The use of intracavitary Radium to treat cervical cancer
began at Washington University in 1920. Then,
as today, the treating physicians understood that there were two targets: the primary cervix tumor and the lymph
nodes. Imaging of the implants was
nonexistent. It was observed clinically that
Radium could cure the primary cervix tumor but not the lymph node metastases. 2-D imaging of brachytherapy implants and the
use of kilovoltage external irradiation to the lymph nodes was performed
beginning in the 1930s. The hallmark of
cervical cancer treatment at Washington University was to apply as much dose as
possible to the cervix (within tolerance) with brachytherapy and to limit the
use of 200-500 kVp external irradiation using small fields to the lymph nodes
only. The results of this treatment were
mixed. The primary cervix tumor was
cured in a very high percentage of cases but control of lymph node metastases
by kilovoltage and orthovoltage irradiation was dismal. In 1954 Washington University installed a 24 MeV
Allis-Chalmers Betatron. The use of 24 MeV
x-rays allowed the pelvic lymph nodes to be successfully treated and cured
without the skin toxicity of lower energy x-rays. Two critical clinical decisions were made at
that time. First, given that the primary
cervix tumor control rates were high with the use of Radium, then, the cervix
would continue to be treated with very high doses of Radium while the lymph
nodes were targeted with 24 MeV x-rays and the primary central tumor would be
blocked out of the 24 MeV external irradiation fields with a midline
rectangular block. Secondly,
brachytherapy and external irradiation would be given concurrently. This treatment paradigm of initiating
treatment with brachytherapy, limiting external irradiation to the primary
cervix tumor, and concurrent external irradiation and brachytherapy was
continued. The only alteration was the
replacement of the midline rectangular block with a midline stepwedge block
whose steps conformed to the falloff of the intracavitary radioisotope
application. Intracavitary applicator
imaging was routinely performed with orthogonal 2-D radiographs. There was no imaging of the primary tumor.
Computerized 2-D
brachytherapy dose distributions were developed at Washington University in
1964 and were then routinely used. Efforts
at computerized tomography (CT) for 3-D brachytherapy imaging and dosimetry
were begun in the mid- to late-1990’s, however, the major limitation to routine
adoption was the metallic artifact from the tungsten-shielded Fletcher-Suit
intracavitary applicators. Our efforts
toward 3-D image guided brachytherapy then focused on the use of FDG-PET
imaging. Using the Fletcher-Suit applicators,
we successfully imaged the applicator in the patient’s tumor by using PET. The FDG isotope was placed in small tubes
inside the applicator as a “dummy”. The
patient was then injected with FDG and subsequently imaged. This allowed us to visualize brachytherapy
source positions within the metabolic tumor volume and calculate 3-D dose
distributions. PET brachytherapy was
continued with the goals of understanding 3-D dose distributions to OARs, tumor
coverage, and metabolic response of the tumor to treatment. PET brachytherapy is a novel research tool
but is not feasible for routine clinical use.
During the period of the early 2000’s, several other technological advances
occurred. CT and MR compatible intracavitary
applicators and 3-D brachytherapy treatment planning systems became
available. LDR brachytherapy was
replaced by HDR brachytherapy. IMRT and volumetric arc therapy are now
routinely used for external irradiation.
The challenges during this transition were then to re-think and
understand OAR toxicity limits and appropriate tumor dose prescriptive
criteria. Much data collected over the
past 20 years have increased our understanding of these issues.
Today at Washington University, we
administer external irradiation with IMRT and continue to limit the external
irradiation dose to the primary cervix tumor while delivering high doses of
brachytherapy given once weekly during external irradiation. We use MR-guided brachytherapy for six weekly
fractions during the 6-week course of external irradiation. OARs and GTVs (as defined by DWI imaging) are
contoured and doses calculated and summed with the external irradiation on each
of the 6 brachytherapy fractions. A
real-time DoseTracker® updates with each radiation fraction and predicts total
cumulative doses as treatment progresses.
D2cc OAR doses are used to limit toxicity and Dmean doses are used as
the GTV prescriptive dose. Examples of
treated cases and toxicity and tumor control rates will be presented.