Epidemiology for women aged 20 to 39 years cervical cancer remained the second leading cause of cancer deaths after breast cancer accounting for about 10 of cancer deaths Despite the declining death rates in ID: 183563
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Slide1
Carcinoma of the CervixSlide2
Epidemiology
for women aged 20 to 39 years, cervical cancer remained the second leading cause of cancer deaths after breast cancer, accounting for about 10% of cancer
deaths.
Despite the declining death rates in
developed countries cervical
cancer remains the leading cause of cancer deaths among women in many medically underserved countries, including many countries of Latin America, Africa, Asia, and eastern Europe.Slide3
کاهش مرگ در اثر کانسر سرویکس
routine
screening programs, including pelvic examinations and cervical
cytologic
evaluation
the
death rates from cervical cancer had begun to decrease before the implementation of
Papanicolaou
(Pap) screening, suggesting that other unknown factors may have played some role.Slide4
International incidencescultural
attitudes
screening programs
liberal
attitudes toward sexual behaviorSlide5
اتیولوژیHPV
prostitutes
first coitus at a young
age
multiple
sexual
partners
bear
children at a young
age
Promiscuous sexual behavior in male partners
a
lower incidence of HPV infection in circumcised than uncircumcised males, with a correspondingly lower incidence of cervical cancer in their female partners.Slide6
prophylactic HPV vaccinea prophylactic HPV vaccine for women between the ages of 9 and 26 years
; this
quadrivalent
vaccine has been demonstrated to be highly effective in preventing
benign warts
and
neoplasia
caused by the most common HPV types (6, 11, 16, and 18).Slide7
علل عدم کاهش انسیدانس ادنوکارسینوما سرویکس
an increase in recognition of cases with glandular elements as adenocarcinomas
cytologic screening methods may be less effective in detecting adenocarcinomas at a preinvasive stageSlide8
ارتباط نقص ایمنی و کنسر سرویکس
T
he
relationship
between
immunosuppression
(particularly HIV-related
immunosuppression
) and the risk of HPV-related disease is complex and incompletely
understood.
Current data strongly suggest that HIV-related
immunosuppression
is correlated with an increased risk of cervical HPV infection
.
an
inverse correlation between CD4+ level and the risk of HPV infection, and patients with low CD4+ levels tend to have higher HPV DNA levels.Slide9
(
HIV) infection also appears to be associated with a higher prevalence of CIN and a faster rate of progression to high-grade CIN.
Iatrogenic
immunosuppression
is
also associated with an increased prevalence of
CIN.
risk of progression from CIN to invasive disease and on the virulence of invasive cervical cancer is less
certain
Antiretroviral therapy
does not appear to affect HPV levels, and
rarely
produces regression of CIN 2 or CIN 3 lesions, even with increases in CD4+ levels
.
Slide10
HIV-positiveOverlapping risk factors tend to confound studies of the association between HIV and HPV-related cancers. However, because of the increased risk of HPV infection in HIV-positive women, vigilant surveillance with
Pap smears
,
pelvic examinations
, and
colposcopy
(when indicated) should be part of the routine care of these women.Slide11
Natural History and Pattern of SpreadMost
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. The greatest risk of
neoplastic
transformation coincides with periods of greatest
metaplastic
activity. Virally induced atypical
squamous
metaplasia
developing in this region can progress to higher-grade
squamous
intraepithelial lesions (SILs).Slide12
The mean age of women with CIN is about 15 years younger than that of women with invasive cancer, suggesting a slow progression of CIN to invasive
carcinoma. Slide13
Natural History and Pattern of Spread
CIN 3
disease progressed in only 14%, whereas it remained the same in 61% and disappeared in the others
spontaneous regression in 38% of high-grade HPV-associated SILs.
mean times to development of carcinoma in situ of 58, 38, and 12 months for patients with
mild
,
moderate
, or
severe dysplasia
, respectively, and predicted that 66% of all cases of dysplasia would progress to carcinoma in situ within 10 years.Slide14
Natural History and Pattern of Spread
exophytic
growths
endocervical
lesions
Tumor
may become fixed to the pelvic wall by direct extension or by coalescence of central tumor with regional
adenopathy
.
bladder
mucosal invasion.
Rectum invasion
Slide15
Three groups of lymphatics
The
upper
branches:
follow the uterine artery,
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. Slide16
The incidence of pelvic and
para
-aortic node involvement is correlated with
tumor stage
and with other tumor characteristics, such as
size
,
histologic
subtype
,
depth of invasion
, and presence of
LVSI
stage
I
disease treated with
radical hysterectomy
, most investigators report
an incidence of positive pelvic nodes of 15% to 20% and an incidence of
para
-aortic nodes of 1% to 5%. Reported incidences are higher for patients with stage I disease treated with
radiation
: 10% to 25% of such patients are reported to have positive
para
-aortic nodes, reflecting the more advanced stage I tumors that are usually selected for treatment with radiation. Slide17
pattern of metastasCervical 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 their cervical cancer
.
The most frequent sites of distant recurrence are
lung
,
extrapelvic
nodes, liver, and boneSlide18
PathologySlide19
Cervical Intraepithelial Neoplasia
cervical
cytologic
findings
(important
characteristics
):
cellular immaturity
cellular disorganization
nuclear
abnormalities
increased
mitotic activity. Slide20
degree of neoplasia
extensiveness of the mitotic activity
immature cell proliferation
nuclear
atypia
If mitoses and immature cells are present only in the lower third of the epithelium, the lesion is usually designated CIN 1. Lesions involving only the lower and middle thirds are designated as CIN 2, and those involving the upper third are designated as CIN 3.Slide21
The term cervical intraepithelial neoplasia
,
refers
only to a lesion that
may
progress
to invasive carcinoma. Although CIN 1 and CIN 2 are sometimes referred to as mild-to-moderate dysplasia,
CIN is now preferred over dysplasia
.
The Bethesda system of classification, designed to further standardize reporting of cervical
cytologic
findings, was developed Slide22
Squamous intraepithelial lesions
SILs include
Condyloma
dysplasia
,
CIN
The Bethesda system divides SILs
low
grade
high
grade(higher likelihood of progressing to invasive cancer)
)
CIN2,CIN3)Slide23
Bethesda system
atypical
squamous
cells of undetermined significance (ASCUS).
most common abnormal Pap smear result in United States
laboratories,
most
cases of ASCUS reflect a
benign
process, about 5% to 10% are associated with an underlying
HSIL
, and
one third or more of HSILs are heralded by a finding of ASCUS
on a Pap
smear.Slide24
three methods of management ASCUS or LSIL
immediate
colposcopy
cytologic
follow-up
HPV DNA testing (ASCUS )
LSIL
ASCUS, HPV DNA testing had a sensitivity in the detection of HSIL similar to that of immediate
colposcopy
and reduced the number of referrals for
colposcopy
by 50%.Slide25
Adenocarcinoma In Situ
About 20% to 50% of women with cervical
adenocarcinoma
in situ also have
squamous
CIN
, and
adenocarcinoma
in situ is often an
incidental
finding in patients operated on for
squamous
carcinoma.
is frequently
multifocal
, cone biopsy margins are unreliable.Slide26
Microinvasive Carcinoma
definition of
microinvasive
carcinoma is based on the maximum depth (no more than 5 mm) and linear extent (no more than 7 mm) of involvement.
