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Cervical Cancer and

Techniques of Radiation

David A. Buck, M.D.


Blue Ridge Cancer Care
Medical Director
Department of Radiation Oncology
Carilion Clinic Cancer Center

Outline
Introduction
Cervical Caner Treatment

Definitive Treatment
Postoperative Treatment
Addition of Chemotherapy
Locally Advanced Cervical Cancer

Radiation Technology

Treatment Delivery
3D Conformal Radiation
IMRT
Brachytherapy

Conclusion

Radiation or Hysterectomy
Landoni F et al. Lancet. 1997 Aug23;350(9077):535-40

343 patients with stage IB-IIA (IB1 61%, IB2 27%, IIA 12%). Treated with radical
hysterectomy vs. radical RT. Median F/U 87 mo.
63% of pts in surgery arm received RT.
5-year outcome: no difference; OS surgery 83% vs. RT 83% (NS), DFS surgery
74% vs. 74% (NS).
AdenoCA: significantly better outcomes with surgery; OS (70% vs. 59%), DFS
(66% vs. 47%).
Complications (Grade 2-3): Surgery 28% vs RT 12%. Severe leg edema - surgery
0%, RT 1%, surgery + RT 9%.
Conclusion: Surgery and RT are both acceptable treatments for early stage
cervical ca; (for bulky tumors, primary surgery a less good option).

Post-Operative Radiation GOG 92


Sedlis A et al. Gynecol Oncol. 1999 May;73(2):177-83

277 pts randomized, stage IB, node negative, but with high estimated risk of recurrence (from
GOG 49) s/p radical hysterectomy and lymphadenectomy randomized to +/- adjuvant pelvic
XRT 46-50.4 Gy.
Included pts with: 1) LVSI, deep 1/3 stromal invasion, any size; 2) LVSI, middle 1/3 invasion,
size >= 2cm; 3) LVSI, superficial 1/3 invasion, >= 5 cm; or 4) no LVSI, deep or middle 1/3
invasion, >= 4 cm.
These pts were estimated to have a 31% recurrence at 3 yrs.
Recurrences in 15% (RT) vs 28% (no RT).
2-year recurrence free rate 88% vs 79%. Hazard ratio=0.53. Grade 3/4 adverse effects were
6% vs 2.1%.
Distant metsases 2% (RT) vs 7% (no RT).
2006 Update - decreased rate of recurrence by 46%; local recurrence 13.9% (RT) vs 20.7% (no
RT), distant 2.9% vs 8.6%. Improved PFS by 42%. Decreased death rate by 30% (28.6% vs
19.7%) but not SS (p=0.07). RT has improved benefit for adenocarcinoma or adenosquamous
histologies (8.8% vs 44% recurrence).

Post-Operative Radiation Sedlis Criteria


Sedlis A et al. Gynecol Oncol. 1999 May;73(2):177-83

LVSI
+
+
+
--

Stromal invasion
Deep 1/3
Middle 1/3
Superficial 1/3
Deep or middle 1/3

Need 2 of 3 features

Tumor size
Any
> 2cm
> 5cm
> 4cm

Locally Advanced Cervical Cancer

RT versus RT and Chemotherapy RTOG 90-01


Morris M et al. N Engl J Med. 1999 Apr 15;340(15):1137-43

403 pts. Stage IIB-IVA, or Stage IB-IIA with >5cm tumor, or LN+.

Randomized to: 1) 45 Gy to pelvis + paraaortic nodes (both at 1.8 Gy/fx) with


upper border at L1/L2, or

2) 45 Gy to pelvis alone plus 3 cycles 5-FU and cisplatin concurrent with RT.
Intracavitary RT given in both arms.

Chemotherapy was cisplatin (75 mg/m2) on Day 1 and 5-FU (4 g/m2 96-hr
infusion,Days 1-5), repeated q3w.

Median F/U 3.6 years.

Estimated 5-year outcome: DFS RT alone 40% vs CRT 67% (SS); OS 58% vs
73% (SS).

Decreased DM and LRR in chemo+RT arm.

8-yr OS 41% vs 67%. Decreased recurrences by 51%.

Chemotherapy

Relative risk of failure

Randomized trials of cisplatin-containing CT-RT lead to an NIH


clinical alert in April, 1999.

Radiation Techniques
The Generation of Photons

Computing and
robotic advances have
allowed for
sophisticated and
precise control of
photons for
radiotherapy delivery.

Things are very


different when
compared to Cobalt60 delivery.

vs. X-Rays

Now therapeutic
X-rays can have
different energies,
different
intensities, and
gaiting to account
for respiratory
motion.

In addition, CT
imaging can be
used for targeting
of tumors and
normal tissues.

Radiation Treatment Planning

The way the photons are directed to ensure


coverage of the target has evolved with time.
Radiation treatment planning was originally
accomplished with fluoroscopic guidance.
A conventional X-ray was used to design where
and how a radiation beam would treat the patient.
This conventional X-ray was used to draw blocks
to attenuate the radiation beam.

Radiation Treatment Planning (2D)

Radiation Treatment Planning

This fluoroscopic image only allowed for 2


dimensional control of the radiation beam.
The advent of CT imaging allowed for 3D
Conformal Radiotherapy (3DCRT).
With CT treatment planning, every patient has a CT
obtained which allows for the definition of radiation
targets in 3 dimensions.
Targeting is therefore much more precise and
allows for improved sparing of the bladder and
rectum.

Radiation Treatment Planning (3D)

Three Dimensional Radiation Treatment


Planning

Despite the improved targeting, large, open fields of


radiation are still required to cover the radiation
target.
The next advancement in radiotherapy was the
ability to break up these large radiation beams into
many small beamlets allowing for more control of
the intensity of the radiation beam or intensity
modulated radiotherapy (IMRT).

IMRT Treatment Delivery

IMRT Rationale

It allows for a higher level of conformation and a


more uniform dose delivery.
It allows for reduced margins while reducing
normal tissue exposure and hence lowering
complications.
It allows for the potential for dose escalation.

Radiation Treatment Planning (IMRT)

PET/CT Fusion
Improved Targeting

Brachytherapy
From the Greek Root Short

Brachytherapy

HDR Brachytherapy
High Dose Rate irradiation uses an Ir132 source
embedded in a wire.

HDR Brachytherapy
Uterine Cervix Applicators

HDR Brachytherapy
Uterine Cervix Smit Sleeve

HDR Brachytherapy

Uterus

HDR Brachytherapy Planning


Uterine Cervix Plain films, CT, MRI

HDR Brachytherapy Planning

HDR Brachytherapy Planning

HDR Brachytherapy Planning

HDR Brachytherapy Planning


Tissues move - a new plan is required for each treatment.

Brachytherapy is Necessary

4 Yr Pelvic Control
Lanciano JROBP 20:95, 1991

4 Yr Survival
Lanciano JROBP 20:95, 1991

Local Control
Montana Cancer 57:148, 1986

External Beam

EB + Brachytherapy

45%

67%

19%

46%

40%

52%

Brachytherapy vs IMRT
Brachytherapy

IMRT

Moves with patient

Does not move with patient


Difficult to adjust with response

Conclusions

Radiation has a long history of effectiveness


in the definitive, post-operative, and locally
advanced settings.
Treatment delivery has increased in precision
over time with improved technologies.
Imaging advancements have improved the
ability to target the involved disease sites.
Brachytherapy continues to be a hallmark of
radiation treatment for cervix cancer.