This study compared extended field concurrent chemoradiation (EF-CCRT) to whole pelvis CCRT (WP-CCRT) in patients with locally advanced cervical cancer and enlarged pelvic nodes but radiologically negative para-aortic lymph nodes. EF-CCRT resulted in significantly fewer para-aortic failures compared to WP-CCRT with similar toxicity profiles. While EF-CCRT showed promising results with improved para-aortic control, the study was limited by its small sample size and lack of PET staging. Larger multicenter trials are needed to validate whether EF-CCRT outcomes are superior to WP-CCRT.
6- mshabeb asiri - is extended field concurrent chemoradiation an option for
1. Is Extended Field Concurrent Chemoradiation an
Option for Radiologic Negative Para-aortic Lymph
Nodes Locally Advanced Cervical Cancer?
Asiri MA, Tunio MA, Mohamed R, Bayoumi Y, Alhadab A,
Saleh RM, AlArifi MS, Alobaid A ,K Salama, B Obaidat
2. CCRT is The standard treatment for locally
advanced cervical cancer .
Five randomized trials showing survival
benefit
Patients with locally advanced cervical
cancer harbor 17-37% para-aortic nodal
micrometastasis at time of diagnosis.
15-25% of patients experience para-
aortic nodal failures after receiving
combined pelvic chemoradiation in long
term follow up.
3. Radiotherapy alone failed to control biopsy proven
para-aortic lymph nodes (PALN),
Poor 5 year survival rates ( 29 to 50%).
Chemotherapy with extended field irradiation for
biopsy proven PALN are associated with significant
gastrointestinal and hematological toxicities
Hypothesis : EF-CCRT leads to results better to
those obtained by WP-CCRT in patients with
locally advanced cervical cancer with radiologic
enlarged pelvic nodes and normal para-aortic
lymph nodes (PALN).
4. PATIENTS AND METHODS:
Starting July 2007
Pathology :
Squamous cell carcinoma,
Adenocarcinoma
Adeno-squamous cell carcinoma
Radiologic negative PALN and enlarged pelvic nodes > 1cm.
Stages IIB-IVA
WP-CCRT (36 patients) and EF-CCRT (38 patients)
5. External beam radiation Therapy (EBRT):
WP-CCRT:
(GTV), uterus, pre-sacral (PS), common iliac (CI), internal iliac (II) and
external iliac (EI) lymph nodes, with 1 cm margins
(PTV-1) with 0.5 to 1 cm margins around CTV
Boost covering enlarged lymph nodes and parametria,
(OAR) including kidneys, small bowel, bladder, rectum and femoral heads
3D-CRT and intensity modulated radiation therapy (IMRT)
Radiation doses were 45-50.4 GY/25-28 fractions
Radiological enlarged lymph nodes were boosted to dose of 50.4-54 GY.
EF-CCRT:
The pelvis was treated similarly as WP-CCRT
Additional paraaortic fields were added as a continuous area
Superior field border at the junction of T12/L1 to cover PALN up to level of
renal hila.
The prescribed radiation dose to paln was 45 GY
HDR brachytherapy for both group 21 GY/ 3 fractions.
9. Toxicity scoring:
Week during CCRT.
weight, performance status, hematologic and blood
chemistry determinations
3 monthly for the first 2 years,
6 monthly thereafter at radiation oncology and
gynecology oncology clinics.
Response evaluation
pelvic examination,
Pap smear,
CT chest and abdomen and pelvic MRI every 6 months
for the first 2 years.
10. RESULTS:
WP-CCRT (36 patients) and EF-CCRT (38 patients)
FIGO stage IIB (66.2%)
FIGO stage IIIB (4.05%)
Radiologic Enlarged pelvic lymph nodes (51.4%).
The median follow-up time was 60 months.
treatment protocol completion rate :
90 % in the WP-CCRT group
88.4% (95% CI,90-100) in the EF-CCRT group
Weekly concurrent cycles of cisplatin in both
treatment arms were completed in all (100%)
patients with no interruption.
Median duration of radiation therapy in both arms
was 55.5 days with 95% CI: 48-58.