This requires a
cervical cone biopsy
With the advent of
cytologic
screening, the proportion of invasive carcinomas that invade less than 5 mm has increased more than tenfold to about 20% in the United StatesSlide27
Microinvasive Carcinoma
The importance of LVSI remains somewhat controversial
the risk of metastatic regional disease appears to be exceedingly low for any tumor that invades less than 3 mm, even in the presence of LVSI.
many think that the risk of regional spread from tumors that have invaded 3 to 5 mm is sufficiently high to warrant treatment of the
parametria
and regional nodes.Slide28
Microinvasive adenocarcinomameasuring the depth of invasion can be difficult.
a subset of patients with very small
adenocarcinomas
have a low likelihood of lymph node metastases or recurrence. In the absence of a consensus definition of
microinvasion
for
adenocarcinoma
, decisions are usually guided by specific descriptions of the depth and extent of invasion and other features that have been correlated with increased risk, such as
high grade
and the
presence of LVSI.Slide29
Invasive Squamous Cell Carcinoma
A number of systems have been used to grade and classify squamous cell carcinomas, but none have consistently been demonstrated to predict prognosis
large cell keratinizing
large cell
nonkeratinizing
small cell carcinoma (poorer prognosis)
Papillary variants of
squamous
carcinoma
1.well differentiated (occasionally confused with immature
condylomata
)
2. very poorly differentiated (resembling high-grade transitional carcinoma)
Verrucous
carcinoma (
DDx
benign
condyloma
)
Sarcomatoid
squamous
carcinoma Slide30
Adenocarcinoma
pure or mixed with
squamous
cell carcinoma (
adenosquamous
carcinoma).
80% of cervical
adenocarcinomas
are of the
endocervical
type
Minimal-deviation
adenocarcinoma
(adenoma
malignum
) is a rare, extremely well-differentiated
adenocarcinoma
that is sometimes associated with
Peutz-Jeghers
syndrome.
Slide31
Adenocarcinoma
Other rare variants of
adenosquamous
carcinoma include
adenoid basal carcinoma (favorable prognosis)
adenoid cystic carcinoma(aggressive behavior )
endometrioid
, serous, or clear cells; mixtures of these cell typesSlide32
Anaplastic Small Cell/Neuroendocrine Carcinoma
Anaplastic
small cell carcinoma resembles oat cell carcinoma of the lung
About 30% to 50% of
anaplastic
small cell carcinomas display
neuroendocrine
features.
Widespread
hematogenous
metastasesSlide33
Other Rare Neoplasms
A variety of
neoplasms
may infiltrate the cervix from adjacent sites, and this makes differential diagnosis difficult. Although
endometrioid
histology suggests endometrial origin and
mucinous
tumors in young patients are most often of
endocervical
origin, both
histologic
types can arise in either site.
Metastatic tumors from the colon, breast, or other sites may involve the cervix secondarily.
Malignant mixed mullerian tumors,
adenosarcomas
, and
leiomyosarcomas
occasionally arise in the cervix but more often involve it secondarily.
Primary lymphomas and melanomas of the cervix are extremely rare.Slide34
Clinical Manifestations
Preinvasive
disease during routine cervical
cytologic
screening.
Early invasive disease usually detected during screening examinations
abnormal vaginal bleeding, often following coitus or vaginal douching.
a clear or foul-smelling vaginal discharge
Pelvic pain
Flank pain (
hydronephrosis
complicated by
pyelonephritis
) The triad of sciatic pain, leg edema, and
hydronephrosis
is almost always associated with extensive pelvic wall involvement by tumor.
hematuria
or incontinence from a
vesicovaginal
fistula
External compression of the rectum by a massive primary tumor may cause constipationSlide35
Diagnosis
an ideal target for cancer screening
cervical cytologic examination and pelvic examination has led to a decrease in the mortality rate
Only nations with well-developed screening programs have experienced substantial decreases in cervical cancer death ratesSlide36
Screening (The American Cancer Society)
3 years after
the onset of vaginal intercourse, but
no later than 21 years of age
annually with conventional cervical cytology smears
every 2 years using liquid-based Pap cytology
( until age 30 years)
Starting at age 30 years, women who have had three consecutive, technically satisfactory negative test results may be screened every 2 to 3 years. Slide37
موارد قطع اسکرینینگ
Women age 70 years and more who have had three consecutive negative
no abnormal test result within 10 years
who have had a total hysterectomy for benign gynecologic disease.
Women with a history of CIN 2 or CIN 3 prior to or as an indication for hysterectomy should be screened until they have had three consecutive normal test results and no abnormal test results for 10 years. Slide38
Women with a history of
cervical cancer
, women exposed in utero to diethylstilbestrol (
DES
), and women who are
immunocompromised
should
continue regular screening
as long as they are in reasonably good health.Slide39
The rate of false-negative findings on the Pap test is about
20% to 30% in women with high-grade CIN
10% to 15% in women with invasive cancer.
Slide40
Dx
Detection of
high endocervical lesions
may be improved when specimens are obtained with a cytobrush.
Because hemorrhage, necrosis, and intense inflammation may obscure the results, the Pap smear is a poor way to
diagnose
gross lesions
; these should always be biopsied.Slide41
the sensitivity of a screening program is usually increased by repeated
annual testing. The sensitivity of individual tests may be improved by ensuring
adequate sampling of the squamocolumnar junction
and
the endocervical canal
; smears without endocervical or metaplastic cells are inadequate, and in such cases the test must be repeated. Because adenocarcinoma in situ originates near or above the transformation zone, it may be missed with conventional cervical smears. Slide42
liquid-based Pap methods greater sensitivity than conventional Pap smears.
the likelihood of drying artifact is reduced,
cellular sampling tends to be better
the cells are more evenly distributed on the slide.
