Running Head: BRACHYTHERAPY: ISOTOPES 1

Brachytherapy: Analyzing Isotopes for Cervical Cancer

Claire Davis, Cristiana Holmes, Rebekah Rivera, Allie Roberts

Armstrong State University

BRACHYTHERAPY: ISOTOPES 2

Abstract

There are two primary types of cervical carcinomas, one being adenocarcinoma, and the most

prevalent being squamous cell carcinoma (Wesola & Jelen, 2015). Pap smears are the

recommended screening device (Castillo et al., 2016) which can detect cervical cancer. In later

stages, cervical cancer can metastasize to organs and lymph nodes. The tolerance doses of

critical structures must be identified and considered during treatment planning to provide the

patient with the best quality of life (Rideaux, 2016). Treatment options include but are not

limited to surgery (Rideaux, 2016), IMRT (Marnitz et al., 2015), chemotherapy (Rose et al.,

2011), and brachytherapy (Viswanathan et al., 2012). During brachytherapy, the radioactive

tandem and ovoid implants are inserted through the intrauterine canal. The most common subsets

of brachytherapy treatment are high-dose rate (HDR), and low-dose rate (LDR) (Wang et al.,

2010). Within brachytherapy, different isotopes are used. Studies show several isotopes having

both positive and negative effects on different patient factors such as, radioresistance, and

reoccurrence rates (Janulionis, Valuckas, Liukpetryte, Samerdokiene, & Atkocius, 2015).

Common isotopes that are used are Iridium-192, Californium-252, Cobalt-60, and Radium-226

(Viswanathan et al., 2017). This review will focus on brachytherapy and analyzing the different

isotopes used in treatment for cervical cancer.

Brachytherapy: Analyzing Isotopes for Cervical Cancer

BRACHYTHERAPY: ISOTOPES 3

Cervical cancer is considered to be one of the most common malignancies in women. It is

a type of cancer that occurs in the lining tissue of the cervix. When cells on the surface level of

the cervix continuously divide, cervical lesions appear, and if the lesions are left untreated, those

cells can turn into cancer. There is no known cause of cervical cancer but there are different

factors that have been associated with it. This cancer affects women in the United States but is

more prevalent in third world countries. With cervical cancer being so prevalent, it is imperative

to know about the different treatments offered.

One effective form of treatment for cervical cancer is brachytherapy. Brachytherapy is

different from external radiation because the source is placed close to or directly into the tumor

which decreases exposure to surrounding organs. Brachytherapy can be broken down into high-

dose rate (HDR) and low-dose rate (LDR). Different isotopes or sources can be used to treat

cervical cancer. The most common sources used for cervical cancer include, but are not limited

to, Iridium 192, Californium-252, Cobalt-60, and Radium-226. Scientific studies have found

advantages and disadvantages to these different isotopes that can provide better or worse

effects/results depending on the patient and their specific diagnosis.

Literature Review

Anatomy, Epidemiology, Etiology

The cervix is part of the female genitalia and is located inside the superior portion of the

vaginal canal where it connects with the uterus. The cervix is commonly broken up into two

anatomical locations: the endocervix, where the cervix meets the uterus; and the exocervix,

where the cervix meets the vagina. The cervix also has an opening called the cervical os that is

made up of squamous cell epithelium. The most common site for cervical cancer is at the
BRACHYTHERAPY: ISOTOPES 4

squamocolumnar junction where the squamous cells of the cervical os meet the columnar cells of

the endocervix (Rideaux, 2016).

Cervical cancer is one of the most common cancers in women, and also has some of the

highest mortality rates (Castillo et al., 2016). Although advanced screenings are reducing

mortality, approximately 500,000 new cases are diagnosed each year with most occurring in less

developed countries, where access to healthcare services is scarce (Wesola & Jele, 2015). The

mean age for cervical cancer patients is vast, covering ages as young as 15 to geriatric patients

over 50 years old (Castillo et al., 2016). There are two classifications of cervical cancer:

squamous cell carcinoma, which constitutes over 85% of cases; and adenocarcinoma which is

more invasive and radio-resistant (Wesola & Jele, 2015).