11. Variables Arm A
Extended Field CCRT
(n=38)
Arm B
Pelvic Field CCRT
(n=36)
p value
Age 52.3 years (32-78) 51.6 years (34-76) 0.9
ECOG performance Scale 0-2 0-2 1.0
Histopathology
Squamous cell Carcinoma
Adenocarcinoma
Adeno-squamous cell carcinoma
34 (89.5%)
3 (7.9%)
1 (2.6%)
33 (91.7%)
2 (5.6%)
1 (2.8%)
0.7
FIGO staging
IIB
IIIA
IIIB
IVA
24 (63.1%)
6 (15.8%)
4 (10.5%)
4 (10.5%)
25 (69.4%)
6 (16.6%)
3 (8.3%)
2 (5.6%)
0.8
Radiological Primary Tumor size
<5 cm
> 5 cm
13 (34.2%)
25 (65.8%)
14 (38.9%)
22 (61.1%)
0.6
Nodal Enlargement
Iliac
Common Iliac
Para-aortic
9 (23.7%)
14 (36.8%)
-
13 (36.1%)
2 (5.6%)
-
0.05
Pre-treatment hemoglobin
>10 gm/dl
<10 gm/dl
35 (92.1%)
3 (7.9%)
34 (94.4%)
2(5.6%)
0.9
Treatment
3DCRT
IMRT
EBRT:
Whole Pelvis
Para-aortic
Parametrial/enlarged LN boost
HDR-BT:
Dose/fraction
Total dose/fraction
Point A BED
ICRU 38 rectal point BED
ICRU 38 bladder point BED
Concurrent weekly Cisplatin cycle:
Dose/week
Mean cycles
30 (78.9%)
8 (21.1%)
45 Gy (42-50.4)
45 Gy (45-50.4)
9 Gy (5-9)
7 Gy/fraction
21 Gy/3
86.4 Gy (80.5-102.7)
85 Gy (80.5-100)
86 Gy (80.5-102)
30mg/m2
5 (4-7)
36 (100.0%)
-
45 Gy (42-50.4)
-
9 Gy (5-9)
7 Gy/ fraction
21 Gy/3
86.4 Gy (80.5-102.7)
85 Gy (80.5-100)
86 Gy (80.5-102)
30mg/m2
5 (4-7)
0.9
Patients’
characteristics
12. RESULTS: Toxicity :
grade 3 or 4 acute hematological and non-hematological
5.2% and 2.6% in the EF-CCRT
5.4% and 2.7% in the WP-CCRT
Both treatment arms had similar grade 3 or 4 acute
gastrointestinal toxicity .
No patient in either arm underwent surgery for
radiation-induced damage or died because of treatment
related side effects.
13. Toxicity Arm A
Extended Field CCRT
(n=38)
Arm B
Pelvic Field
CCRT
(n=36)
p value
Acute:
Hematologic
Neutropenia
Thrombocytopenia
Anemia
Non-hematologic
Nausea/vomiting
Diarrhea
Cystitis
Deranged Renal
Functions
Deranged Liver
Functions
G3 G4
1 (2.6%) 1
(2.6%)
0 0
0 0
0 0
1 (2.6%) 0
0 0
1. 0
0 0
G3 G4
1 (2.7%)
1(2.7%)
0 0
0 0
0 0
0 0
1 (2.7%) 0
1. 0
0 0
0.7
Late:
Chronic cystitis
Intestinal obstruction
Proctitis
Neuropathy/
plexopathy
Hearing loss
Renal
0
1 (2.6%)
0
0
0
0
1.
2.
3.
4.
1 (2.8%)
0
0.8
Acute and Late treatment related toxicity profile
14. RESULTS: Pelvic, Para-aortic Relapse
Pelvic LR :
3 (8.3%) in WP-CCRT arm
3 (7.9%) in EF-CCRT,
Para-aortic nodal failures
5 (13.9%) in WP-CCRT
1 (2.6%) in EF-CCRT (p value 0.02)
5 para-aortic nodal failures were seen at level of junction L2 and L3 vertebrae
and 2 (40%) at level of L1 vertebrae and in EF-CCRT arm one para-aortic
nodal failure was seen at junction of T12 and L1 vertebrae.
15. RESULTS:
Distant failures
7 (19.4%) patients in WP-CCRT
4 (10.5%) patients from EF-
CCRT
Combined distant and para-aortic
nodal failures
4 (11.4%) in WP-CCRT
1 (2.6%) in EF-CCRT group.
16. RESULTS:
At the time of analysis, 32
patients in EF-CCRT and 27
patients in WP-CCRT group
were found without evidence of
disease
18. RTOG 97-20 & 90-01
RTOG-97-20 trial,
EF-RT V WP-RT
10 Y FU
survival gain of 11% in EF-RT
No difference in LRC.
RTOG trial (RTOG 90-01)
EF-RT V WP-CCRT
5-year OS : (41% vs. 67% at 8 years) in favor of WP-
CCRT
para-aortic failures : (7% WPCCRT vs. 4% EF-RT
19. Similar studies
Malfetano et al;
weekly cisplatin concomitant EF-RT
67 women
75% of patients were alive without evidence of disease,
with no para-aortic failures.
Chung YL,
63
Concurrent cisplatin during first and fifth weeks of extended
field irradiation followed by two adjuvant cycles of cisplatin
and 5-flouro-uracil
para-aortic nodal failures only 4.5% and OS rate of 81% at
3 years.
20. limitations of present study
Low sample size.
Selection bias.
Lack of baseline FDG/PET based
staging.
21. Recommendations :
Prophylactic EF-CCRT in patients with locally advanced
cervical cancer patients with PET enlarged pelvic lymph
nodes.
Multicenter, phase III trial using IMRT in prophylactic
extended field irradiation with concurrent chemotherapy in
FDG/PET negative PALN locally advanced cervical patients,
to evaluate whether outcomes of EF-CCRT are truly better
than those of WP-CCRT.
22. CONCLUSION:
Prophylactic EF-CCRT can be a reasonable
option in patients with locally advanced cervical
cancer with radiologic enlarged pelvic lymph
nodes and radiologic negative PALN.
