BIPH6106 neutron radiation therapy oncology

rad oncology

1. https://www.youtube.com/watch?v=X3SfQwM
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Neutron Therapy Treatment
For Advanced and RadioresistantTumors
Neutron Therapy

2. Neutron Therapy at Fermilab
Have been treating since 1976, not experimental
Radioresistant–not well controlled by conventional
photon (x-ray) therapy
Depends on the type of tissue that is cancerous
Location & type

3. Cancer
Stages & Treatment
Stages
Local Tumor
Regional Metastasis
Locally advanced
Systemic Disease
Treatment
Surgery
Radiation Therapy
Chemotherapy

4. What is Radiation Therapy?
(External Beam Therapy)
Radiation directed at the tumor from outside the body
Two critical components
Where the energy is deposited
The type of damage produced
Conventional photon (x-ray) therapy

6. Where is the Energy Deposited?0
20
40
60
80
100
0 5 10 15 20 25 30 35
)Depth in Phantom (cm
Dose, Normalized to Dmax (%)
SAD = 190 cm
SSD = 180 cm
Photons
Neutrons
Protons

7. Neutrons

8. Largeradioresistanttumors are not well
controlled by photon (or proton) therapy
Resting cells are radioresistant
Hypoxic (low oxygen) cells are radioresistant
Neutron therapy is less affected by cell
cycle or oxygen content
Why are Neutrons Needed?

9. The only practical source
of neutrons for clinical
radiotherapy is a cyclotron.
Cyclotron is an electric
device capable of accelerating
positively charged particles,
such as protons or deuterons,
to an energy of millions of
volts
Fast Neutrons. Practical sources

10. Alternative Radiation
Modalities
Fast Neutrons
More recently, cyclotrons to
produce neutrons have been
built using the p+ Be reaction.
The cyclotron can be small
enough to be installed in a hospital.
Neutron spectra produced by the
two processes are shown

11. Percentage Depth Doses for Neutron Beams
An essential factor in the choice of a neutron beam for clinical use
is its ability to penetrate to a sufficient depth.

12. How Do Neutrons Overcome Resistance?
The Type of Damage Produced
Cell killing mechanisms are complicated
DNA damage
Free radicals
Bystander effect
Inflammation
Genetics
Focus on DNA damage through:
Radiation Quality
Linear Energy Transfer -LET

13. Radiation Quality
Photons and Charged Particles Neutrons
Low LET High LET

14. 2 nm 10 nm 30 nm 2 μm
Optimum LET
100 eV/nm
~3 ip
~200 nm
DNA Damage

15. LET Comparison
(Linear Energy Transfer)
Photons & Protons
Neutrons

16. How can we turn LET,
radiation quality,
and all the other complexities of cell
killing
into something we can understand?

17. Survival of Clonogenic DU 145 Prostate Cancer Cells
0.000001
0.00001
0.0001
0.001
0.01
0.1
1
0 5 10 15 20 25 30
Dose in Gray
Photons in 2.00 Gy
fractions
Neutrons in 1.75 Gy
Fractions Relative Biological Effectiveness-RBE -
is the reason for pursuing Neutron Therapy
Blazek, et al
Factor of 3
Neutrons
Photons

18. So What is the Best Therapy?
LET
Low High
Dose
Distribution
Bragg
Exponential
Photons
Protons
Neutrons
Ions
$ $$
$$$ $$$$($)
Cost-effective
High RBE
Therapy

20. How is radiation therapy done?
1. Electron linear accelerator for photon therapy

21. 2. Proton linear accelerator for Neutron therapy

22. Photon & Neutron Collimators

24. Before Neutron Therapy
Prostate
Tumor
Bladder
(with contrast)
displaced
CT scan of prostate cancer

25. After 12.25 Gray of neutrons
Bladder
(no contrast)
Normal position

26. Beginning Of Treatment End of Treatment
Soft Tissue Sarcoma

27. Two Months After Treatment

28. Squamous Cell Carcinoma

29. Results of Neutron Clinical Trials
Reference -Nuclear data for neutron therapy: Status and
future needs -IAEA TECDOC 992 (1997)
“The proportion of patients suitable for neutrons ranges
from 10-20%, but this is probably a lower limit…with high
energy modern cyclotrons neutron therapy will be useful
for a larger proportion of patients.” )page 24)
Tumors where fast neutronsare superiorto conventional x-
rays are:
Salivary -locally extended, well differentiated
Paranasal sinuses -adenocarcinoma, mucoepidermoid,
squamous, adenoid cystic
Head and Neck -locally extended, metastatic
Soft tissue, osteo, and chondrosarcomas
Locally advanced prostate
Inoperable/recurrent melanomas(page 23)

30. Results of Neutron Clinical Trials
IAEA TECDOC 992 (1997) -(continued)
Tumors where more research is needed
Inoperable Pancreatic
Bladder
Esophagus
Recurrent or inoperable rectal
Locally advanced uterine cervix
Neutron boost for brain tumors(pp 13-19)

31. Review of the loco-regional rates for malignant salivary
gland tumors treated with radiation therapy.
Fast Neutrons
Authors Number of
Patients
Loco-regional control
(%)
Saroja et al.(1987) 113 71 (63%)
Catterall and Errington
(1987)
65 50 (77%)
Battermann and Mijnheer
(1986)
32 21 (66%)
Griffin et al.(1988) 32 26 (81%)
Duncan et al.(1987) 22 12 (55%)
Tsunemoto et al.(1989) 21 13 (62%)
Maor et al.(1981) 9 6 (67%)
Ornitz et al. (1979) 8 3 (38%)
Eichhorn (1981) 5 3 (60%)
Skolyszewski (1982) 3 2 (67%)
Overall 310 207 (67%)
Low-LET Radiotherapy Photon and/or Electron
beams
and/or Radioactive Implants
Authors Number of
Patients
Loco-regional
control (%)
Fitzpatrick and Theriault
(1986)
50 6 (12%)
Vikramet et al.(1984) 49 2 (4%)
Borthne et al. (1986) 35 8 (23%)
Rafla (1977) 25 9 (36%)
Fu et al.(1977) 19 6 (32%)
Stewart et al.(1968) 19 9 (47%)
Dobrowsky et al.(1986) 17 7 (41%)
Shidnia et al.(1980) 16 6 (38%)
Elkon et al.(1978) 13 2 (15%)
Rossman (1975) 11 6 (54%)
Overall 254 61 (24%)
Table III. from IAEA-TECDOC-992, “Nuclear data for neutron therapy: Status and future needs,” December 1997, pg. 12.

32. Side EffectsTheraputic Window
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 5 10 15 20 25
Dose (Gy)
Tumor Control
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Complication Rate
tumor control
complication rate
Desired tumor control
Acceptable complication rate
Theraputic Window

33. Comparison of neutron therapy with
photons

34. An Important Point for Potential
Health Care Consumers
Neutron Therapy is NOT a treatment of last resort.
Healthy tissue can only tolerate a certain amount of any type of
radiation.
A specific tumor site cannot be retreated if it has already been
treated with photons.
Patients from both physician and self referral
We presently treat up to 20 patients per year
Very underutilized

35. Current Efforts with Neutrons
Emphasis is being placed on two factors:
•First, subgroups of patients with specific types of tumors
that may benefit from neutrons must be found.
•Second, different fractionation patterns will be tried
for neutrons.

36. Current efforts with neutrons
Emphasis will be placed on slowly growing tumors, in view of
the observation of Breuer and Batterman that neutron RBE,
measured from pulmonary metastases in patients, increases
as tumor volume doubling time increases

37. Summary