The causes for the development of cervical cancer are widely unknown, although more

and more studies are linking increased amounts of unprotected sexual activity with multiple

partners to the development of cervical cancer. Cheah, Koh, Nazarina, Teoh, & Looi (2016)

found that human papillomavirus (HPV) is a significant precursor to the development of cervical

cancer, and Rideaux (2016) has stated that in addition to multiple sexual partners at an early age,

HPV is responsible for nearly 99% of cervical cancers (p. 740). Identification and management

of HPV can aid in the prevention or diagnosis of early-stage cervical cancer, thus reducing the

number of patients given a grave prognosis. On a molecular level, the gene marker p16 has been

proposed as the HPV marker for the high-risk strands 16 & 18 that transform into cervical cancer

(Cheah, Koh, Nazarina, Teoh, & Looi; 2016). P16 prevents the phosphorylation of kinase

inhibitors CDK4 and CDK6 in addition to the retinoblastoma gene product pRb (2016). It has

been proven that the upregulation of p16 causes the transformation of the host cells in

conjunction with hrHPV, the genetic marker for HPV (2016). In genetic screening of patients
BRACHYTHERAPY: ISOTOPES 5

with cervical cancer, squamous cell carcinoma and high-grade squamous intraepithelial lesions

showed positive p16 gene expressions in over 70% of cases where hr HPV was also present

(2016). This finding can aid in the early categorization and treatment of cervical cancer for those

with HPV.

Clinical Presentation and Workup

Squamous cell cervical cancer is an asymptomatic, slow growing tumor that takes years

to develop and causes clinical problems. Symptoms for cervical cancer include: abnormal

vaginal discharge, pelvic or back pain, painful urination, and hematuria or hematochezia with

bowel symptoms present in more advanced stages. The most common form of clinical

presentation for squamous cell is abnormal vaginal bleeding (Castillo et al., 2016). Lymphatic

obstruction or nerve involvement may be indicated by edema in lower extremities or pelvic pain.

The general diagnostic work up for cervical cancer starts with a physical exam and an

interview on the patients medical/family history. Diagnostic procedures that can be done include

a primary screening Papanicolaou smear (Pap smear), colposcopy, conization, punch biopsies,

dilatation and curettage, cystoscopy, and a rectosigmoidoscopy for advanced stage cervical

cancer. The cells of the cervix are examined under a microscope from a pap smear for any visible

abnormalities (Rideaux, 2016). It is suggested that a biopsy should be done even if testing shows

a slight abnormality or lesion. After a diagnosis is made, a complete blood count should be

produced to check hepatic function, renal function, and possible metastasis. Rideaux (2016) also

states that the use of PET/CT scans are becoming extremely beneficial to detect not only the

lymph node involvement, but also the possibility of distant metastasis such as to the bones and

lungs.
BRACHYTHERAPY: ISOTOPES 6

Staging and Metastasis

The most common staging system used for all types of cervical cancer is the International

Federation of Gynecological and Obstetrics, also known as FIGO. With this system, squamous

cell carcinoma of the cervix is categorized into 5 stages between 0 and 4. According the Rideaux

(2016), if a cervical intraepithelial neoplasm (CIN or carcinoma in situ) is present in the

epithelial cells, then it is considered stage 0, which indicates an absence of cancer. The following

stages, according to FIGO, are as follows: Stage I, the cancer cells are in the epithelium

connective tissue, Stage II, the cancer has spread to the upper portion of the vagina, Stage III,

shows signs of spread in the lower portions of the vagina and to the wall of the pelvis, and Stage

IV, shows spread to the mucosa of either the rectum or the bladder, or spreads beyond the true

pelvis. Another staging system that can be used is the TNM (Tumor Node Metastasis) system,

however, it is very similar to the FIGO system but does not include the 0 stage.

Carcinoma of the cervix can metastasize in three ways: through hematogenous spread,

direct invasion, and the lymphatics. All research completed proves that direct invasion often

occurs to the uterus, vagina, parametrium, pelvis, rectum, and bladder. In a study that was

published in 2016, the 3-5 year survival rate for patients with stage IV is 21-48%. 1 in 4 patients

showed rectal invasion with no survival rate above 4 years, and the other 75% showed invasion

to the bladder (Wakatsuki et al., 2016). Even though direct invasion to the vagina and pelvic wall

is the most common form of metastasis, squamous cell carcinomas can also spread to the lungs,

liver, and bone through hematogenous spread, or through lymph to the parametrial nodes and

later to the pelvic nodes.

