Certificate Course in Postgraduate Research (CCPR) - 6th Batch 2024

Module 1:

Assignment 01
Research topic

A study on anatomical changes during volumetric modulated arc radiotherapy

(VMAT) for head and neck cancer, and its effect on pretreatment planning

Background and justification

Cancer is a disease caused when cells divide uncontrollably and spread out through normal
surrounding tissues. Normally Cancer begins when gene changes make one cell or a few
cells. Then it grows and multiplies uncontrollably.(“cancer reseach UK,” 2021) . The cancer
cells grow beyond their usual boundaries, which can invade adjoining parts of the body and
spread to other organs, the latter process is referred to as metastasizing. The metastases are a
major cause of death from cancer.(WHO 2024, )
Head and neck cancer develops from tissues in the mouth, larynx (throat), salivary glands,
nose, sinuses, or the skin of the face. Head and neck cancer is highly prevalent in South Asian
countries like Bangladesh, India, Pakistan, and Sri Lanka, where one-third of all the cancers
reported is oral cancer. The Majority (90%) of the cases reported of oral cancer are attributed
to tobacco consumption in various forms in these regions. According to (GLOBOCAN, 2021)
data, Sri Lanka has the highest Age -standardized rate (ASR) of incidence in South Asia, and
head and neck cancer is the most common cancer among men in Sri Lanka. Head and neck
cancers are also diagnosed more often among people over age 50 than they are among
younger people (“Natinal Cacer Institute(NCI),” 2021). About 2000 cases of oral cancer are
detected in Sri Lanka in 2011. In addition, oral cancer is carrying the highest mortality rate
among all other cancer-causing 2-3 death per day.(“National Cancer Control
Praggramme(NCCP),” 2021).

Radiation therapy (RT) plays a critical role in the current management of patients with head
and neck (H&N) cancer. Radiotherapy aims to deliver a high therapeutic dose to the tumor
while minimizing exposure to the surrounding healthy tissue. At high doses, radiation therapy
kills cancer cells or slows their growth by damaging their DNA. Radiation damage DNA
molecules in cancer cells as well as normal cells. Radiation damage on DNA occurs in 2
ways. They are direct action and indirect action. Radiotherapy can be delivered in two ways:
Two kinds of radiation therapy,(Chang, Lasley, Das, Mendonca, & Dynlacht, 2014)
1) External beam: an external beam radiation therapy machine outside your body aims the
radiation at your cancer cells.
2) Internal or brachytherapy: Sometimes this type of radiation therapy is also called liquid
radiation, because the radiation is placed inside your body, near the cancer cells.

Most patients receive external beam radiation. In external beam radiotherapy, patients are
treated with a Co-60 machine and multiple megavoltage (MV) photon beams generated with
a linear accelerator. Many newest tele-therapy modalities are available such as 3D CRT,
IMRT, IGRT, SBRT, SRT, etc.3DCRT is an older method and nowadays IMRT, IGRT,
SBRT, SRS, and Adaptive radiotherapy are widely used for head and neck cancer. (Xu, Xue;
Li, Mengzhi; Hu, Jun; Chen, Zheng; Yu, Jinyu; Dong, Yan; Sun, Chengtao; Han, 2018).

Volumetric modulate arc radiation therapy (VMAT) has the ability to conform the dose to
target volumes with complex shapes, and at the same time sparing organs at risk (OAR) such
as parotid glands, spinal cord, brainstem and mandible, much greater degree than classical
three-dimensional (3D) conformal RT(Buciuman & Marcu, 2022). IMRT maximizes tumor
coverage and thus leads to a potential increase in the therapeutic index.

Normally radiation is delivered to the patient according to the treatment plan. Current
radiotherapy (RT) treatments are planned using kilovoltage (kV) computed tomography (CT)
scan at a single pretreatment time point to delineate the PTV and OARs. ICRU has provided
useful guidelines and the definitions of target volumes delineation. The gross demonstrable
extent and the location of a malignant growth are defined as Gross Tumor Volume (GTV).
The Clinical Target Volume (CTV) is acquired by adding margin around GTV to include the
microscopic spread of a malignant disease that must be eliminated. The PTV is often
described as the CTV plus a fixed or variable margin. Organs at risk are critical normal
tissues whose radiation sensitivity may significantly influence treatment planning and/or
prescribed dose(Ann Barrett, Jane dobbs, stephen Morris, 2009). Radiotherapy doses are
calculated using the same information and radiation treatment plans are not normally
amended during the course of treatment. However, the shape and position of target volumes
and OARs can change during the course of treatment due to tumor shrinkage and patient
weight loss. This can affect the dosimetry of radiation treatment. This approach, however,
does not take into account potential modifications of the patient’s anatomy and positioning
during a typical 5-7week treatment course. The treatment plan is generally designed based on
a single computed tomography (CT) scan acquired one or more weeks before treatment.
(Brown et al., 2015)

