outcome of patients with FIGO stage IB squamous cell carcinoma of the
uterine cervix. Int J Radiat Oncol Biol Phys 1994;29:9.
• Perez CA, Grigsby PW, Nene SM, et al. Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone. Cancer
1992;69:2796.”

82. • In 1997, Landoni et al. reported results from the only prospective
trial comparing radical surgery with radiotherapy alone for
cervical cancer. In their study, 343 patients with stage IB or IIA
disease were randomly assigned to treatment with radical (type
III) hysterectomy or a combination of external-beam and low-
dose-rate (LDR) intracavitary brachytherapy.
• In the surgery arm, findings of parametrial involvement, positive
margins, deep stromal invasion, or positive nodes led to the use
of postoperative pelvic irradiation in 54% of patients with tumors
4 cm or smaller in diameter and in 84% of patients with larger
tumors.
• Patients in the radiotherapy arm received a relatively low
median dose to point A of 76 Gy.

83. 0 50 100
TUMOUR <4cms
TUMOUR >4cms
percentage
5yearACTURIALDFS

84. • For patients with stage IB1 squamous carcinomas, the choice of
treatment is based primarily on patient preference,
• anesthetic and surgical risks,
• physician preference, and
• an understanding of the nature and incidence of complications with
hysterectomy and radiotherapy.
• Urinary tract complications tend to be more common after surgical
treatment and bowel complications are more common after
radiotherapy.
• Surgical treatment tends to be preferred for young women with small
tumors because it permits
• preservation of ovarian function and
• may cause less vaginal shortening.
• Radiotherapy is often selected for older, postmenopausal women to
avoid the morbidity of a major surgical procedure.

85. • In stage IB2 (bulky) tumors, some surgeons have
advocated the use of radical hysterectomy as
initial treatment.
• “Alvarez RD, Gelder MS,”Gore H, et al. Radical hysterectomy in the treatment of patients with bulky
early stage carcinoma of the cervix uteri. Surg Gynecol Obstet 1993;176:539.
• Bloss JD, Berman ML, Mukhererjee J, et al. Bulky stage IB cervical carcinoma managed by primary
radical hysterectomy followed by tailored radiotherapy. Gynecol Oncol 1992;47:21.
• Rettenmaier MA, Casanova DM, Micha JP, et al. Radical hysterectomy and tailored postoperative
radiation therapy in the management of bulky stage IB cervical cancer. Cancer 1989;63:2220.”
• However, patients who have tumors measuring more
than 4 cm in diameter usually have deep stromal
invasion and are at high risk for lymph node involvement
and parametrial extension.

86. • Patients with these risk factors have an increased
rate of pelvic disease recurrence, surgical treatment
is usually followed by postoperative irradiation or
chemoradiation.
• Two prospective randomized trialsdemonstrated
that patients who are treated with radiation for bulky
stage I cancers benefit from concurrent
administration of cisplatin-containing chemotherapy.
• Eifel PJ. Concurrent chemotherapy and radiation: a major advance for women with cervical
cancer. J Clin Oncol 1999;17:1334.
• Keys HM, Bundy BN, Stehman FB, et al. Cisplatin, radiation, and adjuvant hysterectomy for
bulky stage IB cervical carcinoma. N Engl J Med 1999;340:1154.”

87. • A third study suggested that patients who require
postoperative radiotherapy because of findings of lymph
node metastasis or involved surgical margins also benefit
from concurrent chemoradiation.
• “Peters WA III, Liu PY, Barrett RJ II, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as
adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 2000;18:1606.”
• Patients who have stage IB1 cancers without evidence of regional
involvement have excellent pelvic control rates with radiotherapy
alone (about 97% at 5 years) and probably do not require
chemotherapy when they are treated with primary radiotherapy.
• “Eifel PJ, Morris M, Wharton JT, et al. The influence of tumor size and morphology on the outcome of patients with FIGO stage IB squamous cell
carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 1994;29:9.
• Perez CA, Grigsby PW, Nene SM, et al. Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone.
Cancer 1992;69:2796.”

88. • Consequently, many gynecologic and radiation
oncologists believe that patients with stage IB2
carcinomas are better treated with primary
chemoradiation.

89. Stage IIB, III, and IVA
Disease
• Radiotherapy is the primary local treatment for
most patients with locoregionally advanced
cervical carcinoma.
• The success of radiotherapy depends on a careful
balance between external-beam radiotherapy and
brachytherapy, optimizing the dose to tumor and
normal tissues and the overall duration of
treatment.

90. • For patients treated with radiotherapy alone for
stage IIB, IIIB, and IV disease, 5-year survival
rates of 65% to 75%, 35% to 50%, and 15% to
20%, respectively, have been reported.
• “Benedet J, Odicino F, Maisonneuve P, et al. Carcinoma of the cervix uteri. J Epidemiol Biostat
1998;3:5.
• Logsdon MD, Eifel PJ. FIGO IIIB squamous cell carcinoma of the cervix: an analysis of
prognostic factors emphasizing the balance between external beam and intracavitary radiation
therapy. Int J Radiat Oncol Biol Phys 1999;43:763.”

91. • A series of prospective randomized trials provide compelling
evidence that the addition of concurrent cisplatin-containing
chemotherapy to standard radiotherapy reduces the risk of
disease recurrence by as much as 50% .
• “Peters WA III, Liu PY, Barrett RJ II, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant
therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 2000;18:1606.”
• “Keys HM, Bundy BN, Stehman FB, et al. Cisplatin, radiation, and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 1999;340:1154.”
• “Eifel PJ, Winter K, Morris M, et al. Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an
update of Radiation Therapy Oncology Group trial (RTOG) 90-01. J Clin Oncol 2004;22:872.”
• “Rose PG, Bundy BN, Watkins J, et al. Concurrent cisplatin-based chemotherapy and radiotherapy for locally advanced cervical cancer. N Engl J Med
1999;340:1144.”“
• M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med
1999;340:1137.
• Whitney CW, Sause W, Bundy BN, et al. A randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stages
IIB–IVA carcinoma of the cervix with negative paraaortic lymph nodes: A Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol
1999;17:1339.
• Pearcey R, Brundage M, Drouin P, et al. A clinical trial comparing concurrent cisplatin and radiation therapy versus radiation alone for locally advanced
squamous cell carcinoma of the cervix carried out by the National Cancer Institute of Canada Clinical Trials Group. Proc Am Soc Clin Oncol 2000;19:378a.”