Brachytherapy
BRACHYTHERAPY: ISOTOPES 7

Washington and Leaver define brachytherapy as therapy at short distances. (2015) This

form of therapy utilizes radioactive isotopes coming from an external source or implanted seeds

that deliver the radiation dose. These sources are encased and sealed within a small metal

structure. Seeds were the primary source of brachytherapy treatment in the early 1900s when

radiation was first being discovered as an imaging source and as a form of cancer treatment.

(2015) The first primary isotopes used for brachytherapy were Cesium-137, Radium-226,

Iridium-192, and Cobalt-60. Some were better than others based on their half-life, toxicity, and

specific activity. (2015) The purpose of brachytherapy, like external beam therapy, is to

significantly reduce the tumor volume and cancer cells. The way this is done is by placing the

sources on or near the tumor bed and allowing the sources to expel radiation. Some of the areas

commonly treated with brachytherapy are the prostate, breast, cervix, uterus, and lung. For

cervical cancer particularly, brachytherapy is almost always delivered as an addition to external

beam radiotherapy (EBRT) to act as a treatment boost and help improve control, survival, and

recurrence rates. (Banerjee, 2014) The source, normally Iridium-192, is inserted into the vagina

to the cervix and stays there for an allotted dwell time (Washington, 2015). Brachytherapy is

the only method of radiation treatment seen to deliver a high enough dose to safely control

cervical cancer. (Banerjee, 2014) The intracavitary treatment applicator for cervical cancer is

either a Tandem and Ovoid or Capri depending on the area needing to be treated, the size of the

tumor, and the persons anatomy. (2014) For interstitial treatment, different templates of tubes

are used in order to treat larger tumors that are lower in the vagina and that impede an applicator

to be inserted. (2014)

There are also two branches of brachytherapy treatments: low-dose rate (LDR) and high-

dose rate (HDR). (Washington, 2015) Historically LDR was the brachytherapy treatment of
BRACHYTHERAPY: ISOTOPES 8

choice, but more recently HDR has come to the forefront due to its unique remote after-loading

technique. (Banerjee, 2014) For this process, the radioactive isotope is driven through different

channels inside the applicator and has periods of dwell time inside each channel before it is

retracted. HDR allows for dose sculpting and shorter treatment times, so it is ideal for

outpatients, however LDR is still regularly used for inpatients. The fractionation for cervical

HDR can vary, but most often the patient receives 4 or 5 fractions with 5-7 Gy per fraction.

(2014)

LDR and Sources Used

Cervical carcinoma has traditionally been treated with low-dose rate (LDR)

brachytherapy, with Radium-226 source, which was subsequently replaced by cesium-137

(Gaur et al., 2012). LDR gives a range of 0.4-2Gy per hour, in comparison with HDR which

ranges around 12 Gy per hour. LDR is considered radiobiologically more accurate because it

gives a continuous exposure of the cancer cells non cell cycle specific killing and also decreases

risk of late normal toxicity and increased the repair capacity to normal tissues. LDR can usually

give a dose range of 0.4-2 Gy per hour, most though are given with doses of 2 Gy per hour with

2 implant insertions of 20 Gy each for a total of 40 Gy (Rideaux, 2016).

Radium has a half-life of 1622 years. During treatment, the patient is under anesthesia

and in an operating room for the applicator placement. For the duration of the LDR treatment,

the patient is considered radioactive, and has to be placed into isolation, where the hospital

staff is exposed more often. Radium, in most hospital settings, have been replaced with Cesium-

137 because the half-life is shorter, and because it has a low specific activity.

Cesium-137 is suitable for low dose rate implants because of its low specific activity rate.

It has a half-life of 30.7 years and can be used for a long period of time in the department. The
BRACHYTHERAPY: ISOTOPES 9

photon emission of a Cesium 137 source is 0.662 MeV. The emitted beta particles have the

maximum energy of 0.514 MeV.

Californium-252 (Cf-252) is another isotope that can be used with LDR

brachytherapy treatments. Cf-252 was discovered in 1956 as a high linear energy transfer (LET).

It is a neutron/gamma radioactive source and was found to be used to overcome tumor resistance

to gamma radiation. The first trials with Cf-252 were not convincing, in the 70s, however,

depending on the method of administration it has shown promising results in the recent studies,

(Tacev, Ptackova, & Strnad et al., 2003).