Between radiation treatment planning and delivery as well as throughout radiotherapy,

however, anatomical changes frequently occur. Consequently, the dose delivered differs from
the planned dose. The traditional approach to account for anatomical changes is to apply a
safety margin around the clinical target volume to ensure coverage of these targets.
Consequently, however, surrounding noninvolved tissue is also exposed to high levels of
radiation, increasing the risk of unacceptable side effects. IGRT is the process of acquiring
images of the patient's anatomy (in the treatment room), comparing the position of the tumor
(or surrogate) during treatment with the planned position, and correcting the treatment
position. While IGRT has been widely adopted in clinical practice, it has a limited solution
space as it assumes that the target has an (almost) invariable shape and the dose to the organs-
at-risk (OAR) does not change considerably. Anatomical changes frequently do not match
these assumptions, such as posture changes, differential motion between primary tumor and
involved lymph nodes, shape changes of bladder or cervix, weight loss, and tumor
regression(Sonke, Aznar, & Rasch, 2019).

The main aim of Adaptive radiotherapy (ART) is to deliver radiotherapy accurately and
precisely to target the presence of such anatomical changes. (Nasser et al., 2023). ART uses
an imaging feedback loop to quantify these changes and modify the treatment plan
accordingly. Current ART approaches depend on in-room megavoltage CT, or cone-beam
CTs obtained before daily treatment. The main aim of this study is to evaluate Planning target
volume (PTV) changes for patients by using daily kilovoltage(KV) computed tomography
(CT) studies acquired before each treatment fraction treated with IMRT on LINAC machine
and to assess whether a re-planning strategy needed to be developed.(Buciuman & Marcu,
2022).

Justification
Between radiation treatment planning and delivery as well as throughout radiotherapy,
however, anatomical changes frequently occur. Consequently, the dose delivered differs from
the planned dose. Adaptive RT is a possible solution to overcome these limitations.
Currently, most countries use adaptive radiotherapy for cancer treatment. They use their
protocol to change treatment plans according to anatomical changes. But this method does
not widely practice in radiotherapy centers in Sri Lanka as a very limited number of medical
Linear accelerators are available in our country. Also, Varian Truebeam stx linear accelerator
unit installed in 2018 at American Oncology institution, Asiri Surgical hospital, Narahanpita .
Even after 6 years of installation, no review was done about the anatomical changes of a
cancer patient. Therefore, consideration of anatomical changes of the patient is very
important in VMAT to achieve a better treatment outcome.

References

Ann Barrett, Jane dobbs, stephen Morris, T. roques. (2009). Practical Radiotherapy Planning
(4th Editio; university H. Jonathan Harrowven(Norfolk, Ed.).

Brown, E., Owen, R., Harden, F., Mengersen, K., Oestreich, K., Houghton, W., … Porceddu,
S. (2015). Predicting the need for adaptive radiotherapy in head and neck cancer.
RADIOTHERAPY AND ONCOLOGY. https://doi.org/10.1016/j.radonc.2015.06.025

Buciuman, N., & Marcu, L. G. (2022). Adaptive Radiotherapy in Head and Neck Cancer
Using Volumetric Modulated Arc Therapy. Journal of Personalized Medicine, 12(5).
https://doi.org/10.3390/jpm12050668

cancer reseach UK. (2021). Retrieved January 12, 2021, from

https://www.cancerresearchuk.org/

Chang, D. S., Lasley, F. D., Das, I. J., Mendonca, M. S., & Dynlacht, J. R. (2014). Production
and Properties of Radiation. In Basic Radiotherapy Physics and Biology.
https://doi.org/10.1007/978-3-319-06841-1_3

GLOBOCAN. (2021). 21 413 250 (Vol. 975). Retrieved from

https://gco.iarc.fr/today/data/factsheets/populations/144-sri-lanka-fact-sheets.pdf

Nasser, N., Yang, G. Q., Koo, J., Bowers, M., Greco, K., Feygelman, V., … Redler, G.
(2023). A head and neck treatment planning strategy for a CBCT-guided ring-gantry
online adaptive radiotherapy system. Journal of Applied Clinical Medical Physics,
 24(12), 1–15. https://doi.org/10.1002/acm2.14134

Natinal Cacer Institute(NCI). (2021). Retrieved January 10, 2021, from

https://www.cancer.gov/

National Cancer Control Praggramme(NCCP). (2021). Retrieved January 12, 2021, from
https://www.nccp.health.gov.lk/

Sonke, J., Aznar, M., & Rasch, C. (2019). Adaptive Radiotherapy for Anatomical Changes.
Seminars in Radiation Oncology, 29(3), 245–257.
https://doi.org/10.1016/j.semradonc.2019.02.007

WHO 2024. (n.d.). No Title. Retrieved from https://www.who.int/

Xu, Xue; Li, Mengzhi; Hu, Jun; Chen, Zheng; Yu, Jinyu; Dong, Yan; Sun, Chengtao; Han, J.
(2018). Somatic mitochondrial DNA D - loop mutations in meningioma discovered : A
preliminary data A comprehensive overview of mitochondrial DNA 4977-bp. Journal of
Cancer Research and Therapeutics, 14(7), 1525–1534.
https://doi.org/10.4103/jcrt.JCRT