Greater sensitivity comes at the cost of somewhat poorer specificity, which is balanced by the less frequent need for repetition of the study to achieve adequate screening. Slide43
HPV testing
although it is not yet recommended for routine screening, HPV testing of ASCUS smears followed by colposcopy in patients with HPV-positive lesions appears to provide a highly accurate and cost-effective means of
detecting HSIL
in equivocal smears.Slide44
Patients with abnormal findings on cytologic examination who do not have a gross cervical lesion must be evaluated with colposcopy and directed biopsies. Following application of a 3% acetic-acid solution, the cervix is examined under 10- to 15-fold magnification with a bright, filtered light that enhances the acetowhitening and vascular patterns characteristic of dysplasia or carcinoma. The skilled colposcopist can accurately distinguish between low- and high-grade dysplasia, but microinvasive disease cannot consistently be distinguished from intraepithelial lesions on colposcopy.Slide45
In a patient with an atypical Pap smear finding, if
no abnormalities are found on colposcopic
examination or if the
entire squamocolumnar junction cannot be visualized
, endocervical curettage should be performed. Some authorities advocate the routine addition of endocervical curettage to colposcopic examination to minimize the risk of missing occult cancer within the endocervical canal. However, it is probably reasonable to omit this step in previously untreated women if the entire squamocolumnar junction is visible with a complete ring of unaltered columnar epithelium in the lower canalSlide46
Cervical cone biopsy
is used to diagnose occult
endocervical
lesions
is an essential step in the diagnosis and management of
microinvasive
carcinoma of the cervix. Slide47
Cervical cone biopsy yields an accurate diagnosis and decreases the incidence of inappropriate therapy when (1) the
squamocolumnar
junction is poorly visualized on
colposcopy
and a high-grade lesion is suspected,
(2) high-grade dysplastic epithelium extends into the
endocervical
canal,
(3) the
cytologic
findings suggest high-grade dysplasia or carcinoma in situ,
(4) a
microinvasive
carcinoma is found on directed biopsy,
(5) the
endocervical
curettage specimens show high-grade CIN,
(6) the
cytologic
findings are suggestive of
adenocarcinoma
in situ.Slide48
Clinical Evaluation of Patients with Invasive Carcinoma
detailed history
physical examination,
complete blood cell count and renal function and liver function tests
chest radiography
intravenous pyelography (or computed tomography [CT])
Cystoscopy and either a proctoscopy or a barium enema study should be done in patients with bulky tumors.
CT S or MRI
PET
Slide49
CT S or MRI to evaluate regional nodes, but these studies 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.
PET appears to be a very sensitive noninvasive method of evaluating the regional nodes of patients with cervical cancer
74
and a useful method for following response to treatment,
80
although its high cost has prevented widespread routine use.
MRI can provide useful information about the distribution and depth of invasion of tumors in the cervix but tends to yield less accurate assessments of the parametrium.Slide50
International Federation of Gynecology and Obstetrics Staging of Carcinoma of the Cervix (1994)
0
Carcinoma in situ, intraepithelial carcinoma.
I
The carcinoma is strictly confined to the cervix (extension to the corpus should be disregarded)
IA
microscopically
Invasion is limited to measured
stromal
invasion with a maximum
depth of 5
mm and
no wider than 7 mm
.
Vascular space involvement, either venous or lymphatic, should not alter the staging).
IA1
Measured invasion of
stroma
no greater than 3 mm in depth and no wider than 7 mm.
IA2
Measured invasion of
stroma
greater than 3 mm and no greater than 5 mm in depth and no wider than 7 mm.
IB
Clinical lesions confined to the cervix or preclinical lesions greater than IA
IB1
Clinical lesions no greater than 4 cm in size
IB2
Clinical lesions greater than 4 cm in sizeSlide51
II
The carcinoma extends beyond the cervix, but has not extended onto the pelvic wall; the carcinoma involves the vagina, but not as far as the lower third
IIA
No obvious
parametrial
involvement
IIB
Obvious
parametrial
involvement.
III
carcinoma has extended onto the pelvic wall; on rectal examination there is no cancer-free space between the
tumour
and the pelvic wall; the
tumour
involves the lower third of the vagina; all cases with a
hydronephrosis
or nonfunctioning kidney should be included, unless they are known to be due to other cause.
IIIA
No extension onto the pelvic wall, but involvement of the lower third of the vagina
IIIB
Extension onto the pelvic wall or
hydronephrosis
or nonfunctioning kidney.Slide52
IV
The carcinoma has extended beyond the true pelvis or has clinically involved the mucosa of the bladder or rectum
IVA
Spread of the growth to adjacent organs
IVB
Spread to distant organs.Slide53
Up todateTNM stageFIGO stage
T1b =IB :Clinically visible lesion confined to the cervix or microscopic lesion greater than IA2
AJCC stage grouping
adenocarcinoma in situSlide54
Clinical Staging
FIGO stage is based on careful
clinical examination
and the results of
specific radiologic studies
and
procedures
.
The clinical stage should never be changed on the basis of subsequent findings.
When it is doubtful ,case should be assigned to the earlier stage. Slide55
Clinical Staging
According to FIGO,
growth fixed to the pelvic wall by a short and indurated, but not nodular, parametrium should be allotted to stage IIb.
A case should be classified as stage III only if the parametrium is nodular to the pelvic wall or if the growth itself extends to the pelvic wall.Slide56
FIGO rules for clinical staging,
Palpation
Inspection
Colposcopy
endocervical curettage
hysteroscopy
cystoscopy
Proctoscopy
intravenous urography
radiographic examination of the lungs and skeleton
.Slide57
Suspected bladder or rectal involvement should be confirmed by biopsy
Findings of bullous edema or malignant cells in cytologic washings from the urinary bladder are not sufficient to diagnose bladder involvementSlide58
FIGO specifically states that findings on examinations such as
lymphangiography
Laparoscopy
CT, and MRI :are of value for planning therapy but because these are not yet generally available and the interpretation of results is variable should not be the basis for changing the clinical stage
Examination under anesthesia is desirable but not required. Slide59
The rules and notes outlined in the FIGO staging system are integral parts of the clinical staging system and should be strictly observed to minimize inconsistencies in staging between institutions.Slide60
Although surgically treated patients are sometimes classified according to a TNM pathologic staging system, this practice has not been widely accepted because it cannot be applied to patients who are treated with primary radiotherapy.Slide61
Surgical Evaluation of Regional Spread
transperitoneal
extraperitoneal dissection
laparoscopic lymph node dissection ?
sentinel node ?Slide62
surgical staging(controversial)
identifies patients with microscopic para-aortic or common iliac node involvement
who can benefit from extended-field irradiation.
debulking of large pelvic nodes
before radiotherapy may improve outcome.