Comparison of LDR Sources

Brachytherapy treatment today still utilize both Radium-226 and Cesium-137. Studies

have shown that both isotopes have very similar characteristics for treatment, however, small

differences still exist. The major disadvantage of the use of Radium-226 is the treatment time per

insertion. Intracavitary brachytherapy with Ra-226 usually gives a dose of 75 Gy to point A in

two insertions at a dose rate of 53 cGy per hour (Wang et al., 2014). This gives each treatment

insertion time to around 70 hours. Each insertion is also separated by 7-10 days. With the use of

Cesium-137, Wang (2014) also describes that the dose is reduced to 65 Gy to point A. This

isotope-source also required two insertions, however, gives a higher dose rate per hour at 140-

180 cGy per hour. With that being said, the total treatment time per insertion decreases from 70

hours each to only 20 hours per insertion. A common component of each isotope-source the dose

to the rectum is kept low due to careful vaginal packing during the applicator insertion in the

operating room.

With the highlight of Californium-252 being studied, many factors are coming to light

with the combination of use with Cf-252 with either LDR sources, and the use of external-beam
BRACHYTHERAPY: ISOTOPES 10

radiation therapy. In a long-term randomized study with 227 patients, Cf-252 was given to 117

patients in the 1st week of treatment followed by EBRT and then in the 5th week given either Ra-

226 or Cs-137 (Tacev et al., 2003). The results of the study compared those given Cf-252 with

those 110 patients who did not get the neutron treatment and only received conventional gamma

radiation. The 5- year overall survival rate was 18.9% better in the patients who received Cf-252

treatment, and specifically in patients with Stage IIIB had a 22.8% better 5-year OS rate than the

patients with conventional treatment. The study also focused on tumor recurrence in patients

with advanced stage cervical cancer. The most common site for tumor recurrence was in the

small pelvis, and the patients who received the Cf-252 had a 19% lower recurrence rate of all the

patients (Tacev et al., 2003). What is known about Californium-252 is because it is a neutron

source, it has the ability to attack those cancer cells that are becoming radioresistant and directly

invades the neutrons of the tumor population. Attacking just the neutrons of the tumor cell

population allows for the minimization of post-radiation damage to the healthy tissues

surrounding.

HDR and Sources Used

HDR gets its name because the treatments give off a high-dose of radiation per fraction

in a short amount of time. HDR was developed to overcome the disadvantages of LDR. Those

disadvantages being: radiation exposure to medical staff, prolonged treatment times, mandatory

hospitalization of patients, and applicator movement during treatment waiting period. HDR

brachytherapy machines initially used a cobalt-60 source. More recently, Ir-192 sources have

given strength to the concept of treatment of carcinoma cervix by fractionated HDR

brachytherapy, (Gaur, 2012). The source design for iridium-192 technology has revolutionized

the design of remote afterloading equipment. With HDR, facilities are able to treat more patients,
BRACHYTHERAPY: ISOTOPES 11

however HDR can be very costly due to the afterloader. The higher cost makes HDR a more

difficult treatment method for developing countries, (Mobit, 2015). Also, the high dose per

fraction of HDR can cause late toxicity, (Gaur, 2012). The advantages of HDR include,

computerized optimization of dosimetry, less risk of radiation exposure for medical personnel,

and less chances of organ motion during radiation delivery (Gaur, et al. 2012).

Co-60 has a half-life of 5.27 years, but also has a high specific activity. The average

energy of Co-60 is 1.25 MeV, (Ghorban, 2016). Cobalt is unpopular because of the source sizes

are larger than Ir-192. Co-60 does have a longer half-life than Ir-192, so it only gets changed

every 6-8 years. Co-60 is more economical and attractive for low resource settings. One

disadvantage of Co-60 is the high energy that increases the possibility of toxicity, (Ntekim,

2010).

In comparison, Ir-192 has a half-life of 73.81 days and a high specific activity. The

average energy of Ir-192 is 0.380 MeV. These factors make it very suitable for interstitial

brachytherapy, (Ghorban, 2016). Because of its half-life, Ir-192 has to be changed 3-4 times a

year. Ir-192 is mostly used worldwide. One reason is the smaller size of the source makes it more

cost effective. Though there are many differences between Co-60 and Ir-192, their characteristics

when it comes to treatment are very similar, (Mobit, 2015).