92. • Breaks during or between external-beam and
intracavitary therapy should be discouraged, and every
effort should be made to complete the entire radiation
treatment in less than 7 to 8 weeks.
• Several studies have suggested that treatment courses
longer than 8 weeks are associated with decreased pelvic
disease control and survival rates.
• “Fyles A, Keane TJ, Barton M, et al. The effect of treatment duration in the local control of cervix
cancer. Radiother Oncol 1992;25:273.
• Perez CA, Grigsby PW, Castro-Vita H, et al. Carcinoma of the uterine cervix. I. Impact of
prolongation of overall treatment time and timing of brachytherapy on outcome of radiation
therapy. Int J Radiat Oncol Biol Phys 1995;32:1275.
• Petereit DG, Sarkaria JN, Chappell R, et al. The adverse effect of treatment prolongation in
cervical carcinoma. Int J Radiat Oncol Biol Phys 1995;32:1301.”

93. TECHNIQUES OF RADIATION
• Since the early 1900s, radiation has been used in the curative
management of cervical cancer, with a combination of external-
beam and brachytherapy resulting in the highest survival rates.
• External irradiation is used to treat the whole pelvis. Structures
treated include the
• uterus and
• cervix or,
• in the postoperative cases, the tumor bed, the vagina,
the parametrial tissue, and the pelvic lymph nodes,
including the internal, external, and common iliac
nodes.
• In selected cases the para-aortic lymph nodes may be
treated.

94. • In patients with locally advanced disease, in
addition to external-beam radiation, treatment of
central disease i.e.
• cervix,
• vagina, and
• medial parametria
• relies heavily on dose given with intracavitary
sources through brachytherapy.

95. • EXTERNAL BEAM IRRADIATION-
• External-beam treatments may be routinely administered to
cervical cancer patients with stages IB2 to IVA in a curative
fashion.
• Patients with stages IA to IB1 may be considered for external-
beam treatment if they are deemed inoperable or prefer to
avoid surgery.
• Patients with stage IVB disease may receive palliative
radiation to the pelvis for selected indications such as to
• stop vaginal bleeding,
• relieve pain, or
• alleviate urethral obstruction from extrinsic compression.

96. • In treatment of invasive carcinoma of the uterine
cervix, it is important to deliver adequate doses of
irradiation not only to the primary tumor, but also
to the pelvic lymph nodes to maximize tumor
control.
• The initiation of external-beam radiation typically
precedes brachytherapy.
• The brachytherapy dose to the normal tissues
may be better optimized after maximal tumor
shrinkage; therefore, many institutions prefer to
wait until the completion of 45-Gy treatment
before initiating brachytherapy for patients with
large tumors.

97. • PATIENT POSITIONING-
• Patients may be positioned in either the
• supine position for stability or
• the prone position on a belly board.
• The prone position aids in shifting small bowel out
of the pelvis.
• In patients who have had a hysterectomy, small
bowel may drop into the pelvic area.

98. prone position bell board

99. • For those patients treated for cervical cancer with
an intact cervix,
• the small bowel often lies superior to the uterus
and above the pelvic brim, creating less need to
shift the bowel out of the pelvis.
• For patients receiving IMRT, due to stability of the
pelvis, the supine position is typically preferred
with immobilization devices surrounding the pelvis
to ensure minimal motion during treatment.

100. • PLAIN X-RAY SIMULATION-
• If CT is not available, simple plain film
simulation may be performed.
• The standard plain radiographic simulation to
the pelvis with x-rays, typically using
opposed anterior–posterior:posterior–
anterior (AP-PA) fields, results in
comprehensive coverage of all pelvic
regions.
• Due to the lack of visible soft-tissue detail,
contrast may be placed using
• barium in the rectum,
• a vaginal tube in the vagina, and/or
• a wire marker over surgical scars.

101. • The superior border is set at the L4-5 interspace
in order to cover the common iliac lymph nodes
and
• The lateral borders 1.5 to 2 cm from the pelvic
brim.
• The inferior border covers at least the obturator
foramen.

102. nce are used for stage IB (broken line), and 18 by 15 cm portals are used for more advanced disease (solid
e indicated as A). When the common iliac nodes are to be covered, the upper margin is extended to the L4

103. • When the tumor involves the distal half of the
vagina, the portals should be modified to cover the
inguinal lymph nodes because of the increased
probability of metastases.
• The lateral field borders, in both postoperative and
intact cervix settings,
• the posterior border must be set in such a way
that the entire sacrum is covered because the
uterosacral ligaments are at high risk for
harboring microscopic extension.
• The anterior border on the lateral field should be
set at a vertical line anterior to the pubic
symphysis, since the external iliac lymph nodes
must be covered.

104. • Patients with para-aortic nodal involvement, simple plain film
simulation followed by AP-PA treatments to the para-aortic nodal
chain may overdose the
• kidneys,
• spinal cord, and
• small bowel.
• Dose escalation to para-aortic nodes to approximately >45 Gy is
not feasible with AP-PA fields, given potential bowel complications.
• The use of four fields, including AP-PA and two lateral fields, is
implemented as an alternative to AP-PA alone as a way to reduce
some of the dose to the anterior small bowel.