Because patients with radiographically positive pelvic nodes are at greatest risk for occult metastasis to para-aortic nodes, these patients may have the greatest chance of benefiting from surgical staging
Some authors have advocated pretreatment blind biopsy of the
scalene node
in patients with positive para-aortic nodes and in patients with a central recurrence who are being considered for pelvic exenteration. The reported incidence of supraclavicular metastasis varies widely (5% to 20% or more) for patients with positive para-aortic lymph nodes.Slide63
Prognostic Factors
FIGO stage
Clinical tumor diameter
presence of medial versus lateral parametrial involvement
presence of unilateral versus bilateral parametrial or pelvic wall involvement
Lymph node metastasis
LVSI
deep stromal invasion (10 mm or more or more than 70% invasion)
parametrial extension
inflammatory response
Uterine-body involvement ( distant metastases )
histologic features
histologic grade (adenocarcinomas)
HGB(locally advanced )Slide64
Operative findings often do not agree with clinical estimates of parametrial or pelvic wall involvement, and some authors have found that the predictive power of stage diminishes or is lost when comparisons are corrected for differences in clinical tumor diameter.Slide65
Other clinical and biologic features that have been investigated for their predictive power, with variable results, include :
Age
peritoneal cytology
platelet count
tumor vascularity
DNA ploidy or S phase
cyclooxygenase-2 expression
growth factor receptors.
HPV DNASlide66
Treatment depended on
tumor size
stage
histologic
features
evidence of lymph node metastasis
risk factors for complications of surgery or radiotherapy
patient preference. Slide67
Treatment
HSILs :loop
electroexcision
procedure (LEEP)
stage IA1: conservative surgery (
excisional
conization
or
extrafascial
hysterectomy [type I])
stage IA2 and IB1 and some small stage IIA tumors: modified radical (type II) or radical (type III) hysterectomy or radiotherapy
stages IB2 through IVA: radiotherapy
Selected patients with centrally recurrent disease after RT may be treated with radical
exenterative
surgery
isolated pelvic recurrence after hysterectomy is treated with irradiation.
the routine addition of concurrent
cisplatin
-containing chemotherapy to radiotherapy for patients whose cancers have a high risk of
locoregional
recurrence.Slide68
Preinvasive Disease (Stage 0)
HSILs : (LEEP, LEEP
conization
, or
excisional
[cold knife]
conization
with a scalpel)
LEEP
Conization
: suspicion of occult invasion on
cytologic
or
colposcopic
examination
ablative therapy (
cryotherapy
or CO
2
laser ablation )has declined
low-grade
dysplasias
are often followed without treatment
vaginal or type I abdominal hysterectomy for other gynecologic conditions not for invasive cancerSlide69
LEEPexcise the entire transformation zone and distal canal.
control rates are similar to those achieved with
cryotherapy
or laser ablation.
LEEP is an outpatient office procedure that preserves fertility.
patients require careful post-LEEP surveillanceSlide70
LEEP conization or excisional conization with a scalpel
microinvasive
suspected
invasive cancer suspected
adenocarcinoma
in situ.Slide71
Microinvasive Carcinoma (Stage IA1)
conization
or total (type I) or vaginal hysterectomy.
pelvic
lymphadenectomy
is not usually recommended.
Patients 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.
patients who have this conservative treatment must be followed closely with periodic
cytologic
evaluation
,
colposcopy
,
and
endocervical
curettage
.Slide72
residua
The likelihood of residual invasive disease after cone biopsy is correlated with the status of the internal cone margin and the results of an endocervical curettage performed after cone biopsy.
The authors did not find any correlation between the depth of invasion or the number of invasive foci and residual invasion.Slide73
Therapeutic conization for
microinvasive
disease
is usually performed with a scalpel while the patient is under general or spinal anesthesia
entire specimen must be sectionedSlide74
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
.The
width and depth of the cone should be tailored to produce the least amount of injury while providing clear surgical margins.Slide75
For (FIGO stage IA2), the risk of nodal metastases is approximately 5%.
Therefore, in such patients, a bilateral pelvic lymphadenectomy should be performed in conjunction with a modified radical (type II) hysterectomy.
Although surgical treatment is standard for in situ and microinvasive cancer, patients with severe medical problems or other contraindications to surgical treatment can be successfully treated with radiotherapy. Slide76
Stage IB and IIA Disease
Early stage IB cervical carcinomas can be treated effectively with combined external-beam irradiation and brachytherapy or with radical hysterectomy and bilateral pelvic lymphadenectomy. The goal of both treatments is to destroy malignant cells in the cervix, paracervical tissues, and regional lymph nodes.
Patients who are treated with radical hysterectomy whose tumors are found to have high-risk features may benefit from postoperative radiotherapy or chemoradiation.Slide77
stage IB
Overall survival rates between 80% and 90%,
)
with surgery
=
radiation
(
surgery or radiotherapy?Slide78
stage IB1
choice of treatment is based
patient preference,
anesthetic and surgical risks
physician preference,
an understanding of the nature and incidence of complications with radiotherapy and hysterectomy. Slide79
stage IB1
For patients with similar tumors, the overall rate of major complications is similar with surgery and radiotherapy, although 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.Slide80
stage IB2 (bulky)
radical hysterectomy
radical radiotherapy
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. Because patients with these risk factors have an increased rate of pelvic disease recurrence, surgical treatment is usually followed by postoperative irradiation, which means that the patient is exposed to the risks of both treatments. Consequently, many gynecologic and radiation oncologists believe that patients with stage IB2 carcinomas are better treated with radical radiotherapy.Slide81
concurrent administration of cisplatin-containing chemotherapy
bulky stage I cancers
lymph node metastasis
involved surgical margins
IB2<=Slide82
Patients who have stage IB1 cancers without evidence of regional involvement have excellent pelvic control rates (about 97% at 5 years) with radiotherapy alone and probably do not require chemotherapy when they are treated with primary radiotherapySlide83
Radical Hysterectomy
The standard surgical treatment for
stage IB and IIA
cervical carcinomas is
radical (type III) hysterectomy and bilateral pelvic
lymphadenectomy
Modified radical (type II) hysterectomy
may be used for
selected, small (less than 2-cm diameter) stage IB
lesions.
For premenopausal women (i.e., younger than 50 years), the ovaries usually are not removed. Ovarian metastases are rare in the absence of metastases to lymph nodes or other sites. If
intraoperative
findings suggest a need for postoperative pelvic irradiation, the ovaries may be transposed out of the pelvis.Slide84
postoperative complications
blood loss (mean, 0.8 liter)
ureterovaginal fistula (1% to 2%)
vesicovaginal fistula (less than 1%)
pulmonary embolus (1% to 2%)
small bowel obstruction (1% to 2%)
postoperative fever (25% to 50%) secondary
to:
deep vein thrombosis
pulmonary infection
pelvic cellulitis
urinary tract infection
wound infectionSlide85
Subacute complications
lymphocyst formation and lower-extremity edema
Lymphocysts may obstruct a ureter, but hydronephrosis usually improves with drainage of the lymphocyst.