Comparison of HDR Sources

As mentioned previously, HDR brachytherapy is the more ideal type of brachytherapy

treatment due to the ability to treat more patients in a day in an outpatient setting. Traditional

HDR used Cobalt-60, which is still widely used in developing countries, but also comes with the

risk of higher toxicities due to its high gamma energy. Recently, the switch to Iridium-192 has

been made, however, is not as economical for some due to the half-life difference, and the
BRACHYTHERAPY: ISOTOPES 12

amount of times a year the source needs to be changed out. In a prospective study with 70

patients from July 2008-March 2009, the toxicity rates with the use of Co-60 are described. HDR

with a dose of 19.5 Gy in 3 weekly fractions was given to patients no earlier than the 3rd week of

their EBRT treatment. The traditional tandem and ring applicator was used with each fraction

having a dose of 6.5 Gy. The results described that 50 % of all patients experienced grade 1

proctitis (Inflammation of the lining of the rectum), and 46% experienced grade 1 diarrhea, and

40% experienced grade 1 cystitis and frequent urination (Ntekim, Adenipekun, Akinlade &

Campbell, 2010). With most side effects being a grade 1 and only 2 patients who experienced

grade 3 diarrhea, the use of Co-60 appears to have the same beneficial factors as Ir-192. Previous

studies mentioned by Ntekim et al., stated that 8% of patients show gastrointestinal toxicity using

Ir-192 (2010).

With both isotopes highly used in different parts of the world, many studies are being

done to examine any other possible comparisons between Co-60 and Ir-192 besides the cost

barrier. Palmer, Hayman & Muscat did a study in 2012 involving only 8 patients, however, were

evaluating the differences of Co-60 and Ir-192. In these 8 patients, identical positions and

applicator loadings were performed, as well as all patients received the identical prescribed dose

to Point A. The results showed that the differences between the 2 isotopes if very minimal. Co-

60 showed a slight 3.3% increase dose to the rectum, which also increased to dose along the

extension of the source axis (Palmer et al., 2012). These results show the slight incidences of Co-

60, however, Wang describes that because Co-60 has a higher gamma energy, it increases the

radiation dose to critical structures such as the rectum and bladder (2014). Also described is that

Ir-192 has a lower gamma energy and limits the dose to those structures, and reduces effects on

normal tissue compared to Co-60. Despite the fact that the use of HDR isotopes in general will
BRACHYTHERAPY: ISOTOPES 13

generate higher complications to structures such as the rectum and small bowel, neither source

has a significant influence.

Californium-252 recently has been discussed with the use of LDR brachytherapy, but it

also shows promising effects with the use of HDR as well. Cf-252 not only is a neutron/gamma

source, but it also has a high linear energy transfer or LET. This allows for the inhibition of cell

damage repair of the cancer cells. Using Cf-252 for advanced cervical cancer with high

proportions of cells that are radioresistant shows the greatest results (Janulionis et al., 2015). The

study done with 232 Stage IIB patients from 1989-1999 with HDR Cf-252 was done to find

results compared to patients receiving Co-60 ICBT and EBRT. A total of 121 patients received

Cf-252 and 111 received Co-60 HDR. Both groups started ICBT in the 3rd week of the external

beam therapy, with a total dose of 40 Gy with one fraction a week for a total of 5 fractions. The

OS rate of 5, 10, and 15 for patients in both groups were very similar with Cf-252 having a 5-

year rate of 63.6% and Co-60 with a 62.2%. The major difference lies in tumor recurrence and

distant metastasis between the groups (Janulionis et al., 2015). In the group given Cf-252, 92.6%

of patients presented no tumor recurrence and 91.7% presented no distant metastasis. The group

given Co-60, 82.9% showed no tumor recurrence and 87.4% presented no distant metastasis.

That gives a total of a 9.7% difference of the group in tumor recurrence and a 4.3% difference in

distant metastasis. Another major component difference in the isotopes used was the percentage

of patients who experienced adverse effects such as proctitis, cystitis, and hydronephrosis. Only

10.7% experienced effects with Cf-252, however, 13.5% experienced them with Co-60. When

evaluating the isotopes, Cf-252 has an advantage over Co-60.

