1. Radiotherapy In Gynecologic Oncology – 5 Nov 2017, 30 min
Dr. U.D.Bafna, Professor and Head, Department of Gynecologic Oncology, Kidwai Cancer Institute and BMJ hospitals, Bengaluru

2. Basis of Radiotherapy
The form of radiation used in cancer therapy is known as ionizing radiation because it removes electrons from atoms, thus forming ions.
It breaks up the DNA of cancer cells in such a way as to disrupt their growth and division, and even kill them.
Generally high energy x rays are used

3. X rays vs Gamma rays X rays and Gamma rays are the same and
The key difference between gamma rays and X-rays is how they are produced.
Gamma rays originate from radioactive decay (Cobalt machines)
Whereas X-rays are produced when electrons strike a target ( Linear Accelerators)

4. Era of MegaVoltage radiotherapy
Ordinary x-ray tubes - use low voltages of  keV –
It can treat superficial tumors, but does not have the energy to reach tumors deep in the body.
To have the penetrating ability to reach deep-seated tumors requires rays with high energy of around 1 mega electron volt (MeV), - “Megavoltage" radiation.

5. Higher is the energy of the X rays deeper is the penetration with the sparing of the skin and the underlying adipose tissue.
Ancient deep x ray machines and cobalt machines (Gamma rays) have been replaced with high energy mega voltage (5-15) linear acceleators. (radiation produced when accelerated electrons strike a target)

6. There are two forms of radiation therapy
External beam radiation therapy - the beam of radiation is focused by an external machine onto the treatment area
Internal radiation therapy (such as brachytherapy) - a radioactive substance is placed in or close to the cancerous tissue.

7. Linear accelerator is usually used in external beam radiation therapy to emit X-rays within a specific energy range.
High Dose Rate (HDR) machines are used to deliver brachytherapy. They use higher strength radioactive substance (cesium) to deliver RT unlike older Low dose Rate (LDR) machines which use lower strength radioactive material and therefore duration of therapy is reduced to minutes instead of hours!

8. Accessing the tumor for radiotherapy – the evolution
Initially the tumor for example cervical cancer was treated by simple cobalt machines producing high energy gamma rays.
These beams were directed to the tumor by anterior, posterior and lateral portals. (Four Field Box Technique) or by two fields – AP and PA

9. Evolution of radiotherapy- Four Field Box technique
The entire tumor and the surrounding normal tissues were exposed to radiation.
Traditional four field box technique for cervical cancer determined by bony anatomy has contributed excellent tumor control with acceptable toxicities.

10. Conformal radiotherapy – 3DCRT
Only the tumour ( with safety margins) is exposed to radiotherapy
By Conformal radiation therapy
The same type of machine used for regular radiotherapy treatment is combined with a specialized device called a multi-leaf collimator.
The multi-leaf collimator is made up of metal bars fixed to the radiotherapy machine.
The bars block the radiation beams to change the shape of the area being treated.
Each bar can be adjusted so that the radiation beams conform to the shape and size of the tumour.

11. 3D CRT
CT scan simulator is used to three dimensionally plot the tumor to deliver conformal radiotherapy to
The nodes (Clinical tumor Volume 1 = CTV1)
Primary cervical tumor including the uterus and part of vagina = CTV2
The Parametria = CTV3

12. Intensity Modulated RadioTherapy - IMRT
IMRT is a type of conformal radiotherapy. Conformal radiotherapy
In IMRT each radiotherapy beam is divided into many small beamlets that can vary their intensity.
This allows different doses of radiation to be given across the tumour.

13. IMRT

14. IMRT with 3D CT scan planning

15. IGRT – Integration of Rt machine with CT scan
Image Guided Radio Therapy (IGRT) takes into consideration ( in addition to IMRT) daily bodily movements to precisely image the tumor daily before delivering IMRT by CT scanning.

16. IGRT Today’s high end radiosurgery techniques enlist the use of
Tomotherapy
Cyberknife.

17. Helical Tomotherapy
HT shares similar technology with spiral computed tomography (CT) scan.
A small radiation source, which is a 6 MV linear accelerator, is mounted on a CT ring gantry (It’s a frame) which can helically rotate 360 degree
Radiation is delivered helically through 51 projections per rotation.

18. Helical Tomotherapy
This consistency aids the helical (continuous 360º) IMRT to accurately aim tens of thousands of narrow beamlets, all targeting the tumor and individually-optimized to contribute to the total tumor dose.
This extreme accuracy translates to the most precise conformal radiotherapy available

19. Tomotherapy - Integrated CT scanner and Linear accelerator

20. Cyberknife
In contrast to the standard frame-based (multi leaf collimator frame) radiosurgical instruments, the CyberKnife uses noninvasive image-guided localization and a robotic delivery system.
This combination of technologies enables the CyberKnife to overcome the limitations of older frame-based radiosurgery.
Here Radiotherapy can be delivered from any side as there is no frame.

21. The ability of the CyberKnife to shape the profile of radiation to conform to the patient’s individual anatomy allows for maximum sparing of surrounding normal tissues.
The CyberKnife accomplishes this by accurately cross-firing approximately 150 beams (with thousands of beamlets) of radiation at the target from multiple directions.