The risk of complications may be increased in patients who undergo preoperative or postoperative irradiation.Slide86
Bladder complications
decreased bladder sensation
chronic bladder
hypotonia
or
atony
(3% to 5% )
Bladder dysfunction
stress incontinence(influenced by RT)
bladder contraction and instability(RT post s)
Bowel complications
constipation and, rarely, chronic
obstipation
small bowel obstruction(RT post s)Slide87
The use of
radical vaginal or abdominal
trachelectomy
and
laparoscopic
lymphadenectomy
has been advocated in carefully selected women with
small IB1
(2 cm or less) lesions who are eager to preserve fertility. Slide88
Radiotherapy After Radical Hysterectomy
irradiation decreases the risk of
pelvic recurrence
in patients whose tumors have high-risk features
it has been difficult to determine the
impact of adjuvant irradiation on survival.
adenocarcinomas
or
adenosquamous
carcinomas: post op RT less recurrenceSlide89
CHRTAlthough pelvic irradiation reduces the risk of recurrence for patients with pelvic lymph node metastases or
parametrial
involvement, the risk of pelvic and distant recurrence remains high for these women
CHRT significantly improved rates of pelvic disease control and survivalSlide90
Table 42.2.3 Prospective Randomized Trials that Investigated the Role of Concurrent Radiotherapy and Chemotherapy for Patients with
Locoregionally
Advanced Cervical Cancer
Adj
cht
?Slide91
Radical Radiotherapy
excellent survival and pelvic disease control rates in patients with stage IB cervical cancer.
Survival rates for patients with FIGO stage IIA disease treated with radiation alone range between 70% and 85% and are also strongly correlated with tumor size.
for patients with
bulky tumors
, results may be improved further with
concurrent administration of chemotherapySlide92
Radical radiotherapy
goal of radical radiotherapy =cervix, paracervical tissues, and regional LN
ERT+BT
Even small tumors that involve multiple quadrants of the cervix are usually treated with
total doses of 80 to 85 Gy to point A
. The dose may be reduced by 5% to 10% for very small superficial tumors. Although patients with small tumors may be treated with somewhat smaller fields than patients with more advanced locoregional disease, care must still be taken to adequately cover the
obturator
,
external iliac
,
low common iliac
, and
presacral nodes
. Slide93
Irradiation Followed by Hysterectomy
low pelvic recurrence rates after concurrent treatment with chemotherapy and radiation, suggest that there is little role for routine treatment with adjuvant hysterectomy. Slide94
adjuvant hysterectomy
uterine fibroids or other anatomic variations
involvement of the uterine fundus
In these cases, an extrafascial (type I) hysterectomy is usually performed, in which the uterus, cervix, adjacent tissues, and a small cuff of the upper vagina in a plane outside the pubocervical fascia are removed. This procedure involves minimal disturbance of the bladder and ureters. Slide95
Chemotherapy Followed by Radical Surgery?
A number of investigators have investigated the use of neoadjuvant chemotherapy followed by radical hysterectomy to treat patients with bulky stage IB or stage II cervical carcinomas.
Neoadjuvant chemotherapy has usually included cisplatin and bleomycin plus one or two other drugs. Slide96
Stage IIB, III, and IVA Disease
With appropriate
chemoradiotherapy
, even patients with massive
locoregional
disease have a significant chance for cure.
The success of treatment depends on a careful balance between external-beam radiotherapy and
brachytherapy
that optimizes the
dose
to tumor and normal tissues and the
overall duration
of treatment. Slide97
Stage IIB, III, and IVA Disease
EBRT shrinking bulky tumor and bringing it within the range of the high-dose portion of the
brachytherapy
dose distribution.
Subsequent
brachytherapy
exploits the inverse square law to deliver a high dose to the cervix and
paracervical
tissues while minimizing the dose to adjacent normal tissues.Slide98
Stage IIB, III, and IVA Disease
complete the
entire treatment in less than
7 to 8 weeks
.
longer treatment courses are associated with decreased pelvic disease control and survival rates.Slide99
External-Beam Radiotherapy Technique
High-energy photons
4- to 6-MV photons, four fields are usually usedSlide100
External-Beam Radiotherapy Technique
CT simulation (iliac lymph nodes.)
Information gained from radiologic studies such as MRI, CT, and PET improve estimates of disease extent and assist in localization of regional nodes and
paracervical
tissues that may contain microscopic disease.
The
caudad
extent
of disease (
radiopaque
markers )Slide101
organ motion
positions of the uterus and cervix can vary by as much as 4 cm from day to day.
it is usually wise to cover the entire
presacrococcygeal
region when locally advanced cancers are treated.
some clinicians prefer to use the simpler technique for patients with bulky tumors.Slide102Slide103
Tumor response should be evaluated with periodic pelvic examinations to determine the best time to deliver
brachytherapy
.
a central block after 40Gy?Slide104
Central block
it can result in overdoses to medial structures such as the
ureters
or
underdosage
of posterior
uterosacral
disease. For these reasons, other clinicians prefer to give an initial dose of 40 to 45
Gy
to the whole pelvis, believing that the ability to deliver a homogeneous distribution to the entire region at risk for microscopic disease and the additional tumor shrinkage achieved before
brachytherapySlide105
more than 40 to 45 Gy
to the central pelvis tend to compromise the dose deliverable to
paracentral
tissues and increase the risk of late complications.Slide106
Radiation therapy fields for cervical cancer
Conventional anteroposterior, AP (A), and lateral (B) radiation portals for cervical cancer defined by a superior field border at the L4-L5 disk space, a inferior border extending 3 to 4 cm below the lowest extent of disease or the bottom of the obturator foramen, and a lateral edge 1.5 to 2 cm lateral to the pelvic brim. Slide107
Pelvic radiation therapy field with vaginal marker
Radiograph (A) and computed tomography (CT) scan (B) demonstrating a radiopaque vaginal marker, placed to aid in localization of the vagina for treatment planning. Slide108
Extended field radiation therapy (EFRT) for cervical or endometrial cancer
Extended field anteroposterior (AP) radiation portal covering the para-aortic nodes. Slide109
IMRT
Unlike standard two-field and four-field techniques, IMRT makes it possible to deliver a lower daily dose to the
intrapelvic
contents than to surrounding pelvic lymph nodes .
reduced bone marrow toxicity and acute gastrointestinal side Slide110
IMRT
IMRT is less sparing of bowel.
IMRT allows delivery of doses exceeding 60 Gy with relative sparing of adjacent critical structures.
increase error
influence of internal organ motion and intratreatment tumor response on the doses to tumor and critical structures.Slide111
There is no evidence that IMRT can safely be used as an alternative to brachytherapy for routine treatment of intact cervical cancer.
IMRT cannot accurately reproduce the high-dose gradients produced with intracavitary therapy.
unpredictable variations mandate the use of large treatment marginsSlide112
Role of Para-Aortic Irradiation
para-aortic node involvement :25% to 50% enjoy long-term survival after extended-field irradiation .
even 10% to 15% of patients with gross lymphadenopathy appear to be curable with aggressive management.
