JOURNAL PRESENTATION

1. PATTERNS OF FAILURE AND TREATMENT
RELATED TOXICITY IN ADVANCED
CERVICAL CANCER PATIENTS TREATED
USING EXTENDED FIELD RT WITH
CURATIVE INTENT
ABHIJIT DAS
2ND YEAR PGT
DEPARTMENT OF RADIATION ONCOLOGY
AHRCC

3. AIMS AND OBJECTIVES:
• Efficacy of CTRT in cervical cancer patients treated with EFRT.
• patterns of failure in these patients
• Treatment related toxicity

4. Methods & materials:
Nature of study: retrospective
Place of study: PETER MCCULLUM CANCER CENTRE, Melbourne , Australia
TIME PERIOD: JANUARY 1996 TO JUNE 2007
TOTAL NO PATIENTS : 39 PATIENTS
PATIENTS SELECTION CRITERIA:
• untreated patients with diagnosis of locally advanced ca cervix planned for
definitive RT.
• Histopathology may be squamous cell carcinoma/ adenocarcinoma. ( clear cell ,
endometriod carcinoma and mucinous carcinoma.)
• Evidence of metastasis in common iliac / para aortic nodes (imaging e.g PET CT
and by surgical staging- laparotomy.)
• FIGO staging IB – IIIB
• All are treated with EFRT with curative intent.

5. TREATMENT POLICY
Patients with common iliac /para
aortic nodes confirmed to be positive
EFRT AND BRACHY THERAPY
(concurrent CDDP 40 MG/
M2)
EFRT: 4 FIELD DESIGN WITH 18 MV
PHOTON ( ONE patient treated by
AP PA field due to b/l hip
replacement)
ABDOMINO PELVIC fields – a total dose of
45 gy in 25 #
Positive nodes is treated with 50.4- 54 gy
in 28-30 #
Patients are reviewed per week or more
frequently to check the toxicity.
Within 1 week brachytherapy
started.
HDR: 28-30 GY IN 4-5 #( TWICE
WEEKLY)
LDR: 40-45GY IN 2 #( POINT A
DOSE OF 80 GY)

6. Border
inferior border lower margins of the obturator foramina or 4 cm below the distal vaginal
tumor, whichever was greater.
Lateral borders pelvic field extended 1.5 to 2
cm outside the widest diameter of the true pelvis.
lateral projection the superior and inferior borders were
identical to that of the AP/PA fields. The anterior border was 1 cm
anterior to the symphysis pubis, and the posterior border intersected at
the S2–S3 space
width of the AP/PA 8 cm or at least 2 cm lateral to
the peripheral nodal contour
The anterior
border of the para-
aortic portion of
the field
3 cm anterior to the anterior vertebral surface or 2 cm anterior to the
anterior surface of the involved lymph nodes
Thirty-three (85%) patients were treated up to the vertebral junction between T12 and L1.
Three patients were treated up to the L2– L3 vertebral intersection and 3 patients up to the
L3–L4 vertebral intersection
para-aortic
field

7. FOLLOW UP TIME PERIOD INVESTIGATIONS
1ST 4-6 Wks after RT Every 6 months post RT
PET repeated.
Patients having
suspected of recurrence
is examined using PET
as appropriate.
During 1st year Every 3 months
During 2nd & 3rd year Every 4 months
4th & 5th years Every 6 months
After 5 yrs. Yearly visit
At each follow up a form is filled up using disease
status & late complications.( using RTOG toxicity
criteria: ACUTE TOXICITY is defined as toxicity
within 3 months of start of RT. LATE TOXICITY is
defined as toxicity after 3 months of start of RT.)