105. • Patients receive oral barium approximately 30
minutes before the simulation to ensure blockage
of as much small bowel as feasible superiorly.
• The superior border covers the renal hilum, often
at the T12-L1 interspace, and
• The inferior borders cover the obturator foramen,
unless there is distal vaginal or inguinal node
involvement.
• The para-aortic portion of the field, the anterior
border rests 2 cm in front of the vertebral body or
enlarged nodes as contoured, and posteriorly the
border bisects the mid-vertebral body.

106. 3D CONFORMAL
TREATMENT PLANNING

107. • CT simulation allows direct assessment of the
pelvic vessels and by adjacent location the para-
aortic and pelvic nodes.
• Cerrobend customized blocks or multileaf
collimator blocking is used on each field to block
the radiation to selected areas, including the
• skin,
• muscle,
• soft tissue,
• anterior small bowel, and
• portions of the anus and lower rectum

108. • The superior border is set based on the CT-visualized
bifurcation of the common iliac nodes into the
• external and
• internal iliac nodes,
• which may lie as high as the L3-4 interspace.
• If patients have positive pelvic nodes based on PET imaging,
the superior border may be shifted to either the superior border
of the common iliac nodes or the superior aspect of the renal
hilum to treat the para-aortic nodes.
• In postoperative cases in which the patient has had an
extensive surgical staging, the superior border may be reduced
to the L5-S1 interspace.

109. • Similar to plain x-ray simulation, in patients with
vaginal involvement, the inferior border is
extended to cover 2 cm below the lowest extent of
disease, which may lie in the vulvar tissue, and in
such cases the inguinal lymph nodes are treated,
resulting in a wider AP field.
• Lateral fields- the anterior border covers the front
of the pubic symphysis.
• For the lateral borders in postoperative and intact
cervix cases, posterior coverage of the entire
sacral hollow is imperative.

110. • Zunino et al reviewed the appropriateness of radiation therapy
box technique for cancer of the cervix in 35 sagittal MRIs and 10
lymphangiograms.
• If the posterior border were to be placed at the S2-3 interspace,
for 50% of the patients with FIGO IB and in 67% with stage IIA
disease, the posterior border of the lateral field would not
adequately encompass the planning target volume (PTV).
• In stage IIB, the posterior border was inadequate in eight
patients (42%).
• In patients with stage IIB and IVA disease, the PTV was not
encompassed.
• Zunino S, Rosato O, Lucino S, et al. Anatomic study of the pelvis in carcinoma of the uterine cervix as related to the box
technique. Int J Radiat Oncol Biol Phys 1999;44:53–59.

111. • Finlay et al contoured pelvic blood vessels on CT
scans as surrogates for lymph nodes in 43
patients and found this to be more accurate than
bony landmarks for field delineation.
• In total, 95% of patients planned with conventional
fields had inadequate coverage of some portion of
lymph node coverage, whereas in 56% additional
normal tissue was treated that did not require
radiation.
• Therefore, most centers implement 3D simulation
when feasible.
• Finlay MH, Ackerman I, Tirona RG, et al. Use of CT simulation for treatment of cervical cancer
to assess the adequacy of lymph node coverage of conventional pelvic fields based on bony
landmarks. Int J Radiat Oncol Biol Phys 2006;64:205–209.

112. • Yamazaki et al. compared
• 34 patients with cervical cancer treated with
irregularly shaped four-field whole-pelvis radiation
therapy using CT simulation and
• 40 patients receiving whole-pelvis EBRT with
parallel-opposed fields
• In a nonrandomized study of postoperative
radiation therapy consisting of 50 Gy in 25
fractions in 6 weeks.

113. 0 25 50 75 100 125
ACTURIAL PELVIC TUMOUR CONTROL
BOWEL COMPLICATIONS

114. INTENSITY MODULATED
RADIATION
• IMRT was developed using the techniques
required for inverse planning. That is, one starts
with the necessary dose around the target then
works backward to develop the requisite beam
intensities.
• IMRT spatially modulates the intensity of the
beam using the motion of multileaf collimators.
• The use of IMRT has been standardized in the
postoperative setting but remains a topic of
debate for intact cervix cases.

115. • What constitutes adequate margins in the intact cervix setting
continues to be a matter of concern, given significant organ
motion during treatment.
• Beadle et al. found that mean maximum changes in the center
of the cervix were 2.1, 1.6, and 0.82 cm in the superior–inferior,
anterior–posterior, and right–left lateral dimensions,
respectively.
• “Beadle BM, Jhingran A, Salehpour M, et al. Cervix regression and motion during the course of external beam chemoradiation for cervical cancer. Int J Radiat
Oncol Biol Phys 2009;73:235–241.”
• Mean maximum changes in the perimeter of the cervix were
• 2.3 and 1.3 cm in the superior and inferior,
• 1.7 and 1.8 cm in the anterior and posterior, and
• 0.76 and 0.94 cm in the right and left lateral directions, respectively.

116. • Haripotepornkul et al -cervical motion averages
approximately 3 mm but may be up to 18 mm in any
given direction within and between treatments.
• The mean intrafractional movements in cervical seed
positions in the lateral, vertical, and AP directions were
1.6 mm (standard deviation [SD] ± 2.0), 2.6 mm (SD ±
2.4), and 2.9 mm (SD ± 2.7), respectively, with a range
from 0 to 15 mm for each direction.
• The mean interfractional movements in the lateral,
vertical, and AP directions were 1.9 mm (SD ± 1.9), 4.1
mm (SD ± 3.2), and 4.2 mm (SD ± 3.5), respectively,
with a range from 0 to 18 mm for each direction.
• “Haripotepornkul NH, Nath SK, Scanderbeg D, et al. Evaluation of intra- and inter-fraction movement of the cervix
during intensity modulated radiation therapy. Radiother Oncol 2011;98:347–351.”