Survival is also strongly correlated with the bulk of central disease.
patients who had small primary disease that could be controlled with radiotherapy demonstrates that extensive regional spread can occur without distant metastases and that patients with para-aortic node metastases can often be cured if their primary disease can be sterilized.Slide113
occult disease can be cured if the
para
-aortic nodes are included in the radiation fields
concurrent chemotherapy ?
PET and minimally invasive surgery
add to the expense of treatment and are still infrequently performed in patients with locally advanced cervical cancer, these methods may provide better means of identifying patients with regional metastases
who can benefit from extended regional irradiationSlide114
Radiation Therapy Techniques(
Preze
)
External irradiation is used to treat the whole pelvis and the
parametria
including the common iliac and
para
-aortic lymph nodes
central disease (cervix, vagina, and medial
parametria
) is primarily irradiated with
intracavitary
sources. Slide115
External-beam pelvic irradiation is delivered before intracavitary insertions in patients with:
Bulky cervical lesions or tumors beyond stage IIA to improve the geometry of the
intracavitary
application
Exophytic
, easily bleeding tumors;
Tumors with necrosis or infection
Parametrial
involvement.Slide116
high-risk features need ERTparametrial involvement, deep stromal invasion, or positive nodes, positive or close operative margins, Slide117
Volume Treated
the primary tumor and the pelvic lymph nodes
superior border at the L4-5 (external iliac and hypogastric lymph node)
inferior border at the
inferior edge of the ischium
This margin must be extended to the L3-4 interspace if common iliac nodal coverage is indicated.
1.5-cm -2.5 cm margin on the pelvic rim;
Posterior extension of the
cardinal ligaments
in their attachment to the pelvic side wall was consistently posterior to the rectum and extended to the sacral hollow. The
uterosacral ligaments
also extended posteriorly to the sacrum. These anatomic landmarks must be kept in mind in the correct design of lateral pelvic portals.Slide118
A:
Ap
simulation film .The 15 by 15 cm portals at SSD are used for stage IB (
broken line
), and 18 by 15 cm portals are used for more advanced disease (
solid line
). This allows better coverage of the common iliac lymph nodes. The distal margin is usually placed at the bottom of the
obturator
foramina
.
B:
Standard portal for stage IB tumors is outlined (
solid line indicated as A
). When the common iliac nodes are to be covered, the upper margin is extended to
the L4-5 space?
(
indicated in section B
). If there is vaginal tumor extension, the lower margin of the field is drawn at the
introitus
(
indicated in section C
).Slide119Slide120
lateral field
the anterior border of the lateral fields over the anterior edge of the pubic
symphysis
the posterior margin usually is designed to cover at least 50% of the rectum in stage IB tumors, and it should extend to
the sacral hollow
in patients with more advanced tumors
Three-dimensional treatment planning for pelvic irradiation of cervical carcinoma may reduce the treated volume, but further research must be done to determine whether the complication rate can be decreased as well.Slide121
For stage IB disease, : 15 by 15 cm at the surface (
For patients with stage IIA, IIB, III, and IVA carcinoma, (18 by 15 cm at surface) are required to cover all of the common iliac nodes in addition to the
cephalad
half of the vagina
If there is no vaginal extension, the lower margin of the portal is at the inferior border of the
obturator
foramen.
When there is vaginal involvement, the entire length of this organ should be treated down to the
introitusSlide122
In patients with tumor involving the
distal half
of the vagina, the portals should be modified to cover the
inguinal lymph nodes
because of the increased probability of metastasesSlide123
Midline Shielding in Ap–PA Portals
Depending on the institution and brachytherapy dose administered, midline shielding with rectangular or specially designed blocks are used for a portion of the external beam dose delivered with the
Ap–PA
ports Slide124
Parametrial Boost
When parametrial tumor persists after 50 to 60 Gy is delivered to the parametria, an additional 10 Gy in five or six fractions may be delivered with reduced AP-PA portals (8 by 12 cm for unilateral and 12 by 12 cm portals for bilateral parametrial coverage). The central shield should be in place to protect the bladder and rectum.Slide125
Parametrial boost for cervical cancer
Treatment fields for a parametrial boost for a stage IIB cervical cancer.Slide126
Para-Aortic Lymph Node Irradiation
an extended field or through a separate portal
45 to 50
Gy
to the
para
-aortic area plus a
5 to 10
Gy
boost to enlarged lymph nodes Slide127
separate portal
a “gap calculation( excessive dose to the small intestines)
The upper margin = T12-L1
lower margin at L5-S1
The width of the
para
-aortic portals can be determined by CT scans, MRI, lymphangiography, FDG-PET scans, or IV
pyelography
outlining the
ureters
.Slide128
The spinal cord dose (T12 to L2-3) should be kept below 45 Gy
by interposing a 2-cm wide 5–half-value layer (HVL) shield on the posterior portal (usually after 40-Gy tumor dose) or using lateral ports and the kidneys below 1,800
cGySlide129
Beam Energies
10 MV or higher
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.
With lower-energy photons (Cobalt-60 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 (3 or 4field pelvic box or rotational techniques) while minimizing the dose to the bladder and rectum and to avoid subcutaneous fibrosisSlide130
a metallic prosthesis when using lateral fields or a box pelvic irradiation technique may result in a dose decrease of approximately 2% for 25-MV x-rays and average increases of 2% for 10-MV x-rays and 5% for
60
Co.Slide131
Hyperfractionated Radiation Therapy for Locally
Advanced Cervix Cancer
1.2 Gy to the whole pelvis twice daily at 4- to 6-hour intervals, 5 days per weeka total pelvic dose of 57.5 Gy.A boost dose with brachytherapy Slide132
Concomitant Boost
On Monday, Wednesday, and Friday of the last 3 weeks, an additional 1.6-Gy boost was given 6 hours after the whole pelvis treatment (14.4
Gy
) through lateral fields encompassing the
parametria
and primary tumor, for a total tumor dose of 59.4
Gy
. Slide133
Three-Dimensional or IMRT
patients with stage IIB or IVA cervical cancer with
medical illness
or
severe tumor-related anatomic
distortion that limited delivery of
brachytherapy
.