Conclusion
 BRACHYTHERAPY: ISOTOPES 14

There are a variety of different treatment methods, variations of treatment types, and

combinations of treatment methods for cervical cancer. These being: surgery, chemotherapy, and

radiation therapy. A specific type of radiation therapy is brachytherapy, where isotopes -

radioactive sources- are placed inside of patients for a particular length of time. Brachytherapy

can further be divided into LDR and HDR treatments. For LDR, Ra-226 and Cs-137 are two

isotopes that have similar characteristics for treatment. However, Ra-226 has a treatment

insertion time of 70 hours, while Cs-137 has a treatment insertion time of only 20 hours. Cf-252

has shown positive results in the treatment of patients with LDR in combination with EBRT. For

HDR, Co-60 and Ir-192 are two isotopes used. These two have similar characteristics when it

comes to treatment, but Ir-192 is cheaper than Co-60 due to its smaller size. When Cf-252 was

used in a study compared to Co-60, about 3% less of the patients treated with Cf-252

experienced adverse side effects. As discussed, there are many advantages and disadvantages

that have been studied between isotopes. Science has truly advanced over time, specifically in

the discovery and use of different isotopes in brachytherapy.

Annotated Bibliography

Banerjee, R., Kamrava, M. (2014). Brachytherapy in the treatment of cervical cancer: a review.

International Journal of Womens Health, 2014(6). doi: 10.2147/IJWH.S46247

In this review, gynecologic brachytherapy peer-reviewed studies and experiments are focused
on, especially on recent advances in brachytherapy technology and treatment techniques. Patient
evaluation, staging, applicator selection, treatment planning, clinical outcomes, and toxicity are
also reviewed.
 BRACHYTHERAPY: ISOTOPES 15

Castillo, M., Astudillo, A., Clavero, O., Velasco, J., Ibez, R., & Sanjos, S. D. (2016). Poor cervical

cancer screening attendance and false negatives. A call for organized screening. Plos One, 11(8).

doi:10.1371/journal.pone.0161403

In this study, data was collected from the records of 374 women diagnosed with cervical
cancer from hospitals in Asturias, Spain. They gathered clinical information, staging, and
all previous cytological data to estimate ratios and confidence intervals to evaluate the
difference in women diagnosed with or without prior screenings. The overall goal was to
evaluate the data to suggest that more screening facilities are needed in rural areas.
Cervical cancer radiotherapy side effects. (n.d.). Retrieved November 28, 2016, from

http://www.cancerresearchuk.org/about-cancer/type/cervical-

cancer/treatment/radiotherapy/cervical-cancer-radiotherapy-side-effects

The Cancer Research UK is a registered charity in England, Wales, Scotland, and the Ilse
of Man. Their website strives to provide information about cancer to the public. This web
page addresses the side effects during and after treatment, the long term side effects,
changes to the womb, ovaries and vagina, the bladder and bowel effects, bleeding and
swelling that is all in relation to cervical cancer.
Cheah, P., Koh, C., Nazarina, A., Teoh, K., & Looi, L. (2016). Correlation of p16INK4a

immunoexpression and human papillomavirus (HPV) detected by in-situ hybridization in

cervical squamous neoplasia. Department of Pathology, Faculty of Medicine, University of

Malaya, 38(1). Retrieved from http://www.mjpath.org.my/2016/v38n1/human-

papillomavirus.pdf

This study was done to detect the relationship between the human papillomavirus and
cervical cancer. The researchers assessed this using p16 immunosuppression within
cancerous cervical lesions, specifically low grade squamous intraepithelial lesions, high
grade squamous intraepithelial lesions, and squamous carcinoma.
Gaur, R., Singh, O., Kumar, M., Patel, A.K., Sharma, D., & Rath, G. (2012). Comparison of low- and

high-dose rate brachytherapy in carcinoma cervix: results from a randomized study. Indian

Journal of Clinical Practice, 23(4). Retrieved from

http://medind.nic.in/iaa/t12/i9/iaat12i9p203.pdf
 BRACHYTHERAPY: ISOTOPES 16

This randomized study was done to compare low dose rate (LDR) and high dose rate (HDR)
brachytherapy. 60 patients were randomized into either LDR or HDR groups after completing
external beam therapy. The researchers then assessed and compared the regional control,
toxicity, and side-effects of the two groups.
Gerbaulet, A., Potter, R., Haie-Meder, C., (2002). Cervix carcinoma. In Gerbaulet, A. The GEC ESTRO

handbook of brachytherapy. Brussel: ESTRO.