117. • Tyagi et al. show that a uniform CTV planning treatment volume
margin of 15 mm would not encompass the cervical CTV in 32% of
fractions.
• With IMRT, there is a need for continual replanning (at least every
other week), given
• rapid tumor regression and
• internal-organ motion.“
• Lim K, Chan P, Dinniwell R, et al. Cervical cancer regression measured using weekly magnetic resonance imaging during
fractionated radiotherapy: radiobiologic modeling and correlation with tumor hypoxia. Int J Radiat Oncol Biol Phys 2008;70:126–
133.
• 318. Lee CM, Shrieve DC, Gaffney DK. Rapid involution and mobility of carcinoma of the cervix. Int J Radiat Oncol Biol Phys
2004;58:625–230.
• 319. van de Bunt L, Jurgenliemk-Schulz IM, de Kort GA, et al. Motion and deformation of the target volumes during IMRT for
cervical cancer: what margins do we need? Radiother Oncol 2008;88:233–240.”

118. • The greatest variability in physician contouring was in the
parametrial tissue.
• “Lim K, Small W Jr, Portelance L, et al. Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy for the definitive
treatment of cervix cancer. Int J Radiat Oncol Biol Phys 2011;79:348–355.”

119. • The CTV for the pelvic lymph nodes was based on the
Radiation Therapy Oncology Group (RTOG) atlas for the
female postoperative pelvis.
• Fiducial markers may be placed in the apex of the vagina
for identification on CT scan and show up to 3.5 cm of
vaginal cuff motion during treatment.
• Therefore, for postoperative patients, the vagina is
contoured using a full-bladder CT scan fused to an empty-
bladder CT scan to account for vaginal mobility due to
differences in bladder filling.
• This vaginal target volume has been referred to as an
integrated target volume (ITV).

125. • Generous margins of approximately 2 to 3 cm are
considered, particularly in the regions of the
uterus and cervix or in the postoperative case
around the ITV vagina for the PTV

126. • Dose constraints required for an optimal IMRT plan have not been
standardized.
• RTOG postoperative clinical trial 0921 using IMRT-
• A PTV of 7 mm around the nodal contours is recommended, and the dose is prescribed
to cover 97% of the vaginal PTV and nodal PTV.
• A volume of 0.03 cc within any PTV should not receive >110% of the prescribed
dose.
• No more than 0.03 cc of any PTV will receive <93% of its prescribed dose.
• Any contiguous volume of 0.03 cc or larger of the tissue outside the vaginal/nodal
PTVs must not receive >110% of the dose prescribed to the vaginal/nodal PTV;
• For normal tissues the small/large bowel (30% of the entire bowel volume must not
receive >40 Gy),
• Rectum/sigmoid (60% of the rectosigmoid volume must receive ≤40 Gy),
• Badder (35% of the bladder volume must receive ≤45 Gy), and
• Femoral head (15% of the femoral head volume must receive <35 Gy) constraints
are being tested in RTOG 0921.

127. • Careful attention must be paid to all normal-tissue organ motion because the
bladder and rectum may have 3- to 5-cm shifts due to filling changes in a short
time frame.
• Normal-tissue structures, including the
• rectum,
• sigmoid,
• bladder, and small bowel,
• are routinely contoured for patients treated with IMRT who will be undergoing a
nodal boost in order to limit the dose received primarily to the small bowel.
• Based on an overview of published data-
• absolute volume of small bowel receiving ≥15 Gy should be held to <120 cc
when possible to minimize severe acute toxicity if delineating the contours of
bowel loops themselves.
• Alternatively, if the entire volume of peritoneal space in which the small bowel
can move is delineated the volume receiving >45 Gy should be <195 cc when
possible.

128. • No dose constraint for external beam planning for the bladder
could be identified, although the limits for prostate cancer may
be adopted for gynecologic IMRT.“Viswanathan AN, Yorke ED, Marks LB, et al.
Radiation dose-volume effects of the urinary bladder. Int J Radiat Oncol Biol Phys 2010;76:S116–S122.”
• A dose constraint of
• no more than 15% of the volume to receive a dose >80 Gy,
• no more than 25% of the volume to receive a dose >75 Gy,
• no more than 35% of the volume to receive a dose >70 Gy, or
• no more than 50% of the volume to receive a dose >65 Gy.
• Rectum, dose–volume constraints selected as a
conservative starting point that have not yet been validated
for 3D treatment planning include V50 < 50%, V60 < 35%,
V65 < 25%, V70 < 20%, and V75 < 15%.“Michalski JM, Gay H,
Jackson A, et al. Radiation dose-volume effects in radiation-induced rectal injury. Int J
Radiat Oncol Biol Phys 2010;76:S123–S129.”

129. • Positioning the patient prone on a belly board was
shown to reduce the volume of small-bowel irradiated.
• However, patients on a belly board may have large
daily anatomic shifts that make prone IMRT
unreproducible“Adli M, Mayr NA, Kaiser HS, et al. Does prone positioning reduce small bowel dose in pelvic radiation
with intensity-modulated radiotherapy for gynecologic cancer? Int J Radiat Oncol Biol Phys 2003;57:230–238.”
• Although IMRT has dosimetric advantages over
conventional RT.
• IMRT exposes a greater amount of normal tissues to
lower irradiation levels, which has the potential to
increase the incidence of radiation-induced second
cancers,a phenomenon already described with
conventional RT techniques.“Hall EJ. Intensity-modulated radiation therapy, protons, and the risk
of second cancers. Int J RadiationOncol Biol Phys 2006;65:1–7.”