8. Criteria for assessing outcomes:
Failure Either persistent disease/ recurrence of disease following RT
Date of failure Date of sign of any of these failure either clinical or imaging
Site of failure Nodal relapse: Either in field /outside the treatment field
Distant failure: Any failure outside the treated failure including
supraclav / mediastinal nodes.
Local: Residual/ recurrent disease at cervic /uterus
Overall
survival
Time of beginning of treatment to death due to any cause
Disease free
survival
Time of beginning of treatment to failure or death as aresult of of disease
progression

9. STATISTICAL METHOD:
• Time to event endpoints were calculated
• From it 5 year event free rates are calculated
KAPLAN MEIR
CURVES
• Prognostic factor analyses was dona
• Exploratory analyses is done to maintain the non
violation of cox regression analyses
Cox regression
analysis
• Baseline characteristics of participants eligible to
be included in this study
Simple descriptive
statistics
CLOSE OUT DATE
(MARCH 3,2008)
EARLIEST OF LAST DATES OF F/U OF PATIENTS WHO WERE ALIVE
AND NOT TO LOST FOLLOW UP
FOLLOW UP TIME TIME OF STUDY ENTRY TO ( COMMENCEMENT OF EFRT) TO THE
LAST DATE OF KNOWN F/U OR THE DATE OF CLOSE OUT

10. VARIABLE LEVEL NO OF PATIENTS
AGE MEAN ( RANGE) 54(27-78)
FIGO I 10(26)
II 18(18)
III 11(28)
HP SCC 35(90)
ADENOCARCINOMA 4(10)
TUMOR GRADE MOD. DIFF. 16(41)
POORLY DIFF. 22(56)
UNSPECIFIED 1(3)
ECOG 0 2(5)
1 32(82)
2 4(10)
3 1(3)
NO OF
PATIENTS: 39
(100%)

11. VARIABLE LEVEL NO. OF PATIENTS
NODAL
INVOLVEMENT
COMMON ILIAC ONLY 15(38)
LOWER PARA AORTIC WITH
/WITHOUT COMMON ILIAC
16(41)
UPPER PARA AORTIC WITH
/WITHOUT COMMON ILIAC /
LOWER PARA AORTIC
8(21)
NO. OF NODES MEDIAN (RANGE) 4(1-5)
LN DETECTED PET 28(72)
LAPAROSCOPY 8(21)
PET/ LAPAROSCOPY 3(7)
TUMOR CHARACTERISTICS:

12. VARIABLE LEVEL NO OF PATIENTS(%)
BRACHYTHERAPY LDR 12(31%)
HDR 27(69%)
EFRT CTRT 36(92%)
RT 3(8%)
TREATMENT STATISTICS:

14. NO OF PATIENTS FAILURE SITE
20 INSIDE AND
OUTSIDE THE
TREATMENT FIELD
Among these 16
patients had
failure in nodal sites
outside the treated
field.
7 EXCLUSIVELY
OUTSIDE THE FIELD
3 EXCLUSIVELY
WITHIN THE
TREATED FIELD
PATTERNS OF FAILURE: 30 (77%)
13 patients has
treatment upto
T12-L1 junction.
2 patients
upto L3-L4
junction.
1 patients
upto L2-L3
junction.
These 3
patients
belongs to 1st
group.
90
%
of
tot
al
pa
tie
nts
• Distant failure is noticed in 49 % of patients as site of first
failure.

15. Prognostic factor analyses for failure: Among the patients with
1 to 3 involved nodes, 34.5% of
patients were relapse free at
5-years, whereas, only 5.3% of
patients with 4 nodes were
relapse free at 5-years
Each incremental increase in node
number increased the risk of failure
by 17% (p= 0.046).
Relapse free survival by no. of nodes involved
The number of nodes seems to be an
independent predictor of relapse
status.

16. Treatment-related acute side effects Treatment breaks during EFRT
• only 3 patients (8%) experienced treatment breaks
due to radiation toxicity, with a mean delay of 6.5
days
• Fifteen patients (38%) had overall grade 3 to 4
acute toxicity

17. Treatment-related late side effects
only 2 patients (5%) had significant late
toxicity. One of these patients had
urinary incontinence related to a large
tumor involving the external surface of
the bladder base, and the other patient
had a rectovaginal fistula which resulted
from recurrent tumor.
No deaths occurred due to toxicity.