The toxicity of IMRT was acceptable, and early tumor responses were encouraging.Slide134
IMRT
Although not as critical in older patients, it is important to keep in mind that while 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
.Slide135
Brachytherapy
intracavitary
techniques
(
137
Cs)
(
192
Ir)Slide136Slide137
Remote afterloader for(HDR) brachytherapy
A remote afterloader stores a single (HDR) radioactive source, typically Ir-192, and through a computer controlled mechanism advances it within the catheter or applicator that has been placed in the patient.Slide138
(HDR) cervix brachytherapy applicators
Intrauterine tandem with (A) vaginal ovoids, with (B) vaginal cylinders, or with a (C) vaginal ring.Slide139
Cervical interstitial brachytherapy
Syed-type interstitial implant used for cervical brachytherapySlide140
Brachytherapy reference points
Tandem and ovoid cervical brachytherapy illustration of point A. Slide141
High dose rate (HDR) cervical brachytherapy planning
Orthogonal radiographs, (A) and (B), depicting placement of intrauterine tandem and vaginal
ovoids
. The images show the instruments in place in the uterus and vagina. In addition, there is barium contrast in the rectum, contrast in the Foley catheter balloon and
radiopaque
vaginal packing. Slide142
Vaginal cuff brachytherapy applicators
Vaginal ovoids (A) and vaginal cylinders (B) for vaginal cuff brachytherapy for endometrial cancerSlide143
For LDR treatments:
EBRT dose : 45 to 50
Gy
LDR
brachytherapy
dose :42 and 45
Gy
for early and advanced cancers
For HDR treatments
EBRT dose : 48 to 50
Gy
HDR dose :29 and 30
Gy
for early and advanced cancers.
The median HDR dose per fraction was
6
Gy
with a median of
five fractions
. Slide144
computer-generated dose distributions provide the
best means
of determining the doses to point A, point B, bladder, and rectum
In general, an intrauterine tandem with three or four sources [15 or 20-10-10-(10)
mCi
mgRaEq
with LDR] is inserted in the uterus and two
colpostats
(2 cm in diameter, loaded with 20
mCi
mgRaEq
LDR sources) are placed in the vaginal vault and packed with
iodoform
gauze to deliver 0.6 to 0.8
Gy
per hour to point A.Slide145
With
HDR
intracavitary applicators the use of a
rectal retractor
has been shown to substantially reduce the rectal dose
Interstitial implants with radium (
226
Ra),
137
Cs needles, or
192
Ir afterloading plastic catheters to limited tumor volumes are helpful in specific clinical situations (e.g., localized residual tumor, parametrial extension. Slide146Slide147Slide148
As Fletcher emphasized, conditions for an adequate
intracavitary
insertion include the following
The geometry of the insertion must prevent
underdosing
around the cervix;
Sufficient dose must be delivered to the
paracervical
areas
Vaginal mucosal (and, we add, bladder and rectal) tolerance doses must be respected.Slide149
Biology of High–Dose-Rate Brachytherapy for Cervical Carcinoma
Late damage rises sharply as the number of HDR fractions is decreased.
Displacing the bladder and rectum away from the HDR sources for the short duration of therapy may offset the radiobiologic disadvantage of using a few brachytherapy fractions Slide150
At Washington University
HDR
brachytherapy
with
sedation
and without anesthesia.
bladder
catheter
and
gentle packing of the vagina
with
iodoform
gauze
anteroposterior
and lateral pelvic
radiographs
The usual dose per fraction prescribed at
0.5-cm depth
is 3 to 6
Gy
, and three to six fractions are given once or twice weeklySlide151
HDRfour
fractions of EBRT per week with one HDR treatment per
week
The number of HDR fractions
:
two
to more than
10
.
The optimal time–dose–fractionation
?Slide152
In vivo
bladder and rectal
dosimetry
is performed during the HDR procedure
Other centers obtain normal tissue doses from points located on
dosimetry
films
and dose distribution curvesSlide153
Treatment planning for HDR brachytherapy
can be accomplished by a variety of techniques:
use of
an atlas of applications
and
source loadings
, to planning of only the initial insertion followed by replicating the insertion for subsequent treatments
customized optimization
of source loading for each HDR insertion
Computer treatment planning and a reconstruction system used to achieve individual
dosimetry
. Slide154
Three-Dimensional Brachytherapy Treatment Planning
The advantages of
in vivo
dosimetry
are easy practicability and the possibility to determine rectal dose during radiation.
The advantages of computer-aided planning at ICRU reference points are that calculations are available before radiation and they can be taken into account for treatment planning.Slide155
The CT-based planning provides information on target and organ volumes and dose–volume histograms.
The radiography-based planning provides dimensions and doses only at selected points. Slide156
HDREach institution should follow a consistent treatment policy, including complete documentation of treatment parameters and correlation with clinical outcome (pelvic tumor control, survival, and complications). Slide157
They predicted that, using therapeutic gain ratio, similar results would be obtained with either
brachytherapy
modality with
two to four fractions of LDR
and
four to seven fractions of HDR.Slide158
The American Brachytherapy Society published recommendations for HDR brachytherapy for carcinoma of the cervix
point A
to at least a total LDR equivalent of 80 to 85
Gy
for early stage disease and 85 to 90
Gy
for advanced-stage disease.
The
pelvic sidewall
:50 to 55
Gy
for early lesions and 55 to 65
Gy
for advanced ones.
As with LDR BT, every attempt should be made to keep the bladder and rectal doses below 80
Gy
and 75
Gy
LDR-equivalent doses, respectively. Slide159
4.Interstitial
brachytherapy
should be considered when the tumor cannot be optimally encompassed by
intracavitary
brachytherapy
.
5. It was emphasized that the responsibility for the medical decisions ultimately rests with the treating radiation oncologist.Slide160
Doses of Radiation
Stage IA (
microinvasive
) tumors are treated with
intracavitary
therapy only (LDR 60
Gy
in one insertion or 75 to 80
Gy
in two insertions to point A, or HDR 35 to 42
Gy
in five to six insertions of 7
Gy
to point A, one or two fractions per week).
The optimal dose for invasive carcinoma of the cervix is delivered with a combination of EBRT whole pelvis,
intracavitary
, and, at times, interstitial therapy. Slide161
Illustration of IMRT treatment plan to irradiate pelvic lymph nodes, while sparing organs at risk.Slide162
Brachytherapy D
Fletcher described three conditions that should be met for successful cervical
brachytherapy
:
(1) the geometry of the radioactive sources must prevent
underdosed
regions on and around the cervix
(2) an adequate dose must be delivered to the
paracervical
areas
(3) mucosal tolerance must be respected.Slide163
verify accurate placementRadiographs should be obtained at the time of insertion to verify accurate placement, and the system should be repositioned if positioning can be improved.Slide164
Brachytherapy Dose
Paracentral
doses are most frequently expressed at a single point, usually designated
Point A
.
This reference point has been calculated in a number of different ways.Slide165
The most accepted definition of Point A is a point 2 cm lateral to the cervical collar and 2 cm above the top of the
colpostats
, measured at their intersection with the tandem midpoint on the lateral radiograph
an alternative definition places Point A 2 cm lateral and vertical to the external cervical
os
.
These definitions can produce quite different dose estimates. Point A usually lies approximately at the crossing of the
ureter
and the uterine artery, but it bears no consistent relationship to the tumor or target volume.Slide166
Optimized source placement can rarely correct for a poorly positioned applicator.Slide167
an effort should always be made to deliver at least 85
Gy
(with LDR
brachytherapy
) to Point A for patients with bulky central disease.
without exceeding a dose of 75
Gy
to the bladder reference point or 70
Gy
to the rectal reference point,
The dose to the surface of the lateral wall of the apical vagina should not usually exceed 120 to 140
Gy
. Slide168
A total dose (external-beam and intracavitary
) of 50 to 55
Gy
appears to be sufficient to sterilize microscopic disease in the pelvic nodes in most patients.