130. • PARA AORTIC LYMPH NODE IRRADIATION-
• If para-aortic node are enlarged or suspected to harbor disease,
patients are treated with
• 45 to 50 Gy to the para-aortic area plus
• a sequential 5- to 10-Gy boost to enlarged lymph nodes through reduced
lateral or rotational portals.
• “Poorvu PD, Sadow CA, Townamchai K et al. Duodenal and other gastrointestinal toxicity in cervical and endometrial cancer treated with extended-field intensity modulated radiation
therapy to paraaortic lymph nodes. Int J Radiat Oncol Biol Phys 2012; doi: 10.1016/j.ijrobp.2012.10.004. [epub ahead of print].”
• If feasible,3D planning with IMRT treatment is preferred to spare
normal tissues,
• superiorly covering above the level of the renal hilum or the highest extent of
disease and
• inferiorly covering 2 cm below the lowest extent of disease.

131. • Dose escalation to para-aortic nodes, particularly unresectable nodes with
IMRT- Clinical reports show excellent control of disease with dose
escalation, with one report demonstrating an 85% 2-year nodal control rate
after IMRT with a median dose of 63 Gy.
• “Townamchai K, Lee LJ, Poorvu PD, et al. Clinical outcomes with dose escalation using intensity modulated radiotherapy for node-positive endometrial and cervical cancer. Int J Radiat Oncol
Biol Phys 2012;84:S454.”
• When only conventional techniques are available-,the para-aortic lymph
nodes are irradiated either with an extended field, often using a four-field
approach, that includes both
• the para-aortic nodes and
• the pelvis or
• Through a separate portal- this may be done as one long field, or, in cases
requiring extended distance, one may instead choose to separate the
pelvic and para-aortic fields.
• This requires a “gap calculation” between the pelvic and para-aortic portals
to avoid overlap and excessive dose to the small intestines.

132. • The upper margin of the field is at the T12-L1 interspace and
• The lower margin at L5-S1.
• The width of the para-aortic portals (in general, 8 to 10 cm) can be
determined by
• CT scans,
• MRI,
• lymphangiography,
• FDG-PET scans, or IV pyelography outlining the ureters.
• The spinal cord dose (T12 to L2–3) should be kept to <45 Gy by
interposing a 2-cm-wide 5–half-value-layer shield on the posterior
portal (usually after 40-Gy tumor dose) or using lateral ports and
limiting the kidney dose to <18 Gy.

133. BEAM ENERGIES
• For IMRT, 6-MV energy is used to provide the
most homogeneous dose.
• In conventional irradiation, because of the
thickness of the pelvis, high-energy photon beams
(10 MV or higher) are especially suited for this
treatment.
• They decrease the dose of radiation delivered to the
peripheral normal tissues (particularly bladder and rectum)
and provide a more homogeneous dose distribution in the
central pelvis.

134. • With lower-energy photons (60Co or 4- to 6-MV x-rays),
higher maximum doses must be given, and more
complicated field arrangements should be used to
achieve the same midplane tumor dose (three-field or
four-field pelvic box or rotational techniques) while
minimizing the dose to the bladder and rectum and to
avoid subcutaneous fibrosis
• “ Holcomb K, Gabbur N, Tucker T, et al. 60Cobalt vs. linear accelerator in the treatment of locally advanced
cervix carcinoma: a comparison of survival and recurrence patterns. Eur J Gynaecol Oncol 2001;22:16–19.”
• Mixed-beam external radiation with neutrons and photons
resulted in unacceptably high toxicity rates and is not
recommended.“Maor MH, Gillespie BW, Peters LJ, et al. Neutron therapy in cervical cancer: results
of a phase III RTOG Study. Int J Radiat Oncol Biol Phys 1988;14:885–891.”
• carbon-ion therapy was reported but resulted in major
intestinal complications.“ Kato S, Ohno T, Tsujii H, et al. Dose escalation study of carbon ion
radiotherapy for locally advanced carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 2006;65:388–397.”

135. • Hyperfractionated or Accelerated Hyperfractionated
Radiation Therapy-
• Hyperfractionation is defined as the use of smaller-
than-standard doses per fraction.
• It can be achieved without extending the overall
treatment duration by treating once a day for 6 or 7
days per week but is usually achieved by giving two
fractions per day for 5 days per week.
• Its aim is to increase the therapeutic differential
between late-responding normal tissues and acute-
responding tumors.

136. • MacLeod et al. reported on a phase II trial of 61 patients with
locally advanced cervical cancer treated with accelerated
hyperfractionated radiation therapy.
• 1.25 Gy administered twice daily at least 6 hours apart to a total pelvic
dose of 57.5 Gy.
• A boost dose was administered with either low–dose-rate (LDR)
brachytherapy or EBRT to a smaller volume.
• Thirty patients had acute toxicity that required regular medication.
• One patient died of acute treatment-related toxicity.
• The overall 5-year survival was 27%, relapse-free survival was 36%, and
actuarial local tumor control was 66%.
• There were eight severe late complications observed in seven patients,
who required surgical intervention (actuarial rate of 27%).
• Five patients also required total hip replacement.”

137. • RTOG 88-05 conducted a phase II trial of hyperfractionation.
• 1.2 Gy to the whole pelvis twice daily at 4- to 6-hour intervals,
5 days per week with brachytherapy in 81 patients with locally
advanced carcinoma of the cervix.
• Total dose to the whole pelvis was 24 to 48 Gy, followed by
one or two LDR intracavitary applications to deliver 85 Gy at
point A and 65 Gy to the lateral pelvic nodes.
• The 5-year cumulative rate of grade 3 and 4 late effects for
patients with stage IB2 or IIB tumors was 7% and
• at 8 years was 10%, and
• with stage III or IVA disease, it was 12% at 5
years.

138. • Complications of Radical Radiotherapy.
• During pelvic radiotherapy, most patients have mild fatigue
and mild-to-moderate diarrhea that usually is controllable
with antidiarrheal medications; some patients have mild
bladder irritation.
• When extended fields are treated, patients may have
• nausea,
• gastric irritation, and
• depression of peripheral blood cell counts.
• Hematologic and gastrointestinal complications are
significantly increased in patients receiving concurrent
chemotherapy.