This is a chapter from a book that introduces brachytherapy and treatment techniques used for cervical
cancer. It goes into detail about the different applicator settings for both high dose rate and low
dose rate. The various sources used for each treatment were also discussed with the parameters
of the applicators and toxicities that could occur.
Ghorbani, M., Hashempour, M., Azizi, M., & Meigooni, A.S. (2016). Evaluating the effect of various

intracavity applicators on dosimetric parameters of Ir-192, Cs-137, and Co-60 sources.

Australasian College of Physical Scientists and Engineers in Medicine, 39. doi: 10.1007/s13246-

016-0441-2

This study was done to research various applicators and dosimetry parameters for cervical
carcinoma. The various isodoses studied were Iridium-192, Cesium-137, and Cobalt-60 along
with their dose rate constant, radial dose function and isodose curves. Different applicator types
tested included plastic, titanium, and stainless steel.
Janulionis, E., Valuckas, K.P., Liukpetryte, S., Samerdokiene, V., & Atkocius, V. (2015). Californium

versus cobalt brachytherapy combined with external-beam radiotherapy for IIB stage cervical

cancer: long-term experience of a single institute. Journal of Contemporary Brachytherapy, 7(5).

doi: 10.5114/jcb.2015.55117

This retrospective study compared long-term survival rates, curative effects, and recurrence rates
for stage IIB cervical cancer patients. The two groups studied were either treated with
Californium-252 or Cobalt-60. Survival rates were similar, however tumor recurrence was lower
for the Californium group.
Mobit, P.N., Packianathan, S., He, R., & Yang, C.C. (2015). Comparison of Axxent-xoft, Ir-192, and

Co-60 high-dose-rate brachytherapy sources for image-guided brachytherapy treatment planning

for cervical cancer. British Journal of Radiology, 88(1052). doi: 10.1259/bjr.20150010

 BRACHYTHERAPY: ISOTOPES 17

This retrospective study compared treatment plans for tandem and ovoid insertion with either
Iridium-192 or Cobalt-60. 10 patients who had received treatment with Ir-192 had their plans re-
run with Axxent-xoft software to have them treated with Co-60 instead. These plans were then
compared for organ-at-risk dose differences and treatment volume percentages.
Marnitz, S., Wlodarczyk, W., Neumann, O., Koehler, C., Weihrauch, M., Budach, V., & Cozzi, L.

(2015). Which technique for radiation is most beneficial for patients with locally advanced

cervical cancer? Intensity modulated proton therapy versus intensity modulated photon

treatment, helical tomotherapy and volumetric arc therapy for primary radiation an

intraindividual comparison. Radiation Oncology, 10(1). doi:10.1186/s13014-015-0402-z

This study was conducted with 20 cervical cancer patients were treated with intensity
modulated radiotherapy delivered by helical tomotherapy, RapidArc therapy, or IMRT
with protons. The planning volume A was the cervix, uterus, pelvic, and, in some cases,
the para-aortic lymph nodes. The planning volume B was the parametrium.
Ntekim, A., Adenipekun, A., Akinlade, B., & Campbell, O. (2010). High dose rate brachytherapy in the

treatment of cervical cancer: preliminary experience with cobalt-60 radionuclide source- a

prospective study. Clinical Medicine Insights: Oncology, 4. Retrieved from

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2934612/

This prospective study is comparing the toxicity of Co-60 to Ir-192 in hopes of switching to Co-
60 for cervical brachytherapy in order to be more economically friendly. 70 patients were
selected who had already received external beam treatment and then were given 3 fractions of
HDR with Co-60. Tumor grades were reviewed after treatment and compared to those with Ir-
192 treatment.
Palmer, A., Hayman, O., & Muscat, S. (2012). Treatment planning study of the 3D dosimetric

differences between Co-60 and Ir-192 sources in high dose rate (HDR) brachytherapy for cervix

cancer. Journal of Contemporary Brachytherapy, 4(1). doi: 10.5114/jcb.2012.27952

This study compared Co-60 and Ir-192 sources when using 3D treatment plans. 8 patients were
separated into the two groups and identical dwell positions and loading was used. Although Co-
60 gave a higher rectal dose, the two isotopes gave near-identical treatments.
 BRACHYTHERAPY: ISOTOPES 18

Rideaux, K. (2016). Gynecologic cancers. In Washington, C.M. & Leaver, D (Eds.), Principles and

practice of radiation therapy. (4 ed.) (pp. 740-741). St. Louis, MO: Elsevier.
th

This textbook provides information regarding the epidemiology, etiology, clinical

presentation, screening, detection, diagnosis, imaging studies, staging, and treatment
modalities and considerations for cervical cancer.
Rose, P. G., Sill, M. W., Mcmeekin, D. S., Ahmed, A., Salani, R., Yamada, S. D., . . . Fracasso, P. M.