18. • The patients were followed for an
average period of 26.7 months (median,
19.2 months).
• Of the 39 patients included in this study,
25 have died.
• The median survival was 27.3 months
(95% confidence interval [CI], 14.9–43.7).
• The 5-year overall survival was 26% (95%
CI, 11–44).
• The median DFS was 8.9 months (95% CI,
4.1–20.7).
• The 5-year DFS was 19.4% (95% CI, 8–35)
Overall and failure-free survival

19. DISCUSSION

20. Survival and patterns of failure: • In the present series, the 5-
year OS rate was 26%, with a
median survival time of 2.3
years, whereas most of study
shows a os rate of 30%.
• In this study, the 3-year OS
and DFS rates are 45% and
23%.
GOG
Projected 5-year survival

21. • Patterns of failure in cervix cancer patients treated with EFRT have changed over the last 4 decades.
• Pelvic failure was the predominant site of failure in patients treated with radiotherapy, without the use of
concurrent chemotherapy. An observation was made by Podczaskiet al, who reported a pelvic failure rate of
48% and a distant failure rate of 18% as the initial site of failure. That rate is in contrast to the 49%
incidence of distant failure as the initial site of failure reported in the present study
• The higher incidence of distant metastases as the initial site of failure can be explained by the use of PET
scanning at the time of first relapse.
• Use of concurrent CTRT reduces the tumor size, after which conformal brachytherapy gives a satisfactory
dose distribution.
 The gross nodal disease was treated to 50.4 to 54 Gy, with only 1 patient experiencing isolated in-field
nodal failure.
 These results suggest that the doses used in the present study were adequate to control curable disease.
Some investigators have attempted dose escalation to para-aortic nodes using intensity-modulated RT in
order to improve outcome. However, because the poor survival is related to high failure rates outside the
treatment field, increasing dose within the treatment field is unlikely to improve survival.
in view of a small number (6/39) of patients who were treated with limited EFRT (at L2–L4 junction), it is not
clear whether there is a benefit in treating patients with common iliac or lower para-aortic
nodal disease with large fields extending up to T12–L1.

22. • Prognostic factors:
Lymph node metastasis is the most important prognostic factor in cervical cancer.
In the present study, the univariate estimates show that any para-aortic nodal
involvement increased the risk of any relapse by 11% and death by 49%.
This study was not sufficiently powered to show statistical significance determining the
prognostic value of the level of lymph node involvement. But this study shows
showed a trend toward poorer survival with a higher level of nodal involvement.
• Treatment-related acute toxicities:
Higher rates of acute gastrointestinal and bone marrow toxicity are expected in patients treated with
concurrent chemotherapy and EFRT due to the large field sizes. In this series, 15 patients (38%) had
overall grade 3 to 4 toxicity. This level is much lower than the 85% incidence of acute toxicity
reported in the RTOG 0116 study.
This may be due to 1. parametrial boost used in RTOG trial.(60GY) & Nonpelvic nodes upto
54-59.6gy
2. upper border of T12 used in the portal.
late toxicity: Both the 0116 and the 92-10 RTOG studies reported late toxicity rates of 40% and
21%, respectively whereas only 2 patients (5%) had significant late toxicity.

23. CONCLUSIONS
It is proposed by the author, that
• The involvement of common iliac and para-aortic lymph nodes in cervix cancer patients should
be regarded as systemic disease.
• The standard radiotherapy doses that are currently used are adequate to successfully control
the primary tumor and the involved nodes in curable patients.
• Toxicity has been a limiting factor in the use of EFRT. Advent of conformal EFRT with
concurrent chemotherapy, followed by conformal brachytherapy using moderate doses may
optimize tolerable treatment with acceptable toxicity.