Radiation therapy is one of the main line of management of carcinoma cervix. This presentation is regarding evidences of adjuvant radiation therapy (post operative) in case of early carcinoma cervix.

1. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
R O L E O F R A D I O T H E R A P Y I N
P O S T O P E R A T I V E C A N C E R C E R V I X
E V I D E N C E S
D R . M A L H A R P A T E L
R A D I A T I O N O N C O L O G I S T
C I M S C A N C E R C E N T E R

2. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
D A Y A ,
K U C H T O G A R B A D H A I
L E T S S E E T H E E V I D E N C E S

3. M A R K E T I N G P R O P O S A L
Surgical
Oncologist
Radiation
Oncologist
Medical
Oncologist
A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

4. M A R K E T I N G P R O P O S A L
IIB onwards RTCT
A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

5. M A R K E T I N G P R O P O S A L
W H A T T O D O ?
I A - M I C R O S C O P I C
I B - C O N F I N E D T O C X
I I A - N O T I N V O L V I N G L P W
A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

6. M A R K E T I N G P R O P O S A L
Among 2274 women with stromal invasion < 1 mm, three (0.1 percent) had LN metastases.
The rate of recurrence was 0.4 percent (eight cases).
Among 1324 women with stromal invasion of 1 to 3 mm, five (0.4 percent) had LN metastases.
The rate of recurrence was 1.7 percent (23 cases).
2003
A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

7. S U R G E R Y V S R A D I A T I O N
1997
A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

8. 343 patient
Equivalent rates of 5 year survival (83 % for both)
Disease free survival (DFS; 74 % for both)
Comparable recurrence rates (surgery: 25 %; RT: 26 %)
54% received adjuvant radiation (>=IIB; +ve cut margin, lymph nodes)
A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

9. Survival benefit compared with RT alone (hazard ratio [HR] 0.41, 95% CI 0.350.50)
A limitation of this study was that 49 % of the women in the hysterectomy group received adjuvant RT and
comparisons were not made between women treated solely with surgery versus RT
2009
A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

10. L A C K O F S T U D I E S
S U R G E R Y V S R T C T ? ? ?
Choice of Sx or RT remains controversial in IB to IIA.
Preference of one over other remains over impact on patient's
fertility, on institution, on surgical and radiation oncologist,
general condition of patient and characteristics of lesion
O P E R A B I L I T Y C R I T E R I A S
A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

11. S U R G E R Y
1. In case of pelvic relapse - radiation is an option
2. Lymph noded status
Cervical diameter > 4 cm had the most unfavourable pathological prognostic factors
Risk of a relapse independently from any other clinical factor.
A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

12. L Y M P H N O D E - A K N O W N R I S K F A C T O R
5 year survival
LN negative 82-90%
LN positive 38-61% 1978
A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

13. Large Tumour Diameter (LTD)
Deep Stromal Invasion (DSI)
Capillary Lymphatic Space Invasion (CLS)
Other Risk Factors
(Intermediate)
Chung CK, Nahhas WA, Stryker JA, Curry SL, Abt AS, Mortel R: Analysis of factors contributing to treatment failure in stage IB and IIA carcinoma of the cervix. Am J Obstet
Gynecol 138:550–556, 1980
Boyce J, Fruchter RG, Nicastri A, Ambiavagar P, Reinis MS, Nelson J: Prognostic factors in stage I carcinoma of the cervix. Gynecol Oncol 12:154 –165, 1981
Van Nagell JR, Donaldson Es, Wood E, Parker J: The significance of vascular invasion and lymphocytic infiltration in invasive cervical cancer. Cancer 41:228 –234, 1978
Abdulhayoglu S, Rich WM, Reynold J, DiSaia PJ: Selective radiation therapy in Stage IB uterine cervical carcinoma following radical pelvic surgery. Gynecol Oncol 10:84–92,
1980
Boyce J, Fruchter R, Nicastri AD, De Regt R, Ambiavagar P, Reinis M, Macassaet M, Rotman M: Vascular invasion in stage I carcinoma of the cervix. Cancer 53:1175–1180, 1984
A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

14. GOG Study
Presence of one of the following LTD, DSI, CLS
Probability of cancer recurrence increases 2 to 31%
25% of all IB node negative cervical cancer have these features
A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