Gross disease : a total dose of 60 to 65
Gy
(including the contribution from
brachytherapy
treatments).Slide169
Concurrent Chemoradiation
addition of concurrent cisplatin-containing chemotherapy to standard radiotherapy reduces the risk of disease recurrence by as much as 50%, thereby improving the rates of pelvic disease control and survival
stage IIB-IVA disease Slide170
RT , CHRThighly significant differences were detected in the rates of
local control
,
distant metastasis
,
overall survival
, and
disease-free survival
favoring the treatment arm that included chemotherapy. Slide171
All of the studies explicitly excluded patients with evidence of
para
-aortic lymph node metastases
,
poor performance status
, or
impaired renal function.
در این سه مورد بین
RT
و
CHRT
مقایسه نشده است.Slide172
radiosensitizing effects
cisplatin
epirubicin
mitomycin
5-FU
are being studied :
Paclitaxel
carboplatin,
and several biologic response modifiersSlide173
Neoadjuvant Chemotherapy
CHT RT
بی نتیجه
CHT CRT
تست نشده
CHT
تنها
OUTCOME
بدون تغییر
Slide174
Chemotherapy:
Stage IVB Disease
Single-Agent Chemotherapy
Combination Chemotherapy Slide175
Cisplatin
Ifosfamide
, carboplatin,
irinotecan
, paclitaxel response rates of 10% to 20%
Single-Agent ChemotherapySlide176
Combination Chemotherapy
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
) when it is administered as treatment for recurrent or metastatic carcinoma of the cervix.Slide177
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 diseaseSlide178
Special Treatment Problems
Locally Recurrent
:
if, in irradiated patients, the cervix remains bulky or nodular or cervical
cytologic
findings are abnormal
3 months
or more after RT ; or if symptoms of leg edema, pain, or bleeding develop after initial treatment.
The diagnosis must be confirmed with
a tissue biopsy
, and the extent of disease should be evaluated with appropriate radiographic studies,
cystoscopy
,
proctoscopy
, and serum chemistry studies before treatment is administered.Slide179
Treatment of Locally Recurrent Carcinoma of the Cervix
After Radical Surgery
aggressive radiotherapy. Slide180
TX for patients with an isolated vaginal recurrence is similar to that for patients with a primary carcinoma of the vagina.
Most patients are treated with external-beam radiotherapy with or without
brachytherapy
. Implants may need to be inserted under laparoscopic or
laparotomy
guidance. Slide181
CHRT
در
عود: نتایج امید بخش بوده
استSlide182
After Radical SurgeryTX Pelvic wall recurrences are often treated with external-beam irradiation alone, although
surgery
and
intraoperative
therapy
may contribute to local control in selected patients.
Reported survival rates usually range between 20% and 40% for patients treated with radical radiotherapy.
2Slide183
After Definitive Irradiation
an isolated central recurrence can be cured with surgical treatment.
Less extensive operations, such as
radical hysterectomy
or
anterior exenteration
, are reserved for selected patients with small tumors confined to the cervix or lesions that do not encroach on the rectum, respectively.Slide184
After Definitive Irradiation contraindication for pelvic exenteration
involvement of the pelvic sidewall
The triad of unilateral
leg edema
,
sciatic pain
, and
ureteral
obstruction
advanced ageSlide185
quality of patients' lives after surgical salvage
At all points of evaluation, the patients' quality of life was most affected by
worries about the progression of the tumor
.
Ostomies
vaginal reconstruction
urostomy or colostomy.
Vaginal dryness and vaginal dischargeSlide186
Unresectable diseaseIntraoperative irradiation ( involves the pelvic wall)
chemotherapy alone (previously discussed); response rates and prognosis are generally poor.Slide187
Treatment After Simple Hysterectomy that Reveals Unsuspected Invasive Cancer
invasion
of less than 3 mm without LVSI usually require
no treatment
after simple hysterectomy.
more extensive disease : with postoperative radiotherapy or, in selected cases, with radical
parametrectomy
and
lymphadenectomy
.Slide188
posthysterectomy
treatment
(1)
microinvasive
cancer,
(2) tumor confined to the cervix with negative surgical margins,
(3) positive surgical margins but no gross residual tumor,
(4) gross residual tumor by clinical examination documented by biopsy
(5) patients referred for treatment more than 6 months after hysterectomy (usually for recurrent disease). Slide189
posthysterectomy treatment
more extensive involvement who have
negative margins
are treated with 45 to 50
Gy
of pelvic radiotherapy to treat the pelvic nodes and
paracolpal
tissues. Most clinicians follow this with vaginal
intracavitary
therapy, delivering an additional vaginal surface dose of 30 to 50
Gy
.
ERT+BT
positive margins
: higher dose of
ERTthrough
reduced fields designed to include the region at highest risk (e.g.,
parametria
and posterior bladder wall).
RT+CHT
should probably be considered for patients with group
3 or 4
disease(M+)Slide190
Carcinoma of the Cervical Stump
The natural history, staging, and workup of cervical stump carcinomas are the same as for carcinomas of the intact uterusSlide191
Carcinoma of the Cervical Stump
stage IA1: simple
trachelectomy
selected patients with stage IA2 or small stage IB tumors : radical
trachelectomy
and pelvic lymph node dissection
most patients with irradiation alone using a combination of ERT+ BT.
Slide192
Carcinoma of the Cervical Stump
endocervical
canal is 2 cm or longer, and after ERT, patients can be adequately treated with
intracavitary
therapy.
If the
endocervical
canal cannot accommodate any sources,
aboost
dose
may be delivered to the tumor with interstitial therapy or
transvaginal
irradiation.
Vaginal
ovoids
alone rarely deliver an adequate dose to the cervix. Slide193
When
brachytherapy
is used, most investigators have reported survival rates similar to those for patients with carcinomas of the intact cervix.Slide194
Carcinoma of the Cervix During Pregnancy
Delayed in Diagnosis
a careful pelvic examination and Pap smear at their first antenatal visit
Any suspicious lesion should be biopsied
A
diagnostic
conization
may be necessary. Slide195
delay definitive treatment
Carcinoma in situ or stage IA
disease
whose disease invades less than 3 mm and no LVSI A
vaginal hysterectomy
6 weeks after childbirth
Patients whose disease invades 3 to 5 mm and those with LVSI may also be followed to
termSlide196
IB1 : classic cesarean section followed by radical hysterectomy with pelvic lymph node dissection
stage
II-IV , bulky stage IB : radiotherapy.