139. • Unless the ovaries have been transposed, all premenopausal patients
who receive pelvic radiotherapy experience ovarian failure by the
completion of treatment.
• During the first 3 years after treatment, rectal complications are most
common and include
• bleeding,
• stricture,
• ulceration, and
• fistula.
• Major gastrointestinal complications were rare 3 years or more after
treatment, but a constant low risk of urinary tract complications persisted
for many years.
• “Eifel PJ, Levenback C, Wharton JT, et al. Time course and incidence of late complications in patients treated with radiation therapy for FIGO stage IB carcinoma of the uterine
cervix. Int J Radiat Oncol Biol Phys 1995;32:1289.”

140. CONCURRENT
CHEMORADIATION
• Addition of concurrent cisplatin-containing
chemotherapy to standard radiotherapy reduces
the risk of disease recurrence by as much as
50%.
• Pearcey R, Brundage M, Drouin P, et al. A clinical trial comparing concurrent cisplatin and radiation therapy versus radiation alone for
locally advanced squamous cell carcinoma of the cervix carried out by the National Cancer Institute of Canada Clinical Trials Group. Proc
Am Soc Clin Oncol 2000;19:378a.
• Peters WA III, Liu PY, Barrett RJ II, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy
alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 2000;18:1606.
• “Eifel PJ, Winter K, Morris M, et al. Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk
cervical cancer: an update of Radiation Therapy Oncology Group trial (RTOG) 90-01. J Clin Oncol 2004;22:872.”

141. • NEOADJUVANT CHEMOTHERAPY WITH
RADIOTHERAPY-
• There is no clear advantage when neoadjuvant chemotherapy is given
before radiotherapy.
• Of seven phase 3 trials of this approach,
• five demonstrated no benefit from neoadjuvant therapy and
• two demonstrated a significantly better survival rate with
radiotherapy alone.
• “Leborgne F, Leborgne JH, Doldán R, et al. Induction chemotherapy and radiotherapy of advanced cancer of the cervix: A pilot study and phase III randomized trial. Int J Radiat Oncol Biol Phys
1997;37:343.
• SundfØr K, Trope CG, Hogberg T, et al. Radiotherapy and neoadjuvant chemotherapy for cervical carcinoma. A randomized multicenter study of sequential cisplatin and 5-fluorouracil and
radiotherapy in advanced cervical carcinoma stage 3B and 4A. Cancer 1996;77:2371.
• Tattersall MHN, Ramirez C, Coppleson M. A randomized trial comparing platinum-based chemotherapy followed by radiotherapy vs. radiotherapy alone in patients with locally advanced cervical
cancer. Int J Gynecol Cancer 1992;2:244.”

142. • Stage IVB Disease-
• Patients who present with disease in distant
organs are almost always incurable.
• The care of these patients must emphasize
• palliation of symptoms with use of appropriate pain
medications and
• localized radiotherapy.

143. • Single agent chemotherapy-
• cisplatin is the single most active agent.
• “Thigpen JT, Blessing JA, DiSaia PJ, et al. A randomized comparison of a rapid versus prolonged (24 hr) infusion of cisplatin in therapy
of squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study. Gynecol Oncol 1989;32:198.”
• Although a number of other agents (e.g.,
ifosfamide, carboplatin, irinotecan, and paclitaxel)
have exhibited a modest level of biologic activity in
cervical cancer (producing response rates of 10%
to 15%), the clinical utility of these drugs in patients
who have not responded to cisplatin or who have
experienced recurrence or progression after
chemoradiation is uncertain.
• “Cadron I, Van Gorp T, Amant F, et al. Chemotherapy for recurrent cervical cancer. Gynecol Oncol 2007;107:S113”

144. • COMBINED CHEMOTHERAPY-
• The results of two phase 3 randomized trials, published in 2004
and 2005, have provided the first solid evidence that combination
chemotherapy can improve both progression-free survival
• cisplatin plus paclitaxel vs. single-agent cisplatin,
• cisplatin plus topotecan vs. single-agent cisplatin ) and
• overall survival (cisplatin plus topotecan vs. single-agent cisplatin)
when it is administered for recurrent or metastatic carcinoma of the
cervix.
• “Moore DH, Blessing JA, McQuellon RP, et al. Phase III Study of Cisplatin With or Without Paclitaxel in Stage IVB, Recurrent, or Persistent Squamous Cell Carcinoma of the
Cervix: A Gynecologic Oncology Group Study. J Clin Oncol 2004;22:3113.
• Long HJ III, Bundy BN, Grendys EC Jr, et al. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group
Study. J Clin Oncol 2005;23:4626.”

145. • PALLIATIVE RADIOTHERAPY-
• Localized radiotherapy can provide effective relief
of pain caused by metastases in bone, brain,
lymph nodes, or other sites.
• A rapid course of pelvic radiotherapy can also
provide excellent relief of pain and bleeding for
patients who present with incurable disseminated
disease.

146. • THANK YOU

147. BRACHYTHERAPY IN
CARCINOMA CERVIX
BY- Dr.SAADVIK.R.Y
JR-1
MD(RADIATION ONCOLOGY)

149. INTRODUCTION
• Brachytherapy (BT) (brachy is Greek for “short
distance”) consists of placing sealed radioactive
sources very close to or in contact with the target
tissue.
• The absorbed dose falls off rapidly with increasing
distance from the sources, high doses may be
delivered safely to a localized target region over a
short time.

150. TECHNIQUES
• BASED ON SURGICAL APPROACH-
• Interstitial Brachytherapy,
• Intracavitary brachytherapy,
• Transluminal brachytherapy,
• mold/surface techniques.