22. Non- frame based Cyberknife
Non-frame based radiotherapy(No Mutileaf Collimator) allows cross firing of radiation beams from all directions unlike conventional radiotherapy including tomotherapy

23. The CyberKnife also has limitations
The CyberKnife also has limitations. One of the major limitations is the prolonged treatment time: approximately 30 to 60 minutes during each session.(unlike usual 15 min)
But it requires fewer fractionations – about five over five days against conventional fractions over 5-6 weeks.

24. Radiotherapy general principles
Radiotherapy (Tumoricidal dose) – to a particular site can be delivered only once in life time. It causes permanent endarteritis.
The stipulated dose of radiotherapy should be completed within 7-8 weeks. Any further delay reduces its efficacy
The tumor should be well oxygenated for radiotherapy to be optimally effective.

25. Radiotherapy dose
4500 cGrays dose is tumoricidal only for microscopic residual disease.
Larger tumor require more dose.
Liver, kidneys, small intestine can tolerate <40 Grays ( Therefore, RT for abdominal organs is difficult)
Rectum and bladder can tolerate up to Grays ( Therefore, pelvic radiotherapy is easier)

26. Tumour > 2 cm requires > grays which can be delivered by a combination of External RT and Brachytherapy (which spares normal tissues largely)
In cervical cancer – a very high tumor dose of 110 grays with a dose of 80G to point A can be delivered by this combination

27. Radiotherapy in Gynecology
Cervical Cancer
Vaginal cancer
Endometrial ca
Rarely for other cancers.

28. Invasive Cervical Cancer
All stages of cervical cancer (and vaginal ca) can be managed by radiotherapy.
Surgery is generally restricted to Stage IA and IB1 and small volume stage IIA1
Stages IB2- III are managed by concomitant chemoradiation

29. Invasive ca cervix Stages IB2-III Basic investigations and imaging
FDG PET should be done if possible to rule out extra-pelvic disease.
Conformal Radiotherapy is given by 3D CRT planning to deliver radiation to the tumor(CTV2), parametria (CTV3) and the pelvic lymph nodes (CTV1).
If pelvic lymph nodes are suspicious the radiotherapy field is extended to cover the lower aortic nodes

30. If there are suspicious aortic nodes – extended field RT is given.
It is more toxic. The small bowel needs to be protected by restricting the aortic area dose to 45 G
For larger ( > 1 cm) aortic nodes surgical debulking by retro-peritoneal route may be done.
Or Large node may be irradiated by IGRT to spare the intestines while delivering higher dose of radiation.

31. By following 3D CRT planning the dose to bladder, rectum, pelvic small intestines and the pelvic bones is considerably reduced.
This is in contrast to older two/four portal non-conformal RT.
During radiotherapy the patient is advised to keep the bladder full so that the intestines are pushed into the abdomen

32. Improving radiotherapy efficacy
Its important to correct anemia before and during RT by constant Hb monitoring
Duration of RT should be < 8 weeks.
RT is delayed/withheld for a few days to allow recovery of acute cystitis, proctitis and bone marrow supression
Both External RT and Internal brachytherapy are important

33. Brachytherapy
Brachytherapy by intra-uterine tandem and vaginal ovoids or if not feasible by interstitial needles placement delivers very high dose to the tumor literally charring it.

34. Brachytherapy
The radiotherapy is delivered by remote after loading of the intra-uterine tandem and the vaginal ovoids to prevent radiation exposure to the operating personnel.

35. Brachytherapy
High Dose rate technique is used to deliver very high dose in a few minutes – example 6 G in a single fraction given over a few minutes. Generally three such fraction are given in two to three days.
Older Low dose Rate technique used to deliver the dose over a prolonged period of > 24 hours depending on the radiation source decay.

36. Ca cervix – Total radiotherapy dose
Total RT dose to the Point A – G and Point B is 60 G depending on the tumor size.

37. Thank You

38. Radioisotopes produced gamma rays in the megavolt range,
But prior to World War II virtually the only radioisotope available for radiotherapy was naturally occurring radium (producing 1- 2 MeV gamma rays).
But its extremely expensive ore not freely available in nature.

39. Cobalt Theratronic Machines
The invention of the nuclear reactor made possible the creation of artificial radioisotopes for radiotherapy.
Cobalt-60, produced by neutron irradiation of ordinary cobalt metal in a reactor, is a high activity gamma ray emitter, emitting 1.17 and 1.33 MeV gamma rays.
The main reason for its wide use in radiotherapy is that it has a longer half-life, 5.27 years, than many other gamma emitters.
However the half life still requires cobalt sources to be replaced about every 5 years

40. Linear Accelerators - LINAC
It does not use radioactive substance to produce high energy X rays. (Therefore, there is no worry about disposing it as it does not decay)
The linear accelerator uses microwave technology to accelerate electrons in a part of the accelerator called the "wave guide,"
then allows these electrons to collide with a heavy metal target to produce high-energy x- rays of > 5 mega voltage.

41. CT Simulation CT Simulation:
Patients are kept fasting for minimum 4 hours prior to planning CT scan. They are given oral and rectal contrast for delineating critical structures.
Oral contrast constitutes 20 ml urograffin dissolved in 1 litre water given over 1 hour, before CT scan. Rectal contrast is given by dissolving 20 ml urograffin in 50 ml normal saline.
For intravenous contrast, 100 ml of omnipaque is used . .

42. CT Simulation
After preparation, patient is made to lie supine on couch in CT simulator.
These images are transferred to Eclipse treatment planning system (TPS), Varian and contouring is done for the treatment by the linear accelerator.