(2012). A phase I study of concurrent weekly topotecan and cisplatin chemotherapy with whole

pelvic radiation therapy in locally advanced cervical cancer: A gynecologic oncology group

study. Gynecologic Oncology,125(1). doi:10.1016/j.ygyno.2011.12.431

This literature review showed phase I of a study using the chemotherapy drug cisplatin
with topotecan in combination with radiation therapy and brachytherapy for the treatment
of patients with cervical cancer. This study was done to evaluate the effectiveness of said
treatment method.
Taev, T., Ptkov, B., & Vratislav, S. (2003). Californium-252 versus conventional gamma radiation

in the brachytherapy of advanced cervical carcinoma. Strahlentherapie und Onkologie, 179. doi:

10.1007/s00066-003-1005-4

This randomized study used 227 women with stage IIB cervical carcinoma and separated them
into one of two treatment groups. One group received Californium-252 neutron treatment
whereas the other group received a combination of Radium or Cesium gamma treatment.
Survival rates and recurrence rates were then compared.
Viswanathan, A. N., Moughan, J., Small, W., Levenback, C., Iyer, R., Hymes, S., . . . & Gaffney, D. K.

(2012). The quality of cervical cancer brachytherapy implantation and the impact on local

recurrence and disease-free survival in radiation therapy oncology group prospective trials 0116

and 0128. International Journal of Gynecological Cancer, 22(1), 123-131.

doi:10.1097/igc.0b013e31823ae3c9

In this study, cervical cancer patients received chemoradiation followed by

brachytherapy. Each patient had specific parameters and were treated with slightly
different methods for the brachytherapy treatment depending on their diagnosis, stage and
 BRACHYTHERAPY: ISOTOPES 19

grade of cervical cancer. The purpose of this study was to help the quality of life of the
patients to be cancer free with no reoccurrence.
Wakatsuki, M., Kato, S., Kiyohara, H., Ohno, T., Karasawa, K., Tamaki, T., . . . & Nakano, T. (2016).

The prognostic value of rectal invasion for stage IVA uterine cervical cancer treated with

radiation therapy. BMC Cancer, 16(1). doi:10.1186/s12885-016-2268-3

This literature review was based off a study done with 67 patients with stage IVA
cervical cancer were treated with photon radiation therapy. 53 patients had bladder
invasion. 7 patients had rectal mucosal invasion. The other 7 patients had both bladder
and rectal mucosal invasion. Their outcome and prognostic factors were evaluated
following treatment.
Wang, J., Andrae, B., Sundstrm, K., Strm, P., Ploner, A., Elfstrm, K. M., . . . & Sparn, P. (2016).

Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide

cohort study. Bmj, I276. doi:10.1136/bmj.i276

In Sweden, records were evaluated from 3,054, 328 women's files who received cervical
cytological testing. 14, 625 of the women had glandular cells appear on their tests, 65,
633 women had high grade squamous intraepithelial lesions, and 244, 168 had low grade
squamous intraepithelial lesions. This study was done to examine the correlation between
atypical glandular cells and cervical cancer.
Wang, X., Tian, J.H., Yang, K., Wang, J., Jiang, L., & Hao, X.Y. (2014). High dose rate versus low dose

rate intracavity brachytherapy for locally advanced uterine cervix cancer. Cochrane Database of

Systemic Reviews, 10. doi: 10.1002/14651858.CD007563.pub3

This meta-analysis review evaluated the safety and efficacy of HDR and LDR brachytherapy
with external beam therapy to treat cervical carcinoma. Four studies with 1265 women were used
in the comparison of 5-10 year survival rates, local recurrence, distant metastasis, and organ-at
risk complications.
Wesoa, M., & Jele, M. (2015). Morphometric differentiation of squamous cell carcinoma and

adenocarcinoma of the cervix. Polish Journal of Pathology Pjp, 4, 410-413.

doi:10.5114/pjp.2015.57255
BRACHYTHERAPY: ISOTOPES 20

This study evaluated the differences between two types of cervical cancers in women:
squamous cell carcinoma and adenocarcinoma. The morphometric characteristics of each
type were assessed and compared.