151. • DURATION -
• TEMPORARY- Cs137, Ir192
• PERMANENT- I125, Au198

153. • LOADING OF RADIOACTIVE
SOURCE-
• PRELOADING
• MANUAL AFTERLOADING
• REMOTE AFTERLOADING

154. DOSE RATE (ICRU 38)
• LOW DOSE RATE-
• 0.4-2 Gy/hr
• MEDIUM DOSE RATE-
• 2-12 Gy/hr
• HIGH DOSE RATE-
• >12 Gy/hr
• ULTRA LOW DOSE RATE-
• 0.01-0.3 Gy/hr

155. INTRACAVITARY
BRACHYTHERAPY
• Outlines of the procedure
patient preparation Applicator check
applicator
implantation and
fixation
Imaging
Treatment
planning
Treatment
excecution

157. L/E

161. VERIFICATION X-RAY

162. DOSIMETRIC SYSTEMS
• PARIS SYSTEM
• STOCKHOLM SYSTEM
• MANCHESTER SYSTEM
• MODERN FLETCHER SUIT APPLICATOR
SYSTEM

163. STOCKHOLM SYSTEM
-Fractionated (2-3 applications) delivered within about a month
-The amount of Radium was unequal in uterus (30-90 mg, in linear tube) and in vagina (60-80
mg, in shielded silver or lead boxes)
-Vaginal and uterine applicators were not fixed together
-Each application 20-30 hours
-Total mg-hrs were usually 6500 to 7100 out of which 4500 mg-hrs were in vagina.

164. PARIS SYSTEM
Single application
5 days to deliver 7200-8000 mg-hrs.
Almost equal amounts of Radium were used in uterus and vagina
The intrauterine tube contained three sources in the ratio of 1:1:0.5
Two cork intravaginal cylinders (colpostats) had one source each of almost the same strength as the top intrauterine source.
-Single application
-5 days to deliver 7200-8000 mg-hrs.
-Almost equal amounts of Radium were used in uterus and vagina
-The intrauterine tube contained three sources in the ratio of 1:1:0.5
-Two cork intravaginal cylinders (colpostats) had one source each of almost the same strengt

165. MANCHETSER SYSTEM
• Designed to deliver a constant dose rate to defined points
near cervix ,irrespective of variation in size and shape of
uterus/vagina.
• Application specified in terms of “dose” in Roentgens
delivered at specific points(point A, point B, Bladder
point,Rectal point).
• Duration of implant based on the dose rate calculated at
point A.
• Optimal dose -8000 R(72.3 Gy) in 2 sessions of 72 hrs
each, 4-7 days interval.

166. MODERN FLETCHER SUIT
SYSTEM
• Adhered to the basic Manchester design.
• Afterloading capability was added to the Fletcher
applicator by Suit and co-workers.
• Similar to manchester system the Point A dose rates
are nearly independent of the applicator dimensions.
• Use of cs137 instead of radium.
• Additonal internal shielding was added.

167. • These shields are located on the medial
aspects of the anterior and posterior
colpostat faces and consist of 180-
degree and 150-degree disk-shaped 3-
to 5-mm-thick tungsten sectors to shield
the rectum and bladder, respectively.

168. POINT A
• The reference point A originally was defined as the point
2 cm lateral to the center of the uterine canal and 2 cm
from the mucous membrane of the lateral fornix in the
plane of the uterus
• Area in medial edge of the broad ligament where the
uterine vessels cross the ureter.
• They believed the radiation tolerance of this area, termed
the paracervical triangle, to be the limiting factor in the
treatment of cervical cancer and used point A exposure to
represent its average dose.

170. • Now point A is defined as a point 2cm above the
distal end of the lowest source in the cervical
canal and 2cm lateral to centre of tandem.
• Dose at point A showed a correlation with local
tumour control and the incidence of the late
normal tissue toxicity in the patients.
• Point B is measured 5 cms lateral from patients
midline at the same level of point A and was
intended to quantify dose delivered to pelvic
lymph nodes.

171. Definition of point A shown on a tandem and ovoid applicator based on the American
Brachytherapy Society 2012 Guidelines for Cervical Cancer.

173. BLADDER POINT
• ICRU recommends:
• on a lateral radiograph
dose at a point at
posterior surface of foley
balloon;on AP line
through the center of
balloon.
• on AP radiograph ,
reference point is taken
at the centre of the
ballon.

174. RECTAL REFERENCE
POINT
• The dose is calculated at a
point 5mm posterior to
vaginal cavity along an AP
line midway between
vaginal sources.
• On the frontal radiograph,
this reference point is
taken at the intersection of
(the lower end of) the
intrauterine source through
the plane of the vaginal
sources.

175. APPLICATOR SELECTION
• The most frequently used applicator for locally
advanced cervical cancer patients worldwide is the
tandem and ovoid applicator, which provides radiation
dose covering the Viswanathan AN, Creutzberg CL, Craighead P, et al. International Brachytherapy
Practice Patterns: a survey of the Gynecologic Cancer Intergroup (GCIG). Int J Radiat Oncol Biol Phys 2012;82:250–255.”
• cervix
• uterus,
• inner parametria, and
• approximately 1 to 2 cm of the upper vagina.

176. • The tandem and ring applicator has a slightly na
rrower dose distribution, but with HDR the dose
distribution may be optimized and mimics that
obtained with the tandem and ovoid applicator.
• The tandem and cylinder applicator useful in patients
with very narrow vagina due to stricturing.
• However, this applicator provides insufficient dosing
to the parametrial tissue and should be used with
caution.

177. • tandem and ring applicator
• tandem and cylinder applicator

178. • For patients with large tumors with
• residual bulky disease after external-beam
radiation or those with vaginal extension,
• fistulae, or
• pelvic sidewall invasion,
• A combination of tandem/ring or ovoid with
interstitial applicator or
• Tandem/interstitial applicator alone may be
inserted.