15. GOG 92
A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

16. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
2006

17. B I J O U M E D I A M A R K E T I N G P R O P O S A LA R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

18. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

19. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

20. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
The crude estimate in the reduction in risk in patients receiving
adjuvant radiotherapy was 47% (i.e., relative risk = 0.53) with
the recurrence-free rate of 88% in the radiotherapy group
and 79% in the no-further-therapy group at 2 years
The Cox model analysis indicated that when adjusting for all combinations of
the three risk factors—tumor size, CLS, and the depth of invasion—
The risk of recurrence was significantly reduced by 44% in the radiation group
(P = 0.019, one-tail).
Reduction in the recurrence rate from 28% to 15% with the addition of RT

21. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
The relative mortality rate is estimated at 0.64 which indicates 36% less
mortality in the radiation group; a significance level is not provided because
the survival data are not mature.

22. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
IMRT

23. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
Cervical cancer > 4 cm in diameter determined by preoperative palpation was
associated with a
5-fold increase in pelvic lymph node metastases,
10-fold increase in recurrences
50% decrease in survival

24. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
Deep tumor invasion into cervical stroma (measured either in millimeters or in thirds
of the total cervical thickness) has been also shown in association with
lymph node metastases, recurrence, and poorer survival

25. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
Combination of risk factors correlated better with the survival than one factor alone.
Of the three risk factors, depth of invasion seems the most objective and accurate
method—a direct measurement on the histological slide.

26. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
A reduction in the risk of disease progression at 5 years
(relative risk [RR] 0.58, 95% CI 0.370.91).
No difference in the risk of death at 5 years (RR 0.84, 95% CI 0.32.36),
The wide confidence interval suggests the study was underpowered to assess survival.
2012 Meta-analysis
IB1, IB2, IIA

27. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
Recurrences are much more frequent in patients with LN involvement and
involvement of the parametrium or surgical margins and in patients with large or
deeply invasive lesions
1. Morley GW, Seski JC: Radical pelvic surgery versus radiation therapy for stage 1 carcinoma of the cervix (exclusive of microinva- sion). Am J Obstet Gynecol 126:785-794, 1976
2. Hopkins MP, Morley GW: Radical hysterectomy versus radiation therapy for stage IB squamous cell carcinoma of the cervix. Cancer 68:272-277, 1991
6. Inoue T, Okumura M: Prognostic significance of parametrial extension in patients with cervical carcinoma stages IB, IIA and IIB: A study of 628 cases treated by radical hysterectomy and lymphadenec- tomy with and without postoperative radiation. Cancer 54:1714-1719, 1984
7. Alvarez RD, Soong SJ, Kinney WK, et al: Identification of prognostic factors and risk groups in patients found to have nodal metastasis at time of radical hysterectomy for early-stage squamous carcinoma of the cervix. Gynecol Oncol 35:130-135, 1989
8. Fuller AF Jr, Elliott N, Kosloff C, et al: Determinants of increased risk for recurrence in patients undergoing radical hysterectomy for stage IA and IIB carcinoma of the cervix. Gynecol Oncol 33:34-39, 1989
9. 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 38:352-357, 1990
10. Sevin BU, Lu Y, Bloch BA, et al: Surgically defined prognostic parameters in patients with early cervical carcinoma: A multivariate survival tree analysis. Cancer 78:1438-1446, 1996
11. Zreik TG, Chambers JT, Chambers SK: Parametrial involve- ment, regardless of nodal status: A poor prognostic factor for cervical cancer. Obstet Gynecol 87:741-746, 1996
12. Lin HH, Cheng WF, Chan KW, et al: Risk factors for recurrence in patients with stage IB, IIA and IIB cervical carcinoma after radical hysterectomy and postoperative pelvic irradiation. Obstet Gynecol 88:274-279, 1996
13. Kamura T, Tsukamoto N, Tsuruchi N, et al: Multivariate analysis of the histopathologic prognostic factors of cervical cancer in patients undergoing radical hysterectomy. Cancer 69:181-186, 1992
14. Estape RE, Angioli R, Madrigal M, et al: Close vaginal margins as a prognostic factor after radical hysterectomy. Gynecol Oncol 68:229-232, 1998

28. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
Positive Margin
Lymph node metastasis
Parametrial Involvement
When one or more of these factors is found,
the 5-year survival drops to the 50% to 70% range.

29. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
Retrospective comparisons of patients with positive pelvic lymph nodes treated with postoperative RT have
generally shown a decrease in the local recurrence rate but no improvement in long-term survival.

30. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
Concurrent Chemotherapy?

31. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
316 patients
FIGO stage IB1-IIB
Adjuvant radiotherapy (RT) (n = 124, RT group) or adjuvant CCRT (n = 192, CCRT group)
January 1996 and December 2009.
187 patients displayed high-risk prognostic factors (high-risk group)
129 displayed intermediate-risk prognostic factors (intermediate-risk group).
60 patients with 1 intermediate-risk prognostic factor who received no adjuvant therapy
were also identified and used as controls (NFT group) 2013

32. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

33. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
High-risk group - Adjuvant CCRT was significantly superior to RT alone with regard to
recurrence rate, progression-free survival (PFS), and overall survival.
Intermediate-risk group - CCRT was superior to RT with regard to
recurrence rate and PFS in patents with 2 or more risk factors.
Among the patients with only 1 intermediate-risk factor, although no survival benefit of CCRT
over RT was observed, addition of adjuvant treatment resulted in significantly improved PFS
compared with the NFT group in patients with deep stromal invasion.
CCRT resulted in a lower recurrence rate (9 versus 23 percent, p = 0.049)
Trend towards improved PFS at five years (90 versus 78 percent; HR 2.82, 95% CI 0.998.02).

34. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
1990 and 2010, 110 cervical cancer patients
2 or more intermediate risk factors (DSI, LVSI, and LTD)
adjuvant RT (n=56) or CCRT (n=54) following radical surgery.
Concurrent chemotherapeutic regimens were carboplatin and paclitaxel (n=48).
Five-year relapse-free survival (RFS) rates 85.6% Vs 93.8%.
CCRT had a significant decrease in pelvic recurrence (p=0.012) and distant metastasis (p=0.027).
Acute grade 3 and 4 hematologic toxicities were more frequently observed in CCRT (p=0.001).
Acute grade 3 and 4 gastrointestinal (GI) and chronic toxicities did not differ between the groups. 2012

35. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
Progression-free and overall survival are significantly improved in the patients receiving CT.
Hazard ratios for PFS and OS in the RT only arm versus the RTCT arm are 2.01 (P .003) and 1.96 (P .007)
PFS at 4 years is 63% with RT and 80% with RTCT.
OS at 4 years is 71% with RT and 81% with RTCT.
Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RTCT group.
IA2, IB, IIA
2000

36. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
IA2, IB, IIA 2005

37. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
n = 243 (RT = 116; RT + CT = 127)
The beneficial effect of adjuvant CT was NOT strongly associated with patient age,
histological type, or tumor grade.
The prognostic significance of histological type, tumor size, number of positive
nodes, and parametrial extension in the RT group was less apparent when CT was
added.
The absolute improvement in 5-year survival for adjuvant CT in patients with
tumors <= 2 cm was only 5% (77% versus 82%),
while for those with tumors >2 cm it was 19% (58% versus 77%).
Similarly, the absolute 5-year survival benefit was less evident among patients with
one nodal metastasis (79% versus 83%) than when at least two nodes were positive
(55% versus 75%).
GOG, SWOG, RTOG

38. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
National Cancer Database
(NCDB)
Over 3000 patients with high risk disease treated with hysterectomy and
adjuvant RT with or without chemotherapy,
OS benefit associated with the addition of chemotherapy in patients with
node positive disease (HR 0.58, CI 0.410.81) but
not in patients with positive margins, parametrial invasion, or the combination of
these two features

39. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

40. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L

41. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
GOG 263 = GOG 92
LVSI (CLS)
OR > 2/3rd Cervical Wall Involvement
OR > 2 cm Size
80% Probability of GOG 263 Candidate

42. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
Less than radical hysterectomy
Close or positive surgical cut margin
Large or deep invasive tumours
Parametrial or vaginal involvement =
Extensive LVSI

43. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
SOLVED!!
LTD, LVSI, DSI - Any of these present - RT + CT
Lymph node, positive margin, parametrial involvement - RT + CT
Wait for GOG 263
Brachytherapy???

44. A R O I G U J A R A T C H A P T E R 3 R D A N N U A L M E E T D R . M A L H A R P A T E L
Thank You