179. APPLICATOR POSITIONING
• Applicator position is a critical determinant of dose specification
and pelvic control.
• Fletcher emphasized, conditions for an adequate intracavitary
insertion include the following.
• 1. The geometry of the insertion must prevent underdosing around the cervix.
• 2. Sufficient dose must be delivered to the paracervical areas.
• 3. Vaginal mucosal, bladder, and rectal tolerance doses must be respected.
• “Potish RA. The effect of applicator geometry on dose specification in cervical cancer. Int J Radiat Oncol Biol Phys 1990;18:1513–1520.
• 632. Corn BW, Hanlon AL, Pajak TF, et al. Technically accurate intracavitary insertions improve pelvic control and survival among patients with locally
advanced carcinoma of the uterine cervix. Gynecol Oncol 1994;53:294–300.”

180. • Use the longest tandem that the patients anatomy
can accommodate.
• Increasing the the length increases the point
B(lateral parametrium and pelvic lymph nodes)
contribution relative to the uterine cavity surface
dose.
• The radiocactivity near the ends of the long
tandem contribute to the surface dose( because
of inverse square law), whereas each tandem
segment makes roughly equal contribution to
points remote from the applicator.

181. • Colpostats/ovoids with the largest diameter
clinically indicated should be used to deliver
highest tumor dose at depth for a given mucosal
dose.
• As colpostat diameter increases from 2 to 3cm,
the vaginal surface dose decreases by 35%
relative to the dose 2cm from the applicator
surface: this is simply a consequence of
increasing the source to surface distance.
• Pear shaped dose distribution is to be achieved,
high dose to the cervical and paracervical tissues,
reduced dose to the bladder and rectum.

182. LDR VS HDR
BRACHYTHERAPY
• LDR brachytherapy has been used with good
results in carcinoma of the cervix for almost 100
years.
• However in the recent years HDR brachytherapy
has been becoming popular.
• Hence, it is important to critically analyze how the
results obtained with HDR brachytherapy, which
has a much shorter history, compare with those
obtained with LDR.

183. Randomized studies on HDR brachytherapy

184. OF TOXICITY AND OVERALL AND DISEASE-FREE SURVIVAL

185. TEMPLATE BASED INTERSTITIAL
BRACHYTHERAPY
• Interstitial implants with 226Ra, 137Cs needles, or 192Ir
afterloading plastic catheters to limited tumor volumes are
helpful in specific clinical situations.
• Indications
• large residual bulky cervical tumors after external-beam treatment,
• residual tumor with sidewall invasion,
• vaginal extension,
• presence of a fistula and/or adjacent organ invasion, or
• a prior supracervical hysterectomy

186. • Syed-Neblett and Martinez
perineal applicators are the
most commonly selected.
• A tandem should be inserted
when a uterus is present.
• If the os is not visible,
ultrasound guidance to
determine the proper
placement of the tandem is
advised.

187. • Syed et al. reported on 185 locally
advanced cervical cancer patients
treated with LDR interstitial
brachytherapy from 1977 to 1997.
• Patients received external-beam
treatment to 50.4 Gy, followed by
interstitial brachytherapy to 40 to 50
Gy.
• Local control was 82%;
• 5-year disease-free survival rates were
65%, 67%, 49%, and 17% for patients
with stage IB, II, III, and IV disease,
respectively.
• Eighteen (10%) of the 185 patients
developed RTOG grade 3 or 4 late
complications.

188. PULSED THERAPY
• PDR was developed at the beginning of the 90’s.
• Unit has a similar design as HDR, however the activity is smaller.
• Treatment over the same time as LDR treatment.
• The biologic effect mimics LDR, and the dose optimization mimics
HDR
• In patient procedure: hospitalisation required.
• Source steps out for about 10min per hour and then
retracts.Repeats this every hour to deliver mini fractions(pulses) of
about 1Gy

189. • ADVANTAGES-
• complication rate profile is more similar to that of
LDR
• Between fractions, patient is not
radioactive,allowing for near continous nursing care
during treatment.
• radiation protection.
• DISADVANTAGES-
• long term results not available.

190. TREATMENT OF
RECURRENT Ca CERVIX
• AFTER SURGERY-
• Radiation may salvage approximately 50% of
patients with localized pelvic recurrences after
surgery alone.
• A combination of whole-pelvis external irradiation
(45 to 50 Gy) with concurrent chemotherapy
followed by interstitial brachytherapy is
recommended.

191. • AFTER DEFINITIVE RADIATION-
• Reirradiation of previously irradiated patients must be
undertaken with extreme caution.
• It is very important to analyze the techniques used in the initial
treatment (beam energy, volume, doses delivered with external
or intracavitary irradiation).
• In addition, the period of time between the two treatments must
be taken into consideration because it is postulated that some
repair of the initial damage may take place in the interval.
• In general, external irradiation for recurrent tumor is given to
limited volumes (40 to 45 Gy, 1.8-Gy tumor dose per fraction,
preferentially using lateral portals).

192. • Intraoperative radiation therapy (IORT) has been
used for treatment of locally advanced and
recurrent carcinoma of the cervix.
• 3-year survival rates of 8% to 21% as reported by
Mahé et al.788 and Garton et al Garton GR, Gunderson LL, Webb MJ, et
al. Intraoperative radiation therapy in gynecologic cancer: the Mayo Clinic experience. Gynecol Oncol 1993;48:328–332.”
• a 5-year survival rate of 33% in 14 patients
described by Kinney et al“ Kinney WK, Hodge DO, Egorshin EV, et al. Surgical
treatment of patients with stages IB and IIA carcinoma of the cervix and palpably positive pelvic lymph nodes. Gynecol
Oncol 1995;57:145–149.”
• Significant toxicity included peripheral nerve injury
and ureteral stenosis (with doses >15 to 20 Gy).